As a high-value eudicot family,many famous horticultural crop genomes have been deciphered in Oleaceae.However,there are currently no bioinformatics platforms focused on empowering genome research in Oleaceae.Herein,w...As a high-value eudicot family,many famous horticultural crop genomes have been deciphered in Oleaceae.However,there are currently no bioinformatics platforms focused on empowering genome research in Oleaceae.Herein,we developed the first comprehensive Oleaceae Genome Research Platform(OGRP,https://oleaceae.cgrpoee.top/).In OGRP,70 genomes of 10 Oleaceae species and 46 eudicots and 366 transcriptomes involving 18 Oleaceae plant tissues can be obtained.We built 34 window-operated bioinformatics tools,collected 38 professional practical software programs,and proposed 3 new pipelines,namely ancient polyploidization identification,ancestral karyotype reconstruction,and gene family evolution.Employing these pipelines to reanalyze the Oleaceae genomes,we clarified the polyploidization,reconstructed the ancestral karyotypes,and explored the effects of paleogenome evolution on genes with specific biological regulatory roles.Significantly,we generated a series of comparative genomic resources focusing on the Oleaceae,comprising 108 genomic synteny dot plots,1952225 collinear gene pairs,multiple genome alignments,and imprints of paleochromosome rearrangements.Moreover,in Oleaceae genomes,researchers can efficiently search for 1785987 functional annotations,22584 orthogroups,29582 important trait genes from 74 gene families,12664 transcription factor-related genes,9178872 transposable elements,and all involved regulatory pathways.In addition,we provided downloads and usage instructions for the tools,a species encyclopedia,ecological resources,relevant literatures,and external database links.In short,ORGP integrates rich data resources and powerful analytical tools with the characteristic of continuous updating,which can efficiently empower genome research and agricultural breeding in Oleaceae and other plants.展开更多
INTRODUCTION.Depressive disorders are mental illnesses that seriously affect public health.There are approximately 320 million patients with depression worldwide,accounting for 4.4% of the total disease burden.1Depres...INTRODUCTION.Depressive disorders are mental illnesses that seriously affect public health.There are approximately 320 million patients with depression worldwide,accounting for 4.4% of the total disease burden.1Depression leads to social and occupational impairment,diminished quality of life and an elevated risk of death by suicide.展开更多
Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-targe...Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.展开更多
Inbreeding increases genome homozygosity within populations,which can exacerbate inbreeding depression by exposing homozygous deleterious alleles that are responsible for declines in fitness traits.In small population...Inbreeding increases genome homozygosity within populations,which can exacerbate inbreeding depression by exposing homozygous deleterious alleles that are responsible for declines in fitness traits.In small populations,genetic purging that occurs under the pressure of natural selection acts as an opposing force,contributing to a reduction of deleterious alleles.Both inbreeding and genetic purging are paramount in the field of conservation genomics.The Amur tiger(Panthera tigris altaica)lives in small populations in the forests of Northeast Asia and is among the most endangered animals on the planet.Using genome-wide assessment and comparison,we reveal substantially higher and more extensive inbreeding in wild Amur tigers(F_(ROH)=0.50)than in captive individuals(F_(ROH)=0.24).However,a relatively reduced number of lossof-function mutations in wild Amur tigers is observed compared to captive individuals,indicating genetic purging of inbreeding load with relatively large-effect alleles.The higher ratio of homozygous mutation load and number of fixed damaging alleles in the wild population indicates a less-efficient genetic purging,with purifying selection also contributing to this process.These findings provide valuable insights for the future conservation of Amur tigers.展开更多
The utilization of Lactobacillus plantarum(LP)in chili sauce production is well-known for its capacity to enhance product quality and sensory attributes.However,there is still limited knowledge regarding the taste-act...The utilization of Lactobacillus plantarum(LP)in chili sauce production is well-known for its capacity to enhance product quality and sensory attributes.However,there is still limited knowledge regarding the taste-active metabolites in the sauce.To bridge this gap,our study employed metabolomics and webbased computational tools to investigate the dynamic changes of taste-active metabolites during chili sauce fermentation.By leveraging the advantages of the feature-based molecular network(FBMN),we conducted a rapid annotation of metabolites,successfully identifying 205 metabolites,a considerable portion of which were previously unreported.Through the utilization of the Virtual Taste tool,we identified dihydrosphingosine,lactic acid,isoleucine,phytosphingosine,and gluconic acid as potential taste indicators for quality control.Pathway enrichment analysis further supported their primary involvement in key biochemical pathways,including amino acid t RNA biosynthesis,phenylalanine,tyrosine,tryptophan biosynthesis,and sphingolipid metabolism.This investigation provides valuable insights into the underlying mechanisms contributing to the distinctive flavor profile of chili sauce.展开更多
Background:In this present study,we have screened major phytoconstituents of Nilavembu Kudineer against critical COVID-19 target proteins that cause severe pneumonia globally.In addition,a human receptor protein that ...Background:In this present study,we have screened major phytoconstituents of Nilavembu Kudineer against critical COVID-19 target proteins that cause severe pneumonia globally.In addition,a human receptor protein that facilitates viral entry into the host cell was also targeted.Methods:Phytoconstituents derived from Nilavembu Kudineer formulation were docked against 12 major proteins,which help viral entry,viral proliferation,and a human receptor facilitate the viral entry into the host cells.The major metabolites of Nilavembu Kudineer were retrieved based on literature from the PubChem database.The docked complex was subjected to MD simulation studies to verify its binding mode and the stability of the interactions.The binding energy analysis was performed to estimate the binding affinity between the compounds and their respective receptors using MM/GBSA.Results:Docking studies have shown that three major plants in the polyherbal formulation,Andrographis paniculata,Mollugo cerviana,and Zingiber officinale,have 14 potential compounds that have better binding affinity against COVID-19 proteins and their host receptor protein.MD studies and binding energy calculations also confirmed that these compounds possess better stability and strong binding energy with these proteins.Conclusion:In silico analyses suggest that phytoconstituents from Nilavembu Kudineer possess promising multi-target antiviral activity against COVID-19.These findings provide a rationale for further experimental studies to validate their therapeutic potential for the treatment of COVID-19.展开更多
Autism spectrum disorder(ASD)is a neurodevelopmental disorder where de novo mutations play a significant role.Although coding mutations in ASD have been extensively characterized,the impact of non-coding de novo mutat...Autism spectrum disorder(ASD)is a neurodevelopmental disorder where de novo mutations play a significant role.Although coding mutations in ASD have been extensively characterized,the impact of non-coding de novo mutations(ncDNMs)remains less understood.Here,we integrate cortex cell-specific cis-regulatory element annotations,a deep learning-based variant prediction model,and massively parallel reporter assays to systematically evaluate the functional impact of 227,878 ncDNMs from Simons Simplex Collection(SSC)and Autism Speaks MSSNG resource(MSSNG)cohorts.Our analysis identifies 238 ncDNMs with confirmed functional regulatory effects,including 137 down-regulated regulatory mutations(DrMuts)and 101 up-regulated regulatory mutations(UrMuts).Subsequent association analyses reveal that only DrMuts regulating loss-of-function(LoF)intolerant genes rather than other ncDNMs are significantly associated with the risk of ASD(Odds ratio=4.34;P=0.001).A total of 42 potential ASD-risk DrMuts across 41 candidate ASD-susceptibility genes are identified,including 12 recognized and 29 unreported genes.Interestingly,these noncoding disruptive mutations tend to be observed in genes extremely intolerant to LoF mutations.Our study introduces an optimized approach for elucidating the functional roles of ncDNMs,thereby expanding the spectrum of pathogenic variants and deepening our understanding of the complex molecular mechanisms underlying ASD.展开更多
Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(P...Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.展开更多
Codon usage in chloroplast genome of six seed plants （Arabidopsis thaliana, Populus alba, Zea mays, Triticum aestivum, Pinus koraiensis and Cycas taitungensis） was analyzed to find general patterns of codon usage in...Codon usage in chloroplast genome of six seed plants （Arabidopsis thaliana, Populus alba, Zea mays, Triticum aestivum, Pinus koraiensis and Cycas taitungensis） was analyzed to find general patterns of codon usage in chloroplast genomes of seed plants. The results show that chloroplast genomes of the six seed plants had similar codon usage patterns, with a strong bias towards a high representation of NNA and NNT codons. In chloroplast genomes of the six seed plants, the effective number of codons （ENC） for most genes was similar to that of the expected ENC based on the GC content at the third codon position, but several genes with low ENC values were laying below the expected curve. All of these data indicate that codon usage was dominated by a mutational bias in chloroplast genomes of seed plants and that selection appeared to be limited to a subset of genes and to only subtly affect codon usage. Meantime, four, six, eight, nine, ten and 12 codons were defined as the optimal codons in chloroplast genomes of the six seed plants.展开更多
BACKGROUND Ulcerative colitis(UC)is considered to be closely associated with alteration of intestinal microorganisms.According to the traditional Chinese medicine(TCM)theory,UC can be divided into two disease syndrome...BACKGROUND Ulcerative colitis(UC)is considered to be closely associated with alteration of intestinal microorganisms.According to the traditional Chinese medicine(TCM)theory,UC can be divided into two disease syndromes called Pi-Xu-Shi-Yun(PXSY)and Da-Chang-Shi-Re(DCSR).The relationships among gut microbiota,TCM syndromes,and UC pathogenesis have not been well investigated.AIM To investigate the role of gut microbiota in UC and the distinction of microbiota dysbiosis between PXSY and DCSR syndromes.METHODS From May 2015 to February 2016,UC patients presenting to LongHua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study.Fresh stool specimens of UC patients with PXSY or DCSR were collected.The feces of the control group came from the health examination population of Longhua Hospital.The composition of gut bacterial communities in stool samples was determined by the pyrosequencing of 16S ribosomal RNA.The high-throughput sequencing reads were processed with QIIME,and biological functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.RESULTS The composition of gut bacterial communities in 93 stool samples(30 healthy controls,32 patients with PXSY syndrome,and 31 patients with DCSR syndrome)was determined by the pyrosequencing of 16S ribosomal RNA.Beta diversity showed that the composition of the microbiota was different among the three groups.At the family level,Porphyromonadaceae,Rikeneliaceae,and Lachnospiraceae significantly decreased while Enterococcus,Streptococcus,and other potential pathogens significantly increased in UC patients compared to healthy subjects.At the genus level,Parabacteroides,Dorea,and Ruminococcus decreased while Faeca-libacterium showed increased abundance in UC compared to healthy controls.Five differential taxa were identified between PXSY and DCSR syndromes.At the genus level,a significantly increased abundance of Streptococcus was observed in DCSR patients,while Lachnoclostridium increased in PXSY patients.The differential functional pathways of the gut microbiome between the PXSY and DCSR groups mainly included lipid metabolism,immunity,and the metabolism of polypeptides.CONCLUSION Our study suggests that the gut microbiota contributes to the distinction between the two TCM syndromes of UC.展开更多
A novel series of 5-（（5-substituted-1H-1,2,4-triazol-3-yl）methyl）-4,5,6,7-tetrahydrothieno[3,2-c]pyr- idines 5（a-i） has been synthesized from thienopyridine hydrazide, substituted aromatic nitriles using 4- dime...A novel series of 5-（（5-substituted-1H-1,2,4-triazol-3-yl）methyl）-4,5,6,7-tetrahydrothieno[3,2-c]pyr- idines 5（a-i） has been synthesized from thienopyridine hydrazide, substituted aromatic nitriles using 4- dimethylaminopyridine （DMAP） as a catalyst under microwave irradiation and evaluated for their in vitro antifungal activity. Compound 5g is found to be more potent against Candida albicans when compared with miconazole. Docking study of the newly synthesized compounds was performed, and results showed good binding mode in the active site of fungal enzyme P450 cytochrome lanosterol 14α- demethylase. ADMET properties of synthesized compounds were also analyzed and showed good drug like properties. The results of in vitro antifungal activity, docking study and ADMET prediction revealed that the synthesized compounds have potential antifungal activity and can be further optimized and developed as a lead compound.展开更多
OBJECTIVE:To evaluate the immune modulatory response of Puhuang(Pollen Typhae),ethanolic extract of dried pollens(TP-E)and charcoal activated pollens(CTP-E)were used for their phytochemical evaluation and their modula...OBJECTIVE:To evaluate the immune modulatory response of Puhuang(Pollen Typhae),ethanolic extract of dried pollens(TP-E)and charcoal activated pollens(CTP-E)were used for their phytochemical evaluation and their modulatory response against lipopolysaccharide(LPS)induced inflammatory activity on RAW264.7 macrophage cells.METHODS:Biochemical assays were carried out to quantify the 1,1-Diphenyl-2-picrylhydrazyl Radical Scavenging Activity,Reducing Power,Ferrous ion chelating ability and total polyphenol content and flavonoids.Non-toxic dose of the extract(TP-E and CTP-E)was chosen based on 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Effect of TP-E and CTP-E on lipopolysaccharides-induced inducible nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2)expression was measured by Western blot and quantitative PCR(q RT-PCR).Expression of inflammatory cytokines,such as interleukins(IL-1βand IL-6)and tumor necrosis factorα(TNF-α),was quantified using q RT-PCR.Mitogen-activated protein kinase pathway was analyzed using Western blot.RESULTS:Phytochemical analysis revealed that both TP-E and CTP-E have strong antioxidant activities and high flavonoid and phenolic contents.TP-E and CTP-E effectively inhibit the expression of i NOS and COX-2,thereby inhibiting its downstream proinflammatory regulators,the extracellular signal-related kinase-1/2,that decreases the expression of IL-1β,IL-6 and TNF-α.CONCLUSION:Phytochemical constituents present in Typha angustifolia Linn could be used for treating inflammation-related diseases.展开更多
Initial bacterial adhesion on dental implant abutment is related to its surface chemical composition and physical characteristics.Selection of appropriate abutment materials resistant to bacterial adhesion is importan...Initial bacterial adhesion on dental implant abutment is related to its surface chemical composition and physical characteristics.Selection of appropriate abutment materials resistant to bacterial adhesion is important for dental implant maintenance.The aim of present study was to evaluate the effect of different properties of abutment materials on initial bacterial adhesion in vitro.Polished zirconia(PZ group), polished titanium(PT group) and ground titanium(GT group) samples were prepared to simulate clinical dental implant abutments.Chemical compositions, morphology, roughness, hydrophilicity and surface free energy of materials were analyzed.Oral commensal bacterium Streptococcus mitis was used to evaluate initial bacterial adhesion via turbidity test and colony-forming unit counting.The results showed that GT group presented the highest roughness, hydrophilicity and surface free energy.After 6-h incubation, GT group showed the significantly highest adhered bacteria counts;while non-significant difference existed between PT and PZ groups.Within the clinically applicable range used in present study, the surface physical characteristics, instead of surface chemical composition, of dental abutment material have the pronounced influence on initial 6-h bacterial adhesion.展开更多
Cells of organ systems are endowed with a relatively similar genome while epigenome niches keep varying chronologically and defined explicitly in the respective tissues.The genome of an individual is always influenced...Cells of organ systems are endowed with a relatively similar genome while epigenome niches keep varying chronologically and defined explicitly in the respective tissues.The genome of an individual is always influenced by parental,embryonic,tissue-specific,and environmental epigenomes and the same must have been the possible reason for invariable inquiries relating to familial,environmental and life style patterns in the preliminary investigations of diabetic complications.Unprecedented methylation of lysine residues of histones and cytosines of CpG islands of promoter DNA impede the transcription of genes and homocysteine is the metabolic key player of methyl groups.Gck and COX7A1 are the 2 examples in the present review to elucidate the epigenetic influence on the onset of diabetes.miRNAs are additional promising cellular components influencing both at transcriptional and translational levels and promoting either in favour or against(i.e.,feed back) TFs,signaling factors and proteins through their pliotropic effects and thus are reported to regulate cellular physiology.miR-124a and miR-9 are primarily endemic to nervous tissue and they are now being exploited in islets for their function in executing exocytosis of insulin,which of course is one of the fundamental canons of diabetes.miR-375 persuades beta cells for glucose-induced insulin gene expression.The current approach to evaluate the constellation of genes and their products involved in diabetes in huge number of samples through GWA studies may unravel intricacies involved in the management of diabetes and its associated consequences.展开更多
To evaluate the levels of von Willebrand factor (VWF) and metalloproteinase with thrombospondin type-1 motif, number 13 (ADAMTS13) in inflammatory bowel disease (IBD) and correlate them with the disease activity. METH...To evaluate the levels of von Willebrand factor (VWF) and metalloproteinase with thrombospondin type-1 motif, number 13 (ADAMTS13) in inflammatory bowel disease (IBD) and correlate them with the disease activity. METHODSConsecutive patients with IBD aged 18 years or older were enrolled in the study. Forty-seven patients with ulcerative colitis (UC), 38 with Crohn’s disease (CD), and 50 healthy controls were included. The white blood cell count, haematocrit, platelet count, fibrinogen, partial activated thromboplastin time, C-reactive protein, albumin, VWF antigen level (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), VWF collagen-binding activity (VWF:CB), and ADAMTS13 antigen level (ADAMTS13:Ag) and activity (ADAMTS13act) were measured. The following ratios were assessed: VWF:RCo/VWF:Ag, VWF:CB/VWF:Ag, VWF:Ag/ADAMTS13act, and ADAMTS13act/ADAMTS13:Ag. RESULTSCompared to controls, the odds ratio (OR) of an elevated VWF: Ag > 150% was 8.7 (95%CI: 2.7-28.1) in the UC group and 16.2 (95%CI: 4.8-54.0) in the CD group. VWF:CB was lower in UC patients, and active CD was associated with a higher VWF: RCo (+38%). The ORs of VWF:CB/VWF:Ag < 0.7 (a marker of acquired von Willebrand syndrome) in the UC and CD groups were 11.9 (95%CI: 4.4-32.4) and 13.3 (95%CI: 4.6-38.1), respectively. Active UC was associated with lower ADAMTS13:Ag (-23%) and ADAMTS13act (-20%) compared to UC in remission. Patients with active CD had a 15% lower ADAMTS13act than controls. The activity of UC, but not that of CD, was inversely correlated with ADAMTS13:Ag (r = -0.76) and ADAMTS13act (r = -0.81). CONCLUSIONComplex VWF-ADAMTS13-mediated mechanisms disturb haemostasis in IBD. A reduced WVF:CB is a risk factor for bleeding, while a lower ADAMTS13 level combined with an elevated VWF:Ag could predispose one to thrombosis.展开更多
AIM To determine tissue expression(mRNA, protein) of two types of mucins [mucin 1(MUC1) and mucin 2(MUC2)] in patients with colorectal cancer(CRC).METHODS Expression of membrane-bound mucin(MUC1) and secretory mucin(M...AIM To determine tissue expression(mRNA, protein) of two types of mucins [mucin 1(MUC1) and mucin 2(MUC2)] in patients with colorectal cancer(CRC).METHODS Expression of membrane-bound mucin(MUC1) and secretory mucin(MUC2) in CRC(mRNA, protein) were analyzed in tissue material including fragments of tumorsobtained from CRC patients(n = 34), and fragments of normal colorectal tissue from the same patients(control). The analysis was conducted using real-time quantitative polymerase chain reaction(RT-qPCR)(transcripts), immunohistochemistry(IHC)(apomucins), and the modern approach for morphometric analysis of IHC reaction(HSV filter software). Results on tissue expression of both mucins(mRNA, protein) were compared to histological alterations in colorectal cancer samples and correlated with selected clinical data in the patients. The statistical analysis was conducted using Statistica PL v. 12.0 software.RESULTS Significantly higher expression of the MUC1 mRNA in the CRC, compared with the control and the borderline correlation of mRNA expression with MUC1 protein levels in colorectal samples was observed. The expression of apomucins concerned cell membranes(MUC1) and cytoplasm(MUC2) and occurred both in control tissues and in most cancerous samples. There were no significant relationships between MUC1(mRNA, protein) and the clinicopathological data of patients. MUC2 protein expression was significantly lower as compared to the control, while MUC2 mRNA expression was comparable in both groups. The MUC1/MUC2 ratio was significantly higher in CRC tissues than in the control. The higher expression of MUC2 was a feature of mucinous CRC subtypes, and characterized higher histological stage of tumors. Negative correlations have been obtained between MUC2 and the Ki-67 antigen, as well as between MUC2 and p53 protein expressions in CRC.CONCLUSION A combination of tissue overexpression of MUC1, reduced MUC2 expression, and high ratio of MUC1/MUC2 is a factor of poor prognosis in CRC patients. MUC2 tissue expression allows to differentiate mucinous and nonmucinous CRC subtypes.展开更多
Tuberculosis(TB),is an infectious disease caused by Mycobacterium tuberculosis(M.tuberculosis),and presents with high morbidity and mortality.Alveolar macrophages play an important role in TB pathogenesis although the...Tuberculosis(TB),is an infectious disease caused by Mycobacterium tuberculosis(M.tuberculosis),and presents with high morbidity and mortality.Alveolar macrophages play an important role in TB pathogenesis although there is heterogeneity and functional plasticity.This study aimed to show the characteristics of alveolar macrophages from bronchioalveolar lavage fluid(BALF)in active TB patients.Single-cell RNA sequencing(scRNA-seq)was performed on BALF cells from three patients with active TB and additional scRNA-seq data from three healthy adults were established as controls.Transcriptional profiles were analyzed and compared by differential gene expression and functional enrichment analysis.We applied pseudo-temporal trajectory analysis to investigate correlations and heterogeneity within alveolar macrophage subclusters.Alveolar macrophages from active TB patients at the single-cell resolution are described.We found that TB patients have higher cellular percentages in five macrophage subclusters.Alveolar macrophage subclusters with increased percentages were involved in inflammatory signaling pathways as well as the basic macrophage functions.The TB-increased alveolar macrophage subclusters might be derived from M1-like polarization state,before switching to an M2-like polarization state with the development of M.tuberculosis infection.Cell-cell communications of alveolar macrophages also increased and enhanced in active TB patients.Overall,our study demonstrated the characteristics of alveolar macrophages from BALF in active TB patients by using scRNA-seq.展开更多
BACKGROUND Fecal microbial transplantation(FMT)is a promising new method for treating active ulcerative colitis(UC),but knowledge regarding FMT for quiescent UC is scarce.AIM To investigate FMT for the maintenance of ...BACKGROUND Fecal microbial transplantation(FMT)is a promising new method for treating active ulcerative colitis(UC),but knowledge regarding FMT for quiescent UC is scarce.AIM To investigate FMT for the maintenance of remission in UC patients.METHODS Forty-eight UC patients were randomized to receive a single-dose FMT or autologous transplant via colonoscopy.The primary endpoint was set to the maintenance of remission,a fecal calprotectin level below 200μg/g,and a clinical Mayo score below three throughout the 12-mo follow-up.As secondary endpoints,we recorded the patient’s quality of life,fecal calprotectin,blood chemistry,and endoscopic findings at 12 mo.RESULTS The main endpoint was achieved by 13 out of 24(54%)patients in the FMT group and by 10 out of 24(41%)patients in the placebo group(log-rank test,P=0.660).Four months after FMT,the quality-of-life scores decreased in the FMT group compared to the placebo group(P=0.017).In addition,the disease-specific quality of life measure was higher in the placebo group than in the FMT group at the same time point(P=0.003).There were no differences in blood chemistry,fecal calprotectin,or endoscopic findings among the study groups at 12 mo.The adverse events were infrequent,mild,and distributed equally between the groups.CONCLUSION There were no differences in the number of relapses between the study groups at the 12-mo follow-up.Thus,our results do not support the use of a single-dose FMT for the maintenance of remission in UC.展开更多
Kiwifruit is an economically and nutritionally important fruit crop with extremely high contents of vitamin C.However,the previously released versions of kiwifruit genomes all have a mass of unanchored or missing regi...Kiwifruit is an economically and nutritionally important fruit crop with extremely high contents of vitamin C.However,the previously released versions of kiwifruit genomes all have a mass of unanchored or missing regions.Here,we report a highly continuous and completely gap-free reference genome of Actinidia chinensis cv.‘Hongyang’,named Hongyang v4.0,which is the first to achieve two de novo haploid-resolved haplotypes,HY4P and HY4A.HY4P and HY4A have a total length of 606.1 and 599.6 Mb,respectively,with almost the entire telomeres and centromeres assembled in each haplotype.In comparison with Hongyang v3.0,the integrity and contiguity of Hongyang v4.0 is markedly improved by filling all unclosed gaps and correcting some misoriented regions,resulting in∼38.6–39.5 Mb extra sequences,which might affect 4263 and 4244 protein-coding genes in HY4P and HY4A,respectively.Furthermore,our gap-free genome assembly provides the first clue for inspecting the structure and function of centromeres.Globally,centromeric regions are characterized by higher-order repeats that mainly consist of a 153-bp conserved centromere-specific monomer(Ach-CEN153)with different copy numbers among chromosomes.Functional enrichment analysis of the genes located within centromeric regions demonstrates that chromosome centromeres may not only play physical roles for linking a pair of sister chromatids,but also have genetic features for participation in the regulation of cell division.The availability of the telomere-to-telomere and gap-free Hongyang v4.0 reference genome lays a solid foundation not only for illustrating genome structure and functional genomics studies but also for facilitating kiwifruit breeding and improvement.展开更多
基金supported by the National Natural Science Foundation of China(32470676 and 32170236)Central Guidance on Local Science and Technology Development Fund of Hebei Province(246Z2508G)+2 种基金Hebei Natural Science Foundation(C2020209064)Tangshan Science and Technology Program Project(21130217C)Key research project of North China University of Science and Technology(ZD-YG-202313-23).
文摘As a high-value eudicot family,many famous horticultural crop genomes have been deciphered in Oleaceae.However,there are currently no bioinformatics platforms focused on empowering genome research in Oleaceae.Herein,we developed the first comprehensive Oleaceae Genome Research Platform(OGRP,https://oleaceae.cgrpoee.top/).In OGRP,70 genomes of 10 Oleaceae species and 46 eudicots and 366 transcriptomes involving 18 Oleaceae plant tissues can be obtained.We built 34 window-operated bioinformatics tools,collected 38 professional practical software programs,and proposed 3 new pipelines,namely ancient polyploidization identification,ancestral karyotype reconstruction,and gene family evolution.Employing these pipelines to reanalyze the Oleaceae genomes,we clarified the polyploidization,reconstructed the ancestral karyotypes,and explored the effects of paleogenome evolution on genes with specific biological regulatory roles.Significantly,we generated a series of comparative genomic resources focusing on the Oleaceae,comprising 108 genomic synteny dot plots,1952225 collinear gene pairs,multiple genome alignments,and imprints of paleochromosome rearrangements.Moreover,in Oleaceae genomes,researchers can efficiently search for 1785987 functional annotations,22584 orthogroups,29582 important trait genes from 74 gene families,12664 transcription factor-related genes,9178872 transposable elements,and all involved regulatory pathways.In addition,we provided downloads and usage instructions for the tools,a species encyclopedia,ecological resources,relevant literatures,and external database links.In short,ORGP integrates rich data resources and powerful analytical tools with the characteristic of continuous updating,which can efficiently empower genome research and agricultural breeding in Oleaceae and other plants.
基金funded by the Construction Project of the"Flagship"Department of Chinese and Western Medicine Coordination(LiuL/2024-221)the 2024 Medical Service and Security Capacity Improvement Project(National Clinical Key Specialty Construction)(LiuL/Huwei Medical/2024-65)+5 种基金the Shanghai Traditional Chinese Medicine Standardization Project(LiuL/No.2023JSP03)the Shanghai Key Discipline Construction Project of Traditional Chinese Medicine(Clinical)(LiuL/2024-No.3)the Shanghai Technical Standardization Management and Promotion Project(LiuL/No.SHDC22023212)the Shanghai Municipal Health Commission Traditional Chinese Medicine Research Project(2022)(LiuL/No.2022Cx004)Clinical research project of Shanghai Health Commission-Youth Project(LW/No.20214Y0056)Shanghai Institute of Traditional Chinese Medicine for Mental Health(LW/No.SZB2023201).
文摘INTRODUCTION.Depressive disorders are mental illnesses that seriously affect public health.There are approximately 320 million patients with depression worldwide,accounting for 4.4% of the total disease burden.1Depression leads to social and occupational impairment,diminished quality of life and an elevated risk of death by suicide.
基金supported by the National Natural Science Foundation of China(Grant Nos.:32271292,31872723,32200778,and 22377089)the Jiangsu Students Innovation and Entrepre-neurship Training Program,China(Program No.:202210285081Z)+6 种基金the Project of MOE Key Laboratory of Geriatric Diseases and Immunology,China(Project No.:JYN202404)Proj-ect Funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,Natural Science Foundation of Jiangsu Province,China(Project No.:BK20220494)Suzhou Medical and Health Technology Innovation Project,China(Grant No.:SKY2022107)the Clinical Research Center of Neuro-logical Disease in The Second Affiliated Hospital of Soochow University,China(Grant No.:ND2022A04)State Key Laboratory of Drug Research(Grant No.:SKLDR-2023-KF-05)Jiangsu Shuang-chuang Program for Doctor,Young Science Talents Promotion Project of Jiangsu Science and Technology Association(Program No.:TJ-2023-019)Young Science Talents Promotion Project of Suzhou Science and Technology Association,Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases,and startup funding(Grant Nos.:NH21500221,NH21500122,and NH21500123)to Qifei Cong.
文摘Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.
基金supported by the Fundamental Research Funds for the Central Universities of China(2572022DQ03)the National Natural Science Foundation of China(32170517)+2 种基金the Guangdong Provincial Key Laboratory of Genome Read and Write(2017B030301011)the Start-up Scientific Foundation of Northeast Forestry University(60201524043)supported by China National GeneBank(CNGB).
文摘Inbreeding increases genome homozygosity within populations,which can exacerbate inbreeding depression by exposing homozygous deleterious alleles that are responsible for declines in fitness traits.In small populations,genetic purging that occurs under the pressure of natural selection acts as an opposing force,contributing to a reduction of deleterious alleles.Both inbreeding and genetic purging are paramount in the field of conservation genomics.The Amur tiger(Panthera tigris altaica)lives in small populations in the forests of Northeast Asia and is among the most endangered animals on the planet.Using genome-wide assessment and comparison,we reveal substantially higher and more extensive inbreeding in wild Amur tigers(F_(ROH)=0.50)than in captive individuals(F_(ROH)=0.24).However,a relatively reduced number of lossof-function mutations in wild Amur tigers is observed compared to captive individuals,indicating genetic purging of inbreeding load with relatively large-effect alleles.The higher ratio of homozygous mutation load and number of fixed damaging alleles in the wild population indicates a less-efficient genetic purging,with purifying selection also contributing to this process.These findings provide valuable insights for the future conservation of Amur tigers.
基金the financial support from Sichuan Technology Development Program,China(2020YFN0056,2021ZHCG0051,2020YFN0094,2021YFN0048,2020YFN0151)the Natural Science Foundation of Sichuan Province(2022NSFSC0105)Pidu 100 Innovative Talents Program(2022)。
文摘The utilization of Lactobacillus plantarum(LP)in chili sauce production is well-known for its capacity to enhance product quality and sensory attributes.However,there is still limited knowledge regarding the taste-active metabolites in the sauce.To bridge this gap,our study employed metabolomics and webbased computational tools to investigate the dynamic changes of taste-active metabolites during chili sauce fermentation.By leveraging the advantages of the feature-based molecular network(FBMN),we conducted a rapid annotation of metabolites,successfully identifying 205 metabolites,a considerable portion of which were previously unreported.Through the utilization of the Virtual Taste tool,we identified dihydrosphingosine,lactic acid,isoleucine,phytosphingosine,and gluconic acid as potential taste indicators for quality control.Pathway enrichment analysis further supported their primary involvement in key biochemical pathways,including amino acid t RNA biosynthesis,phenylalanine,tyrosine,tryptophan biosynthesis,and sphingolipid metabolism.This investigation provides valuable insights into the underlying mechanisms contributing to the distinctive flavor profile of chili sauce.
文摘Background:In this present study,we have screened major phytoconstituents of Nilavembu Kudineer against critical COVID-19 target proteins that cause severe pneumonia globally.In addition,a human receptor protein that facilitates viral entry into the host cell was also targeted.Methods:Phytoconstituents derived from Nilavembu Kudineer formulation were docked against 12 major proteins,which help viral entry,viral proliferation,and a human receptor facilitate the viral entry into the host cells.The major metabolites of Nilavembu Kudineer were retrieved based on literature from the PubChem database.The docked complex was subjected to MD simulation studies to verify its binding mode and the stability of the interactions.The binding energy analysis was performed to estimate the binding affinity between the compounds and their respective receptors using MM/GBSA.Results:Docking studies have shown that three major plants in the polyherbal formulation,Andrographis paniculata,Mollugo cerviana,and Zingiber officinale,have 14 potential compounds that have better binding affinity against COVID-19 proteins and their host receptor protein.MD studies and binding energy calculations also confirmed that these compounds possess better stability and strong binding energy with these proteins.Conclusion:In silico analyses suggest that phytoconstituents from Nilavembu Kudineer possess promising multi-target antiviral activity against COVID-19.These findings provide a rationale for further experimental studies to validate their therapeutic potential for the treatment of COVID-19.
基金supported by the National Natural Science of China(82322032 and 82221005)the Outstanding Youth Foundation of Jiangsu Province(BK20220050)+4 种基金the National Key Research&Development(R&D)Program of China(2024YFC2706800 and 2021YFC2700600)the Major Project of Changzhou Medical Center(CZKY1040101)the Major Project of Taizhou Clinical Medical College(TZKY20240003)the Major Program of Gusu School(GSKY20210102)the China Postdoctoral Science Foundation(2024M760296).
文摘Autism spectrum disorder(ASD)is a neurodevelopmental disorder where de novo mutations play a significant role.Although coding mutations in ASD have been extensively characterized,the impact of non-coding de novo mutations(ncDNMs)remains less understood.Here,we integrate cortex cell-specific cis-regulatory element annotations,a deep learning-based variant prediction model,and massively parallel reporter assays to systematically evaluate the functional impact of 227,878 ncDNMs from Simons Simplex Collection(SSC)and Autism Speaks MSSNG resource(MSSNG)cohorts.Our analysis identifies 238 ncDNMs with confirmed functional regulatory effects,including 137 down-regulated regulatory mutations(DrMuts)and 101 up-regulated regulatory mutations(UrMuts).Subsequent association analyses reveal that only DrMuts regulating loss-of-function(LoF)intolerant genes rather than other ncDNMs are significantly associated with the risk of ASD(Odds ratio=4.34;P=0.001).A total of 42 potential ASD-risk DrMuts across 41 candidate ASD-susceptibility genes are identified,including 12 recognized and 29 unreported genes.Interestingly,these noncoding disruptive mutations tend to be observed in genes extremely intolerant to LoF mutations.Our study introduces an optimized approach for elucidating the functional roles of ncDNMs,thereby expanding the spectrum of pathogenic variants and deepening our understanding of the complex molecular mechanisms underlying ASD.
基金supported by Tianjian advanced biomedical laboratory key research and development projectHenan Province Natural Science Foundation(Grant Number 242300421283)Major Science and Technology Project of Henan Province(221100310200)。
文摘Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.
基金supported in part by the Hi-Tech Re-search and Development Program of China ("863" Program) (No. 2007AA02Z329)the National Natural Science Foundation of China (Grant No. 20060213024)
文摘Codon usage in chloroplast genome of six seed plants （Arabidopsis thaliana, Populus alba, Zea mays, Triticum aestivum, Pinus koraiensis and Cycas taitungensis） was analyzed to find general patterns of codon usage in chloroplast genomes of seed plants. The results show that chloroplast genomes of the six seed plants had similar codon usage patterns, with a strong bias towards a high representation of NNA and NNT codons. In chloroplast genomes of the six seed plants, the effective number of codons （ENC） for most genes was similar to that of the expected ENC based on the GC content at the third codon position, but several genes with low ENC values were laying below the expected curve. All of these data indicate that codon usage was dominated by a mutational bias in chloroplast genomes of seed plants and that selection appeared to be limited to a subset of genes and to only subtly affect codon usage. Meantime, four, six, eight, nine, ten and 12 codons were defined as the optimal codons in chloroplast genomes of the six seed plants.
基金Supported by the National Natural Science Foundation of China,No.81704009,No.81873253,No.81573892,and No.81770571the Project of Shanghai Municipal Health and Family Planning Commission,No.201640122
文摘BACKGROUND Ulcerative colitis(UC)is considered to be closely associated with alteration of intestinal microorganisms.According to the traditional Chinese medicine(TCM)theory,UC can be divided into two disease syndromes called Pi-Xu-Shi-Yun(PXSY)and Da-Chang-Shi-Re(DCSR).The relationships among gut microbiota,TCM syndromes,and UC pathogenesis have not been well investigated.AIM To investigate the role of gut microbiota in UC and the distinction of microbiota dysbiosis between PXSY and DCSR syndromes.METHODS From May 2015 to February 2016,UC patients presenting to LongHua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study.Fresh stool specimens of UC patients with PXSY or DCSR were collected.The feces of the control group came from the health examination population of Longhua Hospital.The composition of gut bacterial communities in stool samples was determined by the pyrosequencing of 16S ribosomal RNA.The high-throughput sequencing reads were processed with QIIME,and biological functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.RESULTS The composition of gut bacterial communities in 93 stool samples(30 healthy controls,32 patients with PXSY syndrome,and 31 patients with DCSR syndrome)was determined by the pyrosequencing of 16S ribosomal RNA.Beta diversity showed that the composition of the microbiota was different among the three groups.At the family level,Porphyromonadaceae,Rikeneliaceae,and Lachnospiraceae significantly decreased while Enterococcus,Streptococcus,and other potential pathogens significantly increased in UC patients compared to healthy subjects.At the genus level,Parabacteroides,Dorea,and Ruminococcus decreased while Faeca-libacterium showed increased abundance in UC compared to healthy controls.Five differential taxa were identified between PXSY and DCSR syndromes.At the genus level,a significantly increased abundance of Streptococcus was observed in DCSR patients,while Lachnoclostridium increased in PXSY patients.The differential functional pathways of the gut microbiome between the PXSY and DCSR groups mainly included lipid metabolism,immunity,and the metabolism of polypeptides.CONCLUSION Our study suggests that the gut microbiota contributes to the distinction between the two TCM syndromes of UC.
文摘A novel series of 5-（（5-substituted-1H-1,2,4-triazol-3-yl）methyl）-4,5,6,7-tetrahydrothieno[3,2-c]pyr- idines 5（a-i） has been synthesized from thienopyridine hydrazide, substituted aromatic nitriles using 4- dimethylaminopyridine （DMAP） as a catalyst under microwave irradiation and evaluated for their in vitro antifungal activity. Compound 5g is found to be more potent against Candida albicans when compared with miconazole. Docking study of the newly synthesized compounds was performed, and results showed good binding mode in the active site of fungal enzyme P450 cytochrome lanosterol 14α- demethylase. ADMET properties of synthesized compounds were also analyzed and showed good drug like properties. The results of in vitro antifungal activity, docking study and ADMET prediction revealed that the synthesized compounds have potential antifungal activity and can be further optimized and developed as a lead compound.
基金Supported by Asia University grant number 104-ASIA-09 to R.M.H.Ministry of Science and Technology of Taiwan(MOST)under contract numbers MOST 105-2632-E-468-002 and 109-2321-B-468-001 to J.P.T。
文摘OBJECTIVE:To evaluate the immune modulatory response of Puhuang(Pollen Typhae),ethanolic extract of dried pollens(TP-E)and charcoal activated pollens(CTP-E)were used for their phytochemical evaluation and their modulatory response against lipopolysaccharide(LPS)induced inflammatory activity on RAW264.7 macrophage cells.METHODS:Biochemical assays were carried out to quantify the 1,1-Diphenyl-2-picrylhydrazyl Radical Scavenging Activity,Reducing Power,Ferrous ion chelating ability and total polyphenol content and flavonoids.Non-toxic dose of the extract(TP-E and CTP-E)was chosen based on 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Effect of TP-E and CTP-E on lipopolysaccharides-induced inducible nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2)expression was measured by Western blot and quantitative PCR(q RT-PCR).Expression of inflammatory cytokines,such as interleukins(IL-1βand IL-6)and tumor necrosis factorα(TNF-α),was quantified using q RT-PCR.Mitogen-activated protein kinase pathway was analyzed using Western blot.RESULTS:Phytochemical analysis revealed that both TP-E and CTP-E have strong antioxidant activities and high flavonoid and phenolic contents.TP-E and CTP-E effectively inhibit the expression of i NOS and COX-2,thereby inhibiting its downstream proinflammatory regulators,the extracellular signal-related kinase-1/2,that decreases the expression of IL-1β,IL-6 and TNF-α.CONCLUSION:Phytochemical constituents present in Typha angustifolia Linn could be used for treating inflammation-related diseases.
基金financially supported by the National Yang-Ming University Hospital (Nos.RD 2011-009, RD 2012-021 and RD 2013-013), Taiwan
文摘Initial bacterial adhesion on dental implant abutment is related to its surface chemical composition and physical characteristics.Selection of appropriate abutment materials resistant to bacterial adhesion is important for dental implant maintenance.The aim of present study was to evaluate the effect of different properties of abutment materials on initial bacterial adhesion in vitro.Polished zirconia(PZ group), polished titanium(PT group) and ground titanium(GT group) samples were prepared to simulate clinical dental implant abutments.Chemical compositions, morphology, roughness, hydrophilicity and surface free energy of materials were analyzed.Oral commensal bacterium Streptococcus mitis was used to evaluate initial bacterial adhesion via turbidity test and colony-forming unit counting.The results showed that GT group presented the highest roughness, hydrophilicity and surface free energy.After 6-h incubation, GT group showed the significantly highest adhered bacteria counts;while non-significant difference existed between PT and PZ groups.Within the clinically applicable range used in present study, the surface physical characteristics, instead of surface chemical composition, of dental abutment material have the pronounced influence on initial 6-h bacterial adhesion.
基金One of the authors(Sreerama Krupanidhi)is grateful to DST,and DBT,New Delhi,India,for providing funds through FIST and BIF programmes respectively during the time of which the present review is conceived.
文摘Cells of organ systems are endowed with a relatively similar genome while epigenome niches keep varying chronologically and defined explicitly in the respective tissues.The genome of an individual is always influenced by parental,embryonic,tissue-specific,and environmental epigenomes and the same must have been the possible reason for invariable inquiries relating to familial,environmental and life style patterns in the preliminary investigations of diabetic complications.Unprecedented methylation of lysine residues of histones and cytosines of CpG islands of promoter DNA impede the transcription of genes and homocysteine is the metabolic key player of methyl groups.Gck and COX7A1 are the 2 examples in the present review to elucidate the epigenetic influence on the onset of diabetes.miRNAs are additional promising cellular components influencing both at transcriptional and translational levels and promoting either in favour or against(i.e.,feed back) TFs,signaling factors and proteins through their pliotropic effects and thus are reported to regulate cellular physiology.miR-124a and miR-9 are primarily endemic to nervous tissue and they are now being exploited in islets for their function in executing exocytosis of insulin,which of course is one of the fundamental canons of diabetes.miR-375 persuades beta cells for glucose-induced insulin gene expression.The current approach to evaluate the constellation of genes and their products involved in diabetes in huge number of samples through GWA studies may unravel intricacies involved in the management of diabetes and its associated consequences.
文摘To evaluate the levels of von Willebrand factor (VWF) and metalloproteinase with thrombospondin type-1 motif, number 13 (ADAMTS13) in inflammatory bowel disease (IBD) and correlate them with the disease activity. METHODSConsecutive patients with IBD aged 18 years or older were enrolled in the study. Forty-seven patients with ulcerative colitis (UC), 38 with Crohn’s disease (CD), and 50 healthy controls were included. The white blood cell count, haematocrit, platelet count, fibrinogen, partial activated thromboplastin time, C-reactive protein, albumin, VWF antigen level (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), VWF collagen-binding activity (VWF:CB), and ADAMTS13 antigen level (ADAMTS13:Ag) and activity (ADAMTS13act) were measured. The following ratios were assessed: VWF:RCo/VWF:Ag, VWF:CB/VWF:Ag, VWF:Ag/ADAMTS13act, and ADAMTS13act/ADAMTS13:Ag. RESULTSCompared to controls, the odds ratio (OR) of an elevated VWF: Ag > 150% was 8.7 (95%CI: 2.7-28.1) in the UC group and 16.2 (95%CI: 4.8-54.0) in the CD group. VWF:CB was lower in UC patients, and active CD was associated with a higher VWF: RCo (+38%). The ORs of VWF:CB/VWF:Ag < 0.7 (a marker of acquired von Willebrand syndrome) in the UC and CD groups were 11.9 (95%CI: 4.4-32.4) and 13.3 (95%CI: 4.6-38.1), respectively. Active UC was associated with lower ADAMTS13:Ag (-23%) and ADAMTS13act (-20%) compared to UC in remission. Patients with active CD had a 15% lower ADAMTS13act than controls. The activity of UC, but not that of CD, was inversely correlated with ADAMTS13:Ag (r = -0.76) and ADAMTS13act (r = -0.81). CONCLUSIONComplex VWF-ADAMTS13-mediated mechanisms disturb haemostasis in IBD. A reduced WVF:CB is a risk factor for bleeding, while a lower ADAMTS13 level combined with an elevated VWF:Ag could predispose one to thrombosis.
基金Supported by National Science Center in Poland,No.2015/17/B/NZ7/03043
文摘AIM To determine tissue expression(mRNA, protein) of two types of mucins [mucin 1(MUC1) and mucin 2(MUC2)] in patients with colorectal cancer(CRC).METHODS Expression of membrane-bound mucin(MUC1) and secretory mucin(MUC2) in CRC(mRNA, protein) were analyzed in tissue material including fragments of tumorsobtained from CRC patients(n = 34), and fragments of normal colorectal tissue from the same patients(control). The analysis was conducted using real-time quantitative polymerase chain reaction(RT-qPCR)(transcripts), immunohistochemistry(IHC)(apomucins), and the modern approach for morphometric analysis of IHC reaction(HSV filter software). Results on tissue expression of both mucins(mRNA, protein) were compared to histological alterations in colorectal cancer samples and correlated with selected clinical data in the patients. The statistical analysis was conducted using Statistica PL v. 12.0 software.RESULTS Significantly higher expression of the MUC1 mRNA in the CRC, compared with the control and the borderline correlation of mRNA expression with MUC1 protein levels in colorectal samples was observed. The expression of apomucins concerned cell membranes(MUC1) and cytoplasm(MUC2) and occurred both in control tissues and in most cancerous samples. There were no significant relationships between MUC1(mRNA, protein) and the clinicopathological data of patients. MUC2 protein expression was significantly lower as compared to the control, while MUC2 mRNA expression was comparable in both groups. The MUC1/MUC2 ratio was significantly higher in CRC tissues than in the control. The higher expression of MUC2 was a feature of mucinous CRC subtypes, and characterized higher histological stage of tumors. Negative correlations have been obtained between MUC2 and the Ki-67 antigen, as well as between MUC2 and p53 protein expressions in CRC.CONCLUSION A combination of tissue overexpression of MUC1, reduced MUC2 expression, and high ratio of MUC1/MUC2 is a factor of poor prognosis in CRC patients. MUC2 tissue expression allows to differentiate mucinous and nonmucinous CRC subtypes.
基金funded by grants from the National Natural Science Foundation of China (Grant No. 81800090)the Key Project of National Science & Technology for Infectious Diseases of China (Grant No. 2018ZX10722301-002)
文摘Tuberculosis(TB),is an infectious disease caused by Mycobacterium tuberculosis(M.tuberculosis),and presents with high morbidity and mortality.Alveolar macrophages play an important role in TB pathogenesis although there is heterogeneity and functional plasticity.This study aimed to show the characteristics of alveolar macrophages from bronchioalveolar lavage fluid(BALF)in active TB patients.Single-cell RNA sequencing(scRNA-seq)was performed on BALF cells from three patients with active TB and additional scRNA-seq data from three healthy adults were established as controls.Transcriptional profiles were analyzed and compared by differential gene expression and functional enrichment analysis.We applied pseudo-temporal trajectory analysis to investigate correlations and heterogeneity within alveolar macrophage subclusters.Alveolar macrophages from active TB patients at the single-cell resolution are described.We found that TB patients have higher cellular percentages in five macrophage subclusters.Alveolar macrophage subclusters with increased percentages were involved in inflammatory signaling pathways as well as the basic macrophage functions.The TB-increased alveolar macrophage subclusters might be derived from M1-like polarization state,before switching to an M2-like polarization state with the development of M.tuberculosis infection.Cell-cell communications of alveolar macrophages also increased and enhanced in active TB patients.Overall,our study demonstrated the characteristics of alveolar macrophages from BALF in active TB patients by using scRNA-seq.
基金Academy of Finland(Reetta Satokari),No.323156Sigrid Juselius Foundation+2 种基金University of Helsinki(A Three-year Grant)The Competitive State Research Financing(Perttu Lahtinen),No.200230042The Ella and Georg Ehrnrooth Foundation(Perttu Arkkila)
文摘BACKGROUND Fecal microbial transplantation(FMT)is a promising new method for treating active ulcerative colitis(UC),but knowledge regarding FMT for quiescent UC is scarce.AIM To investigate FMT for the maintenance of remission in UC patients.METHODS Forty-eight UC patients were randomized to receive a single-dose FMT or autologous transplant via colonoscopy.The primary endpoint was set to the maintenance of remission,a fecal calprotectin level below 200μg/g,and a clinical Mayo score below three throughout the 12-mo follow-up.As secondary endpoints,we recorded the patient’s quality of life,fecal calprotectin,blood chemistry,and endoscopic findings at 12 mo.RESULTS The main endpoint was achieved by 13 out of 24(54%)patients in the FMT group and by 10 out of 24(41%)patients in the placebo group(log-rank test,P=0.660).Four months after FMT,the quality-of-life scores decreased in the FMT group compared to the placebo group(P=0.017).In addition,the disease-specific quality of life measure was higher in the placebo group than in the FMT group at the same time point(P=0.003).There were no differences in blood chemistry,fecal calprotectin,or endoscopic findings among the study groups at 12 mo.The adverse events were infrequent,mild,and distributed equally between the groups.CONCLUSION There were no differences in the number of relapses between the study groups at the 12-mo follow-up.Thus,our results do not support the use of a single-dose FMT for the maintenance of remission in UC.
基金supported by funds from the National Natural Science Foundation of China(31972474,90717110)Hubei Natural Science Fund for Distinguished Young Scholars(2020CFA062).
文摘Kiwifruit is an economically and nutritionally important fruit crop with extremely high contents of vitamin C.However,the previously released versions of kiwifruit genomes all have a mass of unanchored or missing regions.Here,we report a highly continuous and completely gap-free reference genome of Actinidia chinensis cv.‘Hongyang’,named Hongyang v4.0,which is the first to achieve two de novo haploid-resolved haplotypes,HY4P and HY4A.HY4P and HY4A have a total length of 606.1 and 599.6 Mb,respectively,with almost the entire telomeres and centromeres assembled in each haplotype.In comparison with Hongyang v3.0,the integrity and contiguity of Hongyang v4.0 is markedly improved by filling all unclosed gaps and correcting some misoriented regions,resulting in∼38.6–39.5 Mb extra sequences,which might affect 4263 and 4244 protein-coding genes in HY4P and HY4A,respectively.Furthermore,our gap-free genome assembly provides the first clue for inspecting the structure and function of centromeres.Globally,centromeric regions are characterized by higher-order repeats that mainly consist of a 153-bp conserved centromere-specific monomer(Ach-CEN153)with different copy numbers among chromosomes.Functional enrichment analysis of the genes located within centromeric regions demonstrates that chromosome centromeres may not only play physical roles for linking a pair of sister chromatids,but also have genetic features for participation in the regulation of cell division.The availability of the telomere-to-telomere and gap-free Hongyang v4.0 reference genome lays a solid foundation not only for illustrating genome structure and functional genomics studies but also for facilitating kiwifruit breeding and improvement.
