Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an imp...Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an important member of the glutathione S-transferase(GSTs)family,which plays an important role in maintaining cell homeostasis and detoxification.This study investigated the role and mechanism of GSTM1 in post-MI fibrosis.Methods:Multi-omics approaches(proteomics/scRNA-seq)identified GSTM1 as a dysregulated target in post-MI fibroblasts.Using a murine coronary ligation model,we assessed GSTM1 dynamics via molecular profiling,such as Western blotting,immunofluorescence,and real-time quantitative polymerase chain reaction.Adeno-associated virus serotype 9(AAV9)-mediated cardiac-specific GSTM1 overexpression was achieved through systemic delivery.In vitro studies employed transforming growth factor-β(TGF-β)-stimulated primary fibroblasts with siRNA/plasmid interventions.Mechanistic insights were derived from transcriptomics and lipid peroxidation assays.Results:The expression of GSTM1 in mouse CFs after MI was significantly down-regulated at both transcriptional and protein levels.In human dilated cardiomyopathy(DCM)patients with severe heart failure,GSTM1 expression was decreased alongside aggravated fibrosis.Overexpression of GSTM1 in post-MI mice improved cardiac function,while significantly reducing infarct size and fibrosis compared with the control group.In vitro models demonstrated that GSTM1 markedly attenuated collagen secretion and activation of fibroblasts,as well as suppressed their proliferation and migration.Further studies revealed that GSTM1 overexpression significantly inhibited the generation of intracellular and mitochondrial reactive oxygen species(ROS)under pathological conditions,suggesting that GSTM1 exerts an antioxidative stress effect in post-infarction fibroblasts.Further investigation of molecular mechanisms indicated that GSTM1 may suppress the initiation and progression of fibrosis by modulating lipid metabolism and ferroptosis-related pathways.Overexpression of GSTM1 significantly reduced lipid peroxidation and free ferrous iron levels in fibroblasts and mitochondria,markedly decreased ferroptosis-related indicators,and alleviated oxidative lipid levels[such as 12-hydroxyeicosapentaenoic acid(HEPE)and 9-,10-dihydroxy octadecenoic acid(DHOME)]under fibrotic conditions.GSTM1 enhanced the phosphorylation of signal transducer and activator of transcription 3(STAT3),thereby upregulating the downstream expression of glutathione peroxidase 4(GPX4),reducing ROS production,and mitigating fibroblast activation and phenotypic transformation by inhibiting lipid peroxidation.Conclusions:This study identifies GSTM1 as a key inhibitor of fibroblast activation and cardiac fibrosis,highlighting its ability to target ferroptosis through redox regulation.AAV-mediated GSTM1 therapy demonstrates significant therapeutic potential for improving outcomes post-MI.展开更多
Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Alt...Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Although specific inflammatory mediators have been implicated in modulating critical features of cardiac remodeling—such as cardiomyocyte hypertrophy and extracellular matrix fibrosis—the precise molecular mechanisms driving these processes remain incompletely characterized.Methods Integrated bioinformatics analysis of HF and hypertrophic cardiomyopathy(HCM)transcriptomic datasets identified pathologically relevant candidate genes.A protein-protein interaction(PPI)network was constructed from these candidates using the STRING database,followed by module analysis.Serum S100 calcium-binding protein A9(S100A9)protein expression in HF patients was quantified by Western blotting under reducing conditions.The functional relevance of prioritized genes was subsequently validated through:(i)in vitro cyclic mechanical stretch in primary neonatal rat cardiomyocytes,and(ii)in vivo pressure overload modeling via transverse aortic constriction(TAC)in mice.Results Bioinformatics analysis of HF and HCM datasets revealed a significant association between immune function and cardiac remodeling.Using CytoNCA,we identified core genes,among which the top 25 included multiple inflammatory pathway-related factors,such as S100A9 and Toll-like receptor 2(TLR2).Notably,S100A9 levels were significantly elevated in the serum of HF patients and in mechanically stretched cardiomyocytes.This increase correlated with upregulated expression of hypertrophy-related markers,including atrial natriuretic peptide(ANP).Furthermore,mechanical stretch-induced S100A9 upregulation markedly enhanced TLR2 expression in cardiomyocytes.Importantly,TLR2 inhibition substantially attenuated the mechanical stretch-induced upregulation of S100A9 mRNA expression,as well as the subsequent hypertrophic and inflammatory responses in cardiomyocytes.Conclusion The inflammatory mediators S100A9 and TLR2 engage in reciprocal activation that amplifies the hypertrophic response in mechanically stretched cardiomyocytes.This pathogenic cross-talk exacerbates maladaptive remodeling and likely accelerates HF progression.展开更多
BACKGROUND Recent advancements in artificial intelligence(AI)have significantly enhanced the capabilities of endoscopic-assisted diagnosis for gastrointestinal diseases.AI has shown great promise in clinical practice,...BACKGROUND Recent advancements in artificial intelligence(AI)have significantly enhanced the capabilities of endoscopic-assisted diagnosis for gastrointestinal diseases.AI has shown great promise in clinical practice,particularly for diagnostic support,offering real-time insights into complex conditions such as esophageal squamous cell carcinoma.CASE SUMMARY In this study,we introduce a multimodal AI system that successfully identified and delineated a small and flat carcinoma during esophagogastroduodenoscopy,highlighting its potential for early detection of malignancies.The lesion was confirmed as high-grade squamous intraepithelial neoplasia,with pathology results supporting the AI system’s accuracy.The multimodal AI system offers an integrated solution that provides real-time,accurate diagnostic information directly within the endoscopic device interface,allowing for single-monitor use without disrupting endoscopist’s workflow.CONCLUSION This work underscores the transformative potential of AI to enhance endoscopic diagnosis by enabling earlier,more accurate interventions.展开更多
A systemic strategy was proposed to improve aerobic granular sludge(AGS)stability and nitrogen(N)removal efficiency by optimizing feeding mode and substrate aiming at complicated wastewater characteristics.Key functio...A systemic strategy was proposed to improve aerobic granular sludge(AGS)stability and nitrogen(N)removal efficiency by optimizing feeding mode and substrate aiming at complicated wastewater characteristics.Key functional groups at the genus level identified by high-throughput sequencing were evaluated as well.The results showed that anaerobic feeding mode and acetate promoted the compact AGS formation with excellent total nitrogen(TN)removal efficiency(averaging 91.7%±4.1%)at various dissolved oxygen conditions.While the aerobic feeding mode led to a loose AGS structure with a vulnerable anaerobic core and poor TN removal efficiency(averaging58.8%±7.4%).Simultaneous nitrification and denitrification process played the dominant role in N removal in compact AGS over the alternating nitrification and denitrification process.High-concentration glucose undermined feast-famine condition with filamentous bacteria growth out of granule and decreased TN removal efficiency to 67.3%±15.2%.Lower food to microorganism ratio may result in a lower N removal rate attributed to the sharply increased biomass concentration fed by glucose.Ammonia-oxidizing bacteria,nitrite-oxidizing bacteria,denitrifying bacteria,and denitrifying phosphorus accumulation organisms enriched during AGS granulation also contributed to the efficient N removal.The proposed strategy provided insights into the relationship between various factors and stable AGS formation,and systemic operation methods for various complicated wastewater treatment.展开更多
In the present study,flavor profiles of Chinese spiced beef in the cooking process were comparatively analyzed by electronic nose,gas chromatography–mass spectrometry(GC–MS)with a thermal desorption system(TDS),and ...In the present study,flavor profiles of Chinese spiced beef in the cooking process were comparatively analyzed by electronic nose,gas chromatography–mass spectrometry(GC–MS)with a thermal desorption system(TDS),and solid-phase microextraction(SPME).A total of 82 volatile compounds were identified,and 3-methyl-butanal,pentanal,hexanal,-xylene,heptanal,limonene,terpinene,octanal,linalool,4-terpinenol,-terpineol,and(E)-anethole were identified as the characteristic flavor compounds in Chinese spiced beef.Variation in the content of volatile components produced by different cooking processes was observed.In general,a cooking time of 4 h resulted in optimal flavor quality and stability.Results indicated that the electronic nose could profile and rapidly distinguish variation among different cooking time.The volatile profiling by TDS-GC–MS and responses from the electronic nose,in combination with multivariate statistical analysis,are a promising tool for control the cooking process of spiced beef.展开更多
BACKGROUND Acute respiratory distress syndrome(ARDS)is a major cause of death in patients with severe acute pancreatitis(SAP).Although a series of prediction models have been developed for early identification of such...BACKGROUND Acute respiratory distress syndrome(ARDS)is a major cause of death in patients with severe acute pancreatitis(SAP).Although a series of prediction models have been developed for early identification of such patients,the majority are complicated or lack validation.A simpler and more credible model is required for clinical practice.AIM To develop and validate a predictive model for SAP related ARDS.METHODS Patients diagnosed with AP from four hospitals located at different regions of China were retrospectively grouped into derivation and validation cohorts.Statistically significant variables were identified using the least absolute shrinkage and selection operator regression method.Predictive models with nomograms were further built using multiple logistic regression analysis with these picked predictors.The discriminatory power of new models was compared with some common models.The performance of calibration ability and clinical utility of the predictive models were evaluated.RESULTS Out of 597 patients with AP,139 were diagnosed with SAP(80 in derivation cohort and 59 in validation cohort)and 99 with ARDS(62 in derivation cohort and 37 in validation cohort).Four identical variables were identified as independent risk factors for both SAP and ARDS:heart rate[odds ratio(OR)=1.05;95%CI:1.04-1.07;P<0.001;OR=1.05,95%CI:1.03-1.07,P<0.001],respiratory rate(OR=1.08,95%CI:1.0-1.17,P=0.047;OR=1.10,95%CI:1.02-1.19,P=0.014),serum calcium concentration(OR=0.26,95%CI:0.09-0.73,P=0.011;OR=0.17,95%CI:0.06-0.48,P=0.001)and blood urea nitrogen(OR=1.15,95%CI:1.09-1.23,P<0.001;OR=1.12,95%CI:1.05-1.19,P<0.001).The area under receiver operating characteristic curve was 0.879(95%CI:0.830-0.928)and 0.898(95%CI:0.848-0.949)for SAP prediction in derivation and validation cohorts,respectively.This value was 0.892(95%CI:0.843-0.941)and 0.833(95%CI:0.754-0.912)for ARDS prediction,respectively.The discriminatory power of our models was improved compared with that of other widely used models and the calibration ability and clinical utility of the prediction models performed adequately.CONCLUSION The present study constructed and validated a simple and accurate predictive model for SAPrelated ARDS in patients with AP.展开更多
The effect of preparation parameters on the performance of zeolite for ammonium (20-300 mg N/L) adsorption from simulated wastewater is reported.It was found that the ratios of Na2O/SiO2 and Si/Al had a more important...The effect of preparation parameters on the performance of zeolite for ammonium (20-300 mg N/L) adsorption from simulated wastewater is reported.It was found that the ratios of Na2O/SiO2 and Si/Al had a more important influence than crystallization time on zeolite adsorption properties.Relatively low Na2O/SiO2 ratios were beneficial for fabrication of zeolites with high proportions of micropore area and volume,which led to the surface adsorption mechanism being dominated by surface free energy and pore effects.However,with decreasing Si/Al ratios,the effect of ion-exchange was more prominent due to the high negative surface potential of zeolite.In addition,the concentration of weak acid sites on the zeolites was increased with lower ratios of Na2O/SiO2 and Si/Al,which may promote ammonium removal.Therefore,the most effective zeolite for ammonium removal,which was fabricated at Na2O/SiO2 =1.375,Si/Al =4 and crystallization time of 48 hr,exhibited the cooperative effects of adsorption,ion-exchange and a large amount of weak acid sites.The maximum ammonium adsorption capacity (35.06 t 0.98 mg/g) and the removal efficiency (94.44%± 4.00%) were obtained at the dosage of 4.0 g/L zeolite NaX at ammonium concentrations of 300 mg N/L and 20 mg N/L,respectively.The Freundlich isotherm and pseudo-first-order kinetics models provided excellent fitting for the ammonium adsorption process.In addition,zeolite NaX showed about 1.23-3.2 times the ammonium adsorption capacity of clinoptilolite.The stable and efficient reusability of zeolite NaX after five regeneration cycles demonstrated that this adsorbent has considerable potential for practical industrial applications.展开更多
The Monte Carlo code MCML(Monte Carlo modeling of light transport in multi-layered tissue)has been the gold standard for simulations of light transport in multi-layer tissue,but it is ineffective in the presence of th...The Monte Carlo code MCML(Monte Carlo modeling of light transport in multi-layered tissue)has been the gold standard for simulations of light transport in multi-layer tissue,but it is ineffective in the presence of three-dimensional(3D)heterogeneity.New techniques have been attempted to resolve this problem,such as MCLS,which is derived from MCML,and tMCimg,which draws upon image datasets.Nevertheless,these approaches are insufficient because of their low precision or simplistic modeling.We report on the development of a novel model for photon migration in voxelized media(MCVM)with 3D heterogeneity.Voxel crossing detection and refractive-index-unmatched boundaries were considered to improve the precision and eliminate dependence on refractive-index-matched tissue.Using a semi-infinite homogeneous medium,steady-state and time-resolved simulations of MCVM agreed well with MCML,with high precision(∼100%)for the total diffuse reflectance and total fractional absorption compared to those of tMCimg(<70%).Based on a refractive-index-matched heterogeneous skin model,the results of MCVM were found to coincide with those of MCLS.Finally,MCVM was applied to a two-layered sphere with multi-inclusions,which is an example of a 3D heterogeneous media with refractive-index-unmatched boundaries.MCVM provided a reliable model for simulation of photon migration in voxelized 3D heterogeneous media,and it was developed to be a flexible and simple software tool that delivers high-precision results.展开更多
Mainstream partial nitritation-anammox(PNA)process easily suffers from performance instability and even reactor collapse in application.Thus,it is of great significance to unveil the characteristic of performance reco...Mainstream partial nitritation-anammox(PNA)process easily suffers from performance instability and even reactor collapse in application.Thus,it is of great significance to unveil the characteristic of performance recovery,understand the intrinsic mechanism and then propose operational strategy.In this study,we combined long-term reactor operation,batch tests,and metagenomics to reveal the succession of microbial community and functional metabolism variation from system collapse to recovery.Proper aeration control(0.10-0.25mg O2/L)was critical for performance recovery.It was also found that Candidatus Brocadia became the dominant flora and its abundance increased from 3.5%to 11.0%.Significant enhancements in carbon metabolism and phospholipid biosynthesis were observed during system recovery,and the genes abundance related to signal transduction was dramatically increased.The up-regulation of sdh and suc genes showed the processes of succinate dehydrogenation and succinyl-CoA synthesis might stimulate the production of amino acids and the synthesis of proteins,thereby possibly improving the activity and abundance of AnAOB,which was conducive to the performance recovery.Moreover,the increase in abundance of hzs and hdh genes suggested the enhancement of the anammox process.Changes in the abundance of key genes involved in nitrogen metabolism indicated that nitrogen removal pathway was more diverse after system recovery.The achievement of performance recovery was driven by anammox,nitrification and denitrification coupled with dissimilatory nitrate reduction to ammonium.These results provide deeper insights into the recovery mechanism of PNA system and also provide a potential regulation strategy for the stable operation of the mainstream PNA process.展开更多
Neurons in the primary auditory area(AUDp)innervate multiple brain regions with long-range projections while receiving informative inputs for diverse functions.However,the brain-wide connections of these neurons have ...Neurons in the primary auditory area(AUDp)innervate multiple brain regions with long-range projections while receiving informative inputs for diverse functions.However,the brain-wide connections of these neurons have not been comprehensively investigated.Here,we simultaneously applied virus-based anterograde and retrograde tracing,labeled the connections of excitatory and inhibitory neurons in the mouse AUDp,and acquired whole-brain information using a dual-channel fuorescence micro-optical sectioning tomography system.Quantified results showed that the two types of neurons received inputs with similar patterns but sent heterogeneous projections to downstream regions.In the isocortex,functionally different areas consistently sent feedback-dominated projections to these neurons,with concomitant laterallydominated projections from the sensory and limbic cortices to inhibitory neurons.In subcortical regions,the dorsal and medial parts of the non-lemniscal auditory thalamus(AT)were reciprocally connected to the AUDp,while the ventral part contained the most fibers of passage from the excitatory neurons and barely sent projections back,indicating the regional heterogeneity of the AUDp-AT circuit.Our results reveal details of the whole-brain network and provide new insights for further physiological and functional studies of the AUDp.展开更多
BACKGROUND Commonly used cleaning brushes in the reprocessing of flexible endoscopes often cause damage within the working channels.AIM To develop a spray flushing system to achieving effective cleaning of the working...BACKGROUND Commonly used cleaning brushes in the reprocessing of flexible endoscopes often cause damage within the working channels.AIM To develop a spray flushing system to achieving effective cleaning of the working channels while minimizing damage.METHODS This prospective study included 60 used endoscopes and 60 Teflon tubes randomly divided into a control group(n=30)and an experimental group(n=30).The material of Teflon tubes was the same as that of the endoscope working channel.Endoscopes in the control group were manually cleaned using traditional cleaning brushes,while those in the experimental group were cleaned using the newly developed spray flushing system.ATP levels,cleanliness,and microbiological testing of the working channels were measured.Additionally,Teflon tubes in the control group underwent 500 passes with a cleaning brush,while those in the experimental group were subjected to the spray flushing system,and channel damage was evaluated.RESULTS The ATP levels(RLU)in the two groups were 32.5(13-66)and 26(16-40),respectively(P>0.05).Cleanliness scores were 1.5(1-2)and 1(1-2),respectively(P>0.05).Debris was found in 73.3%of the control group,which was significantly higher than 46.7%in the experimental group(P<0.05).Microbiological tests for both groups yielded negative results.Teflon tube damage in the control group was rated at 4(4-5.25),which was significantly higher than in the experimental group 4(3-4)(P<0.01).CONCLUSION The spray flushing system demonstrated superior efficacy in removing debris and resulted in less damage to the endoscope working channels compared with traditional cleaning brushes.展开更多
Compared with event-related potential(ERP)which is widely used in psychology research,functional near-infrared imaging(fNIRI)is a new technique providing hemodynamic information related to brain activity,except for el...Compared with event-related potential(ERP)which is widely used in psychology research,functional near-infrared imaging(fNIRI)is a new technique providing hemodynamic information related to brain activity,except for electrophysiological signals.Here,we use both these techniques to study ocular attention.We conducted a series of experiments with a classic paradigm of ocular nonselective attention,and monitored responses with fNIRI and ERP respectively.The results showed that fNIRI measured brain activations in the left prefrontal lobe,while ERPs showed activation in frontal lobe.More importantly,only with the combination measurements of fNIRI and ERP,we were then able to find the pinpoint source of ocular nonselective attention,which is in the left and upper corner in Brodmann area 10.These results demonstrated that fNIRI is a reliable technique in psychology,and the combination of fNIRI and ERP can be promising to reveal more information in the research of brain mechanism.展开更多
The orbitofrontal cortex(ORB),a region crucial for stimulus-reward association,decision-making,and flexible behaviors,extensively connects with other brain areas.However,brain-wide inputs to projection-defined ORB neu...The orbitofrontal cortex(ORB),a region crucial for stimulus-reward association,decision-making,and flexible behaviors,extensively connects with other brain areas.However,brain-wide inputs to projection-defined ORB neurons and the distribution of inhibitory neurons postsynaptic to neurons in specific ORB subregions remain poorly characterized.Here we mapped the inputs of five types of projection-specific ORB neurons and ORB outputs to two types of inhibitory neurons.We found that different projection-defined ORB neurons received inputs from similar cortical and thalamic regions,albeit with quantitative variations,particularly in somatomotor areas and medial groups of the dorsal thalamus.By counting parvalbumin(PV)or somatostatin(SST)interneurons innervated by neurons in specific ORB subregions,we found a higher fraction of PV neurons in sensory cortices and a higher fraction of SST neurons in subcortical regions targeted by medial ORB neurons.These results provide insights into understanding and investigating the function of specific ORB neurons.展开更多
Unlike the role of the membrane in a membrane bioreactor, which is designed to replace a sediment tank, direct sewage membrane filtration(DSMF), with the goal of concentrating organic matters, is proposed as a pretr...Unlike the role of the membrane in a membrane bioreactor, which is designed to replace a sediment tank, direct sewage membrane filtration(DSMF), with the goal of concentrating organic matters, is proposed as a pretreatment process in a novel sewage treatment concept. The concept of membrane-based pretreatment is proposed to divide raw sewage into a concentrated part retaining most organics and a filtered part with less pollutant remaining, so that energy recovery and water reuse, respectively, could be realized by post-treatment. A pilot-scale experiment was carried out to verify the feasibility of coagulant/adsorbent addition for membrane fouling control, which has been the main issue during this DSMF process. The results showed that continuous coagulant addition successfully slowed down the increase in filtration resistance, with the resistance maintained below 1.0 × 1013m^(-1) in the first 70 hr before a jump occurred. Furthermore,the adsorbent addition contributed to retarding the occurrence of the filtration resistance jump, achieving simultaneous fouling control and chemical oxygen demand(COD)concentration improvement. The final concentrated COD amounted to 7500 mg/L after 6 days of operation.展开更多
The mammalian brain is a highly complex network that consists of millions to billions of densely-interconnected neurons.Precise dissection of neural circuits at the mesoscopic level can provide important structural in...The mammalian brain is a highly complex network that consists of millions to billions of densely-interconnected neurons.Precise dissection of neural circuits at the mesoscopic level can provide important structural information for understanding the brain.Optical approaches can achieve submicron lateral resolution and achieve“optical sectioning”by a variety of means,which has the natural advantage of allowing the observation of neural circuits at the mesoscopic level.Automated whole-brain optical imaging methods based on tissue clearing or histological sectioning surpass the limitation of optical imaging depth in biological tissues and can provide delicate structural information in a large volume of tissues.Combined with various fluorescent labeling techniques,whole-brain optical imaging methods have shown great potential in the brain-wide quantitative profiling of cells,circuits,and blood vessels.In this review,we summarize the principles and implementations of various whole-brain optical imaging methods and provide some concepts regarding their future development.展开更多
Hand,foot and mouth disease(HFMD)is a major public health problem among children in the Asia-Pacific region.The optimal specimen for HFMD virological diagnosis remains unclear.Enterovirus A71(EV-A71)neutralizing antib...Hand,foot and mouth disease(HFMD)is a major public health problem among children in the Asia-Pacific region.The optimal specimen for HFMD virological diagnosis remains unclear.Enterovirus A71(EV-A71)neutralizing antibody titres detected in paired sera were considered the reference standard for calculating the sensitivity,specificity,positive and negative predictive value of throat swabs,rectal swabs,stool,blood samples and cerebrospinal fluid(CSF)by RT-PCR or ELISA assay.In this study,clinical samples from 276 HFMD patients were collected for analysing the sensitivity of different kind of specimens.Our results showed that stool had the highest sensitivity(88%,95%CI:74%–96%)and agreement with the reference standard(91%).The order of diagnostic yield for EV-A71 infection was stool samplerectal swab>throat swab>blood sample>CSF sample,and using a combination of clinical samples improved sensitivity for enterovirus detection.The sensitivity of ELISA for IgM antibody detection in sterile-site specimens was significantly higher than that of RT-PCR(serum/plasma:62%vs.2%,CSF:47%vs.0%)(P<0.002).In conclusion,our results suggest that stool has the highest diagnostic yield for EV-A71-infected HFMD.If stool is unavailable,rectal swabs can be collected to achieve a similar diagnostic yield.Otherwise,throat swabs may be useful in detecting positive samples.Although IgM in blood or CSF is diagnostically accurate,it lacks sensitivity,missing 40%–50%of cases.The higher proportion of severe cases and shorter interval between onset and sampling contributed to the increase in congruency between clinical testing and the serological reference standard.展开更多
Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert.However,it remains challenging to obtain the neural activity and the brain-wi...Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert.However,it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons,especially for neurons in subcortical brain regions.Here,by combining in vivo microscopy and high-definition fluorescence microoptical sectioning tomography,we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex,the dorsal hippocampus,and the substantia nigra pars compacta.More importantly,we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype.The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.展开更多
Objective Y-Chromosomal short tandem repeat polymorphism(Y-STR)analysis plays an indispensable role in the identification of male individuals,population genetics,and biogeographic research.While profiles of many popul...Objective Y-Chromosomal short tandem repeat polymorphism(Y-STR)analysis plays an indispensable role in the identification of male individuals,population genetics,and biogeographic research.While profiles of many populations based on Y-STR markers in human genomes are ample,haplotype data for the Wuwei Han are still scarce.Methods In this study,2180 unrelated Wuwei Han male individuals residing in Gansu Province,China were collected and genotyped using the novel Microreader™40Y Plus ID system.Phylogenetic relationship reconstructions,multidimensional scaling(MDS),and heatmap analysis were performed based on the genetic distance(Rst)values between our studied population and other populations of the Ymax module in the Y-STR Haplotype Reference Database(YHRD).Results A total of 2129 unique haplotypes were obtained,and the haplotype diversity(HD)and discrimination capacity(DC)for the Wuwei Han were 0.9999 and 0.9931,respectively.Conclusion Our results demonstrate that the Wuwei Han population had intimate genetic relationships with East Asians,especially the geographically close Han populations.Overall,this Y-Chromosomal assay gives valuable information about paternal lineages in male individual tracking and genealogical database construction.展开更多
Near infrared spectroscopy(NIRS)is generally accepted as a functional brain imaging technology for brain activation study.With multichannel highly sensitive NIRS instruments,it has become possible to assess functional...Near infrared spectroscopy(NIRS)is generally accepted as a functional brain imaging technology for brain activation study.With multichannel highly sensitive NIRS instruments,it has become possible to assess functional connectivity of different brain negions by NIRS.However,the feasibility needs to be validated in complex cognitive activities.In this study,we recorded the hemodynamic activity of the bilateral prefrontal cortex(PFC)during a color-word matching Stroop task.Wavelet transform coberence(WTC)analysis was applied to ascss the functional conectivity of all homologous channel pairs within the leftight PFC.Both the behavioral and brain activ ation results showed signifcant Stroop effects.The results of WTC analysis revealed that,bilateral functional connectivity was significantly stronger during both the incongruent stimuli and neutral stimuli compared to that of the rest period.It also showed significant Stroop effect.Our findings demonstrate that,NIRS bcomes a valuable tool to elucidate the functional conectivity of brain cortex in complex cognitive activities.展开更多
Objective:Myocardial ischemia-reperfusion(I/R)injury is associated with a significant reduction in the mitochondrial membrane potential(MMP,ΔΨm).Fluorescence-based assays are effective for labelling active mitochond...Objective:Myocardial ischemia-reperfusion(I/R)injury is associated with a significant reduction in the mitochondrial membrane potential(MMP,ΔΨm).Fluorescence-based assays are effective for labelling active mitochondria in living cells;their application in heart tissue,however,represents a challenge because of a low yield of viable cardiomyocytes after cardiac perfusion.This study aimed to examine a novel method for detecting the changes in the MMP of mouse heart tissue following I/R injury.Methods:The I/R model was established,which was characterized by distinct ischemic area and apoptosis in heart tissue.The MMP was detected via a confocal microscope after the ascending aorta was clamped and the mitochondrial probe solution(containing Mito-Tracker Deep Red FM)was perfused from the apex via a peristaltic pump.Results:This method enabled the distribution of the probe solution throughout the cardiac tissue via the coronary circulation.Fluorescence detection revealed that the MMP was profoundly reduced in both ischemic area and border area following I/R when compared with that in the sham group.There was no obvious difference in the MMP of the remote area between the I/R group and the sham group.Conclusion:This study presents a novel method for detecting the MMP in heart tissue,and this method will facilitate the evaluation of changes in the MMP in different regions following I/R.展开更多
基金supported by the National Natural Science Foundation of China(82270386,82070252,and 8207025)the Zhejiang Provincial Medical and Health Science and Technology Plan(2023RC020)the Zhejiang Provincial Natural Science Foundation(LR21H020001).
摘要Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an important member of the glutathione S-transferase(GSTs)family,which plays an important role in maintaining cell homeostasis and detoxification.This study investigated the role and mechanism of GSTM1 in post-MI fibrosis.Methods:Multi-omics approaches(proteomics/scRNA-seq)identified GSTM1 as a dysregulated target in post-MI fibroblasts.Using a murine coronary ligation model,we assessed GSTM1 dynamics via molecular profiling,such as Western blotting,immunofluorescence,and real-time quantitative polymerase chain reaction.Adeno-associated virus serotype 9(AAV9)-mediated cardiac-specific GSTM1 overexpression was achieved through systemic delivery.In vitro studies employed transforming growth factor-β(TGF-β)-stimulated primary fibroblasts with siRNA/plasmid interventions.Mechanistic insights were derived from transcriptomics and lipid peroxidation assays.Results:The expression of GSTM1 in mouse CFs after MI was significantly down-regulated at both transcriptional and protein levels.In human dilated cardiomyopathy(DCM)patients with severe heart failure,GSTM1 expression was decreased alongside aggravated fibrosis.Overexpression of GSTM1 in post-MI mice improved cardiac function,while significantly reducing infarct size and fibrosis compared with the control group.In vitro models demonstrated that GSTM1 markedly attenuated collagen secretion and activation of fibroblasts,as well as suppressed their proliferation and migration.Further studies revealed that GSTM1 overexpression significantly inhibited the generation of intracellular and mitochondrial reactive oxygen species(ROS)under pathological conditions,suggesting that GSTM1 exerts an antioxidative stress effect in post-infarction fibroblasts.Further investigation of molecular mechanisms indicated that GSTM1 may suppress the initiation and progression of fibrosis by modulating lipid metabolism and ferroptosis-related pathways.Overexpression of GSTM1 significantly reduced lipid peroxidation and free ferrous iron levels in fibroblasts and mitochondria,markedly decreased ferroptosis-related indicators,and alleviated oxidative lipid levels[such as 12-hydroxyeicosapentaenoic acid(HEPE)and 9-,10-dihydroxy octadecenoic acid(DHOME)]under fibrotic conditions.GSTM1 enhanced the phosphorylation of signal transducer and activator of transcription 3(STAT3),thereby upregulating the downstream expression of glutathione peroxidase 4(GPX4),reducing ROS production,and mitigating fibroblast activation and phenotypic transformation by inhibiting lipid peroxidation.Conclusions:This study identifies GSTM1 as a key inhibitor of fibroblast activation and cardiac fibrosis,highlighting its ability to target ferroptosis through redox regulation.AAV-mediated GSTM1 therapy demonstrates significant therapeutic potential for improving outcomes post-MI.
基金supported by the National Key Research and Development Program of China(No.2023YFC2506504)the National Natural Science Foundation of China(No.82370255,and No.U24A20646)the Shanghai Science and Technology Commission Project(No.23410761200).
摘要Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Although specific inflammatory mediators have been implicated in modulating critical features of cardiac remodeling—such as cardiomyocyte hypertrophy and extracellular matrix fibrosis—the precise molecular mechanisms driving these processes remain incompletely characterized.Methods Integrated bioinformatics analysis of HF and hypertrophic cardiomyopathy(HCM)transcriptomic datasets identified pathologically relevant candidate genes.A protein-protein interaction(PPI)network was constructed from these candidates using the STRING database,followed by module analysis.Serum S100 calcium-binding protein A9(S100A9)protein expression in HF patients was quantified by Western blotting under reducing conditions.The functional relevance of prioritized genes was subsequently validated through:(i)in vitro cyclic mechanical stretch in primary neonatal rat cardiomyocytes,and(ii)in vivo pressure overload modeling via transverse aortic constriction(TAC)in mice.Results Bioinformatics analysis of HF and HCM datasets revealed a significant association between immune function and cardiac remodeling.Using CytoNCA,we identified core genes,among which the top 25 included multiple inflammatory pathway-related factors,such as S100A9 and Toll-like receptor 2(TLR2).Notably,S100A9 levels were significantly elevated in the serum of HF patients and in mechanically stretched cardiomyocytes.This increase correlated with upregulated expression of hypertrophy-related markers,including atrial natriuretic peptide(ANP).Furthermore,mechanical stretch-induced S100A9 upregulation markedly enhanced TLR2 expression in cardiomyocytes.Importantly,TLR2 inhibition substantially attenuated the mechanical stretch-induced upregulation of S100A9 mRNA expression,as well as the subsequent hypertrophic and inflammatory responses in cardiomyocytes.Conclusion The inflammatory mediators S100A9 and TLR2 engage in reciprocal activation that amplifies the hypertrophic response in mechanically stretched cardiomyocytes.This pathogenic cross-talk exacerbates maladaptive remodeling and likely accelerates HF progression.
基金Supported by the 135 High-end Talent Project of West China Hospital,Sichuan University,No.ZYDG23029.
摘要BACKGROUND Recent advancements in artificial intelligence(AI)have significantly enhanced the capabilities of endoscopic-assisted diagnosis for gastrointestinal diseases.AI has shown great promise in clinical practice,particularly for diagnostic support,offering real-time insights into complex conditions such as esophageal squamous cell carcinoma.CASE SUMMARY In this study,we introduce a multimodal AI system that successfully identified and delineated a small and flat carcinoma during esophagogastroduodenoscopy,highlighting its potential for early detection of malignancies.The lesion was confirmed as high-grade squamous intraepithelial neoplasia,with pathology results supporting the AI system’s accuracy.The multimodal AI system offers an integrated solution that provides real-time,accurate diagnostic information directly within the endoscopic device interface,allowing for single-monitor use without disrupting endoscopist’s workflow.CONCLUSION This work underscores the transformative potential of AI to enhance endoscopic diagnosis by enabling earlier,more accurate interventions.
基金supported by the Major Science and Technology Program for Water Pollution Control and Treatment of China (Nos. 2017ZX07102-003, 2017ZX07103)the China Postdoctoral Science Foundation (Nos. 2017M620799, 2018T110108)the National Natural Science Foundation of China (No. 51608298)
摘要A systemic strategy was proposed to improve aerobic granular sludge(AGS)stability and nitrogen(N)removal efficiency by optimizing feeding mode and substrate aiming at complicated wastewater characteristics.Key functional groups at the genus level identified by high-throughput sequencing were evaluated as well.The results showed that anaerobic feeding mode and acetate promoted the compact AGS formation with excellent total nitrogen(TN)removal efficiency(averaging 91.7%±4.1%)at various dissolved oxygen conditions.While the aerobic feeding mode led to a loose AGS structure with a vulnerable anaerobic core and poor TN removal efficiency(averaging58.8%±7.4%).Simultaneous nitrification and denitrification process played the dominant role in N removal in compact AGS over the alternating nitrification and denitrification process.High-concentration glucose undermined feast-famine condition with filamentous bacteria growth out of granule and decreased TN removal efficiency to 67.3%±15.2%.Lower food to microorganism ratio may result in a lower N removal rate attributed to the sharply increased biomass concentration fed by glucose.Ammonia-oxidizing bacteria,nitrite-oxidizing bacteria,denitrifying bacteria,and denitrifying phosphorus accumulation organisms enriched during AGS granulation also contributed to the efficient N removal.The proposed strategy provided insights into the relationship between various factors and stable AGS formation,and systemic operation methods for various complicated wastewater treatment.
基金This work was part of the project“Research and Development of Nutrition and Health Processing for Halal Beef and Muttons”,and was financially supported by Ningxia Hui Autonomous Region Technology R&D Support Program as well as the“13th Five-Year Plan”(No.2016YFD0400703)of National Key Research and Development Program of China.
摘要In the present study,flavor profiles of Chinese spiced beef in the cooking process were comparatively analyzed by electronic nose,gas chromatography–mass spectrometry(GC–MS)with a thermal desorption system(TDS),and solid-phase microextraction(SPME).A total of 82 volatile compounds were identified,and 3-methyl-butanal,pentanal,hexanal,-xylene,heptanal,limonene,terpinene,octanal,linalool,4-terpinenol,-terpineol,and(E)-anethole were identified as the characteristic flavor compounds in Chinese spiced beef.Variation in the content of volatile components produced by different cooking processes was observed.In general,a cooking time of 4 h resulted in optimal flavor quality and stability.Results indicated that the electronic nose could profile and rapidly distinguish variation among different cooking time.The volatile profiling by TDS-GC–MS and responses from the electronic nose,in combination with multivariate statistical analysis,are a promising tool for control the cooking process of spiced beef.
基金Supported by the Chinese Natural Science Foundation,No.32170788.
摘要BACKGROUND Acute respiratory distress syndrome(ARDS)is a major cause of death in patients with severe acute pancreatitis(SAP).Although a series of prediction models have been developed for early identification of such patients,the majority are complicated or lack validation.A simpler and more credible model is required for clinical practice.AIM To develop and validate a predictive model for SAP related ARDS.METHODS Patients diagnosed with AP from four hospitals located at different regions of China were retrospectively grouped into derivation and validation cohorts.Statistically significant variables were identified using the least absolute shrinkage and selection operator regression method.Predictive models with nomograms were further built using multiple logistic regression analysis with these picked predictors.The discriminatory power of new models was compared with some common models.The performance of calibration ability and clinical utility of the predictive models were evaluated.RESULTS Out of 597 patients with AP,139 were diagnosed with SAP(80 in derivation cohort and 59 in validation cohort)and 99 with ARDS(62 in derivation cohort and 37 in validation cohort).Four identical variables were identified as independent risk factors for both SAP and ARDS:heart rate[odds ratio(OR)=1.05;95%CI:1.04-1.07;P<0.001;OR=1.05,95%CI:1.03-1.07,P<0.001],respiratory rate(OR=1.08,95%CI:1.0-1.17,P=0.047;OR=1.10,95%CI:1.02-1.19,P=0.014),serum calcium concentration(OR=0.26,95%CI:0.09-0.73,P=0.011;OR=0.17,95%CI:0.06-0.48,P=0.001)and blood urea nitrogen(OR=1.15,95%CI:1.09-1.23,P<0.001;OR=1.12,95%CI:1.05-1.19,P<0.001).The area under receiver operating characteristic curve was 0.879(95%CI:0.830-0.928)and 0.898(95%CI:0.848-0.949)for SAP prediction in derivation and validation cohorts,respectively.This value was 0.892(95%CI:0.843-0.941)and 0.833(95%CI:0.754-0.912)for ARDS prediction,respectively.The discriminatory power of our models was improved compared with that of other widely used models and the calibration ability and clinical utility of the prediction models performed adequately.CONCLUSION The present study constructed and validated a simple and accurate predictive model for SAPrelated ARDS in patients with AP.
基金supported by the China Postdoctoral Science Foundation(2018M631489)
摘要The effect of preparation parameters on the performance of zeolite for ammonium (20-300 mg N/L) adsorption from simulated wastewater is reported.It was found that the ratios of Na2O/SiO2 and Si/Al had a more important influence than crystallization time on zeolite adsorption properties.Relatively low Na2O/SiO2 ratios were beneficial for fabrication of zeolites with high proportions of micropore area and volume,which led to the surface adsorption mechanism being dominated by surface free energy and pore effects.However,with decreasing Si/Al ratios,the effect of ion-exchange was more prominent due to the high negative surface potential of zeolite.In addition,the concentration of weak acid sites on the zeolites was increased with lower ratios of Na2O/SiO2 and Si/Al,which may promote ammonium removal.Therefore,the most effective zeolite for ammonium removal,which was fabricated at Na2O/SiO2 =1.375,Si/Al =4 and crystallization time of 48 hr,exhibited the cooperative effects of adsorption,ion-exchange and a large amount of weak acid sites.The maximum ammonium adsorption capacity (35.06 t 0.98 mg/g) and the removal efficiency (94.44%± 4.00%) were obtained at the dosage of 4.0 g/L zeolite NaX at ammonium concentrations of 300 mg N/L and 20 mg N/L,respectively.The Freundlich isotherm and pseudo-first-order kinetics models provided excellent fitting for the ammonium adsorption process.In addition,zeolite NaX showed about 1.23-3.2 times the ammonium adsorption capacity of clinoptilolite.The stable and efficient reusability of zeolite NaX after five regeneration cycles demonstrated that this adsorbent has considerable potential for practical industrial applications.
基金This research was supported by the National Natural Science Foundation of China(Grant No.30727002)the National High-Tech R&D Program of China(2006AA020801)111 project,and the Program for Changjiang Scholars and Innovative Research Team in University.
摘要The Monte Carlo code MCML(Monte Carlo modeling of light transport in multi-layered tissue)has been the gold standard for simulations of light transport in multi-layer tissue,but it is ineffective in the presence of three-dimensional(3D)heterogeneity.New techniques have been attempted to resolve this problem,such as MCLS,which is derived from MCML,and tMCimg,which draws upon image datasets.Nevertheless,these approaches are insufficient because of their low precision or simplistic modeling.We report on the development of a novel model for photon migration in voxelized media(MCVM)with 3D heterogeneity.Voxel crossing detection and refractive-index-unmatched boundaries were considered to improve the precision and eliminate dependence on refractive-index-matched tissue.Using a semi-infinite homogeneous medium,steady-state and time-resolved simulations of MCVM agreed well with MCML,with high precision(∼100%)for the total diffuse reflectance and total fractional absorption compared to those of tMCimg(<70%).Based on a refractive-index-matched heterogeneous skin model,the results of MCVM were found to coincide with those of MCLS.Finally,MCVM was applied to a two-layered sphere with multi-inclusions,which is an example of a 3D heterogeneous media with refractive-index-unmatched boundaries.MCVM provided a reliable model for simulation of photon migration in voxelized 3D heterogeneous media,and it was developed to be a flexible and simple software tool that delivers high-precision results.
基金supported by the National Key Research and Development Program of China (No.2021YFC3201504)the National Natural Science Foundations of China (No.52000140)the Social Development Program of Science and Technology Committee Foundations of Shanghai (No.22dz1209200)。
摘要Mainstream partial nitritation-anammox(PNA)process easily suffers from performance instability and even reactor collapse in application.Thus,it is of great significance to unveil the characteristic of performance recovery,understand the intrinsic mechanism and then propose operational strategy.In this study,we combined long-term reactor operation,batch tests,and metagenomics to reveal the succession of microbial community and functional metabolism variation from system collapse to recovery.Proper aeration control(0.10-0.25mg O2/L)was critical for performance recovery.It was also found that Candidatus Brocadia became the dominant flora and its abundance increased from 3.5%to 11.0%.Significant enhancements in carbon metabolism and phospholipid biosynthesis were observed during system recovery,and the genes abundance related to signal transduction was dramatically increased.The up-regulation of sdh and suc genes showed the processes of succinate dehydrogenation and succinyl-CoA synthesis might stimulate the production of amino acids and the synthesis of proteins,thereby possibly improving the activity and abundance of AnAOB,which was conducive to the performance recovery.Moreover,the increase in abundance of hzs and hdh genes suggested the enhancement of the anammox process.Changes in the abundance of key genes involved in nitrogen metabolism indicated that nitrogen removal pathway was more diverse after system recovery.The achievement of performance recovery was driven by anammox,nitrification and denitrification coupled with dissimilatory nitrate reduction to ammonium.These results provide deeper insights into the recovery mechanism of PNA system and also provide a potential regulation strategy for the stable operation of the mainstream PNA process.
基金supported by the National Natural Science Foundation of China(61890953.61890954,and 31871088)the CAMS Innovation Fund for Medical Sciences(2019-12M5014).
摘要Neurons in the primary auditory area(AUDp)innervate multiple brain regions with long-range projections while receiving informative inputs for diverse functions.However,the brain-wide connections of these neurons have not been comprehensively investigated.Here,we simultaneously applied virus-based anterograde and retrograde tracing,labeled the connections of excitatory and inhibitory neurons in the mouse AUDp,and acquired whole-brain information using a dual-channel fuorescence micro-optical sectioning tomography system.Quantified results showed that the two types of neurons received inputs with similar patterns but sent heterogeneous projections to downstream regions.In the isocortex,functionally different areas consistently sent feedback-dominated projections to these neurons,with concomitant laterallydominated projections from the sensory and limbic cortices to inhibitory neurons.In subcortical regions,the dorsal and medial parts of the non-lemniscal auditory thalamus(AT)were reciprocally connected to the AUDp,while the ventral part contained the most fibers of passage from the excitatory neurons and barely sent projections back,indicating the regional heterogeneity of the AUDp-AT circuit.Our results reveal details of the whole-brain network and provide new insights for further physiological and functional studies of the AUDp.
基金West China Nursing Discipline Development Special Fund Project,No.HXHL21029。
摘要BACKGROUND Commonly used cleaning brushes in the reprocessing of flexible endoscopes often cause damage within the working channels.AIM To develop a spray flushing system to achieving effective cleaning of the working channels while minimizing damage.METHODS This prospective study included 60 used endoscopes and 60 Teflon tubes randomly divided into a control group(n=30)and an experimental group(n=30).The material of Teflon tubes was the same as that of the endoscope working channel.Endoscopes in the control group were manually cleaned using traditional cleaning brushes,while those in the experimental group were cleaned using the newly developed spray flushing system.ATP levels,cleanliness,and microbiological testing of the working channels were measured.Additionally,Teflon tubes in the control group underwent 500 passes with a cleaning brush,while those in the experimental group were subjected to the spray flushing system,and channel damage was evaluated.RESULTS The ATP levels(RLU)in the two groups were 32.5(13-66)and 26(16-40),respectively(P>0.05).Cleanliness scores were 1.5(1-2)and 1(1-2),respectively(P>0.05).Debris was found in 73.3%of the control group,which was significantly higher than 46.7%in the experimental group(P<0.05).Microbiological tests for both groups yielded negative results.Teflon tube damage in the control group was rated at 4(4-5.25),which was significantly higher than in the experimental group 4(3-4)(P<0.01).CONCLUSION The spray flushing system demonstrated superior efficacy in removing debris and resulted in less damage to the endoscope working channels compared with traditional cleaning brushes.
基金supported by the National Nature Science Foundation of China(grant No.30070261,60025514).
摘要Compared with event-related potential(ERP)which is widely used in psychology research,functional near-infrared imaging(fNIRI)is a new technique providing hemodynamic information related to brain activity,except for electrophysiological signals.Here,we use both these techniques to study ocular attention.We conducted a series of experiments with a classic paradigm of ocular nonselective attention,and monitored responses with fNIRI and ERP respectively.The results showed that fNIRI measured brain activations in the left prefrontal lobe,while ERPs showed activation in frontal lobe.More importantly,only with the combination measurements of fNIRI and ERP,we were then able to find the pinpoint source of ocular nonselective attention,which is in the left and upper corner in Brodmann area 10.These results demonstrated that fNIRI is a reliable technique in psychology,and the combination of fNIRI and ERP can be promising to reveal more information in the research of brain mechanism.
基金supported by the STI2030-Major Projects(2021ZD0203700/2021ZD0203703)the National Natural Science Foundation of China(31771151 and 32171030 to H.Y.,32100829 to D.L.)+2 种基金the Lingang Lab(Grant LG202104-01-03)Shanghai Municipal Science and Technology Major Project(grant No.2018SHZDZX05)the Strategic Priority Research Program of the Chinese Academy of Sciences(grant No.XDB32010200).
摘要The orbitofrontal cortex(ORB),a region crucial for stimulus-reward association,decision-making,and flexible behaviors,extensively connects with other brain areas.However,brain-wide inputs to projection-defined ORB neurons and the distribution of inhibitory neurons postsynaptic to neurons in specific ORB subregions remain poorly characterized.Here we mapped the inputs of five types of projection-specific ORB neurons and ORB outputs to two types of inhibitory neurons.We found that different projection-defined ORB neurons received inputs from similar cortical and thalamic regions,albeit with quantitative variations,particularly in somatomotor areas and medial groups of the dorsal thalamus.By counting parvalbumin(PV)or somatostatin(SST)interneurons innervated by neurons in specific ORB subregions,we found a higher fraction of PV neurons in sensory cortices and a higher fraction of SST neurons in subcortical regions targeted by medial ORB neurons.These results provide insights into understanding and investigating the function of specific ORB neurons.
基金supported by the Major Science and Technology Program for Water Pollution Control and Treatment of China (No. 2012ZX07205-002)the Tsinghua University Initiative Scientific Research Program (No. 20121087922)the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT1152)
摘要Unlike the role of the membrane in a membrane bioreactor, which is designed to replace a sediment tank, direct sewage membrane filtration(DSMF), with the goal of concentrating organic matters, is proposed as a pretreatment process in a novel sewage treatment concept. The concept of membrane-based pretreatment is proposed to divide raw sewage into a concentrated part retaining most organics and a filtered part with less pollutant remaining, so that energy recovery and water reuse, respectively, could be realized by post-treatment. A pilot-scale experiment was carried out to verify the feasibility of coagulant/adsorbent addition for membrane fouling control, which has been the main issue during this DSMF process. The results showed that continuous coagulant addition successfully slowed down the increase in filtration resistance, with the resistance maintained below 1.0 × 1013m^(-1) in the first 70 hr before a jump occurred. Furthermore,the adsorbent addition contributed to retarding the occurrence of the filtration resistance jump, achieving simultaneous fouling control and chemical oxygen demand(COD)concentration improvement. The final concentrated COD amounted to 7500 mg/L after 6 days of operation.
基金supported by the STI2030-Major Projects(2021ZD0201001 and 2021ZD0201000)the National Natural Science Foundation of China(81827901 and 32192412).
摘要The mammalian brain is a highly complex network that consists of millions to billions of densely-interconnected neurons.Precise dissection of neural circuits at the mesoscopic level can provide important structural information for understanding the brain.Optical approaches can achieve submicron lateral resolution and achieve“optical sectioning”by a variety of means,which has the natural advantage of allowing the observation of neural circuits at the mesoscopic level.Automated whole-brain optical imaging methods based on tissue clearing or histological sectioning surpass the limitation of optical imaging depth in biological tissues and can provide delicate structural information in a large volume of tissues.Combined with various fluorescent labeling techniques,whole-brain optical imaging methods have shown great potential in the brain-wide quantitative profiling of cells,circuits,and blood vessels.In this review,we summarize the principles and implementations of various whole-brain optical imaging methods and provide some concepts regarding their future development.
基金supported by the National Natural Science Fund for Distinguished Young Scholars of China(No.81525023)in whole or in part,by a Wellcome Trust fellowship awarded to LT[205228/Z/16/Z]supported by the National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections(grant no.NIHR200907)at University of Liverpool in partnership with Public Health England(PHE),in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.LT is based at the University of Liverpool.
摘要Hand,foot and mouth disease(HFMD)is a major public health problem among children in the Asia-Pacific region.The optimal specimen for HFMD virological diagnosis remains unclear.Enterovirus A71(EV-A71)neutralizing antibody titres detected in paired sera were considered the reference standard for calculating the sensitivity,specificity,positive and negative predictive value of throat swabs,rectal swabs,stool,blood samples and cerebrospinal fluid(CSF)by RT-PCR or ELISA assay.In this study,clinical samples from 276 HFMD patients were collected for analysing the sensitivity of different kind of specimens.Our results showed that stool had the highest sensitivity(88%,95%CI:74%–96%)and agreement with the reference standard(91%).The order of diagnostic yield for EV-A71 infection was stool samplerectal swab>throat swab>blood sample>CSF sample,and using a combination of clinical samples improved sensitivity for enterovirus detection.The sensitivity of ELISA for IgM antibody detection in sterile-site specimens was significantly higher than that of RT-PCR(serum/plasma:62%vs.2%,CSF:47%vs.0%)(P<0.002).In conclusion,our results suggest that stool has the highest diagnostic yield for EV-A71-infected HFMD.If stool is unavailable,rectal swabs can be collected to achieve a similar diagnostic yield.Otherwise,throat swabs may be useful in detecting positive samples.Although IgM in blood or CSF is diagnostically accurate,it lacks sensitivity,missing 40%–50%of cases.The higher proportion of severe cases and shorter interval between onset and sampling contributed to the increase in congruency between clinical testing and the serological reference standard.
基金supported by the National Natural Science Foundation of China(61890952,61890953,61890954,and 32221003)the National Science and Technology Innovation 2030 Major Program(2021ZD0204404)the New Cornerstone Science Foundation through the XPLORER PRIZE.
摘要Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert.However,it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons,especially for neurons in subcortical brain regions.Here,by combining in vivo microscopy and high-definition fluorescence microoptical sectioning tomography,we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex,the dorsal hippocampus,and the substantia nigra pars compacta.More importantly,we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype.The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
基金supported by grants from the Shaanxi Basic Research Program of Natural Science(No.2021JQ-392)the International Cooperation Project of Shaanxi Province(No.2021KW-47).
摘要Objective Y-Chromosomal short tandem repeat polymorphism(Y-STR)analysis plays an indispensable role in the identification of male individuals,population genetics,and biogeographic research.While profiles of many populations based on Y-STR markers in human genomes are ample,haplotype data for the Wuwei Han are still scarce.Methods In this study,2180 unrelated Wuwei Han male individuals residing in Gansu Province,China were collected and genotyped using the novel Microreader™40Y Plus ID system.Phylogenetic relationship reconstructions,multidimensional scaling(MDS),and heatmap analysis were performed based on the genetic distance(Rst)values between our studied population and other populations of the Ymax module in the Y-STR Haplotype Reference Database(YHRD).Results A total of 2129 unique haplotypes were obtained,and the haplotype diversity(HD)and discrimination capacity(DC)for the Wuwei Han were 0.9999 and 0.9931,respectively.Conclusion Our results demonstrate that the Wuwei Han population had intimate genetic relationships with East Asians,especially the geographically close Han populations.Overall,this Y-Chromosomal assay gives valuable information about paternal lineages in male individual tracking and genealogical database construction.
基金supported by the Science Fund for Creative Research Group of China(Grant No.61121004)National Natural Science Foundation of China(Grant No.61078072)863 Program(Grant No.2012AA02A602).
摘要Near infrared spectroscopy(NIRS)is generally accepted as a functional brain imaging technology for brain activation study.With multichannel highly sensitive NIRS instruments,it has become possible to assess functional connectivity of different brain negions by NIRS.However,the feasibility needs to be validated in complex cognitive activities.In this study,we recorded the hemodynamic activity of the bilateral prefrontal cortex(PFC)during a color-word matching Stroop task.Wavelet transform coberence(WTC)analysis was applied to ascss the functional conectivity of all homologous channel pairs within the leftight PFC.Both the behavioral and brain activ ation results showed signifcant Stroop effects.The results of WTC analysis revealed that,bilateral functional connectivity was significantly stronger during both the incongruent stimuli and neutral stimuli compared to that of the rest period.It also showed significant Stroop effect.Our findings demonstrate that,NIRS bcomes a valuable tool to elucidate the functional conectivity of brain cortex in complex cognitive activities.
基金supported by the National Natural Science Foundation of China(No.82230009,No.82070232)Program of Shanghai Academic Research Leader(No.21XD1403300)Shanghai Science and Technology Commission Project(No.23410761200).
摘要Objective:Myocardial ischemia-reperfusion(I/R)injury is associated with a significant reduction in the mitochondrial membrane potential(MMP,ΔΨm).Fluorescence-based assays are effective for labelling active mitochondria in living cells;their application in heart tissue,however,represents a challenge because of a low yield of viable cardiomyocytes after cardiac perfusion.This study aimed to examine a novel method for detecting the changes in the MMP of mouse heart tissue following I/R injury.Methods:The I/R model was established,which was characterized by distinct ischemic area and apoptosis in heart tissue.The MMP was detected via a confocal microscope after the ascending aorta was clamped and the mitochondrial probe solution(containing Mito-Tracker Deep Red FM)was perfused from the apex via a peristaltic pump.Results:This method enabled the distribution of the probe solution throughout the cardiac tissue via the coronary circulation.Fluorescence detection revealed that the MMP was profoundly reduced in both ischemic area and border area following I/R when compared with that in the sham group.There was no obvious difference in the MMP of the remote area between the I/R group and the sham group.Conclusion:This study presents a novel method for detecting the MMP in heart tissue,and this method will facilitate the evaluation of changes in the MMP in different regions following I/R.