Languages and linguistic resources transport from one locality to another,adapting to the norms,customs,and regulations of a new locality.This process involves translocalization.Translocalization emphasizes the moveme...Languages and linguistic resources transport from one locality to another,adapting to the norms,customs,and regulations of a new locality.This process involves translocalization.Translocalization emphasizes the movement of linguistic resources against the backdrop of globalization and the combination or reframing of resources from different localities.This research explores the extent to which translocalization is reflected by the linguistic landscapes of three distinct commercial areas in Guangzhou,China.It goes on to discuss how translocalization works together with social rescaling to incur the movement of linguistic resources and to result in distinct linguistic landscapes of the three commercial areas.It concludes that some languages or linguistic resources,such as English,pinyin and traditional Chinese writing,are transported to local contexts for the purpose of rescaling,whereas other languages or dialects,like Cantonese,might gradually lose their function of rescaling and retain its function in indexing local identity and solidarity.This study calls for more attention to the local resources and contexts in linguistic landscape studies.It argues for the indexical function of linguistic resources in social rescaling and city planning.展开更多
Exogenous l-phenylalanine application enhances cadmium(Cd)uptake and translocation in Kentucky bluegrass(Poa pratensis L.),offering a potential strategy for the phytoremediation of Cd-contaminated soils.This study inv...Exogenous l-phenylalanine application enhances cadmium(Cd)uptake and translocation in Kentucky bluegrass(Poa pratensis L.),offering a potential strategy for the phytoremediation of Cd-contaminated soils.This study investigated the role of exogenous l-phenylalanine in Cd uptake,translocation,and detoxification in Kentucky bluegrass.We employ a comprehensive approach combining integrated phenotypic analysis,antioxidant characteristics,Cd content determination,full-length transcriptome sequencing,transcriptomic analysis,proteome,and metabolome analyses to elucidate the molecular mechanisms underlying the long-distance Cd transport promotion by exogenous l-phenylalanine in Kentucky bluegrass,and to validate the function of the candidate gene PpNAS in Arabidopsis thaliana.l-phenylalanine at concentrations of 0.1,1,and 10 mg·L−1induced the Cd content in the leaves by 21%,45%,and 64%.However,the malondialdehyde content was not significantly different under 1 mg·L−1l-phenylalanine and Cd treatment compared to that under Cd treatment alone,but the Cd content significantly increased.In addition,1 mg·L−1l-phenylalanine and Cd treatment improved the antioxidant enzyme activity and biomass of Kentucky bluegrass under Cd stress.l-phenylalanine application upregulated genes associated with Cd uptake(HIPPs),long-distance translocation(HMAs,YSLs,and NAS),and vacuolar compartmentalization pathways(OPTs,ABCCs,and MTPS).Overexpression of PpNAS in Arabidopsis thaliana increased the Cd content in leaves and roots,supporting the positive role of l-phenylalanine in long-distance Cd transport.These results demonstrate that exogenous l-phenylalanine targets multiple metabolic pathways and Cd transporters to regulate Cd redistribution in Kentucky bluegrass,providing new strategies for the phytoremediation of Cd-contaminated soils utilizing l-phenylalanine.展开更多
Background:Translocator protein 18 kDa(TSPO)is a well-established biomarker of neuroinflammation and is implicated in the pathophysiology of various neurodegenerative diseases,including Alzheimer's disease(AD).Des...Background:Translocator protein 18 kDa(TSPO)is a well-established biomarker of neuroinflammation and is implicated in the pathophysiology of various neurodegenerative diseases,including Alzheimer's disease(AD).Despite existing radioligands,there remains a critical need for novel TSPO-targeted positron emission tomography(PET)tracers with improved binding specificity,higher brain uptake,and favorable pharmacokinetics.Methods:We designed and synthesized a class of novel TSPO ligand candidates.Following in vitro binding affinity screening,the lead Compound 3(TSPO-1118)was radiolabeled with fluorine-18.[18F]3([18F]TSPO-1118)was evaluated in two transgenic AD mouse models(3xTg and APP/PS1)and compared to age-matched wild-type(WT)controls.Biodistribution and radiometabolite analyses were conducted in CD-1 mice to assess brain penetration and metabolic stability.Results:Compound 3(TSPO-1118)demonstrated superior binding affinity for TSPO(Ki=2.3 nM),outperforming both other analogs in the series and the benchmark tracer GE180.[18F]3([18F]TSPO-1118)exhibited significantly higher brain uptake in both 3xTg and APP/PS1 mice relative to WT controls,including the cortex,thalamus,cerebellum,and hippocampus(p<0.05 to<0.01,Student's two-tailed t-test),consistent with elevated TSPO expression in disease models.The tracer also displayed favorable brain kinetics,high specific binding,and metabolic stability in vivo.Conclusions:[18F]3([18F]TSPO-1118)represents a promising next-generation PET radioligand for imaging TSPO with high affinity,robust brain uptake,and specificity in preclinical models of neurodegeneration.Its favorable profile supports further translational development toward clinical application in neuroinflammatory and neurodegenerative disorders.展开更多
Cadmium(Cd)contamination in agricultural systems poses a threat to human health.Arbuscular mycorrhizal fungi(AMF)and zinc oxide nanoparticles(ZnO NPs)applied alone have been shown to enhance winter wheat growth in Cd-...Cadmium(Cd)contamination in agricultural systems poses a threat to human health.Arbuscular mycorrhizal fungi(AMF)and zinc oxide nanoparticles(ZnO NPs)applied alone have been shown to enhance winter wheat growth in Cd-contaminated soil,but their combined effects remain largely unexplored,especially in naturally Cd-contaminated soils.Two naturally Cd-contaminated soils with different pH levels,an alkaline soil and an acidic soil collected from Henan and Hunan provinces,respectively,in China,were used to assess the effects of AMF and ZnO NPs on growth and Cd accumulation in winter wheat.The combined application of AMF and ZnO NPs significantly reduced(by 41%-71%)Cd concentration in winter wheat grown in Cd-contaminated soils.Specifically,the treatment with AMF and 20 mg kg−1ZnO NPs effectively decreased soil available Cd by 18%-32%and reduced wheat grain Cd concentration by 60%-71%,ensuring compliance with China's food safety threshold(<0.2 mg kg−1).Additionally,this treatment increased Zn concentration in wheat grain by 17.6%-31.3%,meeting the recommended dietary intake value for Zn(45-60 mg kg−1).Structural equation models(SEM)and correlation analysis showed that the reduction in grain Cd concentration was associated with a significant(P<0.01)decrease in soil available Cd,an increase in soil pH(especially in the acidic soil),restricted Cd translocation due to Zn-Cd competitive antagonism,and“dilution effect”resulting from improved plant growth.Overall,this study demonstrated that the combined application of AMF and low-dose ZnO NPs(20 mg kg−1)was the optimized strategy to reduce grain Cd concentration and improve Zn uptake in winter wheat grown in Cd-contaminated soils,regardless of soil pH.展开更多
Impaired nuclear translocation of glucocorticoid receptor(GR)has been implicated in hippocampal vulnerability in Alzheimer's disease(AD),yet the molecular basis of this defect remains poorly understood.This study ...Impaired nuclear translocation of glucocorticoid receptor(GR)has been implicated in hippocampal vulnerability in Alzheimer's disease(AD),yet the molecular basis of this defect remains poorly understood.This study identified Huntingtin-associated protein 1(Hap1)as a critical regulator of GR nuclear translocation in the hippocampus.Specifically,Hap1 expression progressively declined in the hippocampus of APP/PS1 mice with advancing age and pathological burden.,Hippocampal Hap1 knockdown induced pronounced cognitive deficits and synaptic deterioration,asi indicated by reduced dendritic arborization,decreased spine density,impaired long-term potentiation,,and exacerbated amyloid-βdeposition.Mechanistic中analyses showed that Hap1中deficiency increased GR ubiquitination and proteasomal degradation and,more importantly,disrupted ligand-dependent GR translocation to the nucleus,thereby attenuating GRdependent brain-derived neurotrophic factor transcription.In parallel,Hap1 knockdown elevated corticosterone concentration and induced depression-like behavior,consistent with hypothalamic-pituitary-adrenal axis dysregulation.Collectively,these findings establish defective GR nuclear trafficking driven by loss of Hap1function as a key pathomechanism linking intracellular transport failure to synaptic dysfunction in AD and highlight Hap1 as a potential therapeutic target.展开更多
Rye(Secale cereale L.)contains numerous disease resistance genes that can be utilized for wheat(Triticum aestivum)improvement.For example,rye chromosome 6 carries powdery mildew resistance genes.Wheat-rye 6R transloca...Rye(Secale cereale L.)contains numerous disease resistance genes that can be utilized for wheat(Triticum aestivum)improvement.For example,rye chromosome 6 carries powdery mildew resistance genes.Wheat-rye 6R translocation lines are highly useful,but more wheat-rye 6R translocation lines with potential breeding value are needed.In this study,we identified a new wheat-rye T6 BS.6 BL-6 RLKutranslocation chromosome,conferring powdery mildew resistance,from the progeny of the irradiated wheat-rye 6 RLKuditelosomic addition line.Genotyping using the wheat GBW16K array and specific markers revealed that approximately 104.03 Mb of the distal segment of 6 RLKureplaced approximately6.1 Mb of the distal segment of the long arm of 6 B(6 BL)to form the translocation chromosome.OligoFISH painting indicated that the 104.03 Mb segment of 6 RLKuis homologous to homoeologous group 7 chromosomes.Using wheat cultivars Chuanmai 62(CM62)and Chuannong 32(CN32)as backcross parents,we transferred the T6 BS.6 BL-6 RLKuchromosome into the two wheat backgrounds.We selected two translocation lines:CM62-6 RL and CN32-6 RL.Genotyping analysis indicated that the CM62-6 RL and CN32-6 RL genomes are highly similar to those of CM62 and CN32,respectively.The grains of CM62-6 RL were shriveled,whereas those of CN32-6 RL were full.The effect of the T6 BS.6 BL-6 RLKuchromosome on grain width also depended on the genetic background of the wheat.The improved grain lengths of both CM62-6 RL and CN32-6 RL contributed to the improvement in their thousand-kernel weight.The translocation chromosome had no negative effects on other important agronomic traits.These findings highlight the potential breeding value of the wheat-rye 6R translocation chromosome T6 BS.6 BL-6 RLKu.The compensation mechanisms of this translocation chromosome in different wheat backgrounds deserve further study.展开更多
BACKGROUND The gastrointestinal tract plays an important role in host defence during critical illness.Disruption of epithelial integrity,microbiome imbalance,and immune dysregulation have all been linked to the transl...BACKGROUND The gastrointestinal tract plays an important role in host defence during critical illness.Disruption of epithelial integrity,microbiome imbalance,and immune dysregulation have all been linked to the translocation of multidrug-resistant(MDR)organisms from intestinal colonization to invasive infection.However,whether these associations reflect true causal mechanisms remains uncertain,and available human evidence has not been comprehensively synthesized using current methodological standards.AIM To systematically evaluate human evidence examining the relationship between intestinal barrier dysfunction,microbial colonization,and subsequent MDR infection in adult critical illness,with particular attention to study quality,heterogeneity,and potential confounding factors.METHODS This systematic review was conducted in accordance with PRISMA guidelines.A structured literature search was performed in PubMed,EMBASE,and the Cochrane Library(2000-2025)using predefined Boolean combinations and Medical Subject Headings.Prospective and retrospective cohort studies involving intensive care units(ICU)adults were included if they evaluated intestinal colonization,biomarkers of barrier dysfunction(citrulline and intestinal fatty acid-binding protein),microbiome alterations,or endotoxemia.Study selection and data extraction were undertaken independently by two reviewers,with disagreements resolved through discussion.Risk of bias was assessed using the Newcastle-Ottawa Scale and ROBINS-I tool.Owing to methodological and clinical heterogeneity,findings were synthesized using a structured narrative approach rather than meta-analysis.RESULTS Across the included studies,intestinal colonization with carbapenem-resistant Enterobacteriaceae,carbapenemresistant Klebsiella pneumoniae,Acinetobacter baumannii,and vancomycin-resistant Enterococcus was consistently associated with an increased risk of subsequent bloodstream infection.However,progression rates varied considerably across cohorts,likely reflecting differences in patient characteristics,antimicrobial exposure,and ICU practices rather than a consistent effect size.Biomarker studies showed reduced citrulline levels and elevated intestinal fatty acid-binding protein concentrations in patients with gastrointestinal dysfunction;however,these markers indicate enterocyte injury rather than directly measuring intestinal permeability or bacterial translocation.Microbiome analyses demonstrated reduced diversity and impaired colonization resistance,although the extent and timing of these changes were not uniform across studies.Taken together,the evidence supports a biologically plausible link between epithelial injury,dysbiosis,and infection risk,but does not establish a direct causal relationship,largely due to the observational design of available studies and the influence of confounding factors such as illness severity,antimicrobial exposure,and ICU environment.CONCLUSION Gut barrier dysfunction appears to contribute to the pathogenesis of MDR infection in critically ill adults;however,current evidence supports association rather than causation.Early recognition of intestinal colonization and strategies aimed at preserving mucosal integrity may offer potential clinical benefit,although their effectiveness requires confirmation in well-designed prospective and interventional studies.展开更多
Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal micro...Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal microbial homeostasis also plays a crucial role in the pathogenesis of mastitis.Specifically,cows with mastitis exhibit reduced alpha diversity and altered microbial composition in the rumen.Inducing ruminal dysbiosis through a high-concentrate diet has been shown to trigger mastitis in cows,and transplantation of ruminal microbiota from mastitis-affected cows to recipient mice can induce mastitis in mice.Mechanistically,ruminal dysbiosis increases gastrointestinal inflammation and compromises the integrity of the gastrointestinal barrier,thereby facilitating the translocation of harmful bacterial components,metabolites,and pathobionts into the bloodstream.This disruption impairs blood-milk barrier function,leading to systemic inflammation and the development of mastitis.In this review,we summarize recent advances in understanding how ruminal dysbiosis induces mastitis and explore potential prevention and control strategies targeting the modulation of ruminal microbiota.展开更多
Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation...Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation(BT)critically influence stroke outcomes.However,biological variability among commonly used rodent substrains has received limited attention.In this pilot study,we compared poststroke immune responses in two Wistar rat substrains obtained from different suppliers:RccHan(Envigo)and RjHan(Janvier).Naive animals(n=4)and rats subjected to permanent cerebral ischemia(n=8 per substrain)were evaluated 72 h after middle cerebral artery occlusion and stratified according to the presence or absence of BT.Immune cell populations in blood and bone marrow were analyzed using flow cytometry,and leukocyte infiltration into ischemic brain tissue was quantified using immunohisto-chemistry.Differences were considered statistically significant when p<0.05.Both substrains developed significant infarcts and neurological deficits.RccHan rats exhibited larger infarct volumes and more extensive BT across multiple organs.In contrast,RjHan rats exhibited BT mainly confined to mesenteric lymph nodes but exhibited greater IBP.Although dissemination was broader in RccHan rats,overall bacterial burden was slightly lower compared with RjHan,and extraintestinal bacterial composition differed between groups.Particularly,RjHan rats exhibited stronger systemic and central immune activation,with significant alterations in lymphocyte and monocyte populations and enhanced granulocyte and T-cell infiltration within ischemic lesions.These findings demonstrate that substrain origin profoundly influences poststroke intestinal barrier integrity,bacterial dissemination,and immune responses considering substrain-related variability is essential to improve reproducibility and translational relevance in preclinical stroke research.展开更多
Leaf senescence is a programmed physiological process that enhances nutrient use efficiency,thereby promoting plant adaptation and crop productivity.However,the molecular mechanisms that govern the initiation and prec...Leaf senescence is a programmed physiological process that enhances nutrient use efficiency,thereby promoting plant adaptation and crop productivity.However,the molecular mechanisms that govern the initiation and precisely control the progression of senescence remain poorly understood.Here,we identify GERAS1(GER1),a membrane-associated NAC transcription factor that acts as an age-dependent integrator of the leaf senescence program.As leaves age,GER1 expression is induced,and its protein undergoes age-dependent translocation from the plasma membrane to the nucleus.The activation tagging mutant ger1-D exhibits early leaf senescence,while the disruption of GER1 and its three homologs in a quadruple ger1 ger2 ger3 ger4 mutant causes significantly delayed leaf senescence.We further show that the nucleus-localized GER1 directly binds and activates the promoter of the central senescence regulator ORE1.Moreover,GER1 and ORE1 form a transcriptional activation complex that directly upregulates SID2,which encodes a key salicylic acid(SA)biosynthetic enzyme.The accumulation of SA in turn promotes the expression of GER1,establishing a positive feedforward loop that drives leaf senescence.Taken together,these findings not only unveil that GER1 acts as a central spatiotemporal regulator of leaf senescence,but also uncover a straightforward membrane-to-nucleus signaling pathway that finely regulates leaf aging.展开更多
The impact of gut microbiota on immune regulation has received increasing attention in recent years,particularly its role in immune-mediated liver diseases such as autoimmune hepatitis(AIH),primary biliary cholangitis...The impact of gut microbiota on immune regulation has received increasing attention in recent years,particularly its role in immune-mediated liver diseases such as autoimmune hepatitis(AIH),primary biliary cholangitis(PBC),primary sclerosing cholangitis(PSC),and immunoglobulin G4(IgG4)-related sclerosing cholangitis(IgG4-SC).Disturbances in gut microbiota composition(gut dysbiosis)compromise the intestinal barrier and trigger abnormal immune activity,which foster persistent inflammation,autoimmunity and subsequent liver damage.An increase in Veillonella,Streptococcus,and Lactobacillus were found in most studies for all four diseases.A decrease in Clostridium was detected in AIH and PBC,but an increase in these bacteria is observed in PSC and IgG4-SC.Other common changes in AIH and PBC were an increase in Klebsiella and a decrease in Ruminococcus.In contrast,Ruminococcus is often found to be elevated in PSC.Common features of PBC and PSC are an increase in Enterococcus and a decrease in Faecalibacterium,Enterobacterium,and Coprococcus.Gut microbiome changes in IgG4-SC are most similar to PSC.Probiotics have positive effects in AIH and cholestatic liver diseases in small randomized controlled trial(RCTs).Positive effects of butyrate were in mice models of AIH and PBC.A small study found a positive effect of butyrate on patients with PBC.Indole-3-carboxaldehyde reduced the inflammatory activity of Tcells in patients with AIH in vitro and reduced inflammation in a PSC mouse model.Fecal microbiota transplantation showed beneficial effects in mouse models of AIH and in patients with PSC.Many studies demonstrated the effectiveness of microbiota-targeted therapy on mouse models of autoimmune liver diseases.However,these results remain to be verified in RCTs involving humans.展开更多
The exploration and identification of spontaneous weed species in heavy metal–contaminated soils represent a relevant approach for understanding the role and their potential application in phytoremediation.In cacao c...The exploration and identification of spontaneous weed species in heavy metal–contaminated soils represent a relevant approach for understanding the role and their potential application in phytoremediation.In cacao cultivation,cadmium contamination poses a significant risk due to the restrictions established for soils and cacao-derived products,thereby threatening productive sustainability and export viability.The objective of this study was to identify weed species associated with cacao cultivation exhibiting accumulation patterns and phytoremediation potential for Cd and Pb,through the assessment of biomass production and the bioconcentration factor(BCF)and translocation factor(TF),in natural conditions.Soil samples were collected from seven cacao-growing zones,and the site with the highest Cd concentration(1.65 mg kg−1)was selected,where ten dominant weed species were identified and evaluated.Significant interspecific differences were observed in biomass production and in Cd and Pb concentrations(p<0.05).Talinum paniculatum exhibited the highest total biomass(6.15 g)and the highest TF for Cd,whereas Cyperus aggregatus showed the greatest total Cd accumulation(2.68 mg kg−1).BCF and TF values enabled the identification of species with accumulation patterns consistent with Cd phytoextraction(T.paniculatum,C.aggregatus,Pseudelephantopus spiralis,Bidens riparia,Euphorbia heterophylla,and Malvastrum coromandelianum)and with phytostabilization(Ocimum campechianum).For Pb the observed patterns were consistent with potential phytoextractive behavior in B.riparia,P.spiralis,E.heterophylla,Hilleria latifolia,and Acalypha stachyura.Although these results do not constitute functional evidence of remediation,they describe heavy metal accumulation and translocation patterns in native weed species,providing a technical basis for the design of future experimental trials aimed at the sustainable remediation of contaminated soils.展开更多
Diabetic cardiomyopathy(DCM)refers diabetic patients develop cardiomyopathy characterized by cardiac systolic and diastolic dysfunction.Currently,no research has explored the role of ten-eleven translocation(TET)-medi...Diabetic cardiomyopathy(DCM)refers diabetic patients develop cardiomyopathy characterized by cardiac systolic and diastolic dysfunction.Currently,no research has explored the role of ten-eleven translocation(TET)-mediated active DNA demethylation in the development of DCM.Through case-control study,we found that the level of 5-hydroxymethylcystein in peripheral blood DNA of DCM patients was significantly lower than it in the healthy subjects and diabetic patients.Secondly,we had conducted an animal study to explore the effect of thinned young apple polyphenol(TYAP)on DNA demethylation in streptococci-induced diabetic mice.TYAP effectively prevented the ventricular dysfunction and cardiomycyte disarray via alleviating DNA epigenetic modifications metabolic disorders in diabetic mice heart.TYAP increased the stability of TET2 protein via activating phosphorylate AMPK and enhanced the activity of TETs enzymes via improving tricarboxylic acid cycle,then promoted TET-mediated active DNA demethylation.TYAP prevented the occurrence of DCM by promoting TET2-mediated active DNA demethylation in the heart of diabetic mice.展开更多
In plants,nickel(Ni)occurs naturally at 0.01–5μg·g−1dry weight and plays essential roles in physiological processes from germination to fruit development(Seregin and Kozhevnikova,2006).However,excessive Ni d...In plants,nickel(Ni)occurs naturally at 0.01–5μg·g−1dry weight and plays essential roles in physiological processes from germination to fruit development(Seregin and Kozhevnikova,2006).However,excessive Ni disrupts growth,metabolism,enzyme activity,stomatal function,and chlorophyll integrity,ultimately impairing water relations(Heidari et al.,2020;Valivand and Amooaghaie,2021a,2021b).Ni also interferes with mineral uptake and translocation in crops,such as zucchini,tomato,and lettuce(Valivand and Amooaghaie,2021a,2021b;Fortini et al.,2025).Owing to its toxicity and health risks(Das et al.,2019),strict regulatory limits have been established to limit Ni exposure.In Italy,the Ministerial Decree on wastewater reuse sets a maximum Ni concentration of 0.2 mg·L−1for long-term irrigation.展开更多
A key objective of wheat(Triticum aestivum)breeding is the simultaneous improvement of disease resistance and bread making quality.The Glu-V1 locus encoding the high-molecular-weight glutenin subunit(HMW-GS)V71 and th...A key objective of wheat(Triticum aestivum)breeding is the simultaneous improvement of disease resistance and bread making quality.The Glu-V1 locus encoding the high-molecular-weight glutenin subunit(HMW-GS)V71 and the powdery mildew resistance gene Pm67 were previously identified on chromosome arm 1 VS of the wild wheat species Dasypyrum villosum.Here,we generated the T1 DL.1V#4S translocation line NAU195,which carried the V71 subunit for improved bread-making quality but was susceptible to all 18 isolates of the powdery mildew fungus Bgt examined.By contrast,the previously developed T1 DL.1V#5S line NAU196 harbors the Pm67 gene conferring broad-spectrum powdery mildew resistance but lacks the V71 subunit.Genetic analysis of F1 and F2 progenies from a cross between NAU195 and NAU196 confirmed that Pm67 is a single dominant gene.By screening 2954 F2 plants,we fine mapped Pm67 to an approximately 2.1 Mb interval on chromosome arm 1 VS in the reference genome.We identified 35 high-confidence protein-coding genes in this region,including eight candidate genes encoding nucleotide binding site leucine rich repeat(NLR)proteins.We identified 12 recombinant T1 DL.1 VS translocation lines harboring both the V71 subunit and Pm67 genes,and introgressed one of the corresponding translocations into the high-yielding cultivar NMZ119.Plant development in the resulting T1 DL.1 VS translocation lines harboring the V71 subunit and Pm67 genes was comparable to that of NMZ119,with no significant yield penalty but with markedly improved powdery mildew resistance and gluten strength.Overall,our strategy for mapping and pyramiding alien genes in the common wheat background allowed us to generate a valuable genetic resource and molecular tool for accelerating the concurrent improvement of powdery mildew resistance and bread making quality.展开更多
The unique regulatory effect of pH on electrostatic interactions offers a powerful approach for manipulating and separating singlestranded DNA(ssDNA)molecules.In this study,we employ Langevin dynamics simulations to i...The unique regulatory effect of pH on electrostatic interactions offers a powerful approach for manipulating and separating singlestranded DNA(ssDNA)molecules.In this study,we employ Langevin dynamics simulations to investigate the translocation dynamics of two ssDNAs,poly(dA)and poly(dT),through a silicon nitride nanopore under acidic conditions.The key distinction between the two chains is their different pH-dependent protonation.At low pH,the highly protonated adenine bases experience repulsive interactions from the similarly protonated nanopore surface and the retarding force from the external voltage,whereas neutral thymine bases do not.Consequently,compared to poly(dT),poly(dA)exhibits a lower capture probability and slower translocation speed under strongly acidic conditions.However,the difference in the translocation behaviors between the two chains gradually diminishes as the pH increases.Based on their distinct pH-dependent behaviors,poly(dA)and poly(dT)of identical length can be successfully separated through the translocation strategy at low pH,even when they are initially mixed on the same side of the nanopore.展开更多
Alzheimer's disease(AD)is a complex and multifactorial neurodegenerative disorder,marked by a variety of pathological hallmarks such as oxidative stress(OS),metal accumulation,and the aggregation of amyloid-beta(A...Alzheimer's disease(AD)is a complex and multifactorial neurodegenerative disorder,marked by a variety of pathological hallmarks such as oxidative stress(OS),metal accumulation,and the aggregation of amyloid-beta(Aβ)proteins.Erucin,a natural compound present in cruciferous plants,has demonstrated promising therapeutic potential in modulating neurodegenerative diseases,hinting at its neuroprotective capabilities.In this study,we engineered an innovative intracellular protein delivery system centered around erucin.This delivery platform operates through a cell membrane perforation mechanism,enabling the swift translocation of target proteins into the cytoplasm.As a result,it substantially shortens the time required for the proteins to exert their functions.Significantly,this delivery system inherently possesses the capacity to inhibit Aβaggregation.In PC12 cell models,the delivery of the antioxidant enzyme superoxide dismutase(SOD)successfully mitigated the OS triggered by Aβaggregation and decreased cytotoxicity.This multifaceted therapeutic strategy holds great promise as an effective approach for the treatment of AD.展开更多
BACKGROUND Tendon stem/progenitor cells(TSPCs)are a novel type of stem cell.TSPCs share common characteristics with stem cells,including their proliferation,pluripotency,and self-renewal abilities.Circular RNA plasmac...BACKGROUND Tendon stem/progenitor cells(TSPCs)are a novel type of stem cell.TSPCs share common characteristics with stem cells,including their proliferation,pluripotency,and self-renewal abilities.Circular RNA plasmacytoma variant translocation 1(circ_PVT1)has been reported to inhibit senescence in TSPCs.However,the mechanism by which circ_PVT1 regulates the proliferation and differentiation of TSPCs remains unclear.AIM To explore how circ_PVT1 regulates the proliferation and differentiation of TSPCs.METHODS Mouse TSPCs were isolated from the Achilles tendon of 12 male C57Bl/6 mice at postnatal day 30,and 5 ng/mL of transforming growth factor(TGF)-β1 was used to induce the tenogenic differentiation in TSPCs.Picro-Sirius red staining was used to assess the proliferation,migration,and apoptosis of TSPCs.Biochemical kits were used to determine the levels of reactive oxygen species,malondialdehyde,glutathione,superoxide dismutase,and ATP.Then,N6-methyladenosine(m6A)dot blot and methylated RNA immunoprecipitation polymerase chain reaction(RIP-PCR)were used to examine the m6A levels.Moreover,RNA pulldown and RIP-PCR were performed to analyze the interaction between WTAP and circ_PVT1.RESULTS TGF-β1 treatment induced tenogenic differentiation of TSPCs.Circ_PVT1 knockdown reversed the increase of tendon-specific protein,cell proliferation,and migration that was induced by TGF-β1 treatment.In addition,circ_PVT1 inhibition promoted oxidative stress and mitochondrial damage in the TGF-β1-induced TSPCs.The m6A modification level of circ_PVT1 was upregulated in the TGF-β1-induced TSPCs.Furthermore,RNA pulldown and RIP-PCR showed that circ_PVT1 interacted with WTAP in TSPCs,and the WTAP-mediated m6A modification of circ_PVT1 regulated the differentiation of TSPCs.CONCLUSION WTAP-mediated m6A modification of circ_PVT1 promotes the proliferation and tenogenic differentiation of TSPCs,thereby indicating a promising therapeutic strategy for tendon repair.展开更多
Severe acute pancreatitis(SAP),a prevalent and life-threatening abdominal emergency,is characterized by its abrupt onset,rapid progression,and high mortality rate,frequently precipitating multiple organ dysfunction sy...Severe acute pancreatitis(SAP),a prevalent and life-threatening abdominal emergency,is characterized by its abrupt onset,rapid progression,and high mortality rate,frequently precipitating multiple organ dysfunction syndromes.Acute lung injury(ALI)represents the most common early complication of SAP.ALI may progress to acute respiratory distress syndrome,which constitutes the primary cause of mortality in patients with SAP.However,the precise pathogenesis underlying ALI in SAP remains incompletely elucidated.Notably,recent advances in gut-lung axis research have significantly advanced our understanding of SAPassociated ALI(SAP-ALI).The gut-lung axis,a sophisticated bidirectional communication network linking the intestines and lungs,facilitates crosstalk between the microbiota and their metabolites across both organs via lymphatic and circulatory systems alongside the mucosal immune system.Critically,research confirms that SAP induces severe gut microbiota dysbiosis.This dysbiosis disrupts the intestinal mucosal barrier,enabling bacterial and endotoxin translocation to the lungs through lymphatic and hematogenous routes.Concurrently,gutderived immune cells migrate to the lungs via the bloodstream,directly contributing to pulmonary immune-inflammatory imbalance.Consequently,this review synthesized the central role of the gut-lung axis in SAP-ALI pathogenesis and explored emerging therapeutic strategies targeting this pivotal axis,aiming to provide novel insights for the clinical prevention and treatment of SAP-ALI.展开更多
AIM:To investigate the role of pyruvate kinase M2(PKM2)in high glucose(HG)-stimulated retinal endothelial cells and its underlying molecular mechanisms and signaling pathways in retinal angiogenesis.METHODS:Human reti...AIM:To investigate the role of pyruvate kinase M2(PKM2)in high glucose(HG)-stimulated retinal endothelial cells and its underlying molecular mechanisms and signaling pathways in retinal angiogenesis.METHODS:Human retinal microvascular endothelial cells(HRMECs)were cultured and divided into the following groups:normal glucose(NG,5.5 mmol/L),HG(30 mmol/L),HG with PKM2 knockdown(HG+shPKM2),and HG treated with the pharmacological activator TEPP‑46(HG+TEPP‑46).Cellular viability,proliferation,migration,and tube‑forming ability were assessed using CCK‑8,EdU,wound healing/Transwell,and Matrigel assays,respectively.The expression levels of PKM2,phosphorylated PKM2(p‑PKM2,Y105),hypoxia-inducible factor-1α(HIF‑1α),and vascular endothelial growth factor A(VEGFA)were detected by Western blotting.The oligomerization status of PKM2 was analyzed via native gel electrophoresis.The subcellular localization of PKM2 was examined by immunofluorescence and nuclear‑cytoplasmic fractionation.RESULTS:Under HG stimulation,the expression level of PKM2 was significantly increased(P<0.05).Knockdown of PKM2 was found to markedly suppress cell viability,proliferation,migration,and tube formation in HRMECs(P<0.05).Mechanistic studies revealed that phosphorylation of PKM2 at the Y105 site was promoted by HG treatment,which induced its dissociation from a tetramer to a dimer,thereby driving its nuclear translocation.Upon entering the nucleus,PKM2 was shown to exert critical non‑metabolic functions;it was physically bound to HIF‑1αand acted as its co‑activator,leading to significant upregulation of VEGFA expression(P<0.05).In contrast,the PKM2 activator TEPP‑46 effectively prevented dimerization and nuclear translocation of PKM2 by promoting its tetramerization.Consequently,the PKM2/HIF‑1αaxis‑mediated upregulation of VEGFA was blocked,ultimately resulting in the reversal of HG‑induced angiogenesis.CONCLUSION:HG influences retinal endothelial cell function by inducing PKM2 phosphor ylation,dimerization,and nuclear translocation.The shift in PKM2 phosphorylation and oligomerization status represents a key mechanism through which TEPP-46 reverses HGinduced angiogenesis.展开更多
基金supported by MOE Project of Humanities and Social Sciences for Young Researchers(Project No.:16YJC740023)Project of Humanities and Social Sciences in Universities and Colleges in Guangdong Province[Project No.:2016WTSCX033]the support from the Chinese MOE Research Project of Humanities and Social Science(Project No.:16JJD740006)conducted by the Center for Linguistics and Applied Linguistics,Guangdong University of Foreign Studies.
摘要Languages and linguistic resources transport from one locality to another,adapting to the norms,customs,and regulations of a new locality.This process involves translocalization.Translocalization emphasizes the movement of linguistic resources against the backdrop of globalization and the combination or reframing of resources from different localities.This research explores the extent to which translocalization is reflected by the linguistic landscapes of three distinct commercial areas in Guangzhou,China.It goes on to discuss how translocalization works together with social rescaling to incur the movement of linguistic resources and to result in distinct linguistic landscapes of the three commercial areas.It concludes that some languages or linguistic resources,such as English,pinyin and traditional Chinese writing,are transported to local contexts for the purpose of rescaling,whereas other languages or dialects,like Cantonese,might gradually lose their function of rescaling and retain its function in indexing local identity and solidarity.This study calls for more attention to the local resources and contexts in linguistic landscape studies.It argues for the indexical function of linguistic resources in social rescaling and city planning.
基金supported by the Open Competition Projects to Select the Best Candidates for Leading Key Initiatives of the Key Laboratory of Grassland Ecosystems,Gansu Agricultural University,Ministry of Education(Grant No.KLGE-2024-03)the National Natural Science Foundation of China(Grant No.32071886)the Fostering Foundation for the Excellent Ph.D.Dissertation of Gansu Agricultural University(Grant No.YB2022003)。
摘要Exogenous l-phenylalanine application enhances cadmium(Cd)uptake and translocation in Kentucky bluegrass(Poa pratensis L.),offering a potential strategy for the phytoremediation of Cd-contaminated soils.This study investigated the role of exogenous l-phenylalanine in Cd uptake,translocation,and detoxification in Kentucky bluegrass.We employ a comprehensive approach combining integrated phenotypic analysis,antioxidant characteristics,Cd content determination,full-length transcriptome sequencing,transcriptomic analysis,proteome,and metabolome analyses to elucidate the molecular mechanisms underlying the long-distance Cd transport promotion by exogenous l-phenylalanine in Kentucky bluegrass,and to validate the function of the candidate gene PpNAS in Arabidopsis thaliana.l-phenylalanine at concentrations of 0.1,1,and 10 mg·L−1induced the Cd content in the leaves by 21%,45%,and 64%.However,the malondialdehyde content was not significantly different under 1 mg·L−1l-phenylalanine and Cd treatment compared to that under Cd treatment alone,but the Cd content significantly increased.In addition,1 mg·L−1l-phenylalanine and Cd treatment improved the antioxidant enzyme activity and biomass of Kentucky bluegrass under Cd stress.l-phenylalanine application upregulated genes associated with Cd uptake(HIPPs),long-distance translocation(HMAs,YSLs,and NAS),and vacuolar compartmentalization pathways(OPTs,ABCCs,and MTPS).Overexpression of PpNAS in Arabidopsis thaliana increased the Cd content in leaves and roots,supporting the positive role of l-phenylalanine in long-distance Cd transport.These results demonstrate that exogenous l-phenylalanine targets multiple metabolic pathways and Cd transporters to regulate Cd redistribution in Kentucky bluegrass,providing new strategies for the phytoremediation of Cd-contaminated soils utilizing l-phenylalanine.
摘要Background:Translocator protein 18 kDa(TSPO)is a well-established biomarker of neuroinflammation and is implicated in the pathophysiology of various neurodegenerative diseases,including Alzheimer's disease(AD).Despite existing radioligands,there remains a critical need for novel TSPO-targeted positron emission tomography(PET)tracers with improved binding specificity,higher brain uptake,and favorable pharmacokinetics.Methods:We designed and synthesized a class of novel TSPO ligand candidates.Following in vitro binding affinity screening,the lead Compound 3(TSPO-1118)was radiolabeled with fluorine-18.[18F]3([18F]TSPO-1118)was evaluated in two transgenic AD mouse models(3xTg and APP/PS1)and compared to age-matched wild-type(WT)controls.Biodistribution and radiometabolite analyses were conducted in CD-1 mice to assess brain penetration and metabolic stability.Results:Compound 3(TSPO-1118)demonstrated superior binding affinity for TSPO(Ki=2.3 nM),outperforming both other analogs in the series and the benchmark tracer GE180.[18F]3([18F]TSPO-1118)exhibited significantly higher brain uptake in both 3xTg and APP/PS1 mice relative to WT controls,including the cortex,thalamus,cerebellum,and hippocampus(p<0.05 to<0.01,Student's two-tailed t-test),consistent with elevated TSPO expression in disease models.The tracer also displayed favorable brain kinetics,high specific binding,and metabolic stability in vivo.Conclusions:[18F]3([18F]TSPO-1118)represents a promising next-generation PET radioligand for imaging TSPO with high affinity,robust brain uptake,and specificity in preclinical models of neurodegeneration.Its favorable profile supports further translational development toward clinical application in neuroinflammatory and neurodegenerative disorders.
基金supported by the Natural Science Basic Research Program of Shaanxi,China(No.2023-JC-ZD-17)the National Natural Science Foundation of China(Nos.42077325 and 41571456).
摘要Cadmium(Cd)contamination in agricultural systems poses a threat to human health.Arbuscular mycorrhizal fungi(AMF)and zinc oxide nanoparticles(ZnO NPs)applied alone have been shown to enhance winter wheat growth in Cd-contaminated soil,but their combined effects remain largely unexplored,especially in naturally Cd-contaminated soils.Two naturally Cd-contaminated soils with different pH levels,an alkaline soil and an acidic soil collected from Henan and Hunan provinces,respectively,in China,were used to assess the effects of AMF and ZnO NPs on growth and Cd accumulation in winter wheat.The combined application of AMF and ZnO NPs significantly reduced(by 41%-71%)Cd concentration in winter wheat grown in Cd-contaminated soils.Specifically,the treatment with AMF and 20 mg kg−1ZnO NPs effectively decreased soil available Cd by 18%-32%and reduced wheat grain Cd concentration by 60%-71%,ensuring compliance with China's food safety threshold(<0.2 mg kg−1).Additionally,this treatment increased Zn concentration in wheat grain by 17.6%-31.3%,meeting the recommended dietary intake value for Zn(45-60 mg kg−1).Structural equation models(SEM)and correlation analysis showed that the reduction in grain Cd concentration was associated with a significant(P<0.01)decrease in soil available Cd,an increase in soil pH(especially in the acidic soil),restricted Cd translocation due to Zn-Cd competitive antagonism,and“dilution effect”resulting from improved plant growth.Overall,this study demonstrated that the combined application of AMF and low-dose ZnO NPs(20 mg kg−1)was the optimized strategy to reduce grain Cd concentration and improve Zn uptake in winter wheat grown in Cd-contaminated soils,regardless of soil pH.
基金supported by the Brain Science and Brainlike Intelligence Technology-National Science and Technology Major Project(2022ZD0211600)Natural Science Foundation of Hubei Province(2022CFB216)National Natural Science Foundation of China(82371444)。
摘要Impaired nuclear translocation of glucocorticoid receptor(GR)has been implicated in hippocampal vulnerability in Alzheimer's disease(AD),yet the molecular basis of this defect remains poorly understood.This study identified Huntingtin-associated protein 1(Hap1)as a critical regulator of GR nuclear translocation in the hippocampus.Specifically,Hap1 expression progressively declined in the hippocampus of APP/PS1 mice with advancing age and pathological burden.,Hippocampal Hap1 knockdown induced pronounced cognitive deficits and synaptic deterioration,asi indicated by reduced dendritic arborization,decreased spine density,impaired long-term potentiation,,and exacerbated amyloid-βdeposition.Mechanistic中analyses showed that Hap1中deficiency increased GR ubiquitination and proteasomal degradation and,more importantly,disrupted ligand-dependent GR translocation to the nucleus,thereby attenuating GRdependent brain-derived neurotrophic factor transcription.In parallel,Hap1 knockdown elevated corticosterone concentration and induced depression-like behavior,consistent with hypothalamic-pituitary-adrenal axis dysregulation.Collectively,these findings establish defective GR nuclear trafficking driven by loss of Hap1function as a key pathomechanism linking intracellular transport failure to synaptic dysfunction in AD and highlight Hap1 as a potential therapeutic target.
基金supported by the National Key Research and Development Program of China(2024YFD1201202)the National Natural Science Foundation of China(31770373)。
摘要Rye(Secale cereale L.)contains numerous disease resistance genes that can be utilized for wheat(Triticum aestivum)improvement.For example,rye chromosome 6 carries powdery mildew resistance genes.Wheat-rye 6R translocation lines are highly useful,but more wheat-rye 6R translocation lines with potential breeding value are needed.In this study,we identified a new wheat-rye T6 BS.6 BL-6 RLKutranslocation chromosome,conferring powdery mildew resistance,from the progeny of the irradiated wheat-rye 6 RLKuditelosomic addition line.Genotyping using the wheat GBW16K array and specific markers revealed that approximately 104.03 Mb of the distal segment of 6 RLKureplaced approximately6.1 Mb of the distal segment of the long arm of 6 B(6 BL)to form the translocation chromosome.OligoFISH painting indicated that the 104.03 Mb segment of 6 RLKuis homologous to homoeologous group 7 chromosomes.Using wheat cultivars Chuanmai 62(CM62)and Chuannong 32(CN32)as backcross parents,we transferred the T6 BS.6 BL-6 RLKuchromosome into the two wheat backgrounds.We selected two translocation lines:CM62-6 RL and CN32-6 RL.Genotyping analysis indicated that the CM62-6 RL and CN32-6 RL genomes are highly similar to those of CM62 and CN32,respectively.The grains of CM62-6 RL were shriveled,whereas those of CN32-6 RL were full.The effect of the T6 BS.6 BL-6 RLKuchromosome on grain width also depended on the genetic background of the wheat.The improved grain lengths of both CM62-6 RL and CN32-6 RL contributed to the improvement in their thousand-kernel weight.The translocation chromosome had no negative effects on other important agronomic traits.These findings highlight the potential breeding value of the wheat-rye 6R translocation chromosome T6 BS.6 BL-6 RLKu.The compensation mechanisms of this translocation chromosome in different wheat backgrounds deserve further study.
摘要BACKGROUND The gastrointestinal tract plays an important role in host defence during critical illness.Disruption of epithelial integrity,microbiome imbalance,and immune dysregulation have all been linked to the translocation of multidrug-resistant(MDR)organisms from intestinal colonization to invasive infection.However,whether these associations reflect true causal mechanisms remains uncertain,and available human evidence has not been comprehensively synthesized using current methodological standards.AIM To systematically evaluate human evidence examining the relationship between intestinal barrier dysfunction,microbial colonization,and subsequent MDR infection in adult critical illness,with particular attention to study quality,heterogeneity,and potential confounding factors.METHODS This systematic review was conducted in accordance with PRISMA guidelines.A structured literature search was performed in PubMed,EMBASE,and the Cochrane Library(2000-2025)using predefined Boolean combinations and Medical Subject Headings.Prospective and retrospective cohort studies involving intensive care units(ICU)adults were included if they evaluated intestinal colonization,biomarkers of barrier dysfunction(citrulline and intestinal fatty acid-binding protein),microbiome alterations,or endotoxemia.Study selection and data extraction were undertaken independently by two reviewers,with disagreements resolved through discussion.Risk of bias was assessed using the Newcastle-Ottawa Scale and ROBINS-I tool.Owing to methodological and clinical heterogeneity,findings were synthesized using a structured narrative approach rather than meta-analysis.RESULTS Across the included studies,intestinal colonization with carbapenem-resistant Enterobacteriaceae,carbapenemresistant Klebsiella pneumoniae,Acinetobacter baumannii,and vancomycin-resistant Enterococcus was consistently associated with an increased risk of subsequent bloodstream infection.However,progression rates varied considerably across cohorts,likely reflecting differences in patient characteristics,antimicrobial exposure,and ICU practices rather than a consistent effect size.Biomarker studies showed reduced citrulline levels and elevated intestinal fatty acid-binding protein concentrations in patients with gastrointestinal dysfunction;however,these markers indicate enterocyte injury rather than directly measuring intestinal permeability or bacterial translocation.Microbiome analyses demonstrated reduced diversity and impaired colonization resistance,although the extent and timing of these changes were not uniform across studies.Taken together,the evidence supports a biologically plausible link between epithelial injury,dysbiosis,and infection risk,but does not establish a direct causal relationship,largely due to the observational design of available studies and the influence of confounding factors such as illness severity,antimicrobial exposure,and ICU environment.CONCLUSION Gut barrier dysfunction appears to contribute to the pathogenesis of MDR infection in critically ill adults;however,current evidence supports association rather than causation.Early recognition of intestinal colonization and strategies aimed at preserving mucosal integrity may offer potential clinical benefit,although their effectiveness requires confirmation in well-designed prospective and interventional studies.
基金supported by the National Key R&D Program of China(2023YFD1801100)China National Postdoctoral Program for Innovative Talents(BX20230140)China Postdoctoral Science Foundation(2023M741348)。
摘要Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal microbial homeostasis also plays a crucial role in the pathogenesis of mastitis.Specifically,cows with mastitis exhibit reduced alpha diversity and altered microbial composition in the rumen.Inducing ruminal dysbiosis through a high-concentrate diet has been shown to trigger mastitis in cows,and transplantation of ruminal microbiota from mastitis-affected cows to recipient mice can induce mastitis in mice.Mechanistically,ruminal dysbiosis increases gastrointestinal inflammation and compromises the integrity of the gastrointestinal barrier,thereby facilitating the translocation of harmful bacterial components,metabolites,and pathobionts into the bloodstream.This disruption impairs blood-milk barrier function,leading to systemic inflammation and the development of mastitis.In this review,we summarize recent advances in understanding how ruminal dysbiosis induces mastitis and explore potential prevention and control strategies targeting the modulation of ruminal microbiota.
基金Leducq Trans-Atlantic Network of Excellence,Grant/Award Number:TNE-21CVD04Spanish Ministry of Science and Innovation,Grant/Award Number:PID2020-117765RB-I00 and PID2022-140616OB-I00+1 种基金Instituto de Salud Carlos Ⅲ,European Development Regional Fund,RICORS-ICTUS Grant/Award Number:RD21/0006/0001the FORTALECE program. Grant/Award Number:FORT23/00023。
摘要Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation(BT)critically influence stroke outcomes.However,biological variability among commonly used rodent substrains has received limited attention.In this pilot study,we compared poststroke immune responses in two Wistar rat substrains obtained from different suppliers:RccHan(Envigo)and RjHan(Janvier).Naive animals(n=4)and rats subjected to permanent cerebral ischemia(n=8 per substrain)were evaluated 72 h after middle cerebral artery occlusion and stratified according to the presence or absence of BT.Immune cell populations in blood and bone marrow were analyzed using flow cytometry,and leukocyte infiltration into ischemic brain tissue was quantified using immunohisto-chemistry.Differences were considered statistically significant when p<0.05.Both substrains developed significant infarcts and neurological deficits.RccHan rats exhibited larger infarct volumes and more extensive BT across multiple organs.In contrast,RjHan rats exhibited BT mainly confined to mesenteric lymph nodes but exhibited greater IBP.Although dissemination was broader in RccHan rats,overall bacterial burden was slightly lower compared with RjHan,and extraintestinal bacterial composition differed between groups.Particularly,RjHan rats exhibited stronger systemic and central immune activation,with significant alterations in lymphocyte and monocyte populations and enhanced granulocyte and T-cell infiltration within ischemic lesions.These findings demonstrate that substrain origin profoundly influences poststroke intestinal barrier integrity,bacterial dissemination,and immune responses considering substrain-related variability is essential to improve reproducibility and translational relevance in preclinical stroke research.
基金supported by the Excellent Research Group Project of the National Natural Science Foundation of China(grant no.32488102)the National Natural Science Foundation of China(grant no.31970194)the National Science Fund for Distinguished Young Scholars of China(grant no.31725005).
摘要Leaf senescence is a programmed physiological process that enhances nutrient use efficiency,thereby promoting plant adaptation and crop productivity.However,the molecular mechanisms that govern the initiation and precisely control the progression of senescence remain poorly understood.Here,we identify GERAS1(GER1),a membrane-associated NAC transcription factor that acts as an age-dependent integrator of the leaf senescence program.As leaves age,GER1 expression is induced,and its protein undergoes age-dependent translocation from the plasma membrane to the nucleus.The activation tagging mutant ger1-D exhibits early leaf senescence,while the disruption of GER1 and its three homologs in a quadruple ger1 ger2 ger3 ger4 mutant causes significantly delayed leaf senescence.We further show that the nucleus-localized GER1 directly binds and activates the promoter of the central senescence regulator ORE1.Moreover,GER1 and ORE1 form a transcriptional activation complex that directly upregulates SID2,which encodes a key salicylic acid(SA)biosynthetic enzyme.The accumulation of SA in turn promotes the expression of GER1,establishing a positive feedforward loop that drives leaf senescence.Taken together,these findings not only unveil that GER1 acts as a central spatiotemporal regulator of leaf senescence,but also uncover a straightforward membrane-to-nucleus signaling pathway that finely regulates leaf aging.
摘要The impact of gut microbiota on immune regulation has received increasing attention in recent years,particularly its role in immune-mediated liver diseases such as autoimmune hepatitis(AIH),primary biliary cholangitis(PBC),primary sclerosing cholangitis(PSC),and immunoglobulin G4(IgG4)-related sclerosing cholangitis(IgG4-SC).Disturbances in gut microbiota composition(gut dysbiosis)compromise the intestinal barrier and trigger abnormal immune activity,which foster persistent inflammation,autoimmunity and subsequent liver damage.An increase in Veillonella,Streptococcus,and Lactobacillus were found in most studies for all four diseases.A decrease in Clostridium was detected in AIH and PBC,but an increase in these bacteria is observed in PSC and IgG4-SC.Other common changes in AIH and PBC were an increase in Klebsiella and a decrease in Ruminococcus.In contrast,Ruminococcus is often found to be elevated in PSC.Common features of PBC and PSC are an increase in Enterococcus and a decrease in Faecalibacterium,Enterobacterium,and Coprococcus.Gut microbiome changes in IgG4-SC are most similar to PSC.Probiotics have positive effects in AIH and cholestatic liver diseases in small randomized controlled trial(RCTs).Positive effects of butyrate were in mice models of AIH and PBC.A small study found a positive effect of butyrate on patients with PBC.Indole-3-carboxaldehyde reduced the inflammatory activity of Tcells in patients with AIH in vitro and reduced inflammation in a PSC mouse model.Fecal microbiota transplantation showed beneficial effects in mouse models of AIH and in patients with PSC.Many studies demonstrated the effectiveness of microbiota-targeted therapy on mouse models of autoimmune liver diseases.However,these results remain to be verified in RCTs involving humans.
基金funded by Instituto Nacional de Innovación Agraria—INIA.Within the frame-work of the investment project“Improvement of research and technology transfer services in the management and recovery of degraded agricultural soils and irrigation water in small and medium-sized agriculture in the departments of Lima,Ancash,San Martín,Cajamarca,Lambayeque,Junín,Ayacucho,Arequipa,Puno and Ucayali”,with CUI N◦2487112.
摘要The exploration and identification of spontaneous weed species in heavy metal–contaminated soils represent a relevant approach for understanding the role and their potential application in phytoremediation.In cacao cultivation,cadmium contamination poses a significant risk due to the restrictions established for soils and cacao-derived products,thereby threatening productive sustainability and export viability.The objective of this study was to identify weed species associated with cacao cultivation exhibiting accumulation patterns and phytoremediation potential for Cd and Pb,through the assessment of biomass production and the bioconcentration factor(BCF)and translocation factor(TF),in natural conditions.Soil samples were collected from seven cacao-growing zones,and the site with the highest Cd concentration(1.65 mg kg−1)was selected,where ten dominant weed species were identified and evaluated.Significant interspecific differences were observed in biomass production and in Cd and Pb concentrations(p<0.05).Talinum paniculatum exhibited the highest total biomass(6.15 g)and the highest TF for Cd,whereas Cyperus aggregatus showed the greatest total Cd accumulation(2.68 mg kg−1).BCF and TF values enabled the identification of species with accumulation patterns consistent with Cd phytoextraction(T.paniculatum,C.aggregatus,Pseudelephantopus spiralis,Bidens riparia,Euphorbia heterophylla,and Malvastrum coromandelianum)and with phytostabilization(Ocimum campechianum).For Pb the observed patterns were consistent with potential phytoextractive behavior in B.riparia,P.spiralis,E.heterophylla,Hilleria latifolia,and Acalypha stachyura.Although these results do not constitute functional evidence of remediation,they describe heavy metal accumulation and translocation patterns in native weed species,providing a technical basis for the design of future experimental trials aimed at the sustainable remediation of contaminated soils.
基金supported by research project grants from the Natural Science Foundation of Shandong Province(ZR2021QH342)the National Natural Science Foundation of China(82304143 and 82404267)。
摘要Diabetic cardiomyopathy(DCM)refers diabetic patients develop cardiomyopathy characterized by cardiac systolic and diastolic dysfunction.Currently,no research has explored the role of ten-eleven translocation(TET)-mediated active DNA demethylation in the development of DCM.Through case-control study,we found that the level of 5-hydroxymethylcystein in peripheral blood DNA of DCM patients was significantly lower than it in the healthy subjects and diabetic patients.Secondly,we had conducted an animal study to explore the effect of thinned young apple polyphenol(TYAP)on DNA demethylation in streptococci-induced diabetic mice.TYAP effectively prevented the ventricular dysfunction and cardiomycyte disarray via alleviating DNA epigenetic modifications metabolic disorders in diabetic mice heart.TYAP increased the stability of TET2 protein via activating phosphorylate AMPK and enhanced the activity of TETs enzymes via improving tricarboxylic acid cycle,then promoted TET-mediated active DNA demethylation.TYAP prevented the occurrence of DCM by promoting TET2-mediated active DNA demethylation in the heart of diabetic mice.
基金supported by the Agritech National Research Center and received funding from the European Union Next-Generation EU [PIANO NAZIONALE DI RIPRESA E RESILIENZA (PNRR), CN00000022] and in part by “VIRMA: Velivolo Intelligente Robotico per il Monitoraggio Agro-Ambientale (CUP J55F21004270001)-finanziato dal MUR nell’ambito del Fondo per la promozione e lo sviluppo delle politiche del Programma nazionale per la ricerca_PNR, in coerenza con il Regolamento UE n. 241/2021 e con il PNRR 2021-2026”
摘要In plants,nickel(Ni)occurs naturally at 0.01–5μg·g−1dry weight and plays essential roles in physiological processes from germination to fruit development(Seregin and Kozhevnikova,2006).However,excessive Ni disrupts growth,metabolism,enzyme activity,stomatal function,and chlorophyll integrity,ultimately impairing water relations(Heidari et al.,2020;Valivand and Amooaghaie,2021a,2021b).Ni also interferes with mineral uptake and translocation in crops,such as zucchini,tomato,and lettuce(Valivand and Amooaghaie,2021a,2021b;Fortini et al.,2025).Owing to its toxicity and health risks(Das et al.,2019),strict regulatory limits have been established to limit Ni exposure.In Italy,the Ministerial Decree on wastewater reuse sets a maximum Ni concentration of 0.2 mg·L−1for long-term irrigation.
基金supported by the National Key Research and Development Program of China(2024YFD1201101)the Fundamental Research Funds for the Central Universities(YDZX2026025)+2 种基金the National Natural Science Foundation of China(32572300,W2412009)the National Natural Science Foundation of Jiangsu province(BK20242061)the open funds of the State Key Laboratory of Crop Genetics&Germplasm Enhancement and Utilization(ZW202409)。
摘要A key objective of wheat(Triticum aestivum)breeding is the simultaneous improvement of disease resistance and bread making quality.The Glu-V1 locus encoding the high-molecular-weight glutenin subunit(HMW-GS)V71 and the powdery mildew resistance gene Pm67 were previously identified on chromosome arm 1 VS of the wild wheat species Dasypyrum villosum.Here,we generated the T1 DL.1V#4S translocation line NAU195,which carried the V71 subunit for improved bread-making quality but was susceptible to all 18 isolates of the powdery mildew fungus Bgt examined.By contrast,the previously developed T1 DL.1V#5S line NAU196 harbors the Pm67 gene conferring broad-spectrum powdery mildew resistance but lacks the V71 subunit.Genetic analysis of F1 and F2 progenies from a cross between NAU195 and NAU196 confirmed that Pm67 is a single dominant gene.By screening 2954 F2 plants,we fine mapped Pm67 to an approximately 2.1 Mb interval on chromosome arm 1 VS in the reference genome.We identified 35 high-confidence protein-coding genes in this region,including eight candidate genes encoding nucleotide binding site leucine rich repeat(NLR)proteins.We identified 12 recombinant T1 DL.1 VS translocation lines harboring both the V71 subunit and Pm67 genes,and introgressed one of the corresponding translocations into the high-yielding cultivar NMZ119.Plant development in the resulting T1 DL.1 VS translocation lines harboring the V71 subunit and Pm67 genes was comparable to that of NMZ119,with no significant yield penalty but with markedly improved powdery mildew resistance and gluten strength.Overall,our strategy for mapping and pyramiding alien genes in the common wheat background allowed us to generate a valuable genetic resource and molecular tool for accelerating the concurrent improvement of powdery mildew resistance and bread making quality.
基金financially supported by the Zhejiang Provincial Natural Science Foundation of China under(No.LZ24A040003)。
摘要The unique regulatory effect of pH on electrostatic interactions offers a powerful approach for manipulating and separating singlestranded DNA(ssDNA)molecules.In this study,we employ Langevin dynamics simulations to investigate the translocation dynamics of two ssDNAs,poly(dA)and poly(dT),through a silicon nitride nanopore under acidic conditions.The key distinction between the two chains is their different pH-dependent protonation.At low pH,the highly protonated adenine bases experience repulsive interactions from the similarly protonated nanopore surface and the retarding force from the external voltage,whereas neutral thymine bases do not.Consequently,compared to poly(dT),poly(dA)exhibits a lower capture probability and slower translocation speed under strongly acidic conditions.However,the difference in the translocation behaviors between the two chains gradually diminishes as the pH increases.Based on their distinct pH-dependent behaviors,poly(dA)and poly(dT)of identical length can be successfully separated through the translocation strategy at low pH,even when they are initially mixed on the same side of the nanopore.
基金the supports from the National Key R&D Program of China(No.2024YFA1210100)the National Natural Science Foundation of China(No.22135002)East China Normal University Multifunctional Platform for Innovation(004)。
摘要Alzheimer's disease(AD)is a complex and multifactorial neurodegenerative disorder,marked by a variety of pathological hallmarks such as oxidative stress(OS),metal accumulation,and the aggregation of amyloid-beta(Aβ)proteins.Erucin,a natural compound present in cruciferous plants,has demonstrated promising therapeutic potential in modulating neurodegenerative diseases,hinting at its neuroprotective capabilities.In this study,we engineered an innovative intracellular protein delivery system centered around erucin.This delivery platform operates through a cell membrane perforation mechanism,enabling the swift translocation of target proteins into the cytoplasm.As a result,it substantially shortens the time required for the proteins to exert their functions.Significantly,this delivery system inherently possesses the capacity to inhibit Aβaggregation.In PC12 cell models,the delivery of the antioxidant enzyme superoxide dismutase(SOD)successfully mitigated the OS triggered by Aβaggregation and decreased cytotoxicity.This multifaceted therapeutic strategy holds great promise as an effective approach for the treatment of AD.
基金Supported by Natural Science Foundation of Fujian Province,No.2024J011037。
摘要BACKGROUND Tendon stem/progenitor cells(TSPCs)are a novel type of stem cell.TSPCs share common characteristics with stem cells,including their proliferation,pluripotency,and self-renewal abilities.Circular RNA plasmacytoma variant translocation 1(circ_PVT1)has been reported to inhibit senescence in TSPCs.However,the mechanism by which circ_PVT1 regulates the proliferation and differentiation of TSPCs remains unclear.AIM To explore how circ_PVT1 regulates the proliferation and differentiation of TSPCs.METHODS Mouse TSPCs were isolated from the Achilles tendon of 12 male C57Bl/6 mice at postnatal day 30,and 5 ng/mL of transforming growth factor(TGF)-β1 was used to induce the tenogenic differentiation in TSPCs.Picro-Sirius red staining was used to assess the proliferation,migration,and apoptosis of TSPCs.Biochemical kits were used to determine the levels of reactive oxygen species,malondialdehyde,glutathione,superoxide dismutase,and ATP.Then,N6-methyladenosine(m6A)dot blot and methylated RNA immunoprecipitation polymerase chain reaction(RIP-PCR)were used to examine the m6A levels.Moreover,RNA pulldown and RIP-PCR were performed to analyze the interaction between WTAP and circ_PVT1.RESULTS TGF-β1 treatment induced tenogenic differentiation of TSPCs.Circ_PVT1 knockdown reversed the increase of tendon-specific protein,cell proliferation,and migration that was induced by TGF-β1 treatment.In addition,circ_PVT1 inhibition promoted oxidative stress and mitochondrial damage in the TGF-β1-induced TSPCs.The m6A modification level of circ_PVT1 was upregulated in the TGF-β1-induced TSPCs.Furthermore,RNA pulldown and RIP-PCR showed that circ_PVT1 interacted with WTAP in TSPCs,and the WTAP-mediated m6A modification of circ_PVT1 regulated the differentiation of TSPCs.CONCLUSION WTAP-mediated m6A modification of circ_PVT1 promotes the proliferation and tenogenic differentiation of TSPCs,thereby indicating a promising therapeutic strategy for tendon repair.
摘要Severe acute pancreatitis(SAP),a prevalent and life-threatening abdominal emergency,is characterized by its abrupt onset,rapid progression,and high mortality rate,frequently precipitating multiple organ dysfunction syndromes.Acute lung injury(ALI)represents the most common early complication of SAP.ALI may progress to acute respiratory distress syndrome,which constitutes the primary cause of mortality in patients with SAP.However,the precise pathogenesis underlying ALI in SAP remains incompletely elucidated.Notably,recent advances in gut-lung axis research have significantly advanced our understanding of SAPassociated ALI(SAP-ALI).The gut-lung axis,a sophisticated bidirectional communication network linking the intestines and lungs,facilitates crosstalk between the microbiota and their metabolites across both organs via lymphatic and circulatory systems alongside the mucosal immune system.Critically,research confirms that SAP induces severe gut microbiota dysbiosis.This dysbiosis disrupts the intestinal mucosal barrier,enabling bacterial and endotoxin translocation to the lungs through lymphatic and hematogenous routes.Concurrently,gutderived immune cells migrate to the lungs via the bloodstream,directly contributing to pulmonary immune-inflammatory imbalance.Consequently,this review synthesized the central role of the gut-lung axis in SAP-ALI pathogenesis and explored emerging therapeutic strategies targeting this pivotal axis,aiming to provide novel insights for the clinical prevention and treatment of SAP-ALI.
基金Supported by the National Natural Science Foundation of China[Young Scientists Program(No.82501314)]Jiangsu Provincial Health Commission Scientific Research Project(No.M2024093)Natural Science Foundation(Youth Fund)of Science and Technology Bureau of Nantong City(No.JC2023028).
摘要AIM:To investigate the role of pyruvate kinase M2(PKM2)in high glucose(HG)-stimulated retinal endothelial cells and its underlying molecular mechanisms and signaling pathways in retinal angiogenesis.METHODS:Human retinal microvascular endothelial cells(HRMECs)were cultured and divided into the following groups:normal glucose(NG,5.5 mmol/L),HG(30 mmol/L),HG with PKM2 knockdown(HG+shPKM2),and HG treated with the pharmacological activator TEPP‑46(HG+TEPP‑46).Cellular viability,proliferation,migration,and tube‑forming ability were assessed using CCK‑8,EdU,wound healing/Transwell,and Matrigel assays,respectively.The expression levels of PKM2,phosphorylated PKM2(p‑PKM2,Y105),hypoxia-inducible factor-1α(HIF‑1α),and vascular endothelial growth factor A(VEGFA)were detected by Western blotting.The oligomerization status of PKM2 was analyzed via native gel electrophoresis.The subcellular localization of PKM2 was examined by immunofluorescence and nuclear‑cytoplasmic fractionation.RESULTS:Under HG stimulation,the expression level of PKM2 was significantly increased(P<0.05).Knockdown of PKM2 was found to markedly suppress cell viability,proliferation,migration,and tube formation in HRMECs(P<0.05).Mechanistic studies revealed that phosphorylation of PKM2 at the Y105 site was promoted by HG treatment,which induced its dissociation from a tetramer to a dimer,thereby driving its nuclear translocation.Upon entering the nucleus,PKM2 was shown to exert critical non‑metabolic functions;it was physically bound to HIF‑1αand acted as its co‑activator,leading to significant upregulation of VEGFA expression(P<0.05).In contrast,the PKM2 activator TEPP‑46 effectively prevented dimerization and nuclear translocation of PKM2 by promoting its tetramerization.Consequently,the PKM2/HIF‑1αaxis‑mediated upregulation of VEGFA was blocked,ultimately resulting in the reversal of HG‑induced angiogenesis.CONCLUSION:HG influences retinal endothelial cell function by inducing PKM2 phosphor ylation,dimerization,and nuclear translocation.The shift in PKM2 phosphorylation and oligomerization status represents a key mechanism through which TEPP-46 reverses HGinduced angiogenesis.