Sperm quality is crucial for sperm function and can even affect embryo quality and offspring health.Spermatid maturation is extremely complex,as spermatids undergo morphological changes,laying the foundation for the e...Sperm quality is crucial for sperm function and can even affect embryo quality and offspring health.Spermatid maturation is extremely complex,as spermatids undergo morphological changes,laying the foundation for the execution of sperm function.The function of sperm acrosome-associated 4(SPACA4)in spermatogenesis is not well known.The present study revealed that SPACA4 was specifically expressed in the acrosomes and cytoplasm of mouse spermatids.Spaca4 knockout mice demonstrated that the loss of SPACA4 led to male subfertility.The quality of mature sperm was abnormal in Spaca4−/−mice,manifested by decreased motility and multiple deformities.Spaca4-/-sperm exhibited irregular nuclear shapes,abnormal nuclei with vacuoles,missing or incompletely fused acrosomes,and multiple cross-sections enclosed in the same sperm cell membrane.Electron microscopy and molecular expression analyses of testicles revealed that the loss of SPACA4 affected the differentiation of the acrosome,acroplaxome,and manchette,resulting in abnormalities in nuclear elongation,chromatin condensation,and flagellar development.Interestingly,SPACA4 did not regulate spermiogenesis via the acetylcholine signaling pathway.Analysis of the differential protein expression profile revealed that the expression of 9 proteins was significantly decreased in Spaca4−/−spermatids.A decreased protein,transformation-related protein 53 target 5(TRP53TG5),was knocked down in spermatids and found that the phenotype was consistent with Spaca4 knockout mice.These results revealed that the absence of SPACA4 leads to abnormal spermatid maturation and affects sperm quality in mice.Abnormal sperm quality in Spaca4−/−mice results in decreased sperm capacitation and a decreased acrosome response,ultimately affecting the fertility of male mice.展开更多
Enamel,the hardest mineralized material in the human body,protects the underlying living tissues,the dentin and pulp of the tooth.However,over 90%of adults have lost or damaged enamel and cannot regenerate the protect...Enamel,the hardest mineralized material in the human body,protects the underlying living tissues,the dentin and pulp of the tooth.However,over 90%of adults have lost or damaged enamel and cannot regenerate the protective structure due to lack of enamel-producing cells,ameloblasts.iPSC-derived secretory Ameloblasts(isAM)have promise in future regenerative dentistry.Today,it is not known why iAM maturation requires intimate contact with the dentin-producing cell type,odontoblast.Here,we reveal that one of the critical signaling ligands emanating from odontoblasts for ameloblast maturation is Delta,the ligand for Notch receptor.We showed that our designed,soluble Notch agonist can induce iAM organoid maturation in an unprecedented manner,without interactions with odontoblast layer.Notably,soluble Notch agonist induces the iAM maturation to a novel,WDR72-positive mature secretory AM stage(ismAM)in our ameloblast organoid model.When transplanted under the kidney capsule of NOD-SCID mice,these ismAM organoids generated enamel-like calcified material,as confirmed by microCT analysis,marking the first demonstration that Notch-activated iAM organoids can form such tissue in vivo.This novel maturation procedure enabled us to analyze the specific requirements of DLX3 function in ameloblasts,independent of its known function in odontoblasts.We now show that DLX3,a gene associated with Amelogenesis Imperfecta,is required on a cell-autonomous manner in human ameloblasts for the expression of Enamelin,MMP20,and WDR72,a role not previously demonstrated in mouse models.展开更多
Flowering time is a critical agronomic trait with a profound effect on the productivity and adaptabillity of rapeseed(Brassica napus L.).Strategically advancing flowering time can reduce the risk of yield losses due t...Flowering time is a critical agronomic trait with a profound effect on the productivity and adaptabillity of rapeseed(Brassica napus L.).Strategically advancing flowering time can reduce the risk of yield losses due to extreme climatic conditions and facilitate the cultivation of subsequent crops on the same land,thereby enhancing overall agricultural efficiency.In this review,we synthesize current information on flowering time regulation in rapeseed through an integrated analysis of its genetic,hormonal,and environmental dimensions,emphasizing their crosstalk and implications for yield.We consolidate multi-omics evidence from population genetics,functional genomics,and systems biology to create a haplotype-based framework that overcomes the trade-off between flowering time and yield,providing support for the precision breeding of early-maturing cultivars.The insights presented here could inform future research on flowering time regulation and guide strategies for increasing rapeseed productivity.展开更多
N,N-dimethylformamide(DMF)is extensively utilized as an industrial solvent,with its emissions posing a significant air pollution concern.While the liver and gastrointestinal tract are the primary organs affected by DM...N,N-dimethylformamide(DMF)is extensively utilized as an industrial solvent,with its emissions posing a significant air pollution concern.While the liver and gastrointestinal tract are the primary organs affected by DMF,it also exhibits reproductive toxicity in females.The potential intergenerational impact of maternal DMF exposure on oocyte development and maturation remain largely uninvestigated.This study demonstrates that maternal DMF exposure administered at doses of 200 and 400 milligram per kilogram body weight per day adversely influences oogenesis in female progeny,impairing primordial follicle assembly and disrupting the expression of genes and proteins involved in primordial folliculogenesis within the offspring’s ovaries.Additionally,it compromises follicular development by inhibiting granulosa cell proliferation,glycolysis and inducing apoptosis in these cells.The regulation of genes and proteins associated with oocyte growth is markedly altered in the ovaries of female offspring.Furthermore,maternal DMF exposure results in mitochondrial dysfunction and the accumulation of reactive oxygen species in germinal vesicle oocytes.The maturation of oocytes is significantly affected,evidenced by reduced rates of germinal vesicle breakdown and polar body extrusion,alongside abnormal spindle structure and chromosome alignment in MII stage oocytes.These findings collectively establish that maternal DMF exposure exerts intergenerational toxic effects on oogenesis and oocyte maturation in female offspring.展开更多
Background:U6 biogenesis 1(USB1)gene mutations cause poikiloderma with neutropenia(PN),which is clinically characterized by skin hyperpigmentation,nail dysplasia,neutropenia,and an elevated risk of cancer.USB1 functio...Background:U6 biogenesis 1(USB1)gene mutations cause poikiloderma with neutropenia(PN),which is clinically characterized by skin hyperpigmentation,nail dysplasia,neutropenia,and an elevated risk of cancer.USB1 functions as an RNA exonuclease involved in RNA maturation and stability regulation,although its precise mechanism of action in the hematopoietic system remains unclear.Methods:We established a myeloid cell-specific USB1 knockout mouse model(USB1fl/fl-Lyz2-cre)using CRISPR/Cas9.Using a combination of research methods,including Western blot,flow cytometry,messenger RNA(mRNA)sequencing,microRNA(miRNA)sequencing,and quantitative polymerase chain reaction(qPCR),we investigated the effects of USB1 deficiency on neutrophil development and differentiation,along with the underlying signaling molecular mechanisms.Results:Experimental results indicated that USB1 deficiency in mouse myeloid cells not only leads to dysregulation of miRNA expression but also interferes with the developmental,differentiation,and maturation processes of neutrophils by affecting key genes,such as IL1a,Selp,and Kilt.This impact can be traced back to the stages of myeloid progenitor cells.Conclusions:USB1 influences neutrophil maturation and myeloid progenitor cell differentiation by regulating the expression of specific miRNAs and mRNAs.This provides novel in vivo experimental evidence for understanding the pathogenesis of PN in patients.展开更多
Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsedefractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclea...Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsedefractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.展开更多
To develop a nanovaccine capable of synchronously delivering antigens and adjuvants for effective dendritic cell(DC)maturation,we covalently conjugated the stimulator of interferon gene(STING)agonist MSA-2 with the mo...To develop a nanovaccine capable of synchronously delivering antigens and adjuvants for effective dendritic cell(DC)maturation,we covalently conjugated the stimulator of interferon gene(STING)agonist MSA-2 with the model antigen CSIINFEKL via a cleavable linker.The resulting prodrug was co-assembled with phosphoethanolamine-polyethylene glycol(DSPE-PEG)to form a nanovaccine(termed NVAA).The NVAA exhibited a uniform spherical morphology with an average hydrodynamic diameter of approximately 20 nm and a zeta potential of-14 mV.Upon internalization by DCs,the covalently conjugated antigen and STING agonist enabled their synchronized intracellular delivery,leading to efficient activation of the STING signaling pathway.As a result,NVAA significantly enhanced the secretion of IFN-β,IL-6,and IL-12,and upregulated the expression of costimulatory molecules CD80 and CD86 on DCs.These findings demonstrate that the covalent conjugation-based nanovaccine NVAA effectively promotes DC maturation via STING pathway activation,providing a promising strategy for cancer immunotherapy.展开更多
Chili fermentation is one of the most important processes in the production of Pixian Douban(PXDB),which determines the flavor and product quality of PXDB.However,the maturity of fermented chili mainly depends on empi...Chili fermentation is one of the most important processes in the production of Pixian Douban(PXDB),which determines the flavor and product quality of PXDB.However,the maturity of fermented chili mainly depends on empirical judgment,which can not satisfy the need for standardized production of PXDB.Therefore,this study aimed to investigate volatile and non-volatile substances during the maturation process and to find markers related to the maturity of fermented chili.Two-dimensional gas chromatography-mass spectrometry(GC×GC-MS)combined with multivariate statistical analysis and relative odor activity values(ROAV)analysis revealed that 2-methoxy-3-isobutyl pyrazine,linalool,3-(methylthio)propionaldehyde,myrcene,and decanal(ROAV≥1,VIP>1,P<0.05)were regarded as potentially active aromatic markers for differentiating fermentation time.Additionally,ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLCQTOF-MS)combined with multivariate statistical analysis revealed that 25 compounds could serve as differentiated non-volatile compounds.The correlation of maturity-related physicochemical indicators with volatile and nonvolatile compounds revealed that four volatile compounds(2-methoxy-3-isobutylpyrazine,linalool,myrcene,and decanal)along with seven non-volatile compounds could serve as markers for evaluating the maturity of fermented chili.This study is expected to establish a standard for the determination of the maturity the fermented chili and lay the foundation for intelligent production of PXDB.展开更多
Tumor-associated neutrophils(TANs)exhibit highly func-tional heterogeneity across cancers.Although TANs pro-mote inflammatory responses and contribute to tumor clearance,they frequently undergo context-dependent repro...Tumor-associated neutrophils(TANs)exhibit highly func-tional heterogeneity across cancers.Although TANs pro-mote inflammatory responses and contribute to tumor clearance,they frequently undergo context-dependent reprogramming within the tumor microenvironment(TME)into highly immunosuppressive phenotypes that facilitate cancer dissemination and immunotherapy resist-ance1,2.We contend that an underappreciated,upstream determinant of this divergence is the maturation stage of TANs3,4.The developmental stage of TANs determines the migration patterns and constrains the functional capacity,and the developmental stage also constrains the extent of TME-driven re-education,together shaping pro-or anti-tu-mor outcomes3-5.In this Perspective,we place maturation at the core of TAN biology and discuss current definitions for TAN developmental stages and the measurable mark-ers that researchers and clinicians can use(Figure 1).In addition,spatial and temporal transitions in TAN matu-ration stages and the factors that govern these transitions are elucidated.We explain how maturation status shapes TAN function and articulate the key differences between mouse and human TAN maturation systems to highlight the value of human immune system(HIS)mouse models.Based on this framework,functional biomarkers and signa-tures of TAN maturation are introduced and we show how to embed them into patient stratification and longitudinal monitoring.Finally,we outline immunotherapy strategies targeting TAN maturation,selecting interventions guided by maturation markers to reinforce treatment benefits for cancer patients.展开更多
Sexual maturation heterosis has been widely exploited in animal crossbreeding.However,the underlying mechanism has been rarely explored in chicken.In the present study,we performed the reciprocal crossing between Whit...Sexual maturation heterosis has been widely exploited in animal crossbreeding.However,the underlying mechanism has been rarely explored in chicken.In the present study,we performed the reciprocal crossing between White Leghorn and Beijing You chicken to evaluate the phenotypes related to sexual maturation,and profiled the ovary circRNAs of purebreds(WW,YY)and crossbreds(WY,YW)to elucidate the molecular mechanism underlying heterosis for sexual maturation.Pubic space and oviduct length exhibited positive heterosis,and age at first egg(AFE)exhibited negative heterosis in the crossbreds.We identified 3,025 known circRNAs and 624 putative circRNAs,which were mainly derived from the exons.Among these circRNAs,141 and 178circRNAs were specially expressed in WY and YW,respectively.There were 52.38 and 64.63%of total circRNAs in WY and YW exhibited non-additive expression pattern,respectively.GO enrichment and KEGG pathway analysis showed that the host genes of non-additive circRNAs were mainly involved in TGF-beta signaling pathway,oocyte development,ATPase activator activity,oocyte meiosis,progesterone-mediated oocyte maturation and GnRH signaling pathway.Weighted gene co-expression network analysis identified that 4 modules were significantly(P<0.05)correlated with oviduct length and pubic space.The host genes of non-additive circRNAs harbored in the 4 modules were associated with MAPK signaling pathway and Wnt signaling pathway.Furthermore,competing endogenous RNAs(ceRNA)network analysis characterized non-additive circRNAs gal-FGFR2_0005 and galMAPKAP1_0004 could interact with gga-miR-1612 and gga-miR-12235-5p to regulate CNOT6,COL8A1,and FHL2,which were essential for ovary development,indicating that the non-additive circRNAs involved in the formation of sexual maturation heterosis through regulating genes related to the reproductive and developmental process.The findings would provide a deeper understanding of the molecular mechanism underlying sexual maturation heterosis from a novel perspective.展开更多
Background: Biological maturation refers to the progressive process through which individuals transition toward an adult state during growth and development. To address the challenges posed by differences in biologica...Background: Biological maturation refers to the progressive process through which individuals transition toward an adult state during growth and development. To address the challenges posed by differences in biological maturity and the limitations of existing testing methods, particularly in adolescent sports contexts, there is a pressing need for a non-invasive method that is convenient, accurate, and broadly applicable to monitor the biological maturity of adolescent athletes comprehensively. In response to this need, a maturity assessment method based on the smartphone application Maturo has been developed. This study evaluates the accuracy and validity of the Maturo software, an automated tool for estimating biological age and related maturation metrics.Methods: A sample of 103 actively training teenage athletes aged 9-17 years. The sample included 76 males(age = 11.74 ± 1.55 years, mean ±SD) and 27 females(age = 13.95 ± 1.40 years), all without medical conditions that might impact growth or development.Results: Compared to traditional expert evaluations, the intraclass correlation coefficients(ICCs) and Pearson correlation coefficients demonstrated reliable positive correlations and significant agreement between the Maturo software and expert methods across multiple metrics, such as biological age(ICC = 0.965, R = 0.97), corrected biological age(ICC = 0.973, R = 0.99), predicted adult height(ICC = 0.991, R = 0.99), and percentage of adult height achieved(ICC = 0.955, R = 0.97). The Bland-Altman plots provided additional evidence of the validity of the Maturo software estimations, showing low systematic error in most measures. The linear regression analysis produced excellent adjusted R2values: 0.95for biological age and 0.99 for anticipated adult height. The Maturo approach demonstrated a high level of dependability in classifying teenagers into groups based on their maturity status and timing. The κ coefficients of 0.93 for maturity status and 0.82 for maturity timing indicate a nearly perfect agreement with the expert technique.Conclusion: While the Maturo software's non-invasive nature, cost-effectiveness, and ease of use could make it a potential tool for regular monitoring of growth and maturation in young athletes, its promising results in assessing maturation should be interpreted with caution due to limitations such as sample size and demographic constraints. Further longitude research with larger and more diverse populations is needed to validate these preliminary findings and strengthen the evidence for its broader applicability.展开更多
Seed maturation is a critical development transition and it largely affects the final yield and quality of crops.Abscisic acid(ABA)-activated sucrose-non-fermentation kinase subfamily 2(SnRK2s)constitute a well-known ...Seed maturation is a critical development transition and it largely affects the final yield and quality of crops.Abscisic acid(ABA)-activated sucrose-non-fermentation kinase subfamily 2(SnRK2s)constitute a well-known regulatory network that modulate seed maturation in Arabidopsis;however,the underlying genetic and regulatory mechanisms in cereal crops remain largely unknown.Here,we found that ABA levels exhibited two distinct peaks during kernel development in maize,corresponding to the lag and maturation phase,respectively.Integrated transcriptome and proteome profiling of kernels treated with exogenous ABA at the pre-maturation stage suggested that the second peak of ABA acts as a trigger for kernel maturation program.Knockout of ZmSnRK2s demonstrated that subclassⅢZmSnRK2s are required for kernel maturation in maize,and the loss-of-function of subclassⅢZmSnRK2s showed a disruption in kernel dehydration and dormancy.We identified a conserved ABA–SnRK2–b ZIP signaling pathway mediating this process in maize.Additionally,ZmSnRK2.10 overexpression accelerates kernel dehydration during maturity,achieving reduced kernel moisture content(KMC)at physiological maturity(PM).Overall,our findings establish ABA-activated SnRK2s as central regulators of kernel maturation in maize and provide valuable genetic resources for breeding maize varieties with low moisture content at harvest.展开更多
Pharyngeal cartilage morphogenesis is crucial for the formation of craniofacial structures.Cranial neural crest cells are specified at the neural plate border,migrate to pharyngeal arches,and differentiate into pharyn...Pharyngeal cartilage morphogenesis is crucial for the formation of craniofacial structures.Cranial neural crest cells are specified at the neural plate border,migrate to pharyngeal arches,and differentiate into pharyngeal chondrocytes,which subsequently flatten,elongate,and stack like coins during maturation.Although the developmental processes prior to chondrocyte maturation have been extensively studied,their subsequent changes in morphology and organization remain largely elusive.Here,we show that wnt2bb is expressed in the pharyngeal ectoderm adjacent to the chondrogenic precursor cells in zebrafish.Inactivation of Wnt2bb leads to a reduction in nuclearβ-catenin,which impairs chondrogenic precursor proliferation and disrupts chondrocyte morphogenesis and organization,eventually causing a severe shrinkage of pharyngeal cartilages.Moreover,the decrease ofβ-catenin in wnt2bb-/-mutants is accompanied by the reduction of Yap expression.Reactivation of Yap can restore the proliferation of chondrocyte progenitors as well as the proper size,shape,and stacking of pharyngeal chondrocytes.Our findings suggest that Wnt/β-catenin signaling promotes Yap expression to regulate pharyngeal cartilage formation in zebrafish.展开更多
Rising global energy needs have intensified the search for unconventional hydrocarbon sources,especially in under-selected areas like the Northeast Java Basin.This region harbors promising unconventional hydrocarbon r...Rising global energy needs have intensified the search for unconventional hydrocarbon sources,especially in under-selected areas like the Northeast Java Basin.This region harbors promising unconventional hydrocarbon reserves,where source rocks function as dual-phase systems for both hydrocarbon generation and storage.This research investigates how metal-based catalysts,particularly iron(Fe),can expedite hydrocarbon maturation in such reservoirs.Combining well logging,geochemical assessments,seismic data,and advanced lab techniques,including X-ray Diffraction(XRD),we pinpoint optimal zones for exploration.Results indicate that the Tuban,Kujung,and Ngimbang formations contain economically viable unconventional deposits,exhibiting tight reservoir properties(permeability:0.01–1 md)and moderate to good Total Organic Carbon(TOC)levels(1%–2%).Spatial analysis reveals elevated density concentrations in the northern sector,indicative of high-viscosity hydrocarbons typical of unconventional plays.Crucially,Fe additives were found to markedly enhance organic matter conversion,shortening maturation periods and boosting hydrocarbon yield.XRD data confirms that Fe alters crystalline configurations,increasing reactivity and speeding up thermal breakdown(shifting immature organic compounds toward maturity at an accelerated rate).These findings contribute to the evolving discourse on unconventional resource exploitation by proposing an innovative recovery enhancement strategy.The study also sets a precedent for investigating metal-assisted hydrocarbon conversion in geologically comparable basins globally.展开更多
[Objective] This study aimed to improve the in vitro maturation quality of denuded porcine oocytes and provide scientific basis for establishing a stable and efficient denuded oocyte culture system. [Method] The first...[Objective] This study aimed to improve the in vitro maturation quality of denuded porcine oocytes and provide scientific basis for establishing a stable and efficient denuded oocyte culture system. [Method] The first polar body extrusion rate, oocyte glutathione (GSH) content, positive rate of brilliant cresyl blue (BCB) staining and development potential of activated oocytes or fertilized oocytes were employed as main indicators to investigate the effects of follicular mural granulosa cell (MGC) coculture on cytoplasmic maturation of cumulus cell-removal oocytes (Denuded Oocyte, DO). [Result] According to in vitro maturation results, compared with DO group, the first polar body extrusion rate of porcine oocytes in DO+MGC group was not significantly different, but the nuclear maturation process was improved and was more similar to that in COC (cumulus-oocyte complex) group. Detection of GSH content in mature oocytes showed that there was no significant difference between DO+ MGC group (optical density of 1 053.67) and COC group (optical density of 1 426.00) or between DO+MGC group and COC+GC group (optical density of 1 541.00), however, GSH content in mature oocytes of DO group (optical density of 724.67) was significantly lower than that of COC group and COC+GC group (P0.05). Detection of glucose-6-phosphate dehydrogenase (G6PDH) activity showed that there was no significant difference in BCB positive oocyte rate between DO +MGC group (88.26% ) and COC group (92.75%) or between DO+MGC group and DO group (82.86% ), however, BCB positive oocyte rate of DO group was significantly lower than that of COC group (P0.05). Furthermore, the cleavage rate and blastocyst rate of activated mature oocytes derived from DO +MGC group (94.98% and 43.67% , respectively) were significantly higher than those from DO group (52.54% and 8.97%, respectively) (P0.05), and were not significantly different compared with those from COC group (97.11% and 38.30%, respectively). In addition, the cleavage rate of fertilized oocytes derived from DO+MGC group (72.65%) showed no significant difference compared with that from DO group (63.59%), but the blastocyst rate of DO+MGC group was significantly higher than that of DO group (9.88%) (P0.05). [Conclusion] MGC coculture can significantly improve the in vitro cytoplasmic maturation quality of denuded porcine oocytes, thereby enhancing the subsequent developmental potential.展开更多
Previous studies have shown that microglia impact the proliferation and differentiation of neu- rons during hippocampal neurogenesis via the fractalkine/CX3 chemokine receptor i (CX3CRI) signaling pathway. However, ...Previous studies have shown that microglia impact the proliferation and differentiation of neu- rons during hippocampal neurogenesis via the fractalkine/CX3 chemokine receptor i (CX3CRI) signaling pathway. However, whether microglia can influence the maturation and dendritic growth of newborn neurons during hippocampal neurogenesis remains unclear. In the present study, we found that the number of doublecortin-positive cells in the hippocampus was decreased, and the dendritic length and number of intersections in newborn neurons in the hippocampus were reduced in transgenic adult mice with CX3CR1 deficiency (CX3CRl^GFP/GFe). Furthermore, after experimental seizures were induced with kainic acid in these CX3CRl-deficient mice, the expression of c-fos, a marker of neuronal activity, was reduced compared with wild-type mice. Collectively, the experimental findings indicate that the functional maturation of newborn neu- rons during hippocampal neurogenesis in adult mice is delayed by CX3CR1 deficiency.展开更多
Age, maturation and population structure of the Humboldt squid Dosidicus gigas were studied based on random sampling of the Chinese jigging fishery off the Peruvian Exclusive Economic Zones (EEZ) during 2008-2010. E...Age, maturation and population structure of the Humboldt squid Dosidicus gigas were studied based on random sampling of the Chinese jigging fishery off the Peruvian Exclusive Economic Zones (EEZ) during 2008-2010. Estimated ages ranged from 144 to 633 days, confirming that the squid is a short-lived species with longevity no longer than 2 years. Occurrence of mature females and hatching in each month indicated that Humboldt squid spawned year-round. Back-calculated hatching dates for the samples were from January 22^nd, 2008 to April 22nd, 2010 with a peak between January and March. Two size-based and two hatching date-based populations could be defined from mantle length (ML) at maturity and back-calculated hatching dates, respectively. Females matured at a larger size than males, and there was a significant difference in ML at maturity between the two hatching groups (P〈0.05). The waters adjacent to 1 l^S off the Peruvian EEZ may be a potential spawning ground. This study shows the complexity of the population structure and large variability in key life history parameters in the Humboldt squid off the Peruvian EEZ, which should be considered in the assessment and management of this important resource.展开更多
Cholesterol is a key molecule in the mammalian physiology of especial particular importance for the reproductive system as it is the common precursor for steroid hormone synthesis. Cholesterol is also a recognized mod...Cholesterol is a key molecule in the mammalian physiology of especial particular importance for the reproductive system as it is the common precursor for steroid hormone synthesis. Cholesterol is also a recognized modulator of sperm functions, not only at the level of gametogenesis. Cholesterol homeostasis regulation is crucial for posttesticular sperm maturation, and imbalanced cholesterol levels may particularly affect these posttesticular events. Metabolic lipid disorders (dyslipidemia) affect male fertility but are most of the time studied from the angle of endocrineesticular consequences. This review will focus on the deleterious effects of a particular dyslipidemia, Le., hypercholesterolemia, on posttesticular maturation of mammalian spermatozoa.展开更多
The age, growth and maturation of Sthenoteuthis oualaniensis were determined with statolith data collected with a light purse seine from the Bashi Channel of central Pacific Ocean. The estimated longevity of the squid...The age, growth and maturation of Sthenoteuthis oualaniensis were determined with statolith data collected with a light purse seine from the Bashi Channel of central Pacific Ocean. The estimated longevity of the squid was no more than 6 months for females, and no more than 5 months for males. Growth in mantle length(ML) was best described by logistic models for both females and males, while growth in body weight(BW) was best fitted by power curves. The maximum absolute growth rate(AGR) and instantaneous growth rate(IGR) in ML or BW both occurred at 91–105 days for females and 76–90 days for males. Back calculated hatching dates were from October to January, with a peak in December, although the short duration of sampling date might have had an influence on the result. The lower percentage of mature females(37.2%) suggested that the study area during the sampling date was not a spawning ground for the species. Size and age at first maturity were 183 mm ML and 136 days for females, whereas they were 156 mm ML and 85 days for males.展开更多
Brain damage can cause lung injury. To explore the mechanism underlying the lung injury induced by acute cerebral ischemia(ACI), we established a middle cerebral artery occlusion(MCAO) model in male Sprague-Dawley rat...Brain damage can cause lung injury. To explore the mechanism underlying the lung injury induced by acute cerebral ischemia(ACI), we established a middle cerebral artery occlusion(MCAO) model in male Sprague-Dawley rats. We focused on glia maturation factor b(GMFB) based on quantitative analysis of the global rat serum proteome.Polymerase chain reaction, western blotting, and immunofluorescence revealed that GMFB was overexpressed in astrocytes in the brains of rats subjected to MCAO. We cultured rat primary astrocytes and confirmed that GMFB was also up-regulated in primary astrocytes after oxygen-glucose deprivation(OGD). We subjected the primary astrocytes to Gmfb RNA interference before OGD and collected the conditioned medium(CM) after OGD.We then used the CM to culture pulmonary microvascular endothelial cells(PMVECs) acquired in advance and assessed their status. The viability of the PMVECs improved significantly when Gmfb was blocked. Moreover,ELISA assays revealed an elevation in GMFB concentration in the medium after OGD. Cell cultures containing recombinant GMFB showed increased levels of reactive oxygen species and a deterioration in the state of the cells.In conclusion, GMFB is up-regulated in astrocytes after ACI, and brain-derived GMFB damages PMVECs by increasing reactive oxygen species. GMFB might thus be an initiator of the lung injury induced by ACI.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.82071702,No.82271636 and No.31871164).
摘要Sperm quality is crucial for sperm function and can even affect embryo quality and offspring health.Spermatid maturation is extremely complex,as spermatids undergo morphological changes,laying the foundation for the execution of sperm function.The function of sperm acrosome-associated 4(SPACA4)in spermatogenesis is not well known.The present study revealed that SPACA4 was specifically expressed in the acrosomes and cytoplasm of mouse spermatids.Spaca4 knockout mice demonstrated that the loss of SPACA4 led to male subfertility.The quality of mature sperm was abnormal in Spaca4−/−mice,manifested by decreased motility and multiple deformities.Spaca4-/-sperm exhibited irregular nuclear shapes,abnormal nuclei with vacuoles,missing or incompletely fused acrosomes,and multiple cross-sections enclosed in the same sperm cell membrane.Electron microscopy and molecular expression analyses of testicles revealed that the loss of SPACA4 affected the differentiation of the acrosome,acroplaxome,and manchette,resulting in abnormalities in nuclear elongation,chromatin condensation,and flagellar development.Interestingly,SPACA4 did not regulate spermiogenesis via the acetylcholine signaling pathway.Analysis of the differential protein expression profile revealed that the expression of 9 proteins was significantly decreased in Spaca4−/−spermatids.A decreased protein,transformation-related protein 53 target 5(TRP53TG5),was knocked down in spermatids and found that the phenotype was consistent with Spaca4 knockout mice.These results revealed that the absence of SPACA4 leads to abnormal spermatid maturation and affects sperm quality in mice.Abnormal sperm quality in Spaca4−/−mice results in decreased sperm capacitation and a decreased acrosome response,ultimately affecting the fertility of male mice.
基金supported by ISCRM Fellows Program(Anjali Patni)grants from the National Institutes of Health DE033016(J.M.,R.A.C.and H.R-B.),1P01GM081619,R01GM097372,R01GM083867+6 种基金NHLBI Progenitor Cell Biology Consortium(U01HL099997UO1HL099993)SCGE COF220919(H.R-B)Molecule(J.M.and H.R-B.)AHA 19IPLOI34760143Brotman Baty Institute(BBI)DOD PR203328 W81XWH-21-1-0006Stem Cell Gift Funds for H.R-B。
摘要Enamel,the hardest mineralized material in the human body,protects the underlying living tissues,the dentin and pulp of the tooth.However,over 90%of adults have lost or damaged enamel and cannot regenerate the protective structure due to lack of enamel-producing cells,ameloblasts.iPSC-derived secretory Ameloblasts(isAM)have promise in future regenerative dentistry.Today,it is not known why iAM maturation requires intimate contact with the dentin-producing cell type,odontoblast.Here,we reveal that one of the critical signaling ligands emanating from odontoblasts for ameloblast maturation is Delta,the ligand for Notch receptor.We showed that our designed,soluble Notch agonist can induce iAM organoid maturation in an unprecedented manner,without interactions with odontoblast layer.Notably,soluble Notch agonist induces the iAM maturation to a novel,WDR72-positive mature secretory AM stage(ismAM)in our ameloblast organoid model.When transplanted under the kidney capsule of NOD-SCID mice,these ismAM organoids generated enamel-like calcified material,as confirmed by microCT analysis,marking the first demonstration that Notch-activated iAM organoids can form such tissue in vivo.This novel maturation procedure enabled us to analyze the specific requirements of DLX3 function in ameloblasts,independent of its known function in odontoblasts.We now show that DLX3,a gene associated with Amelogenesis Imperfecta,is required on a cell-autonomous manner in human ameloblasts for the expression of Enamelin,MMP20,and WDR72,a role not previously demonstrated in mouse models.
基金supported by the National Key Research and Development Program of China(2022YFD1200400)the National Natural Science Foundation of China(32272111)+4 种基金Special fund for youth team of the Southwest Universities(SWU-XJPY202306)Chongqing Natural Science Foundation(CSTB2024NSCQLZX0012)Modern Agro-industry Technology Research System(CARS-12)Chongqing Modern Agricultural Industry Technology System(COMAITS202504)Biological Breeding-National Science and Technology Major Project(2022ZD04008).We sincerely appreciate the Plant Editors team for English language editing of the manuscript,which significantly improved its clarity and overall quality.
摘要Flowering time is a critical agronomic trait with a profound effect on the productivity and adaptabillity of rapeseed(Brassica napus L.).Strategically advancing flowering time can reduce the risk of yield losses due to extreme climatic conditions and facilitate the cultivation of subsequent crops on the same land,thereby enhancing overall agricultural efficiency.In this review,we synthesize current information on flowering time regulation in rapeseed through an integrated analysis of its genetic,hormonal,and environmental dimensions,emphasizing their crosstalk and implications for yield.We consolidate multi-omics evidence from population genetics,functional genomics,and systems biology to create a haplotype-based framework that overcomes the trade-off between flowering time and yield,providing support for the precision breeding of early-maturing cultivars.The insights presented here could inform future research on flowering time regulation and guide strategies for increasing rapeseed productivity.
基金supported by the National Natural Science Foundation of China(No.32370904)Shandong Excellent Young Scientists Fund Program(Overseas)(No.2022HWYQ-026)+1 种基金the Natural Science Foundation of Shandong Province(No.ZR2022MC005)the Qilu Scholarship of Shandong University(No.61200082163142).
摘要N,N-dimethylformamide(DMF)is extensively utilized as an industrial solvent,with its emissions posing a significant air pollution concern.While the liver and gastrointestinal tract are the primary organs affected by DMF,it also exhibits reproductive toxicity in females.The potential intergenerational impact of maternal DMF exposure on oocyte development and maturation remain largely uninvestigated.This study demonstrates that maternal DMF exposure administered at doses of 200 and 400 milligram per kilogram body weight per day adversely influences oogenesis in female progeny,impairing primordial follicle assembly and disrupting the expression of genes and proteins involved in primordial folliculogenesis within the offspring’s ovaries.Additionally,it compromises follicular development by inhibiting granulosa cell proliferation,glycolysis and inducing apoptosis in these cells.The regulation of genes and proteins associated with oocyte growth is markedly altered in the ovaries of female offspring.Furthermore,maternal DMF exposure results in mitochondrial dysfunction and the accumulation of reactive oxygen species in germinal vesicle oocytes.The maturation of oocytes is significantly affected,evidenced by reduced rates of germinal vesicle breakdown and polar body extrusion,alongside abnormal spindle structure and chromosome alignment in MII stage oocytes.These findings collectively establish that maternal DMF exposure exerts intergenerational toxic effects on oogenesis and oocyte maturation in female offspring.
基金National Key Research and Development Project,Grant/Award Number:2022YFA1103803CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-035。
摘要Background:U6 biogenesis 1(USB1)gene mutations cause poikiloderma with neutropenia(PN),which is clinically characterized by skin hyperpigmentation,nail dysplasia,neutropenia,and an elevated risk of cancer.USB1 functions as an RNA exonuclease involved in RNA maturation and stability regulation,although its precise mechanism of action in the hematopoietic system remains unclear.Methods:We established a myeloid cell-specific USB1 knockout mouse model(USB1fl/fl-Lyz2-cre)using CRISPR/Cas9.Using a combination of research methods,including Western blot,flow cytometry,messenger RNA(mRNA)sequencing,microRNA(miRNA)sequencing,and quantitative polymerase chain reaction(qPCR),we investigated the effects of USB1 deficiency on neutrophil development and differentiation,along with the underlying signaling molecular mechanisms.Results:Experimental results indicated that USB1 deficiency in mouse myeloid cells not only leads to dysregulation of miRNA expression but also interferes with the developmental,differentiation,and maturation processes of neutrophils by affecting key genes,such as IL1a,Selp,and Kilt.This impact can be traced back to the stages of myeloid progenitor cells.Conclusions:USB1 influences neutrophil maturation and myeloid progenitor cell differentiation by regulating the expression of specific miRNAs and mRNAs.This provides novel in vivo experimental evidence for understanding the pathogenesis of PN in patients.
摘要Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsedefractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.
基金Donghua University 2024 Cultivation Project of Discipline Innovation,China。
摘要To develop a nanovaccine capable of synchronously delivering antigens and adjuvants for effective dendritic cell(DC)maturation,we covalently conjugated the stimulator of interferon gene(STING)agonist MSA-2 with the model antigen CSIINFEKL via a cleavable linker.The resulting prodrug was co-assembled with phosphoethanolamine-polyethylene glycol(DSPE-PEG)to form a nanovaccine(termed NVAA).The NVAA exhibited a uniform spherical morphology with an average hydrodynamic diameter of approximately 20 nm and a zeta potential of-14 mV.Upon internalization by DCs,the covalently conjugated antigen and STING agonist enabled their synchronized intracellular delivery,leading to efficient activation of the STING signaling pathway.As a result,NVAA significantly enhanced the secretion of IFN-β,IL-6,and IL-12,and upregulated the expression of costimulatory molecules CD80 and CD86 on DCs.These findings demonstrate that the covalent conjugation-based nanovaccine NVAA effectively promotes DC maturation via STING pathway activation,providing a promising strategy for cancer immunotherapy.
基金supported by the Sichuan Provincial Department of Science and Technology(2024ZHCG0086)the Chongqing Science and Technology Commission(cstc2021jscx-cylhX0014).
摘要Chili fermentation is one of the most important processes in the production of Pixian Douban(PXDB),which determines the flavor and product quality of PXDB.However,the maturity of fermented chili mainly depends on empirical judgment,which can not satisfy the need for standardized production of PXDB.Therefore,this study aimed to investigate volatile and non-volatile substances during the maturation process and to find markers related to the maturity of fermented chili.Two-dimensional gas chromatography-mass spectrometry(GC×GC-MS)combined with multivariate statistical analysis and relative odor activity values(ROAV)analysis revealed that 2-methoxy-3-isobutyl pyrazine,linalool,3-(methylthio)propionaldehyde,myrcene,and decanal(ROAV≥1,VIP>1,P<0.05)were regarded as potentially active aromatic markers for differentiating fermentation time.Additionally,ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLCQTOF-MS)combined with multivariate statistical analysis revealed that 25 compounds could serve as differentiated non-volatile compounds.The correlation of maturity-related physicochemical indicators with volatile and nonvolatile compounds revealed that four volatile compounds(2-methoxy-3-isobutylpyrazine,linalool,myrcene,and decanal)along with seven non-volatile compounds could serve as markers for evaluating the maturity of fermented chili.This study is expected to establish a standard for the determination of the maturity the fermented chili and lay the foundation for intelligent production of PXDB.
基金funded by grants from the National Natural Science Foundation of China(Grant Nos.82373263 and 82403835)the National Key Research and Development Program of China(Grant No.2023YFC2506400)+2 种基金China Postdoctoral Science Foundation(Grant No.2024M751405)Jiangsu Provincial Natural Science Foundation Youth Project(Grant No.BK20240247)General Project of Nanjing Health Science and Technology Development Program(Grant No.YKK24084).
摘要Tumor-associated neutrophils(TANs)exhibit highly func-tional heterogeneity across cancers.Although TANs pro-mote inflammatory responses and contribute to tumor clearance,they frequently undergo context-dependent reprogramming within the tumor microenvironment(TME)into highly immunosuppressive phenotypes that facilitate cancer dissemination and immunotherapy resist-ance1,2.We contend that an underappreciated,upstream determinant of this divergence is the maturation stage of TANs3,4.The developmental stage of TANs determines the migration patterns and constrains the functional capacity,and the developmental stage also constrains the extent of TME-driven re-education,together shaping pro-or anti-tu-mor outcomes3-5.In this Perspective,we place maturation at the core of TAN biology and discuss current definitions for TAN developmental stages and the measurable mark-ers that researchers and clinicians can use(Figure 1).In addition,spatial and temporal transitions in TAN matu-ration stages and the factors that govern these transitions are elucidated.We explain how maturation status shapes TAN function and articulate the key differences between mouse and human TAN maturation systems to highlight the value of human immune system(HIS)mouse models.Based on this framework,functional biomarkers and signa-tures of TAN maturation are introduced and we show how to embed them into patient stratification and longitudinal monitoring.Finally,we outline immunotherapy strategies targeting TAN maturation,selecting interventions guided by maturation markers to reinforce treatment benefits for cancer patients.
基金funded by the National Natural Science Foundation of China(32172721)the China Agriculture Research System(CARS-40)+1 种基金the Central Publicinterest Scientific Institution Basal Research Fund,China(2021-YWF-ZYSQ-12)the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences(ASTIP-IAS04)。
摘要Sexual maturation heterosis has been widely exploited in animal crossbreeding.However,the underlying mechanism has been rarely explored in chicken.In the present study,we performed the reciprocal crossing between White Leghorn and Beijing You chicken to evaluate the phenotypes related to sexual maturation,and profiled the ovary circRNAs of purebreds(WW,YY)and crossbreds(WY,YW)to elucidate the molecular mechanism underlying heterosis for sexual maturation.Pubic space and oviduct length exhibited positive heterosis,and age at first egg(AFE)exhibited negative heterosis in the crossbreds.We identified 3,025 known circRNAs and 624 putative circRNAs,which were mainly derived from the exons.Among these circRNAs,141 and 178circRNAs were specially expressed in WY and YW,respectively.There were 52.38 and 64.63%of total circRNAs in WY and YW exhibited non-additive expression pattern,respectively.GO enrichment and KEGG pathway analysis showed that the host genes of non-additive circRNAs were mainly involved in TGF-beta signaling pathway,oocyte development,ATPase activator activity,oocyte meiosis,progesterone-mediated oocyte maturation and GnRH signaling pathway.Weighted gene co-expression network analysis identified that 4 modules were significantly(P<0.05)correlated with oviduct length and pubic space.The host genes of non-additive circRNAs harbored in the 4 modules were associated with MAPK signaling pathway and Wnt signaling pathway.Furthermore,competing endogenous RNAs(ceRNA)network analysis characterized non-additive circRNAs gal-FGFR2_0005 and galMAPKAP1_0004 could interact with gga-miR-1612 and gga-miR-12235-5p to regulate CNOT6,COL8A1,and FHL2,which were essential for ovary development,indicating that the non-additive circRNAs involved in the formation of sexual maturation heterosis through regulating genes related to the reproductive and developmental process.The findings would provide a deeper understanding of the molecular mechanism underlying sexual maturation heterosis from a novel perspective.
摘要Background: Biological maturation refers to the progressive process through which individuals transition toward an adult state during growth and development. To address the challenges posed by differences in biological maturity and the limitations of existing testing methods, particularly in adolescent sports contexts, there is a pressing need for a non-invasive method that is convenient, accurate, and broadly applicable to monitor the biological maturity of adolescent athletes comprehensively. In response to this need, a maturity assessment method based on the smartphone application Maturo has been developed. This study evaluates the accuracy and validity of the Maturo software, an automated tool for estimating biological age and related maturation metrics.Methods: A sample of 103 actively training teenage athletes aged 9-17 years. The sample included 76 males(age = 11.74 ± 1.55 years, mean ±SD) and 27 females(age = 13.95 ± 1.40 years), all without medical conditions that might impact growth or development.Results: Compared to traditional expert evaluations, the intraclass correlation coefficients(ICCs) and Pearson correlation coefficients demonstrated reliable positive correlations and significant agreement between the Maturo software and expert methods across multiple metrics, such as biological age(ICC = 0.965, R = 0.97), corrected biological age(ICC = 0.973, R = 0.99), predicted adult height(ICC = 0.991, R = 0.99), and percentage of adult height achieved(ICC = 0.955, R = 0.97). The Bland-Altman plots provided additional evidence of the validity of the Maturo software estimations, showing low systematic error in most measures. The linear regression analysis produced excellent adjusted R2values: 0.95for biological age and 0.99 for anticipated adult height. The Maturo approach demonstrated a high level of dependability in classifying teenagers into groups based on their maturity status and timing. The κ coefficients of 0.93 for maturity status and 0.82 for maturity timing indicate a nearly perfect agreement with the expert technique.Conclusion: While the Maturo software's non-invasive nature, cost-effectiveness, and ease of use could make it a potential tool for regular monitoring of growth and maturation in young athletes, its promising results in assessing maturation should be interpreted with caution due to limitations such as sample size and demographic constraints. Further longitude research with larger and more diverse populations is needed to validate these preliminary findings and strengthen the evidence for its broader applicability.
基金supported by the National Natural Science Foundation of China(32201696)the Natural Science Foundation of Sichuan Province(23NSFSC4071)。
摘要Seed maturation is a critical development transition and it largely affects the final yield and quality of crops.Abscisic acid(ABA)-activated sucrose-non-fermentation kinase subfamily 2(SnRK2s)constitute a well-known regulatory network that modulate seed maturation in Arabidopsis;however,the underlying genetic and regulatory mechanisms in cereal crops remain largely unknown.Here,we found that ABA levels exhibited two distinct peaks during kernel development in maize,corresponding to the lag and maturation phase,respectively.Integrated transcriptome and proteome profiling of kernels treated with exogenous ABA at the pre-maturation stage suggested that the second peak of ABA acts as a trigger for kernel maturation program.Knockout of ZmSnRK2s demonstrated that subclassⅢZmSnRK2s are required for kernel maturation in maize,and the loss-of-function of subclassⅢZmSnRK2s showed a disruption in kernel dehydration and dormancy.We identified a conserved ABA–SnRK2–b ZIP signaling pathway mediating this process in maize.Additionally,ZmSnRK2.10 overexpression accelerates kernel dehydration during maturity,achieving reduced kernel moisture content(KMC)at physiological maturity(PM).Overall,our findings establish ABA-activated SnRK2s as central regulators of kernel maturation in maize and provide valuable genetic resources for breeding maize varieties with low moisture content at harvest.
基金support of the National Natural Science Foundation of China(32025014 and 32330029 to Q.W.)the National Key Research and Development Program of China(2020YFA0804000 to Q.W.)+2 种基金Guangdong Excellent Youth Team Project(2024B1515040019 to Q.W.)Guangzhou Science and Technology Plan Project(202201010323 to X.H.)the Fundamental Research Funds for the Central Universities(to Q.W.).
摘要Pharyngeal cartilage morphogenesis is crucial for the formation of craniofacial structures.Cranial neural crest cells are specified at the neural plate border,migrate to pharyngeal arches,and differentiate into pharyngeal chondrocytes,which subsequently flatten,elongate,and stack like coins during maturation.Although the developmental processes prior to chondrocyte maturation have been extensively studied,their subsequent changes in morphology and organization remain largely elusive.Here,we show that wnt2bb is expressed in the pharyngeal ectoderm adjacent to the chondrogenic precursor cells in zebrafish.Inactivation of Wnt2bb leads to a reduction in nuclearβ-catenin,which impairs chondrogenic precursor proliferation and disrupts chondrocyte morphogenesis and organization,eventually causing a severe shrinkage of pharyngeal cartilages.Moreover,the decrease ofβ-catenin in wnt2bb-/-mutants is accompanied by the reduction of Yap expression.Reactivation of Yap can restore the proliferation of chondrocyte progenitors as well as the proper size,shape,and stacking of pharyngeal chondrocytes.Our findings suggest that Wnt/β-catenin signaling promotes Yap expression to regulate pharyngeal cartilage formation in zebrafish.
摘要Rising global energy needs have intensified the search for unconventional hydrocarbon sources,especially in under-selected areas like the Northeast Java Basin.This region harbors promising unconventional hydrocarbon reserves,where source rocks function as dual-phase systems for both hydrocarbon generation and storage.This research investigates how metal-based catalysts,particularly iron(Fe),can expedite hydrocarbon maturation in such reservoirs.Combining well logging,geochemical assessments,seismic data,and advanced lab techniques,including X-ray Diffraction(XRD),we pinpoint optimal zones for exploration.Results indicate that the Tuban,Kujung,and Ngimbang formations contain economically viable unconventional deposits,exhibiting tight reservoir properties(permeability:0.01–1 md)and moderate to good Total Organic Carbon(TOC)levels(1%–2%).Spatial analysis reveals elevated density concentrations in the northern sector,indicative of high-viscosity hydrocarbons typical of unconventional plays.Crucially,Fe additives were found to markedly enhance organic matter conversion,shortening maturation periods and boosting hydrocarbon yield.XRD data confirms that Fe alters crystalline configurations,increasing reactivity and speeding up thermal breakdown(shifting immature organic compounds toward maturity at an accelerated rate).These findings contribute to the evolving discourse on unconventional resource exploitation by proposing an innovative recovery enhancement strategy.The study also sets a precedent for investigating metal-assisted hydrocarbon conversion in geologically comparable basins globally.
基金Supported by National Natural Science Foundation of China (30871431)Outstanding Youth Fund of Heilongjiang Province (JC200905)~~
摘要[Objective] This study aimed to improve the in vitro maturation quality of denuded porcine oocytes and provide scientific basis for establishing a stable and efficient denuded oocyte culture system. [Method] The first polar body extrusion rate, oocyte glutathione (GSH) content, positive rate of brilliant cresyl blue (BCB) staining and development potential of activated oocytes or fertilized oocytes were employed as main indicators to investigate the effects of follicular mural granulosa cell (MGC) coculture on cytoplasmic maturation of cumulus cell-removal oocytes (Denuded Oocyte, DO). [Result] According to in vitro maturation results, compared with DO group, the first polar body extrusion rate of porcine oocytes in DO+MGC group was not significantly different, but the nuclear maturation process was improved and was more similar to that in COC (cumulus-oocyte complex) group. Detection of GSH content in mature oocytes showed that there was no significant difference between DO+ MGC group (optical density of 1 053.67) and COC group (optical density of 1 426.00) or between DO+MGC group and COC+GC group (optical density of 1 541.00), however, GSH content in mature oocytes of DO group (optical density of 724.67) was significantly lower than that of COC group and COC+GC group (P0.05). Detection of glucose-6-phosphate dehydrogenase (G6PDH) activity showed that there was no significant difference in BCB positive oocyte rate between DO +MGC group (88.26% ) and COC group (92.75%) or between DO+MGC group and DO group (82.86% ), however, BCB positive oocyte rate of DO group was significantly lower than that of COC group (P0.05). Furthermore, the cleavage rate and blastocyst rate of activated mature oocytes derived from DO +MGC group (94.98% and 43.67% , respectively) were significantly higher than those from DO group (52.54% and 8.97%, respectively) (P0.05), and were not significantly different compared with those from COC group (97.11% and 38.30%, respectively). In addition, the cleavage rate of fertilized oocytes derived from DO+MGC group (72.65%) showed no significant difference compared with that from DO group (63.59%), but the blastocyst rate of DO+MGC group was significantly higher than that of DO group (9.88%) (P0.05). [Conclusion] MGC coculture can significantly improve the in vitro cytoplasmic maturation quality of denuded porcine oocytes, thereby enhancing the subsequent developmental potential.
摘要Previous studies have shown that microglia impact the proliferation and differentiation of neu- rons during hippocampal neurogenesis via the fractalkine/CX3 chemokine receptor i (CX3CRI) signaling pathway. However, whether microglia can influence the maturation and dendritic growth of newborn neurons during hippocampal neurogenesis remains unclear. In the present study, we found that the number of doublecortin-positive cells in the hippocampus was decreased, and the dendritic length and number of intersections in newborn neurons in the hippocampus were reduced in transgenic adult mice with CX3CR1 deficiency (CX3CRl^GFP/GFe). Furthermore, after experimental seizures were induced with kainic acid in these CX3CRl-deficient mice, the expression of c-fos, a marker of neuronal activity, was reduced compared with wild-type mice. Collectively, the experimental findings indicate that the functional maturation of newborn neu- rons during hippocampal neurogenesis in adult mice is delayed by CX3CR1 deficiency.
基金Supported by the National Natural Science Foundation of China (No.41276156)the National High Technology Research and Development Program of China (863 Program) (No. 2012AA092303)+3 种基金the Innovation Program of Shanghai Municipal Education Commission (No. 13YZ091)Shanghai Leading Academic Disciplin Projectsupported by National Distant-Water Fisheries Engineering Research Center, and Scientific Observing and Experimental Station of Oceanic Fishery Resources, Ministry of AgricultureYong Chen’s involvement in the project was supported by the Shanghai Dongfang Scholar Program
摘要Age, maturation and population structure of the Humboldt squid Dosidicus gigas were studied based on random sampling of the Chinese jigging fishery off the Peruvian Exclusive Economic Zones (EEZ) during 2008-2010. Estimated ages ranged from 144 to 633 days, confirming that the squid is a short-lived species with longevity no longer than 2 years. Occurrence of mature females and hatching in each month indicated that Humboldt squid spawned year-round. Back-calculated hatching dates for the samples were from January 22^nd, 2008 to April 22nd, 2010 with a peak between January and March. Two size-based and two hatching date-based populations could be defined from mantle length (ML) at maturity and back-calculated hatching dates, respectively. Females matured at a larger size than males, and there was a significant difference in ML at maturity between the two hatching groups (P〈0.05). The waters adjacent to 1 l^S off the Peruvian EEZ may be a potential spawning ground. This study shows the complexity of the population structure and large variability in key life history parameters in the Humboldt squid off the Peruvian EEZ, which should be considered in the assessment and management of this important resource.
摘要Cholesterol is a key molecule in the mammalian physiology of especial particular importance for the reproductive system as it is the common precursor for steroid hormone synthesis. Cholesterol is also a recognized modulator of sperm functions, not only at the level of gametogenesis. Cholesterol homeostasis regulation is crucial for posttesticular sperm maturation, and imbalanced cholesterol levels may particularly affect these posttesticular events. Metabolic lipid disorders (dyslipidemia) affect male fertility but are most of the time studied from the angle of endocrineesticular consequences. This review will focus on the deleterious effects of a particular dyslipidemia, Le., hypercholesterolemia, on posttesticular maturation of mammalian spermatozoa.
基金supported by the Natural National Science Foundation of China (Nos. 41306127 and 41276156)the Innovation Program of Shanghai Municipal Education Commission (No.13YZ091)+1 种基金the Ph.D Programs Foundation of Ministry of Education of China (No. 20133104120001)Shanghai Universities First-class Disciplines Project (Fisheries A)
摘要The age, growth and maturation of Sthenoteuthis oualaniensis were determined with statolith data collected with a light purse seine from the Bashi Channel of central Pacific Ocean. The estimated longevity of the squid was no more than 6 months for females, and no more than 5 months for males. Growth in mantle length(ML) was best described by logistic models for both females and males, while growth in body weight(BW) was best fitted by power curves. The maximum absolute growth rate(AGR) and instantaneous growth rate(IGR) in ML or BW both occurred at 91–105 days for females and 76–90 days for males. Back calculated hatching dates were from October to January, with a peak in December, although the short duration of sampling date might have had an influence on the result. The lower percentage of mature females(37.2%) suggested that the study area during the sampling date was not a spawning ground for the species. Size and age at first maturity were 183 mm ML and 136 days for females, whereas they were 156 mm ML and 85 days for males.
摘要Brain damage can cause lung injury. To explore the mechanism underlying the lung injury induced by acute cerebral ischemia(ACI), we established a middle cerebral artery occlusion(MCAO) model in male Sprague-Dawley rats. We focused on glia maturation factor b(GMFB) based on quantitative analysis of the global rat serum proteome.Polymerase chain reaction, western blotting, and immunofluorescence revealed that GMFB was overexpressed in astrocytes in the brains of rats subjected to MCAO. We cultured rat primary astrocytes and confirmed that GMFB was also up-regulated in primary astrocytes after oxygen-glucose deprivation(OGD). We subjected the primary astrocytes to Gmfb RNA interference before OGD and collected the conditioned medium(CM) after OGD.We then used the CM to culture pulmonary microvascular endothelial cells(PMVECs) acquired in advance and assessed their status. The viability of the PMVECs improved significantly when Gmfb was blocked. Moreover,ELISA assays revealed an elevation in GMFB concentration in the medium after OGD. Cell cultures containing recombinant GMFB showed increased levels of reactive oxygen species and a deterioration in the state of the cells.In conclusion, GMFB is up-regulated in astrocytes after ACI, and brain-derived GMFB damages PMVECs by increasing reactive oxygen species. GMFB might thus be an initiator of the lung injury induced by ACI.