This study compared three cryopreservation protocols on sperm functions, IVF outcomes, and embryo development. Epididymal spermatozoa cryopreserved using slow-cooling （18% w/v raffinose, RS-C） were compared with spe...This study compared three cryopreservation protocols on sperm functions, IVF outcomes, and embryo development. Epididymal spermatozoa cryopreserved using slow-cooling （18% w/v raffinose, RS-C） were compared with spermatozoa vitrified using 0.25 M sucrose （SV） or 18% w/v raffinose （RV）. The motility, vitality, and DNA damage （TUNEL assay） of fresh control （FC） spermatozoa were compared with post-thawed or warmed RS-C, RV, and SV samples. Mouse oocytes （n = 267） were randomly assigned into three groups for insemination： RV （n = 102）, RS-C （n = 86）, and FC （n = 79）. The number and the proportion of two-cell embryos and blastocysts from each treatment were assessed. Sperm motility （P 〈 0.01） and vitality （P 〈 0.05） were significantly reduced after vitrification compared with slow-cooled spermatozoa. However, DNA fragmentation was significantly reduced in spermatozoa vitrified using sucrose （15 - 1.8% [SV] vs 26 - 2.8% [RV] and 27 - 1.2% [RS-C]; P 〈 0.01）. Although the number of two-cell embryos produced by RS-C, RV, and FC spermatozoa was not significantly different, the number of blastocysts produced from two-cell embryos using RV spermatozoa was significantly higher than FC spermatozoa （P = 0.0053）. This simple, small volume vitrification protocol and standard insemination method allows successful embryo production from small numbers of epididymal spermatozoa and may be applied clinically to circumvent the need for ICSI, which has the disadvantage of bypassing sperm selection.展开更多
Polycystic ovary syndrome(PCOS)is a heterogeneous disorder with evidence of polygenetic components,and obesity may be a risk factor for hyperandrogen ism.Previous studies have shown that LHCGR is en riched in the ovar...Polycystic ovary syndrome(PCOS)is a heterogeneous disorder with evidence of polygenetic components,and obesity may be a risk factor for hyperandrogen ism.Previous studies have shown that LHCGR is en riched in the ovary and LHCGR deficiency causes infertility without typical PCOS phenotypes.ALMS1 is implicated in obesity and hyperandrogenism,the common phenotypes among PCOS patients.Through whole-exome sequencing of 22 PCOS families and targeted candidate gene sequencing of additional 65 sporadic PCOS patients,we identified potential causative mutations in LHCGR and ALMS1 in a sibling-pair PCOS family and three sporadic PCOS patients.The expression of LHCGRL638 P in granulosa-like tumor cell line(KGN)cells promoted cyclic adenosine monophosphate production and granulosa cell proliferation,indicating that LHCGRL638 P is an activating mutation.Lhcgr~(L642 P/L642 P)mice showed an irregular estrous cycle,reduced follicles with dynamic folliculogenesis,and increased testosterone(T),estradiol(E2),and dehydroepiandrosterone.Lhcgr~(+/L642 P)AIms1~(+/PB)mice displayed increased T and E2 but decreased late secondary and preovulatory follicles.We showed that activating mutation of LHCGR likely plays important roles in the pathophysiology of PCOS involving abnormal reproductive physiology,whereas ALMS1 deficiency may promote anovulatory infertility via elevated androgens,suggesting that the disturbed LHCGR and ALMS1 cooperatively induce PCOS phenotypes,characterized as anovulation and hyperandrogenemia frequently observed in PCOS patients with obesity.展开更多
DEAR EDITOR,Sox9 is a member of the Sry-related high-mobility group box(Sox)transcription factor family in animals.In teleost fish,Sox9 undergoes duplication to generate two duplicates,namely Sox9a and Sox9b.However,t...DEAR EDITOR,Sox9 is a member of the Sry-related high-mobility group box(Sox)transcription factor family in animals.In teleost fish,Sox9 undergoes duplication to generate two duplicates,namely Sox9a and Sox9b.However,the functions of these duplicates in the teleost Nile tilapia(Oreochromis niloticus)remain unclear.In this study,we characterized the roles of Nile tilapia Sox9a in chondrogenesis and gonadal development.In situ hybridization assays showed that Sox9a was mainly expressed in cartilage tissues and somatic cells surrounding germ cells of the gonads.CRISPR/Cas9-mediated homozygous mutation of the Sox9a gene resulted in craniofacial deformities and missed mandibles,as well as impaired the expression of Col2a1a that is involved in chondrogenesis.In addition,germ cell number and DNA replication in somatic cells in the gonads of both sexes were reduced following Sox9a mutation.Taken together,this study demonstrates that Sox9a is involved in cartilage development and germ cell proliferation in Nile tilapia.展开更多
Withania somnifera(L.)Dunal(WS),or Ashwagandha,is used clinically against arthritis,anxiety and insomnia etc,however,its potential in aquafeeds is largely unexplored.We investigated the stress-alleviation and hepatopr...Withania somnifera(L.)Dunal(WS),or Ashwagandha,is used clinically against arthritis,anxiety and insomnia etc,however,its potential in aquafeeds is largely unexplored.We investigated the stress-alleviation and hepatoprotective mechanisms of dietary WS supplementation in adult female darkbarbel catfish.Fish were fed with WS dietary for 5 weeks,subjected to a physical stressor(saline injection),and sampled.Brain were processed for RNA-seq to identify differentially expressed genes(DEGs)linked to stress;serum were assayed for stress-and immune-related biochemical markers;livers were examined for lipid content(Oil Red O staining)and proliferation(PCNA immunos-taining).Network pharmacology were employed to construct a"compound-target"net-work:The bioactive compounds of WS were retrieved from ChEBI and PCIDB,probable targets predicted via Swiss Target Prediction,and the“WS-ingredient-target”regulatory network was constructed using Cytoscape;key ligand-protein interactions were validated by molecular docking.Findings were replicated in juvenile fish and in SG3 cells challenged with Withanolide A.Physical stress evoked 1451 DEGs in control brains,whereas WS-supplemented reduced this to 397,indicating marked mitigation of the oxid-ative-and immune-stress response.Network pharmacology and molecular docking pre-dicted that 13 bioactive compounds in WS,especially Withanolide A and Withanolide J,can interact with targets such as MAPK8,CRHR1,NR3C2,and IARS1,being associated with stress and liver function regulation respectively.Moreover,it was proved that Withanolide A could significantly modulate stress response in juveniles and enhanced pro-liferation potency of SG3 cells.Intriguingly,in theadult female darkbarbel catfish,dietary WS lowered serum cortisol,glucose,ROS,TNF-α,and IL-6(P<0.05),up-regulated hepatocyte PCNA expression,and allievated stress-induced liver injury.These findings provide novel insights and vital basis for elucidating the mechanisms whereby herbs,including WS act in stress-relief and hepatoprotection in darkbarbel catfish.And provide a framework for advancing traditional Chinese medicine(TCM)applications in aquaculture.展开更多
Objectives:This study aimed to explore the perceptions and recommendations of multiparas and health-related professionals regarding appropriate birth intervals(Bis)and key determinants.Methods:In-depth semi-structured...Objectives:This study aimed to explore the perceptions and recommendations of multiparas and health-related professionals regarding appropriate birth intervals(Bis)and key determinants.Methods:In-depth semi-structured interviews were conducted between April 1 and June 30,2022.Nine multiparas and thirteen health-related professionals were purposefully sampled until data saturation was reached.A thematic analysis approach was applied to the interview transcripts,utilizing dual independent coding and consensus validation in NVivo 12.0.Results:The data generated two overarching categories:1)balanced decision-making on the appropriate birth intervals and 2)internal and external determinants integrated with health and societal considerations.Four key themes emerged following the two categories:1)consistency and discrepancy between the actual and recommended birth intervals of multiparas;2)health-and developmentoriented professional recommendations;3)internal determinants related to individual-level factors;and 4)external determinants related to child-related factors,family support,and social security.Weighing women's reproductive health and career development,multiparas and health-related professionals perceived a length between 18 and 36 months as the appropriate Bl.Conclusion:Multiparas and health-related professionals shaped their balanced recommendations on a relatively appropriate birth interval ranging from 18 to 36 months,which was influenced by women's individual-level factors,child-related factors,family support,and social security.Targeted social and healthcare services should be offered to women and their families during the Bls.展开更多
BACKGROUND Uterine injury can cause uterine scarring,leading to a series of complications that threaten women’s health.Uterine healing is a complex process,and there are currently no effective treatments.Although our...BACKGROUND Uterine injury can cause uterine scarring,leading to a series of complications that threaten women’s health.Uterine healing is a complex process,and there are currently no effective treatments.Although our previous studies have shown that bone marrow mesenchymal stem cells(BMSCs)promote uterine damage repair,the underlying mechanisms remain unclear.However,exploring the specific regulatory roles of BMSCs in uterine injury treatment is crucial for further understanding their functions and enhancing therapeutic efficacy.AIM To investigate the underlying mechanism by which BMSCs promote the process of uterine healing.METHODS In in vivo experiments,we established a model of full-thickness uterine injury and injected BMSCs into the uterine wound.Transcriptome sequencing was per-formed to determine the enrichment of differentially expressed genes at the wound site.In in vitro experiments,we isolated rat uterine smooth muscle cells(USMCs)and cocultured them with BMSCs to observe the interaction between BMSCs and USMCs in the microenvironment.RESULTS We found that the differentially expressed genes were mainly related to cell growth,tissue repair,and angiogenesis,while the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathway was highly enriched.Quantitative reverse-transcription polymerase chain reaction was used to validate differentially expressed genes,and the results demonstrated that BMSCs can upregulate genes related to regeneration and downregulate genes related to inflammation.Coculturing BMSCs promoted the migration and proliferation of USMCs,and the USMC microenvironment promoted the myogenic differentiation of BMSCs.Finally,we validated the PI3K/AKT pathway in tissues and cells and showed that BMSCs activate the PI3K/AKT pathway to promote the regeneration of uterine smooth muscle both in vivo and in vitro.CONCLUSION BMSCs upregulated uterine wound regeneration and anti-inflammatory factors and enhanced uterine smooth muscle proliferation through the PI3K/AKT pathway both in vivo and in vitro.展开更多
Avian genomes exhibit compact organization and remarkable chromosomal stability.However,the extent and mechanisms by which structural variation in avian genomes differ from those in other vertebrate lineages are poorl...Avian genomes exhibit compact organization and remarkable chromosomal stability.However,the extent and mechanisms by which structural variation in avian genomes differ from those in other vertebrate lineages are poorly explored.This study generated a diploid genome assembly for the golden pheasant(Chrysolophus pictus),a species distinguished by the vibrant plumage of males.Each haploid genome assembly included complete chromosomalmodels,incorporatingall microchromosomes.Analysis revealed extensive tandem amplification of immune-related genes across the smallest microchromosomes(dot chromosomes),with an average copy number of 54.Structural variation between the haploid genomes was primarily shaped by large insertions and deletions(indels),with minimal contributions from inversions or duplications.Approximately 28%of these large indels were associated with recent insertions of transposable elements,despite their typically low activity in bird genomes.Evidence for significant effects of transposable elements on gene expression was minimal.Evolutionary strata on the sex chromosomes were identified,along with a drastic rearrangement of the W chromosome.These analyses of the high-quality diploid genome of the golden pheasant provide valuable insights into the evolutionary patterns of structural variation in avian genomes.展开更多
BACKGROUND A large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery.Persistent obstructive symptoms may result in faecal stasis that can develop into...BACKGROUND A large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery.Persistent obstructive symptoms may result in faecal stasis that can develop into Hirschsprung-associated enterocolitis,a potential life-threatening condition.Important treatment to improve faecal passage is internal anal sphincter relaxation using botulinum toxin injections.AIM To give an overview of all empirical evidence on the effectiveness of botulinum toxin injections in patients with Hirschsprung disease.METHODS A systematic review and meta-analysis was done by searching PubMed,EMBASE and the Cochrane Library,using entry terms related to:(1)Hirschsprung disease;and(2)Botulinum toxin injections.14 studies representing 278 patients met eligibility criteria.Data that were extracted were proportion of patients with improvement of obstructive symptoms or less enterocolitis after injection,proportion of patients with adverse effects and data on type botulinum toxin,mean dose,average age at first injection and patients with associated syndromes.Random-effects meta-analysis was used to aggregate effects and random-effects meta-regression was used to test for possible confounding factors.RESULTS Botulinum toxin injections are effective in treating obstructive symptoms in on average 66%of patients[event rate(ER)=0.66,P=0.004,I2=49.5,n=278 patients].Type of botulinum toxin,average dose,average age at first injections and proportion of patients with associated syndromes were not predictive for this effect.Mean 7 duration of improvement after one botulinum toxin injections was 6.4 mo and patients needed on average 2.6 procedures.There was a significant higher response rate within one month after botulinum toxin injections compared to more than one month after Botulinum toxin injections(ER=0.79,vs ER=0.46,Q=19.37,P<0.001).Botulinum toxin injections were not effective in treating enterocolitis(ER 0.58,P=0.65,I2=71.0,n=52 patients).There were adverse effects in on average 17%of patients(ER=0.17,P<0.001,I2=52.1,n=187 patients),varying from temporary incontinence to mild anal pain.CONCLUSION Findings from this systematic review and meta-analysis indicate that botulinum toxin injections are effective in treating obstructive symptoms and that adverse effects were present,but mild and temporary.展开更多
We tested the utility of chemical marking techniques in the juvenile black rockfish Sebastes schlegelii. Juveniles （30-40 mm total length） were immersed in a range of tetracycline hydrochloride （TC） solutions at c...We tested the utility of chemical marking techniques in the juvenile black rockfish Sebastes schlegelii. Juveniles （30-40 mm total length） were immersed in a range of tetracycline hydrochloride （TC） solutions at concentrations ranging from 300 to 500 mg/L, and alizarin complexone （ALC） solutions at concentrations ranging from 200 to 400 mg/L in filtered sea water （salinity of 30） for 24 h, respectively. Otoliths （sagittae, asteriscus）, scales, fin rays （dorsal, pectoral, ventral, anal, and caudal fin rays）, and fin spines （dorsal, ventral, and anal fin spines） were sampled and used to detect fluorescent marks after a 60-day growth experiment. With the exception of 300 mg/L TC, acceptable marks were produced in the otoliths and fin spines by all concentrations of TC and ALC. In particular, we observed clearly visible marks in the sagittae, asteriscus, and fin spines under normal light at concentrations of200~00 mg/L, 250-400 mg/L, and 250-400 mg/L ALC, respectively. Scales and fin rays had acceptable marks at much higher concentrations （_〉350 mg/L TC, 〉250 mg/L ALC for scales and _〉350 mg/L TC, 〉300 mg/L ALC for fin rays）. The best mark quality （i.e., acceptable marks were observed in all sampled structures after immersion marking） were obtained following immersion in TC at between 350-500 rag/L, and ALC between 300-400 mg/L. In addition, there was no significant difference in survival and growth of TC and ALC marked fish compared to their controls up to 60 days post-marking （P〉0.05）.展开更多
Bacterial or viral infections,such as Brucella,mumps virus,herpes simplex virus,and Zika virus,destroy immune homeostasis of the testes,leading to spermatogenesis disorder and infertility.Of note,recent research shows...Bacterial or viral infections,such as Brucella,mumps virus,herpes simplex virus,and Zika virus,destroy immune homeostasis of the testes,leading to spermatogenesis disorder and infertility.Of note,recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells,leading to male reproductive dysfunction.Due to the many side effects associated with antibiotic therapy,finding alternative treatments for inflammatory injury remains critical.Here,we found that Dmrt1 plays an important role in regulating testicular immune homeostasis.Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells.Chromatin immunoprecipitation sequencing(ChIP-seq)and RNA sequencing(RNA-seq)revealed that Dmrt1 positively regulated the expression of Spry1,an inhibitory protein of the receptor tyrosine kinase(RTK)signaling pathway.Furthermore,immunoprecipitation-mass spectrometry(IP-MS)and co-immunoprecipitation(Co-IP)analysis indicated that SPRY1 binds to nuclear factor kappa B1(NF-κB1)to prevent nuclear translocation of p65,inhibit activation of NF-κB signaling,prevent excessive inflammatory reaction in the testis,and protect the integrity of the blood-testis barrier.In view of this newly identified Dmrt1-Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis,our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.展开更多
Fish morphological phenotypes are important resources in artificial breeding,functional gene mapping,and population-based studies in aquaculture and ecology.Traditional morphological measurement of phenotypes is rathe...Fish morphological phenotypes are important resources in artificial breeding,functional gene mapping,and population-based studies in aquaculture and ecology.Traditional morphological measurement of phenotypes is rather expensive in terms of time and labor.More importantly,manual measurement is highly dependent on operational experience,which can lead to subjective phenotyping results.Here,we developed 3DPhenoFish software to extract fish morphological phenotypes from three-dimensional(3D)point cloud data.Algorithms for background elimination,coordinate normalization,image segmentation,key point recognition,and phenotype extraction were developed and integrated into an intuitive user interface.Furthermore,18 key points and traditional 2D morphological traits,along with 3D phenotypes,including area and volume,can be automatically obtained in a visualized manner.Intuitive fine-tuning of key points and customized definitions of phenotypes are also allowed in the software.Using 3DPhenoFish,we performed high-throughput phenotyping for four endemic Schizothoracinae species,including Schizopygopsis younghusbandi,Oxygymnocypris stewartii,Ptychobarbus dipogon,and Schizothorax oconnori.Results indicated that the morphological phenotypes from 3DPhenoFish exhibited high linear correlation(>0.94)with manual measurements and offered informative traits to discriminate samples of different species and even for different populations of the same species.In summary,we developed an efficient,accurate,and customizable tool,3DPhenoFish,to extract morphological phenotypes from point cloud data,which should help overcome traditional challenges in manual measurements.3DPhenoFish can be used for research on morphological phenotypes in fish,including functional gene mapping,artificial selection,and conservation studies.3DPhenoFish is an open-source software and can be downloaded for free at https://github.com/lyh24k/3DPhenoFish/tree/master.展开更多
BACKGROUND Patients with Hirschsprung disease(HD)are at risk of persistent constipation,fecal incontinence or recurrent enterocolitis after surgical treatment,which in turn may impact physical and psychosocial functio...BACKGROUND Patients with Hirschsprung disease(HD)are at risk of persistent constipation,fecal incontinence or recurrent enterocolitis after surgical treatment,which in turn may impact physical and psychosocial functioning.Generic health-related quality of life(HRQoL)and disease-specific health-related quality of life are relevant outcome measures to assess the impact of HD on the QoL of these patients.AIM To summarize all available evidence on HRQoL of patients with HD after surgery and the impact of possible moderating factors.METHODS Pubmed,Web of Sciences,Psyc Info and Embase were searched with search terms related to’Hirschsprung disease’,’Pediatrics’and’Quality of life’.Mean and standard deviation of generic HRQoL overall and domain scores were extracted from each study,as well as data describing potential factors associated with QoL.Random effect models were used for meta-analytic aggregation of generic HRQoL scores.Meta-regression was used to assess the relationship between patient and clinical characteristics and generic HRQoL.Disease-specific HRQoL outcomes of patients with HD were systematically reviewed.RESULTS Seventeen articles were included in the systematic review(n=1137 patients)and 15 in the quantitative meta-analysis(n=1024 patients).Four studies reported disease-specific HRQoL.Patient’s age ranged between 0 and 21 years.Meta-analytic aggregation showed a nonsignificantly impaired generic HRQoL(d=-0.168[95%CI:-0.481;0.145],P=0.293,I^(2)=94.9)in patients with HD compared to healthy controls.Physical(d=-0.042[95%CI:-0.419;0.335],P=0.829,I^(2)=95.1),psychosocial(d=-0.159[95%CI:-0.458;0.141],P=0.299,I^(2)=93.6)and social HRQoL(d=-0.092[95%CI:-0.642;0.457],P=0.742,I^(2)=92.3)were also not significantly lower compared to healthy controls.There was no relation between health-related outcomes and the sex of the patients and whether generic HRQoL was measured by parental proxy or self-report.Disease-specific complaints of patients with HD impaired physical HRQoL,but not psychosocial and social HRQoL.CONCLUSION In this systematic review and meta-analysis,no evidence was found for impaired generic HRQoL in patients with HD compared to healthy controls,neither for moderating effects of sex,parental proxy or self-report.展开更多
Wnt signaling pathways,including the canonical Wnt/β-catenin pathway,planar cell polarity pathway,and Wnt/Ca2+signaling pathway,play important roles in neural development during embryonic stages.The DVL genes encode ...Wnt signaling pathways,including the canonical Wnt/β-catenin pathway,planar cell polarity pathway,and Wnt/Ca2+signaling pathway,play important roles in neural development during embryonic stages.The DVL genes encode the hub proteins for Wnt signaling pathways.The mutations in DVL2 and DVL3 were identified from patients with neural tube defects(NTDs),but their functions in the pathogenesis of human neural diseases remain elusive.Here,we sequenced the coding regions of three DVL genes in 176 stillborn or miscarried fetuses with NTDs or Dandy-Walker malformation(DWM)and 480 adult controls from a Han Chinese population.Four rare mutations were identified:DVL1 p.R558 H,DVL1 p.R606 C,DVL2 p.R633 W,and DVL3 p.R222 Q.To assess the effect of these mutations on NTDs and DWM,various functional analyses such as luciferase reporter assay,stress fiber formation,and in vivo teratogenic assay were performed.The results showed that the DVL2 p.R633 W mutation destabilized DVL2 protein and upregulated activities for all three Wnt signalings(Wnt/β-catenin signaling,Wnt/planar cell polarity signaling,and Wnt/Ca2+signaling)in mammalian cells.In contrast,DVL1 mutants(DVL1 p.R558 H and DVL1 p.R606 C)decreased canonical Wnt/β-catenin signaling but increased the activity of Wnt/Ca2+signaling,and DVL3 p.R222 Q only decreased the activity of Wnt/Ca2+signaling.We also found that only the DVL2 p.R633 W mutant displayed more severe teratogenicity in zebrafish embryos than wild-type DVL2.Our study demonstrates that these four rare DVL mutations,especially DVL2 p.R633 W,may contribute to human neural diseases such as NTDs and DWM by obstructing Wnt signaling pathways.展开更多
Ribosome biogenesis is essential for the cell growth and division. Disruptions in ribosome biogenesis result in developmental defects and a group of diseases, known as ribosomopathies. Here, we report a mutation in ze...Ribosome biogenesis is essential for the cell growth and division. Disruptions in ribosome biogenesis result in developmental defects and a group of diseases, known as ribosomopathies. Here, we report a mutation in zebrafish urb1, which encodes an essential ribosome biogenesis protein. The urb1 cq31 mutant exhibits hypoplastic digestive organs, which is caused by impaired cell proliferation with the differentiation of digestive organ progenitors unaffected. Knockdown of mtor or raptor leads to similar hypoplastic phenotypes and reduced expression of urb1 in the digestive organs. Overexpression of Urb1 results in overgrowth of digestive organs, and can efficiently rescue the hypoplastic liver and pancreas in the mtor and raptor morphants. Reduced syntheses of free ribosomal subunits and impaired assembly of polysomes are observed in the urb1 mutant as well as in the mtor and raptor morphants, which can be rescued by the Urb1 overexpression. These data demonstrate that Urb1 plays an important role in governing ribosome biogenesis and protein synthesis downstream of mammalian/mechanistic target of rapamycin complex 1（mTORC1）, thus regulating the development of digestive organs. Our study indicates the requirement of hyperactive protein synthesis for the digestive organ development.展开更多
During spermiogenesis,haploid spermatids undergo dramatic morphological changes to form slender sperm flagella and cap-like acrosomes,which are required for successful fertilization.Severe deformities in flagella caus...During spermiogenesis,haploid spermatids undergo dramatic morphological changes to form slender sperm flagella and cap-like acrosomes,which are required for successful fertilization.Severe deformities in flagella cause a male infertility syndrome,multiple morphological abnormalities of the flagella(MMAF),while acrosomal hypoplasia in some cases leads to sub-optimal embryonic developmental potential.However,evidence regarding the occurrence of acrosomal hypoplasia in MMAF is limited.Here,we report the generation of base-edited mice knocked out for coiled-coil domain-containing 38(Ccdc38)via inducing a nonsense mutation and find that the males are infertile.The Ccdc38-KO sperm display acrosomal hypoplasia and typical MMAF phenotypes.We find that the acrosomal membrane is loosely anchored to the nucleus and fibrous sheaths are disorganized in Ccdc38-KO sperm.Further analyses reveal that Ccdc38 knockout causes a decreased level of TEKT3,a protein associated with acrosome biogenesis,in testes and an aberrant distribution of TEKT3 in sperm.We finally show that intracytoplasmic sperm injection overcomes Ccdc38-related infertility.Our study thus reveals a previously unknown role for CCDC38 in acrosome biogenesis and provides additional evidence for the occurrence of acrosomal hypoplasia in MMAF.展开更多
Evolutionary biologists are always interested in deciphering the geographic context of diversification,therefore they introduced the concept of comparative phylogeography,which helps to identify common mechanisms that...Evolutionary biologists are always interested in deciphering the geographic context of diversification,therefore they introduced the concept of comparative phylogeography,which helps to identify common mechanisms that contribute to shared genetic structures among organisms from the same region.Here,we used multi-locus genetic data along with environmental data to investigate shared phylogeographic patterns among three Asianendemic newt genera,Cynops,Paramesotriton and Pachytriton,which occurred in montane/submontane streams or ponds in southern China.Our 222samples from 78 localities covered the entire range of the three genera and represented the largest dataset of this group to date.We reconstructed matrilineal genealogies from two protein-coding,mitochondrial genes,and gene network from two nuclear genes.We also estimated divergence times of major cladogenetic events and used occurrence data to evaluate niche difference and similarity between lineages.Our results revealed a common basal split in all three genera that corresponds to the separation of two geographic terrains of southern China.Those ancient divergence occurred during middle to late Miocene and likely correlate with paleoclimatic fluctuations caused by the uplift of the Qinghai-Xizang(Tibet)Plateau(QTP).Particularly,the strengthening and weakening of Asian summer monsoons during the Miocene may have profoundly impacted southern China and led to repeatedly vicariance in those newts.However,despite differences in realized niches between lineages,there is no evidence for divergence of fundamental niches.Preservation of old newt matriline lineages in mountains of southern China suggests that the region acts as both museums and cradles of speciation.Based on those results,we advocate a multi-pronged protection strategy for newts in the three genera.展开更多
Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the pr...Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.展开更多
Recent progress by versatile approaches supports the new hypothesis that multi-potent hematopoietic stein cells （HSCs） are directly formed from a rare population of endothelial cells in mid-gestation mouse embryos. ...Recent progress by versatile approaches supports the new hypothesis that multi-potent hematopoietic stein cells （HSCs） are directly formed from a rare population of endothelial cells in mid-gestation mouse embryos. This process is therefore known as the endothelial-to- hematopoietic transition （EHT）. Nevertheless, there is no functional evidence that documents the HSC transition from purified endothelial cells. In this study, we developed an OP9-DLl-based co-culture system that was able to facilitate the HSC specification and/or expansion in vitro of mouse embryonic day 10.5 （El0.5） Tie2~ cells remarkably. Then, the immunophenotypically defined endothelial ceils were harvested by a combination of surface markers （Flkl＋CD31 ~CD41 CD45 Ter119 ） from the caudal half of EI0.0-EI 1.0 mouse embryos. The transplantation of the endothelia/OP9-DL1 co-cultures led to long-term, high-level, multi-lineage, and multi-organ he- matopoietic reconstitution in the irradiated adult recipients. The induced HSC activity was initially observed at El0.5, and a significant increase was detected at El 1.0, which suggests a temporally specific regulation. Taken together, tbr the first time, we provide functional evidence showing the HSC potential of purified embryonic endothelial cells, which is indispensable for the emerging EHT concept. Moreover, the newly defined co-culture system will aid the exploration of the key molecules governing the HSC transition from embryonic and even postnatal endothelial cells, which has enormous significance in basic and translational research.展开更多
From the published data, the present mini-review attempts to answer two fundamental questions about the gestational trophoblastic neoplasms. In addition, it extrapolates the findings to other cancers that produce smal...From the published data, the present mini-review attempts to answer two fundamental questions about the gestational trophoblastic neoplasms. In addition, it extrapolates the findings to other cancers that produce small amounts of hCG and how a novel therapies could be developed.展开更多
Globally,infertility is a serious health problem affecting about 15%of reproductive age couples according to the data reported by the World Health Organization.Non-obstructive azoospermia(NOA)is acknowledged as one of...Globally,infertility is a serious health problem affecting about 15%of reproductive age couples according to the data reported by the World Health Organization.Non-obstructive azoospermia(NOA)is acknowledged as one of the most serious phenotypes of male infertility.Approximately 1%of the male population and 10%of infertile men were affected by NOA(Xie et al.,2022).As reported,meiotic arrest is one of the major etiologies leading to the NOA.展开更多
文摘This study compared three cryopreservation protocols on sperm functions, IVF outcomes, and embryo development. Epididymal spermatozoa cryopreserved using slow-cooling （18% w/v raffinose, RS-C） were compared with spermatozoa vitrified using 0.25 M sucrose （SV） or 18% w/v raffinose （RV）. The motility, vitality, and DNA damage （TUNEL assay） of fresh control （FC） spermatozoa were compared with post-thawed or warmed RS-C, RV, and SV samples. Mouse oocytes （n = 267） were randomly assigned into three groups for insemination： RV （n = 102）, RS-C （n = 86）, and FC （n = 79）. The number and the proportion of two-cell embryos and blastocysts from each treatment were assessed. Sperm motility （P 〈 0.01） and vitality （P 〈 0.05） were significantly reduced after vitrification compared with slow-cooled spermatozoa. However, DNA fragmentation was significantly reduced in spermatozoa vitrified using sucrose （15 - 1.8% [SV] vs 26 - 2.8% [RV] and 27 - 1.2% [RS-C]; P 〈 0.01）. Although the number of two-cell embryos produced by RS-C, RV, and FC spermatozoa was not significantly different, the number of blastocysts produced from two-cell embryos using RV spermatozoa was significantly higher than FC spermatozoa （P = 0.0053）. This simple, small volume vitrification protocol and standard insemination method allows successful embryo production from small numbers of epididymal spermatozoa and may be applied clinically to circumvent the need for ICSI, which has the disadvantage of bypassing sperm selection.
基金jointly supported by the National Key Research and Development Program of China(2018YFC1002104 to L.W.,2018YFC1004904 to B.-L.W.and J.F.,2016YFC1000500 to H.Y.W.and W.F.T.)the National Natural Science Foundation of China([81930036,31521003,31771669]to H.Y.W.)+1 种基金the Commission for Science and Technology of Shanghai Municipality(17JC1400902to H.Y.W.)the MDA-CHB Research Grant to B.-L.W。
文摘Polycystic ovary syndrome(PCOS)is a heterogeneous disorder with evidence of polygenetic components,and obesity may be a risk factor for hyperandrogen ism.Previous studies have shown that LHCGR is en riched in the ovary and LHCGR deficiency causes infertility without typical PCOS phenotypes.ALMS1 is implicated in obesity and hyperandrogenism,the common phenotypes among PCOS patients.Through whole-exome sequencing of 22 PCOS families and targeted candidate gene sequencing of additional 65 sporadic PCOS patients,we identified potential causative mutations in LHCGR and ALMS1 in a sibling-pair PCOS family and three sporadic PCOS patients.The expression of LHCGRL638 P in granulosa-like tumor cell line(KGN)cells promoted cyclic adenosine monophosphate production and granulosa cell proliferation,indicating that LHCGRL638 P is an activating mutation.Lhcgr~(L642 P/L642 P)mice showed an irregular estrous cycle,reduced follicles with dynamic folliculogenesis,and increased testosterone(T),estradiol(E2),and dehydroepiandrosterone.Lhcgr~(+/L642 P)AIms1~(+/PB)mice displayed increased T and E2 but decreased late secondary and preovulatory follicles.We showed that activating mutation of LHCGR likely plays important roles in the pathophysiology of PCOS involving abnormal reproductive physiology,whereas ALMS1 deficiency may promote anovulatory infertility via elevated androgens,suggesting that the disturbed LHCGR and ALMS1 cooperatively induce PCOS phenotypes,characterized as anovulation and hyperandrogenemia frequently observed in PCOS patients with obesity.
基金supported by the National Key Research and Development Program of China(2022YFD1201600)National Natural Science Foundation of China(31861123001,31302170,and 31772831)+1 种基金Chongqing Science and Technology Bureau(CSTB2022NSCQ-MSX1608 and cstc2021ycjh-bgzxm0024)Chongqing Fishery Technology Innovation Union(2023)。
文摘DEAR EDITOR,Sox9 is a member of the Sry-related high-mobility group box(Sox)transcription factor family in animals.In teleost fish,Sox9 undergoes duplication to generate two duplicates,namely Sox9a and Sox9b.However,the functions of these duplicates in the teleost Nile tilapia(Oreochromis niloticus)remain unclear.In this study,we characterized the roles of Nile tilapia Sox9a in chondrogenesis and gonadal development.In situ hybridization assays showed that Sox9a was mainly expressed in cartilage tissues and somatic cells surrounding germ cells of the gonads.CRISPR/Cas9-mediated homozygous mutation of the Sox9a gene resulted in craniofacial deformities and missed mandibles,as well as impaired the expression of Col2a1a that is involved in chondrogenesis.In addition,germ cell number and DNA replication in somatic cells in the gonads of both sexes were reduced following Sox9a mutation.Taken together,this study demonstrates that Sox9a is involved in cartilage development and germ cell proliferation in Nile tilapia.
文摘Withania somnifera(L.)Dunal(WS),or Ashwagandha,is used clinically against arthritis,anxiety and insomnia etc,however,its potential in aquafeeds is largely unexplored.We investigated the stress-alleviation and hepatoprotective mechanisms of dietary WS supplementation in adult female darkbarbel catfish.Fish were fed with WS dietary for 5 weeks,subjected to a physical stressor(saline injection),and sampled.Brain were processed for RNA-seq to identify differentially expressed genes(DEGs)linked to stress;serum were assayed for stress-and immune-related biochemical markers;livers were examined for lipid content(Oil Red O staining)and proliferation(PCNA immunos-taining).Network pharmacology were employed to construct a"compound-target"net-work:The bioactive compounds of WS were retrieved from ChEBI and PCIDB,probable targets predicted via Swiss Target Prediction,and the“WS-ingredient-target”regulatory network was constructed using Cytoscape;key ligand-protein interactions were validated by molecular docking.Findings were replicated in juvenile fish and in SG3 cells challenged with Withanolide A.Physical stress evoked 1451 DEGs in control brains,whereas WS-supplemented reduced this to 397,indicating marked mitigation of the oxid-ative-and immune-stress response.Network pharmacology and molecular docking pre-dicted that 13 bioactive compounds in WS,especially Withanolide A and Withanolide J,can interact with targets such as MAPK8,CRHR1,NR3C2,and IARS1,being associated with stress and liver function regulation respectively.Moreover,it was proved that Withanolide A could significantly modulate stress response in juveniles and enhanced pro-liferation potency of SG3 cells.Intriguingly,in theadult female darkbarbel catfish,dietary WS lowered serum cortisol,glucose,ROS,TNF-α,and IL-6(P<0.05),up-regulated hepatocyte PCNA expression,and allievated stress-induced liver injury.These findings provide novel insights and vital basis for elucidating the mechanisms whereby herbs,including WS act in stress-relief and hepatoprotection in darkbarbel catfish.And provide a framework for advancing traditional Chinese medicine(TCM)applications in aquaculture.
基金supported by the Key Discipline Program of the Fifth Round of the Three-Year Public Health Action Plan(2020-2022 Year)of Shanghai,China(GWV-10.1-XK08).
文摘Objectives:This study aimed to explore the perceptions and recommendations of multiparas and health-related professionals regarding appropriate birth intervals(Bis)and key determinants.Methods:In-depth semi-structured interviews were conducted between April 1 and June 30,2022.Nine multiparas and thirteen health-related professionals were purposefully sampled until data saturation was reached.A thematic analysis approach was applied to the interview transcripts,utilizing dual independent coding and consensus validation in NVivo 12.0.Results:The data generated two overarching categories:1)balanced decision-making on the appropriate birth intervals and 2)internal and external determinants integrated with health and societal considerations.Four key themes emerged following the two categories:1)consistency and discrepancy between the actual and recommended birth intervals of multiparas;2)health-and developmentoriented professional recommendations;3)internal determinants related to individual-level factors;and 4)external determinants related to child-related factors,family support,and social security.Weighing women's reproductive health and career development,multiparas and health-related professionals perceived a length between 18 and 36 months as the appropriate Bl.Conclusion:Multiparas and health-related professionals shaped their balanced recommendations on a relatively appropriate birth interval ranging from 18 to 36 months,which was influenced by women's individual-level factors,child-related factors,family support,and social security.Targeted social and healthcare services should be offered to women and their families during the Bls.
基金support from the“111 program”of Ministry of Education of China and State Administration of Foreign Experts Affairs of China.
文摘BACKGROUND Uterine injury can cause uterine scarring,leading to a series of complications that threaten women’s health.Uterine healing is a complex process,and there are currently no effective treatments.Although our previous studies have shown that bone marrow mesenchymal stem cells(BMSCs)promote uterine damage repair,the underlying mechanisms remain unclear.However,exploring the specific regulatory roles of BMSCs in uterine injury treatment is crucial for further understanding their functions and enhancing therapeutic efficacy.AIM To investigate the underlying mechanism by which BMSCs promote the process of uterine healing.METHODS In in vivo experiments,we established a model of full-thickness uterine injury and injected BMSCs into the uterine wound.Transcriptome sequencing was per-formed to determine the enrichment of differentially expressed genes at the wound site.In in vitro experiments,we isolated rat uterine smooth muscle cells(USMCs)and cocultured them with BMSCs to observe the interaction between BMSCs and USMCs in the microenvironment.RESULTS We found that the differentially expressed genes were mainly related to cell growth,tissue repair,and angiogenesis,while the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathway was highly enriched.Quantitative reverse-transcription polymerase chain reaction was used to validate differentially expressed genes,and the results demonstrated that BMSCs can upregulate genes related to regeneration and downregulate genes related to inflammation.Coculturing BMSCs promoted the migration and proliferation of USMCs,and the USMC microenvironment promoted the myogenic differentiation of BMSCs.Finally,we validated the PI3K/AKT pathway in tissues and cells and showed that BMSCs activate the PI3K/AKT pathway to promote the regeneration of uterine smooth muscle both in vivo and in vitro.CONCLUSION BMSCs upregulated uterine wound regeneration and anti-inflammatory factors and enhanced uterine smooth muscle proliferation through the PI3K/AKT pathway both in vivo and in vitro.
基金supported by the Foundation of Gansu Key Laboratory of Protection and Utilization for Biological Resources and Ecological Restoration in Longdong (LDSWZY202103)Natural Science Foundation of Gansu Province (22JR5RM210)to B.P.L.Gansu Ziwuling Ecosystem Observation and Research Station (20JR10RA658)。
文摘Avian genomes exhibit compact organization and remarkable chromosomal stability.However,the extent and mechanisms by which structural variation in avian genomes differ from those in other vertebrate lineages are poorly explored.This study generated a diploid genome assembly for the golden pheasant(Chrysolophus pictus),a species distinguished by the vibrant plumage of males.Each haploid genome assembly included complete chromosomalmodels,incorporatingall microchromosomes.Analysis revealed extensive tandem amplification of immune-related genes across the smallest microchromosomes(dot chromosomes),with an average copy number of 54.Structural variation between the haploid genomes was primarily shaped by large insertions and deletions(indels),with minimal contributions from inversions or duplications.Approximately 28%of these large indels were associated with recent insertions of transposable elements,despite their typically low activity in bird genomes.Evidence for significant effects of transposable elements on gene expression was minimal.Evolutionary strata on the sex chromosomes were identified,along with a drastic rearrangement of the W chromosome.These analyses of the high-quality diploid genome of the golden pheasant provide valuable insights into the evolutionary patterns of structural variation in avian genomes.
文摘BACKGROUND A large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery.Persistent obstructive symptoms may result in faecal stasis that can develop into Hirschsprung-associated enterocolitis,a potential life-threatening condition.Important treatment to improve faecal passage is internal anal sphincter relaxation using botulinum toxin injections.AIM To give an overview of all empirical evidence on the effectiveness of botulinum toxin injections in patients with Hirschsprung disease.METHODS A systematic review and meta-analysis was done by searching PubMed,EMBASE and the Cochrane Library,using entry terms related to:(1)Hirschsprung disease;and(2)Botulinum toxin injections.14 studies representing 278 patients met eligibility criteria.Data that were extracted were proportion of patients with improvement of obstructive symptoms or less enterocolitis after injection,proportion of patients with adverse effects and data on type botulinum toxin,mean dose,average age at first injection and patients with associated syndromes.Random-effects meta-analysis was used to aggregate effects and random-effects meta-regression was used to test for possible confounding factors.RESULTS Botulinum toxin injections are effective in treating obstructive symptoms in on average 66%of patients[event rate(ER)=0.66,P=0.004,I2=49.5,n=278 patients].Type of botulinum toxin,average dose,average age at first injections and proportion of patients with associated syndromes were not predictive for this effect.Mean 7 duration of improvement after one botulinum toxin injections was 6.4 mo and patients needed on average 2.6 procedures.There was a significant higher response rate within one month after botulinum toxin injections compared to more than one month after Botulinum toxin injections(ER=0.79,vs ER=0.46,Q=19.37,P<0.001).Botulinum toxin injections were not effective in treating enterocolitis(ER 0.58,P=0.65,I2=71.0,n=52 patients).There were adverse effects in on average 17%of patients(ER=0.17,P<0.001,I2=52.1,n=187 patients),varying from temporary incontinence to mild anal pain.CONCLUSION Findings from this systematic review and meta-analysis indicate that botulinum toxin injections are effective in treating obstructive symptoms and that adverse effects were present,but mild and temporary.
基金Supported by the Special Fund for Agro-Scientific Research in the Public Interest(No.201003068)the National Natural Science Foundation of China(Nos.31172447,41176117)
文摘We tested the utility of chemical marking techniques in the juvenile black rockfish Sebastes schlegelii. Juveniles （30-40 mm total length） were immersed in a range of tetracycline hydrochloride （TC） solutions at concentrations ranging from 300 to 500 mg/L, and alizarin complexone （ALC） solutions at concentrations ranging from 200 to 400 mg/L in filtered sea water （salinity of 30） for 24 h, respectively. Otoliths （sagittae, asteriscus）, scales, fin rays （dorsal, pectoral, ventral, anal, and caudal fin rays）, and fin spines （dorsal, ventral, and anal fin spines） were sampled and used to detect fluorescent marks after a 60-day growth experiment. With the exception of 300 mg/L TC, acceptable marks were produced in the otoliths and fin spines by all concentrations of TC and ALC. In particular, we observed clearly visible marks in the sagittae, asteriscus, and fin spines under normal light at concentrations of200~00 mg/L, 250-400 mg/L, and 250-400 mg/L ALC, respectively. Scales and fin rays had acceptable marks at much higher concentrations （_〉350 mg/L TC, 〉250 mg/L ALC for scales and _〉350 mg/L TC, 〉300 mg/L ALC for fin rays）. The best mark quality （i.e., acceptable marks were observed in all sampled structures after immersion marking） were obtained following immersion in TC at between 350-500 rag/L, and ALC between 300-400 mg/L. In addition, there was no significant difference in survival and growth of TC and ALC marked fish compared to their controls up to 60 days post-marking （P〉0.05）.
基金supported by the National Natural Science Foundation of China(32072806,31572399)National Key Research and Development Program of China(2022YFD1302201)+3 种基金Program of Shaanxi Province Science and Technology Innovation Team(2019TD-036)Major Projects of Natural Science Foundation of Inner Mongolia Autonomous Region(2020ZD10)Key Research and Development Program of Shaanxi Province(2022NY-044)Key Technologies Demonstration of Animal Husbandry in Shaanxi Province(20221086)。
文摘Bacterial or viral infections,such as Brucella,mumps virus,herpes simplex virus,and Zika virus,destroy immune homeostasis of the testes,leading to spermatogenesis disorder and infertility.Of note,recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells,leading to male reproductive dysfunction.Due to the many side effects associated with antibiotic therapy,finding alternative treatments for inflammatory injury remains critical.Here,we found that Dmrt1 plays an important role in regulating testicular immune homeostasis.Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells.Chromatin immunoprecipitation sequencing(ChIP-seq)and RNA sequencing(RNA-seq)revealed that Dmrt1 positively regulated the expression of Spry1,an inhibitory protein of the receptor tyrosine kinase(RTK)signaling pathway.Furthermore,immunoprecipitation-mass spectrometry(IP-MS)and co-immunoprecipitation(Co-IP)analysis indicated that SPRY1 binds to nuclear factor kappa B1(NF-κB1)to prevent nuclear translocation of p65,inhibit activation of NF-κB signaling,prevent excessive inflammatory reaction in the testis,and protect the integrity of the blood-testis barrier.In view of this newly identified Dmrt1-Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis,our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.
基金supported by the National Natural Science Foundation of China(32072980)Key Research and Development Projects in Tibet(XZ202001ZY0016N,XZ201902NB02,XZNKY-2019-C-053)。
文摘Fish morphological phenotypes are important resources in artificial breeding,functional gene mapping,and population-based studies in aquaculture and ecology.Traditional morphological measurement of phenotypes is rather expensive in terms of time and labor.More importantly,manual measurement is highly dependent on operational experience,which can lead to subjective phenotyping results.Here,we developed 3DPhenoFish software to extract fish morphological phenotypes from three-dimensional(3D)point cloud data.Algorithms for background elimination,coordinate normalization,image segmentation,key point recognition,and phenotype extraction were developed and integrated into an intuitive user interface.Furthermore,18 key points and traditional 2D morphological traits,along with 3D phenotypes,including area and volume,can be automatically obtained in a visualized manner.Intuitive fine-tuning of key points and customized definitions of phenotypes are also allowed in the software.Using 3DPhenoFish,we performed high-throughput phenotyping for four endemic Schizothoracinae species,including Schizopygopsis younghusbandi,Oxygymnocypris stewartii,Ptychobarbus dipogon,and Schizothorax oconnori.Results indicated that the morphological phenotypes from 3DPhenoFish exhibited high linear correlation(>0.94)with manual measurements and offered informative traits to discriminate samples of different species and even for different populations of the same species.In summary,we developed an efficient,accurate,and customizable tool,3DPhenoFish,to extract morphological phenotypes from point cloud data,which should help overcome traditional challenges in manual measurements.3DPhenoFish can be used for research on morphological phenotypes in fish,including functional gene mapping,artificial selection,and conservation studies.3DPhenoFish is an open-source software and can be downloaded for free at https://github.com/lyh24k/3DPhenoFish/tree/master.
文摘BACKGROUND Patients with Hirschsprung disease(HD)are at risk of persistent constipation,fecal incontinence or recurrent enterocolitis after surgical treatment,which in turn may impact physical and psychosocial functioning.Generic health-related quality of life(HRQoL)and disease-specific health-related quality of life are relevant outcome measures to assess the impact of HD on the QoL of these patients.AIM To summarize all available evidence on HRQoL of patients with HD after surgery and the impact of possible moderating factors.METHODS Pubmed,Web of Sciences,Psyc Info and Embase were searched with search terms related to’Hirschsprung disease’,’Pediatrics’and’Quality of life’.Mean and standard deviation of generic HRQoL overall and domain scores were extracted from each study,as well as data describing potential factors associated with QoL.Random effect models were used for meta-analytic aggregation of generic HRQoL scores.Meta-regression was used to assess the relationship between patient and clinical characteristics and generic HRQoL.Disease-specific HRQoL outcomes of patients with HD were systematically reviewed.RESULTS Seventeen articles were included in the systematic review(n=1137 patients)and 15 in the quantitative meta-analysis(n=1024 patients).Four studies reported disease-specific HRQoL.Patient’s age ranged between 0 and 21 years.Meta-analytic aggregation showed a nonsignificantly impaired generic HRQoL(d=-0.168[95%CI:-0.481;0.145],P=0.293,I^(2)=94.9)in patients with HD compared to healthy controls.Physical(d=-0.042[95%CI:-0.419;0.335],P=0.829,I^(2)=95.1),psychosocial(d=-0.159[95%CI:-0.458;0.141],P=0.299,I^(2)=93.6)and social HRQoL(d=-0.092[95%CI:-0.642;0.457],P=0.742,I^(2)=92.3)were also not significantly lower compared to healthy controls.There was no relation between health-related outcomes and the sex of the patients and whether generic HRQoL was measured by parental proxy or self-report.Disease-specific complaints of patients with HD impaired physical HRQoL,but not psychosocial and social HRQoL.CONCLUSION In this systematic review and meta-analysis,no evidence was found for impaired generic HRQoL in patients with HD compared to healthy controls,neither for moderating effects of sex,parental proxy or self-report.
基金supported by Research and Development Program of China(2016YFC1000500)to H.W.and W.T.the National Natural Science Foundation of China(81430005,31521003,31771669)to H.W.and(31601029)to Y.G.the Commission for Science and Technology of Shanghai Municipality(17JC1400902)to H.W.
文摘Wnt signaling pathways,including the canonical Wnt/β-catenin pathway,planar cell polarity pathway,and Wnt/Ca2+signaling pathway,play important roles in neural development during embryonic stages.The DVL genes encode the hub proteins for Wnt signaling pathways.The mutations in DVL2 and DVL3 were identified from patients with neural tube defects(NTDs),but their functions in the pathogenesis of human neural diseases remain elusive.Here,we sequenced the coding regions of three DVL genes in 176 stillborn or miscarried fetuses with NTDs or Dandy-Walker malformation(DWM)and 480 adult controls from a Han Chinese population.Four rare mutations were identified:DVL1 p.R558 H,DVL1 p.R606 C,DVL2 p.R633 W,and DVL3 p.R222 Q.To assess the effect of these mutations on NTDs and DWM,various functional analyses such as luciferase reporter assay,stress fiber formation,and in vivo teratogenic assay were performed.The results showed that the DVL2 p.R633 W mutation destabilized DVL2 protein and upregulated activities for all three Wnt signalings(Wnt/β-catenin signaling,Wnt/planar cell polarity signaling,and Wnt/Ca2+signaling)in mammalian cells.In contrast,DVL1 mutants(DVL1 p.R558 H and DVL1 p.R606 C)decreased canonical Wnt/β-catenin signaling but increased the activity of Wnt/Ca2+signaling,and DVL3 p.R222 Q only decreased the activity of Wnt/Ca2+signaling.We also found that only the DVL2 p.R633 W mutant displayed more severe teratogenicity in zebrafish embryos than wild-type DVL2.Our study demonstrates that these four rare DVL mutations,especially DVL2 p.R633 W,may contribute to human neural diseases such as NTDs and DWM by obstructing Wnt signaling pathways.
基金supported by the National Key Basic Research Program of China(2015CB942800)the National Natural Science Foundation of China(Nos.31330051 and 31730060)+2 种基金the 111 Program(B14037)the Natural Science Foundation Project of Chongqing(cstc2014jcyj A10088)the Fundamental Research Funds for the Central Universities(XDJK2015B011)
文摘Ribosome biogenesis is essential for the cell growth and division. Disruptions in ribosome biogenesis result in developmental defects and a group of diseases, known as ribosomopathies. Here, we report a mutation in zebrafish urb1, which encodes an essential ribosome biogenesis protein. The urb1 cq31 mutant exhibits hypoplastic digestive organs, which is caused by impaired cell proliferation with the differentiation of digestive organ progenitors unaffected. Knockdown of mtor or raptor leads to similar hypoplastic phenotypes and reduced expression of urb1 in the digestive organs. Overexpression of Urb1 results in overgrowth of digestive organs, and can efficiently rescue the hypoplastic liver and pancreas in the mtor and raptor morphants. Reduced syntheses of free ribosomal subunits and impaired assembly of polysomes are observed in the urb1 mutant as well as in the mtor and raptor morphants, which can be rescued by the Urb1 overexpression. These data demonstrate that Urb1 plays an important role in governing ribosome biogenesis and protein synthesis downstream of mammalian/mechanistic target of rapamycin complex 1（mTORC1）, thus regulating the development of digestive organs. Our study indicates the requirement of hyperactive protein synthesis for the digestive organ development.
基金supported by the National Key Research and Development Program of China(2021YFC2701400)in part by the National Natural Science Foundation of China(32000393 and 32288101).
文摘During spermiogenesis,haploid spermatids undergo dramatic morphological changes to form slender sperm flagella and cap-like acrosomes,which are required for successful fertilization.Severe deformities in flagella cause a male infertility syndrome,multiple morphological abnormalities of the flagella(MMAF),while acrosomal hypoplasia in some cases leads to sub-optimal embryonic developmental potential.However,evidence regarding the occurrence of acrosomal hypoplasia in MMAF is limited.Here,we report the generation of base-edited mice knocked out for coiled-coil domain-containing 38(Ccdc38)via inducing a nonsense mutation and find that the males are infertile.The Ccdc38-KO sperm display acrosomal hypoplasia and typical MMAF phenotypes.We find that the acrosomal membrane is loosely anchored to the nucleus and fibrous sheaths are disorganized in Ccdc38-KO sperm.Further analyses reveal that Ccdc38 knockout causes a decreased level of TEKT3,a protein associated with acrosome biogenesis,in testes and an aberrant distribution of TEKT3 in sperm.We finally show that intracytoplasmic sperm injection overcomes Ccdc38-related infertility.Our study thus reveals a previously unknown role for CCDC38 in acrosome biogenesis and provides additional evidence for the occurrence of acrosomal hypoplasia in MMAF.
基金supported by the Strategic Priority Research Program,CAS(XDB31040202,XDA19050303)China’s Biodiversity Observation Network(Sino-BON),Digitalization,Development and Application of Biotic Resource(202002AA100007)+5 种基金Animal Branch of the Germplasm Bank of Wild Species,Chinese Academy of Sciences(Large Research Infrastructure Funding)National Natural Science Foundation of China(32170478)Yunnan FundamentalResearchProject(202001AW070016,202005AC160046)Young Talent Project of China Association for Science and Technology(2019-2021QNRC001)Second Tibetan Plateau Scientific Expedition and Research Program(2019QZKK0501)supported by the CAS President’s International Fellowship Initiative(PIFI)to R.W.M.
文摘Evolutionary biologists are always interested in deciphering the geographic context of diversification,therefore they introduced the concept of comparative phylogeography,which helps to identify common mechanisms that contribute to shared genetic structures among organisms from the same region.Here,we used multi-locus genetic data along with environmental data to investigate shared phylogeographic patterns among three Asianendemic newt genera,Cynops,Paramesotriton and Pachytriton,which occurred in montane/submontane streams or ponds in southern China.Our 222samples from 78 localities covered the entire range of the three genera and represented the largest dataset of this group to date.We reconstructed matrilineal genealogies from two protein-coding,mitochondrial genes,and gene network from two nuclear genes.We also estimated divergence times of major cladogenetic events and used occurrence data to evaluate niche difference and similarity between lineages.Our results revealed a common basal split in all three genera that corresponds to the separation of two geographic terrains of southern China.Those ancient divergence occurred during middle to late Miocene and likely correlate with paleoclimatic fluctuations caused by the uplift of the Qinghai-Xizang(Tibet)Plateau(QTP).Particularly,the strengthening and weakening of Asian summer monsoons during the Miocene may have profoundly impacted southern China and led to repeatedly vicariance in those newts.However,despite differences in realized niches between lineages,there is no evidence for divergence of fundamental niches.Preservation of old newt matriline lineages in mountains of southern China suggests that the region acts as both museums and cradles of speciation.Based on those results,we advocate a multi-pronged protection strategy for newts in the three genera.
基金supported by the GRF RGC&CRF,Hong Kong(Grant Nos.:475012 and C5045-20 EF)HMRF,Hong Kong(Grant No.:03141386)+3 种基金ITF,Hong Kong(Grant No.:ITS/209/12)UGC Direct Grant 2011,2012,2021.032HKOG Trust Fund 2011,2014,2019the National Natural Science Foundation of China(Grant Nos.:81974225 and 82201823)。
文摘Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.
基金supported by the Chinese National Key Program on Basic Research(Nos.2011CB964800 and 2012CB966904)the National Natural Science Foundation of China(No. 30911130360)
文摘Recent progress by versatile approaches supports the new hypothesis that multi-potent hematopoietic stein cells （HSCs） are directly formed from a rare population of endothelial cells in mid-gestation mouse embryos. This process is therefore known as the endothelial-to- hematopoietic transition （EHT）. Nevertheless, there is no functional evidence that documents the HSC transition from purified endothelial cells. In this study, we developed an OP9-DLl-based co-culture system that was able to facilitate the HSC specification and/or expansion in vitro of mouse embryonic day 10.5 （El0.5） Tie2~ cells remarkably. Then, the immunophenotypically defined endothelial ceils were harvested by a combination of surface markers （Flkl＋CD31 ~CD41 CD45 Ter119 ） from the caudal half of EI0.0-EI 1.0 mouse embryos. The transplantation of the endothelia/OP9-DL1 co-cultures led to long-term, high-level, multi-lineage, and multi-organ he- matopoietic reconstitution in the irradiated adult recipients. The induced HSC activity was initially observed at El0.5, and a significant increase was detected at El 1.0, which suggests a temporally specific regulation. Taken together, tbr the first time, we provide functional evidence showing the HSC potential of purified embryonic endothelial cells, which is indispensable for the emerging EHT concept. Moreover, the newly defined co-culture system will aid the exploration of the key molecules governing the HSC transition from embryonic and even postnatal endothelial cells, which has enormous significance in basic and translational research.
文摘From the published data, the present mini-review attempts to answer two fundamental questions about the gestational trophoblastic neoplasms. In addition, it extrapolates the findings to other cancers that produce small amounts of hCG and how a novel therapies could be developed.
基金supported by the National Natural Science Foundation of China(82071700,82101679,and 32288101)The University Synergy Innovation Program of Anhui Province in China(GXXT-2021-071).
文摘Globally,infertility is a serious health problem affecting about 15%of reproductive age couples according to the data reported by the World Health Organization.Non-obstructive azoospermia(NOA)is acknowledged as one of the most serious phenotypes of male infertility.Approximately 1%of the male population and 10%of infertile men were affected by NOA(Xie et al.,2022).As reported,meiotic arrest is one of the major etiologies leading to the NOA.
