The fish brain is crucial for adjusting to environmental changes.Metabolic changes play a vital role in the adaptation to salinity change in aquatic animals.However,few studies have evaluated the responses of the fish...The fish brain is crucial for adjusting to environmental changes.Metabolic changes play a vital role in the adaptation to salinity change in aquatic animals.However,few studies have evaluated the responses of the fish brain to salinity changes.To evaluate the response to various salinities,spotted scat(Scatophagus argus)was cultured in water with salinity levels of 5(low salinity:LS),25(control group:Ctrl),and 35(high salinity group:HS)for 22 days.The brain transcriptome was analyzed.In total,1698 differentially expressed genes(DEGs)were identified between the HS and Ctrl groups,and 841 DEGs were identified between the LS and Ctrl groups.KEGG analysis showed that the DEGs in the HS vs.Ctrl comparison were involved in steroid biosynthesis,terpenoid backbone biosynthesis,fatty acid biosynthesis,ascorbate and aldarate metabolism,other types of O-glycan biosynthesis,and fatty acid metabolism.Glyoxylate and dicarboxylate metabolism,one carbon pool by folate,steroid biosynthesis,and cysteine and methionine metabolism were significantly enriched in the LS vs.Ctrl comparison.Additionally,the genes related to metabolism(acc,fas,hmgcr,hmgcs1,mvd,soat1,nsdhl,sqle,cel,fdft1,dnmt3a and mtr)were significantly up-regulated in the HS vs.Ctrl comparison.The genes related to metabolism(lipa,sqle,acc,fas,bhmt,mpst,dnmt3a,mtr,hao2,LOC111225351 and hmgcs1)were significantly up-regulated,while hmgcr and soat1 were significantly down-regulated in the LS vs.Ctrl compparison.These results suggest that salinity stress affects signaling pathways and genes’expressions involved in metabolic processes in the brain,and the differences in metabolism play an important role in adaptation to hyperhaline or hypohaline environments in spotted scat.This research provides a comprehensive overview of transcriptional changes in the brain under hyperhaline or hypohaline conditions,which is helpful to understand the mechanisms underlying salinity adaptation in euryhaline fishes.展开更多
BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provid...BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.AIM To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing cholangitis.METHODS A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding.Upon sacrifice,the liver and the serum were collected from each mouse.The hepatobiliary injuries,hepatic inflammation and fibrosis were evaluated.The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot.RESULTS rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk.The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary fibrosis.Furthermore,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic inflammation.CONCLUSION Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.展开更多
Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosi...Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.展开更多
Human normal flora is a source of probiotics.The safety characteristics of a specific isolate determine its application in foods or drugs.The food-borne-pathogen antagonist strain Lactobacillus gasseri HMV18 is one of...Human normal flora is a source of probiotics.The safety characteristics of a specific isolate determine its application in foods or drugs.The food-borne-pathogen antagonist strain Lactobacillus gasseri HMV18 is one of the isolates from normal human flora.In this work,we assessed the in vitro pH tolerance,bile tolerance,biogenic amine production,mucin utilization,and safety of in vivo administration to mice to evaluate general health,organ-body weight index,organ histopathological change,whether L.gasseri HMV18 can colonize in the gut or modulate the gut microbiota after oral administration.The results suggest that L.gasseri HMV18 can tolerate pH 3 for 2 h,3%bile for 3 h,biogenic amine negative,mucin usage negative,does not encode verified toxins,and cause no visible change in mice's organs.L.gasseri HMV18 might not colonize in mice's gut,but can significantly affect the structure of gut microbiota.A bibliographical survey suggested that there were as few as 8 opportunistic infection cases from 1984 to 2022 and that the possibility for L.gasseri to cause infection is relatively low.Therefore,this work provides a basis for the foods or drugs application of L.gasseri HMV18 and gives a map of experiments for the safety assessment of probiotics.展开更多
[Objectives]To study the effect and mechanism of baicalin on the activation of NLRP3 inflammasome in human fibroblast like synoviocytes of rheumatoid arthritis(HFLS-RA).[Methods]To confirm that baicalin alleviated the...[Objectives]To study the effect and mechanism of baicalin on the activation of NLRP3 inflammasome in human fibroblast like synoviocytes of rheumatoid arthritis(HFLS-RA).[Methods]To confirm that baicalin alleviated the activation of NLRP3 inflammasome in HFLS-RA,the expression of NLRP3 before and after baicalin treatment was observed by immunofluorescence.Western blot was used to detect the protein expression of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1 after baicalin treatment for 48 h,and the contents of IL-1 and IL-18 in the supernatents were detected by ELISA.In order to explore the mechanism of baicalin alleviating the activation of NLRP3 inflammasome,the corresponding relationship between let-7i-3p and PIK3CA was verified by double luciferin and Westen blot analysis.The expression of let-7i-3p and PI3K before and after baicalin intervention was detected by RT-qPCR.let-7i-3p interference was used to verify whether baicalin mitigated the activation of enhanced NLRP3 inflammasome.[Results]Baicalin(50 and 100 mg/L)significantly reduced the activation of NLRP3 inflammasome,inhibited the protein expressions of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1,and the secretion of IL-1 and IL-18.let-7i-3p and PIK3CA had a targeted correspondence,and baicalin up-regulated the expression of let-7i-3p and down-regulated the expression of PIK3CA.Baicalin attenuated the activation of NLRP3 inflammasome enhanced by let-7i-3p interference.[Conclusions]Baicalin can up-regulate let-7i-3p expression,inhibit PI3K/Akt/NF-κB signal transduction,and thus reduce the activation of NLRP3 inflammasome in HFLS-RA.展开更多
Studies have shown that non-alcoholic fatty liver disease(NAFLD)may be associated with sleep disorders.In order to explore the explicit relationship between the two,we systematically reviewed the effects of sleep diso...Studies have shown that non-alcoholic fatty liver disease(NAFLD)may be associated with sleep disorders.In order to explore the explicit relationship between the two,we systematically reviewed the effects of sleep disorders,especially obstructive sleep apnea(OSA),on the incidence of NAFLD,and analyzed the possible mechanisms after adjusting for confounding factors.NAFLD is independently associated with sleep disorders.Different sleep disorders may be the cause of the onset and aggravation of NAFLD.An excessive or insufficient sleep duration,poor sleep quality,insomnia,sleep-wake disorders,and OSA may increase the incidence of NAFLD.Despite that some research suggests a unidirectional causal link between the two,specifically,the onset of NAFLD is identified as a result of changes in sleep characteristics,and the reverse relationship does not hold true.Nevertheless,there is still a lack of specific research elucidating the reasons behind the higher risk of developing sleep disorders in individuals with NAFLD.Further research is needed to establish a clear relationship between NAFLD and sleep disorders.This will lay the groundwork for earlier identification of potential patients,which is crucial for earlier monitoring,diagnosis,effective prevention,and treatment of NAFLD.展开更多
To search for a new eco-friendly therapy for infectious disease caused by Escherichia coli,Staphylococcus aureus or Klebsiella oxytoca,we collected the vaginal swabs from healthy women,screened for Lactobacillus and f...To search for a new eco-friendly therapy for infectious disease caused by Escherichia coli,Staphylococcus aureus or Klebsiella oxytoca,we collected the vaginal swabs from healthy women,screened for Lactobacillus and found a strain repressing the growth of pathogenic bacteria.The new isolate was identified as L.gasseri by the colony morphology,Gram staining,biochemical reactions and confirmed by the 16 S rDNA sequencing.The HMV18 strain inhibited the growth of food-borne pathogens such as E.coli,S.aureus and K.oxytoca.The HMV18 strain was sensitive to penicillin,ampicillin,erythromycin,tetracycline and chloramphenicol.The HMV18 strain producedα-hemolysis.Pathological histology of the mice ileum showed that the mucosa,villi,lamina propria and crypt depth remained intact and there was no inflammation or hyperemia in the L.gasseri HMV18 gavaged group.L.gasseri HMV18 could not up-regulate inflammatory cytokines level of plasma.All the results suggested L.gasseri HMV18 is a candidate probiotic to be an additive for food preservation or drug to prevent food-borne diseases.展开更多
Through a modified agar well diffusion assay,antagonism of a novel chitinase-producing strain C3 against the phy- topathogenic fungi including Phoma wasabiae Yokogi,Cochlibolus Heterostrophus,Exserohilum Turcicum,Curu...Through a modified agar well diffusion assay,antagonism of a novel chitinase-producing strain C3 against the phy- topathogenic fungi including Phoma wasabiae Yokogi,Cochlibolus Heterostrophus,Exserohilum Turcicum,Curuvularia Lunata (Walk)Boed,Thantephorus cucumris,Fusarium graminearum was tested.The data showed that the crude extracts of strain C3 had stable antifungal activity in the range of pH 5.0 to pH 8.0.The active components were heat labile and sensitive to proteinase K.A series of experiments supported that the compound responsible for inhibitory aetivity appeared to be chitinase.The 16s rDNA analysis indicated that C3 was subject to genus Burkholderia.Phenotypic characterization of C3 was also consisted with the result of molecular identification.展开更多
Pine wood nematode(B ursaphelenchus xylophilus),one of the most destructive invasive species,has caused extremely serious economic,ecological and social losses in many countries throughout the world.Since the high rep...Pine wood nematode(B ursaphelenchus xylophilus),one of the most destructive invasive species,has caused extremely serious economic,ecological and social losses in many countries throughout the world.Since the high reproductive rate of B.xylophilus PWN is the main cause of rapid death of its pine hosts(Pinus spp.),understanding the reproductive and population biology and the ecology of this nmatode are of great importance.This study mainly focused on analyzing the mating process and population structure under different combinations of sex ratios for mating.Reproductive efficiency of B.xylophilus peaked when the sex ratio(female to male)was 3.4:1.Phases of the mating process for the different sex-ratio combinations indicated that B.xylophilus had evolved alternative reproductive strategies to cope with complex copulating conditions to obtain a suitable population structure for further propagation.This research provides fundamental information on the mechanism that is responsible for the rapid population growth of B.xylophilus.展开更多
The frequent emergence of coronavirus(CoV)epidemics has seriously threatened public health and stock farming.The major hosts for CoVs are birds and mammals.Although most CoVs inhabit their specific natural hosts,some ...The frequent emergence of coronavirus(CoV)epidemics has seriously threatened public health and stock farming.The major hosts for CoVs are birds and mammals.Although most CoVs inhabit their specific natural hosts,some may occasionally cross the host barrier to infect livestock and even people,causing a variety of diseases.Since the beginning of the new century,increasing attention has been given to research on CoVs due to the emergence of highly pathogenic and genetically diverse CoVs that have caused several epidemics,including the recent COVID-19 pandemic.CoVs belong to the Coronaviridae family of the Nidovirales order.Recently,advanced techniques for viral detection and viral genome analyses have enabled characterization of many new nidoviruses than ever and have greatly expanded the Nidovirales order with new classification and nomenclature.Here,we first provide an overview of the latest research progress in the classification of the Nidovirales order and then introduce the host range,genetic variation,genomic pattern and pathogenic features of epidemic CoVs and other epidemic viruses.This information will promote understanding of the phylogenetic relationship and infectious transmission of various pathogenic nidoviruses,including epidemic CoVs,which will benefit virological research and viral disease control.展开更多
The screening practices for hepatitis D virus(HDV)are diverse and nonstandardized worldwide,and the exact prevalence of HDV is uncertain.AIM To estimate HDV prevalence and investigate viral marker quantity trends in p...The screening practices for hepatitis D virus(HDV)are diverse and nonstandardized worldwide,and the exact prevalence of HDV is uncertain.AIM To estimate HDV prevalence and investigate viral marker quantity trends in patients with hepatitis D.METHODS We collected 5594 serum samples from patients with hepatitis B in Jilin Province,China(3293 males and 2301 females,age range of 2 to 89 years).We then conducted tests for hepatitis B surface antigen(HBsAg),hepatitis B Virus(HBV)DNA,anti-hepatitis D antigen(HDAg),and HDV RNA.RESULTS We found that the prevalence of anti-HDAg and HDV RNA among hepatitis B patient were 3.6%(3.2-4.2%)and 1.2%(0.9-1.5%),respectively,87.69%of hepatitis D patients were 51-70 years old.HDV infection screening positive rate of patients with HBV DNA levels below 2000 IU/mL(2.0%)was higher than those above 2000 IU/mL(0.2%).Among anti-HDAg positive patients,the HDV RNA positive rate was positively correlated with the HBsAg level and anti-HDAg level.There was a weak correlation between HBsAg and anti-HDAg levels among hepatitis D patients.CONCLUSION Our study highlights the importance of considering multiple factors when assessing the severity of HDV infection,comprehensive evaluation of patients’clinical and laboratory parameters is necessary for proper diagnosis and treatment.展开更多
The rapid spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) in recent years not only caused a global pandemic but resulted in enormous social,economic,and health burdens worldwide.Despite considera...The rapid spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) in recent years not only caused a global pandemic but resulted in enormous social,economic,and health burdens worldwide.Despite considerable efforts to combat coronavirus disease 2019(COVID-19),various SARS-CoV-2 variants have emerged,and their underlying mechanisms of pathogenicity remain largely unknown.Furthermore,effective therapeutic drugs are still under development.Thus,an ideal animal model is crucial for studying the pathogenesis of COVID-19 and for the preclinical evaluation of vaccines and antivirals against SARS-CoV-2 and variant infections.Currently,several animal models,including mice,hamsters,ferrets,and nonhuman primates(NHPs),have been established to study COVID-19.Among them,ferrets are naturally susceptible to SARS-CoV-2 infection and are considered suitable for COVID-19 study.Here,we summarize recent developments and application of SARS-CoV-2 ferret models in studies on pathogenesis,therapeutic agents,and vaccines,and provide a perspective on the role of these models in preventing COVID-19 spread.展开更多
Background:Amarogentin(AMA)is a secoiridoid glycoside extracted from Swertia and Gentiana roots and exhibits many biological effects such as antioxidative,antiinflammatory,and antitumor activities.Atopic dermatitis(AD...Background:Amarogentin(AMA)is a secoiridoid glycoside extracted from Swertia and Gentiana roots and exhibits many biological effects such as antioxidative,antiinflammatory,and antitumor activities.Atopic dermatitis(AD)is a chronic inflammatory skin disease caused by disorders in the regulation of multiple inflammatory cytokines.No effective cure has been found for AD now.Methods:We constructed the HaCat and splenocyte model and tested the inhibitory effect of AMA on IL-4,IL-6,and IL-13 secretions using enzyme-linked immunosorbent assay(ELISA).The AD mouse model was constructed and treated with AMA,the severity of skin lesions was observed,epidermal tissue was collected,and epidermal thickness and mast cell infiltration were observed using hematoxylin and eosin and toluidine blue staining,respectively.The expression of kallikrein-related peptidase 7(KLK7)and filaggrin(FLG)was detected using immunostaining and Western blot analysis.The mRNA expression of KLK7 and FLG was detected using quantitative polymerase chain reaction(qPCR).Blood immunoglobulin E(IgE)secretion was detected.Results:AMA inhibited IL-6 secreted by tumor necrosis factor(TNF)-α-induced HaCaT cells and reduced IL-4 and IL-13 secreted by phytohemagglutinin(PHA)-induced primary cells in the mice spleen.It was found that the treatment of AMA with 2,4-din itrochlorobenzene-induced AD-like mice could promote the recovery of dermatitis,reduce the score of dermatitis severity and the scratching frequency,treat the skin lesions,reduce the epidermal thickness,decrease the infiltration of mast cells,reduce the IgE level in serum,decrease the expression levels of AD-related cytokines,increase protein and mRNA expression of FLG,and reduce the protein and mRNA expression of KLK7 in the skin tissues of AD-like mice.Conclusion:In conclusion,AMA inhibits inflammatory response at the cellular level,and AMA reduces the validation response of specific dermatitis mice,relieves pruritus,and repairs the damaged skin barrier.展开更多
Arenaviruses belong to the family of RNA viruses that can infect humans in various ways and cause different degrees of mortality.Rodents is the mainly hosts.Human pathogenic arenaviruses include lymphocytic choroid me...Arenaviruses belong to the family of RNA viruses that can infect humans in various ways and cause different degrees of mortality.Rodents is the mainly hosts.Human pathogenic arenaviruses include lymphocytic choroid meningitis,Lassa virus group and Takarib virus group,which cause human lymphocytic choriomeningitis and human hemorrhagic diseases.Rodents account for about 43%of mammalian species.At present,more than 30 highly pathogenic viruses have been found in rodents,including arenaviruses.The arenaviridae that infects rodents are mainly mammalian arenaviruses.This article reviews the etiology,clinicopathology,epidemiology,prevention and control of arenavirus,and provides references for the research and prevention of arenavirus.展开更多
BACKGROUND Wild rats have the potential to hold zoonotic infectious agents that can spread to humans and cause disease.AIM To better understand the composition of gut bacterial communities in rats is essential for pre...BACKGROUND Wild rats have the potential to hold zoonotic infectious agents that can spread to humans and cause disease.AIM To better understand the composition of gut bacterial communities in rats is essential for preventing and treating such diseases.As a tropical island located in the south of China,Hainan province has abundant rat species.Here,we examined the gut bacterial composition in wild adult rats from Hainan province.METHODS Fresh fecal samples were collected from 162 wild adult rats,including three species(Rattus norvegicus,Leopoldamys edwardsi,and Rattus losea),from nine regions of Hainan province between 2017-2018.RESULTS We analyzed the composition of gut microbiota using the 16S rRNA gene amplicon sequencing.We identified 4903 bacterial operational taxonomic units(30 phyla,175 families,and 498 genera),which vary between samples of different rat species in various habitats at various times of the year.In general,Firmicutes were the most abundant phyla,followed by Bacteroidetes(15.55%),Proteobacteria(6.13%),and Actinobacteria(4.02%).The genus Lactobacillus(20.08%),unidentified_Clostridiales(5.16%),Romboutsia(4.33%),unidentified_Ruminococcaceae(3.83%),Bacteroides(3.66%),Helicobacter(2.40%)and Streptococcus(2.37%)were dominant.CONCLUSION The composition and abundance of the gut microbial communities varied between rat species and locations.This work provides fundamental information to identify microbial communities useful for disease control in Hainan province.展开更多
Host-directed therapy(HDT)is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus(S.aureus)infection.Functioning as the indispensable specific cellular receptor for a-toxin(Hla),a-disinteg...Host-directed therapy(HDT)is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus(S.aureus)infection.Functioning as the indispensable specific cellular receptor for a-toxin(Hla),a-disintegrin and metalloproteinase 10(ADAM10)is exploited to accelerate S.aureus infection through diverse mechanisms.The extraordinary contribution of ADAM10 to S.aureus pathogenesis renders it an attractive HDT target for combating S.aureus infection.Our study is the first to demonstrate the indispensable role of ADAM10 in S.aureus-induced necroptosis,and it enhances our knowledge of the role of ADAM10 in S.aureus infection.Using a fluorogenic substrate assay,we further identified kaempferol as a potent ADAM10 inhibitor that effectively protected mice from S.aureus infection by suppressing Hla-mediated barrier disruption and necroptosis.Collectively,our work presents a novel hostdirected therapeutic strategy for using the promising candidate kaempferol to treat S.aureus infection and other diseases relevant to the disordered upregulation of ADAM10.展开更多
BACKGROUND The coronavirus disease 2019(COVID-19)epidemic disrupted education systems by forcing systems to shift to emergency online leaning.Online learning satisfaction affects academic achievement.Many factors affe...BACKGROUND The coronavirus disease 2019(COVID-19)epidemic disrupted education systems by forcing systems to shift to emergency online leaning.Online learning satisfaction affects academic achievement.Many factors affect online learning satisfaction.However there is little study focused on personal characteristics,mental status,and coping style when college students participated in emergency online courses.regression analyses were performed to identify factors that affected online learning satisfaction.RESULTS Descriptive findings indicated that 62.9%(994/1580)of students were satisfied with online learning.Factors that had significant positive effects on online learning satisfaction were online learning at scheduled times,strong exercise intensity,good health,regular schedule,focusing on the epidemic less than one hour a day,and maintaining emotional stability.Positive coping styles were protective factors of online learning satisfaction.Risk factors for poor satisfaction were depression,neurasthenia,and negative coping style.CONCLUSION College students with different personal characteristics,mental status,and coping style exhibited different degrees of online learning satisfaction.Our findings provide reference for educators,psychologists,and school adminis-trators to conduct health education intervention of college students during emergency online learning.展开更多
We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More impor...We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.展开更多
基金funded by the National Natural Science Foundation of China(Nos.31972775 and 32172971).
文摘The fish brain is crucial for adjusting to environmental changes.Metabolic changes play a vital role in the adaptation to salinity change in aquatic animals.However,few studies have evaluated the responses of the fish brain to salinity changes.To evaluate the response to various salinities,spotted scat(Scatophagus argus)was cultured in water with salinity levels of 5(low salinity:LS),25(control group:Ctrl),and 35(high salinity group:HS)for 22 days.The brain transcriptome was analyzed.In total,1698 differentially expressed genes(DEGs)were identified between the HS and Ctrl groups,and 841 DEGs were identified between the LS and Ctrl groups.KEGG analysis showed that the DEGs in the HS vs.Ctrl comparison were involved in steroid biosynthesis,terpenoid backbone biosynthesis,fatty acid biosynthesis,ascorbate and aldarate metabolism,other types of O-glycan biosynthesis,and fatty acid metabolism.Glyoxylate and dicarboxylate metabolism,one carbon pool by folate,steroid biosynthesis,and cysteine and methionine metabolism were significantly enriched in the LS vs.Ctrl comparison.Additionally,the genes related to metabolism(acc,fas,hmgcr,hmgcs1,mvd,soat1,nsdhl,sqle,cel,fdft1,dnmt3a and mtr)were significantly up-regulated in the HS vs.Ctrl comparison.The genes related to metabolism(lipa,sqle,acc,fas,bhmt,mpst,dnmt3a,mtr,hao2,LOC111225351 and hmgcs1)were significantly up-regulated,while hmgcr and soat1 were significantly down-regulated in the LS vs.Ctrl compparison.These results suggest that salinity stress affects signaling pathways and genes’expressions involved in metabolic processes in the brain,and the differences in metabolism play an important role in adaptation to hyperhaline or hypohaline environments in spotted scat.This research provides a comprehensive overview of transcriptional changes in the brain under hyperhaline or hypohaline conditions,which is helpful to understand the mechanisms underlying salinity adaptation in euryhaline fishes.
基金Supported by the National Natural Science Foundation of China,No.82172297Natural Science Foundation of Jiangsu Province of China,No.BK20211346 and No.BK20201011+1 种基金Natural Science Foundation of Jiangsu Higher Education Institutions of China,No.22KJA310007Xuzhou Science and Technology Project,No.KC22055.
文摘BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.AIM To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing cholangitis.METHODS A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding.Upon sacrifice,the liver and the serum were collected from each mouse.The hepatobiliary injuries,hepatic inflammation and fibrosis were evaluated.The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot.RESULTS rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk.The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary fibrosis.Furthermore,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic inflammation.CONCLUSION Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.
基金supported by Jiangsu Provincial Medical Key Discipline,No.ZDXK202217(to CFL)Jiangsu Planned Projects for Postdoctoral Research Funds,No.1601056C(to SL).
文摘Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.
基金financially supported by postdoctoral funding of Hebei Medical UniversityHebei Province Postdoctoral Research Project Funding(B2022003035)+5 种基金Natural Science Foundation of Hebei Province(H2020206579)CAMS Innovation Found for Medical Sciences(2019-I2M-5-055)2023 Scientific Research Projects of Colleges and Universities in Hebei Province(QN2023131)S&T Program of Hebei(18277743D)Undergraduate Innovation Experiment Project from Hebei Medical University(USIP2019008)Spring rain project of Hebei Medical University(CYCZ201906)。
文摘Human normal flora is a source of probiotics.The safety characteristics of a specific isolate determine its application in foods or drugs.The food-borne-pathogen antagonist strain Lactobacillus gasseri HMV18 is one of the isolates from normal human flora.In this work,we assessed the in vitro pH tolerance,bile tolerance,biogenic amine production,mucin utilization,and safety of in vivo administration to mice to evaluate general health,organ-body weight index,organ histopathological change,whether L.gasseri HMV18 can colonize in the gut or modulate the gut microbiota after oral administration.The results suggest that L.gasseri HMV18 can tolerate pH 3 for 2 h,3%bile for 3 h,biogenic amine negative,mucin usage negative,does not encode verified toxins,and cause no visible change in mice's organs.L.gasseri HMV18 might not colonize in mice's gut,but can significantly affect the structure of gut microbiota.A bibliographical survey suggested that there were as few as 8 opportunistic infection cases from 1984 to 2022 and that the possibility for L.gasseri to cause infection is relatively low.Therefore,this work provides a basis for the foods or drugs application of L.gasseri HMV18 and gives a map of experiments for the safety assessment of probiotics.
基金Supported by the National Natural Science Foundation of China(82360802):the Natural Science Foundation of Ningxia Province,China(2022AAC 03152).
文摘[Objectives]To study the effect and mechanism of baicalin on the activation of NLRP3 inflammasome in human fibroblast like synoviocytes of rheumatoid arthritis(HFLS-RA).[Methods]To confirm that baicalin alleviated the activation of NLRP3 inflammasome in HFLS-RA,the expression of NLRP3 before and after baicalin treatment was observed by immunofluorescence.Western blot was used to detect the protein expression of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1 after baicalin treatment for 48 h,and the contents of IL-1 and IL-18 in the supernatents were detected by ELISA.In order to explore the mechanism of baicalin alleviating the activation of NLRP3 inflammasome,the corresponding relationship between let-7i-3p and PIK3CA was verified by double luciferin and Westen blot analysis.The expression of let-7i-3p and PI3K before and after baicalin intervention was detected by RT-qPCR.let-7i-3p interference was used to verify whether baicalin mitigated the activation of enhanced NLRP3 inflammasome.[Results]Baicalin(50 and 100 mg/L)significantly reduced the activation of NLRP3 inflammasome,inhibited the protein expressions of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1,and the secretion of IL-1 and IL-18.let-7i-3p and PIK3CA had a targeted correspondence,and baicalin up-regulated the expression of let-7i-3p and down-regulated the expression of PIK3CA.Baicalin attenuated the activation of NLRP3 inflammasome enhanced by let-7i-3p interference.[Conclusions]Baicalin can up-regulate let-7i-3p expression,inhibit PI3K/Akt/NF-κB signal transduction,and thus reduce the activation of NLRP3 inflammasome in HFLS-RA.
基金Supported by National Natural Science Foundation of China,No.82360880,and 82060661Jiangxi Provincial Natural Science Foundation of China,No.20232ACB206057+3 种基金Key project of Jiangxi Provincial Department of Education,No.GJJ218104Teaching reform research project of Jiangxi Province of China,No.JXJG-22-130-1National Natural Science Foundation of China,No.81660151Jiangxi Provincial Natural Science Foundation of China,No.20212BAB206092.
文摘Studies have shown that non-alcoholic fatty liver disease(NAFLD)may be associated with sleep disorders.In order to explore the explicit relationship between the two,we systematically reviewed the effects of sleep disorders,especially obstructive sleep apnea(OSA),on the incidence of NAFLD,and analyzed the possible mechanisms after adjusting for confounding factors.NAFLD is independently associated with sleep disorders.Different sleep disorders may be the cause of the onset and aggravation of NAFLD.An excessive or insufficient sleep duration,poor sleep quality,insomnia,sleep-wake disorders,and OSA may increase the incidence of NAFLD.Despite that some research suggests a unidirectional causal link between the two,specifically,the onset of NAFLD is identified as a result of changes in sleep characteristics,and the reverse relationship does not hold true.Nevertheless,there is still a lack of specific research elucidating the reasons behind the higher risk of developing sleep disorders in individuals with NAFLD.Further research is needed to establish a clear relationship between NAFLD and sleep disorders.This will lay the groundwork for earlier identification of potential patients,which is crucial for earlier monitoring,diagnosis,effective prevention,and treatment of NAFLD.
基金supported by Natural Science Foundation of Hebei Province(H2020206579)S&T Program of Hebei(18277743D)+3 种基金CAMS Innovation Fund for Medical Sciences(2019-I2M-5-055)Key R&D projects in Hebei Province(20327125D)the Training Plan for Young Innovative Talents in Science and Technology(TJZR202008)Spring rain project of Hebei Medical University(CYCZ201906)。
文摘To search for a new eco-friendly therapy for infectious disease caused by Escherichia coli,Staphylococcus aureus or Klebsiella oxytoca,we collected the vaginal swabs from healthy women,screened for Lactobacillus and found a strain repressing the growth of pathogenic bacteria.The new isolate was identified as L.gasseri by the colony morphology,Gram staining,biochemical reactions and confirmed by the 16 S rDNA sequencing.The HMV18 strain inhibited the growth of food-borne pathogens such as E.coli,S.aureus and K.oxytoca.The HMV18 strain was sensitive to penicillin,ampicillin,erythromycin,tetracycline and chloramphenicol.The HMV18 strain producedα-hemolysis.Pathological histology of the mice ileum showed that the mucosa,villi,lamina propria and crypt depth remained intact and there was no inflammation or hyperemia in the L.gasseri HMV18 gavaged group.L.gasseri HMV18 could not up-regulate inflammatory cytokines level of plasma.All the results suggested L.gasseri HMV18 is a candidate probiotic to be an additive for food preservation or drug to prevent food-borne diseases.
文摘Through a modified agar well diffusion assay,antagonism of a novel chitinase-producing strain C3 against the phy- topathogenic fungi including Phoma wasabiae Yokogi,Cochlibolus Heterostrophus,Exserohilum Turcicum,Curuvularia Lunata (Walk)Boed,Thantephorus cucumris,Fusarium graminearum was tested.The data showed that the crude extracts of strain C3 had stable antifungal activity in the range of pH 5.0 to pH 8.0.The active components were heat labile and sensitive to proteinase K.A series of experiments supported that the compound responsible for inhibitory aetivity appeared to be chitinase.The 16s rDNA analysis indicated that C3 was subject to genus Burkholderia.Phenotypic characterization of C3 was also consisted with the result of molecular identification.
基金funded by the National Key R&D Program of China(2018YFC1200400)。
文摘Pine wood nematode(B ursaphelenchus xylophilus),one of the most destructive invasive species,has caused extremely serious economic,ecological and social losses in many countries throughout the world.Since the high reproductive rate of B.xylophilus PWN is the main cause of rapid death of its pine hosts(Pinus spp.),understanding the reproductive and population biology and the ecology of this nmatode are of great importance.This study mainly focused on analyzing the mating process and population structure under different combinations of sex ratios for mating.Reproductive efficiency of B.xylophilus peaked when the sex ratio(female to male)was 3.4:1.Phases of the mating process for the different sex-ratio combinations indicated that B.xylophilus had evolved alternative reproductive strategies to cope with complex copulating conditions to obtain a suitable population structure for further propagation.This research provides fundamental information on the mechanism that is responsible for the rapid population growth of B.xylophilus.
基金funded by the National Natural Science Foundation of China(No.32041001,81902070,U2002218)the Provincial Natural Science Foundation of Hunan Province(No.2019JJ20004 and 2019JJ50035).
文摘The frequent emergence of coronavirus(CoV)epidemics has seriously threatened public health and stock farming.The major hosts for CoVs are birds and mammals.Although most CoVs inhabit their specific natural hosts,some may occasionally cross the host barrier to infect livestock and even people,causing a variety of diseases.Since the beginning of the new century,increasing attention has been given to research on CoVs due to the emergence of highly pathogenic and genetically diverse CoVs that have caused several epidemics,including the recent COVID-19 pandemic.CoVs belong to the Coronaviridae family of the Nidovirales order.Recently,advanced techniques for viral detection and viral genome analyses have enabled characterization of many new nidoviruses than ever and have greatly expanded the Nidovirales order with new classification and nomenclature.Here,we first provide an overview of the latest research progress in the classification of the Nidovirales order and then introduce the host range,genetic variation,genomic pattern and pathogenic features of epidemic CoVs and other epidemic viruses.This information will promote understanding of the phylogenetic relationship and infectious transmission of various pathogenic nidoviruses,including epidemic CoVs,which will benefit virological research and viral disease control.
基金the National Natural Science Foundation of Jilin Provence,No.YDZJ202201ZTYS016and Jilin Provincial Health Commission,No.2022JC053.
文摘The screening practices for hepatitis D virus(HDV)are diverse and nonstandardized worldwide,and the exact prevalence of HDV is uncertain.AIM To estimate HDV prevalence and investigate viral marker quantity trends in patients with hepatitis D.METHODS We collected 5594 serum samples from patients with hepatitis B in Jilin Province,China(3293 males and 2301 females,age range of 2 to 89 years).We then conducted tests for hepatitis B surface antigen(HBsAg),hepatitis B Virus(HBV)DNA,anti-hepatitis D antigen(HDAg),and HDV RNA.RESULTS We found that the prevalence of anti-HDAg and HDV RNA among hepatitis B patient were 3.6%(3.2-4.2%)and 1.2%(0.9-1.5%),respectively,87.69%of hepatitis D patients were 51-70 years old.HDV infection screening positive rate of patients with HBV DNA levels below 2000 IU/mL(2.0%)was higher than those above 2000 IU/mL(0.2%).Among anti-HDAg positive patients,the HDV RNA positive rate was positively correlated with the HBsAg level and anti-HDAg level.There was a weak correlation between HBsAg and anti-HDAg levels among hepatitis D patients.CONCLUSION Our study highlights the importance of considering multiple factors when assessing the severity of HDV infection,comprehensive evaluation of patients’clinical and laboratory parameters is necessary for proper diagnosis and treatment.
基金supported by the S&T Program of Hebei(20277705D and 20372601D)Natural Science Foundation of Hebei Province,China (H2020206352)+2 种基金Science and Technology Project of Hebei Education Department (QN2018150)Hebei Medical Science Research Project (20220973)Chinese Medicine Research Program of Hebei Province (2021119)。
文摘The rapid spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) in recent years not only caused a global pandemic but resulted in enormous social,economic,and health burdens worldwide.Despite considerable efforts to combat coronavirus disease 2019(COVID-19),various SARS-CoV-2 variants have emerged,and their underlying mechanisms of pathogenicity remain largely unknown.Furthermore,effective therapeutic drugs are still under development.Thus,an ideal animal model is crucial for studying the pathogenesis of COVID-19 and for the preclinical evaluation of vaccines and antivirals against SARS-CoV-2 and variant infections.Currently,several animal models,including mice,hamsters,ferrets,and nonhuman primates(NHPs),have been established to study COVID-19.Among them,ferrets are naturally susceptible to SARS-CoV-2 infection and are considered suitable for COVID-19 study.Here,we summarize recent developments and application of SARS-CoV-2 ferret models in studies on pathogenesis,therapeutic agents,and vaccines,and provide a perspective on the role of these models in preventing COVID-19 spread.
基金The present study was supported by the National Natural Science Foundation of China(grant numbers:81902067 and 82078189)the Medical Scientific Research Foundation of Guangdong Province(grant number:A2019502)+2 种基金the Shenzhen Science and Technology Innovation Committee(grant numbers:JCY20180305124849781 and 20200812211704001)the SZU Top Ranking Project(grant number:86000000210)the Hospital Project of Huazhong University of Science and Technology Union Shenzhen Hospital(grant number:2021042).
文摘Background:Amarogentin(AMA)is a secoiridoid glycoside extracted from Swertia and Gentiana roots and exhibits many biological effects such as antioxidative,antiinflammatory,and antitumor activities.Atopic dermatitis(AD)is a chronic inflammatory skin disease caused by disorders in the regulation of multiple inflammatory cytokines.No effective cure has been found for AD now.Methods:We constructed the HaCat and splenocyte model and tested the inhibitory effect of AMA on IL-4,IL-6,and IL-13 secretions using enzyme-linked immunosorbent assay(ELISA).The AD mouse model was constructed and treated with AMA,the severity of skin lesions was observed,epidermal tissue was collected,and epidermal thickness and mast cell infiltration were observed using hematoxylin and eosin and toluidine blue staining,respectively.The expression of kallikrein-related peptidase 7(KLK7)and filaggrin(FLG)was detected using immunostaining and Western blot analysis.The mRNA expression of KLK7 and FLG was detected using quantitative polymerase chain reaction(qPCR).Blood immunoglobulin E(IgE)secretion was detected.Results:AMA inhibited IL-6 secreted by tumor necrosis factor(TNF)-α-induced HaCaT cells and reduced IL-4 and IL-13 secreted by phytohemagglutinin(PHA)-induced primary cells in the mice spleen.It was found that the treatment of AMA with 2,4-din itrochlorobenzene-induced AD-like mice could promote the recovery of dermatitis,reduce the score of dermatitis severity and the scratching frequency,treat the skin lesions,reduce the epidermal thickness,decrease the infiltration of mast cells,reduce the IgE level in serum,decrease the expression levels of AD-related cytokines,increase protein and mRNA expression of FLG,and reduce the protein and mRNA expression of KLK7 in the skin tissues of AD-like mice.Conclusion:In conclusion,AMA inhibits inflammatory response at the cellular level,and AMA reduces the validation response of specific dermatitis mice,relieves pruritus,and repairs the damaged skin barrier.
基金Hainan Provincial Higher Education Science Research Project(Hnky 2020‑33)Key Research and Development Plan of Hainan Province(ZDYF2020150)+4 种基金Major Science and Technology Project of Hainan Province(ZDKJ202003)National Natural Science Foundation of China(32060015)High level Talent Program of Hainan Natural Science Foundation(2019RC218)Hainan Academician Innovation Platform Project(YSPTZX202004)Hainan Academician Workstation Project(SRC200003)。
文摘Arenaviruses belong to the family of RNA viruses that can infect humans in various ways and cause different degrees of mortality.Rodents is the mainly hosts.Human pathogenic arenaviruses include lymphocytic choroid meningitis,Lassa virus group and Takarib virus group,which cause human lymphocytic choriomeningitis and human hemorrhagic diseases.Rodents account for about 43%of mammalian species.At present,more than 30 highly pathogenic viruses have been found in rodents,including arenaviruses.The arenaviridae that infects rodents are mainly mammalian arenaviruses.This article reviews the etiology,clinicopathology,epidemiology,prevention and control of arenavirus,and provides references for the research and prevention of arenavirus.
基金Supported by Hainan Province Science and Technology Special Fund,No.ZDYF2022SHFZ114Hainan Provincial Natural Science Foundation of China,No.820RC650+1 种基金National Natural Science Foundation of China,No.82060377Innovative Research Project for Graduate Students of Hainan Medical University,No.HYYS2020-18,No.HYYS2021A09,and No.HYYS2021A22.
文摘BACKGROUND Wild rats have the potential to hold zoonotic infectious agents that can spread to humans and cause disease.AIM To better understand the composition of gut bacterial communities in rats is essential for preventing and treating such diseases.As a tropical island located in the south of China,Hainan province has abundant rat species.Here,we examined the gut bacterial composition in wild adult rats from Hainan province.METHODS Fresh fecal samples were collected from 162 wild adult rats,including three species(Rattus norvegicus,Leopoldamys edwardsi,and Rattus losea),from nine regions of Hainan province between 2017-2018.RESULTS We analyzed the composition of gut microbiota using the 16S rRNA gene amplicon sequencing.We identified 4903 bacterial operational taxonomic units(30 phyla,175 families,and 498 genera),which vary between samples of different rat species in various habitats at various times of the year.In general,Firmicutes were the most abundant phyla,followed by Bacteroidetes(15.55%),Proteobacteria(6.13%),and Actinobacteria(4.02%).The genus Lactobacillus(20.08%),unidentified_Clostridiales(5.16%),Romboutsia(4.33%),unidentified_Ruminococcaceae(3.83%),Bacteroides(3.66%),Helicobacter(2.40%)and Streptococcus(2.37%)were dominant.CONCLUSION The composition and abundance of the gut microbial communities varied between rat species and locations.This work provides fundamental information to identify microbial communities useful for disease control in Hainan province.
基金supported by the National Natural Science Foundation of China(U22A20523,32172912,and 32102722)the Interdisciplinary Integration and Innovation Project of Jilin University(JLUXKJC2021QZ04)。
文摘Host-directed therapy(HDT)is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus(S.aureus)infection.Functioning as the indispensable specific cellular receptor for a-toxin(Hla),a-disintegrin and metalloproteinase 10(ADAM10)is exploited to accelerate S.aureus infection through diverse mechanisms.The extraordinary contribution of ADAM10 to S.aureus pathogenesis renders it an attractive HDT target for combating S.aureus infection.Our study is the first to demonstrate the indispensable role of ADAM10 in S.aureus-induced necroptosis,and it enhances our knowledge of the role of ADAM10 in S.aureus infection.Using a fluorogenic substrate assay,we further identified kaempferol as a potent ADAM10 inhibitor that effectively protected mice from S.aureus infection by suppressing Hla-mediated barrier disruption and necroptosis.Collectively,our work presents a novel hostdirected therapeutic strategy for using the promising candidate kaempferol to treat S.aureus infection and other diseases relevant to the disordered upregulation of ADAM10.
基金The study protocol was approved by the Ethics Committee of Hebei General University and complied strictly with ethical requirements.Ethics Review No.2020 scientific ethics No.30.
文摘BACKGROUND The coronavirus disease 2019(COVID-19)epidemic disrupted education systems by forcing systems to shift to emergency online leaning.Online learning satisfaction affects academic achievement.Many factors affect online learning satisfaction.However there is little study focused on personal characteristics,mental status,and coping style when college students participated in emergency online courses.regression analyses were performed to identify factors that affected online learning satisfaction.RESULTS Descriptive findings indicated that 62.9%(994/1580)of students were satisfied with online learning.Factors that had significant positive effects on online learning satisfaction were online learning at scheduled times,strong exercise intensity,good health,regular schedule,focusing on the epidemic less than one hour a day,and maintaining emotional stability.Positive coping styles were protective factors of online learning satisfaction.Risk factors for poor satisfaction were depression,neurasthenia,and negative coping style.CONCLUSION College students with different personal characteristics,mental status,and coping style exhibited different degrees of online learning satisfaction.Our findings provide reference for educators,psychologists,and school adminis-trators to conduct health education intervention of college students during emergency online learning.
基金supported by the National Natural Science Foundation of China,Nos. 82071304 (to QXZ), 81671149 (to QXZ),and 81971179 (to XML)the Natural Science Foundation of Jiangsu Province,Nos. BK20191463 (to XML) and BK20161167 (to QXZ)。
文摘We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.