BACKGROUND Skin wounds are highly common in diabetic patients,and with increasing types of pathogenic bacteria and antibiotic resistance,wounds and infections in diabetic patients are difficult to treat and heal.AIM T...BACKGROUND Skin wounds are highly common in diabetic patients,and with increasing types of pathogenic bacteria and antibiotic resistance,wounds and infections in diabetic patients are difficult to treat and heal.AIM To explore the effects of betaine ointment(BO)in promoting the healing of skin wounds and reducing the inflammation and apoptosis of skin cells in microbially infected diabetic mice.METHODS By detecting the minimum inhibitory concentrations(MICs)of betaine and plant monomer components such as psoralen,we prepared BO with betaine as the main ingredient,blended it with traditional Chinese medicines such as gromwell root and psoralen,and evaluated its antibacterial effects and safety in vitro and in vivo.The skin infection wound models of ordinary mice and diabetic mice were constructed,and the OTC drugs mupirocin ointment and Zicao ointment were used as controls to evaluate the antibacterial effects in vivo and the anti-inflammatory and anti-apoptotic effects of BO.RESULTS The MICs of betaine against microorganisms such as Staphylococcus aureus(S.aureus),Candida albicans and Cryptococcus neoformans ranged from 4 to 32μg/mL.Gromwell root and psoralea,both of which contain antimicrobial components,mixed to prepare BO with MICs ranging from 16 to 64μg/mL,which is 32-256 times lower than those of Zicao ointment,although the MIC is greater than that of betaine.After 15 days of treatment with BO for USA300-infected ordinary mice,the wound scab removal rates were 83.3%,while those of mupirocin ointment and Zicao ointment were 66.7%and 0%,respectively,and the differences were statistically significant.In diabetic mice,the wound scab removal rate of BO and mupirolacin ointment was 80.0%,but BO reduced wound inflammation and the apoptosis of skin cells and facilitated wound healing.CONCLUSION The ointment prepared by mixing betaine and traditional Chinese medicine can effectively inhibit common skin microorganisms and has a strong effect on the skin wounds of sensitive or drug-resistant S.aureus-infected ordinary mice and diabetic mice.展开更多
LysM proteins contain the lysin domain(LysM),bind chitin and are found in various organisms including fungi.In phytopathogenic fungi,certain LysM proteins act as effectors to inhibit host immunity,thus increasing fung...LysM proteins contain the lysin domain(LysM),bind chitin and are found in various organisms including fungi.In phytopathogenic fungi,certain LysM proteins act as effectors to inhibit host immunity,thus increasing fungal virulence.However,our understanding of the LysM protein family in Setosphaeria turcica is limited.In this study,eight StLysM genes are identified and designated as StLysM1 to StLysM8.The analysis of sequence features indicates that five proteins(StLysM1,StLysM2,StLysM5,StLysM6,and StLysM7)are potential effectors.Phylogenetic analysis suggests that the StLysMs are divided into fungal/bacterial and fungus-specific subclasses.Domain architecture analysis reveals that the five StLysM effectors exclusively harbor the LysM domain,whereas the other three StLysM proteins contain additional functional domains.Sequence conservation analysis shows that the fungal-specific LysM domain sequences share the ^(8)GDxTC^(12) and ^(29)WNP^(31) motifs as well as three highly conserved cysteine residues.Conversely,the LysM domain sequences from the bacterial/fungal branch have few conserved sites.Moreover,expression profiling analysis shows that the StLysM1 gene is significantly upregulated during the infection of maize.Yeast secretion assays and transient expression experiments demonstrate that StLysM1 is a secreted protein that can suppress BAX/INF1-induced programmed cell death in Nicotiana benthamiana.Further functional analysis suggests that St Lys M1 cannot interact with itself but it can bind chitin.The transient expression of StLysM1 inhibits the chitin-triggered plant immune response,increasing susceptibility to the phytopathogenic fungus Botrytis cinerea in N.benthamiana.This study reveals that the S.turcica LySM protein family consists of eight members,highlighting the significance of StLysM1 as a vital effector in regulating plant immunity.The results provide insight into StLysMs and establish a foundation for understanding the roles of StLysM proteins in the pathogenic process of S.turcica.展开更多
Objective To assess the independent and combined effects of air pollutants,meteorological factors,and greenspace exposure on new tuberculosis(TB)cases.Methods TB case data from Shanghai(2013–2018)were obtained from t...Objective To assess the independent and combined effects of air pollutants,meteorological factors,and greenspace exposure on new tuberculosis(TB)cases.Methods TB case data from Shanghai(2013–2018)were obtained from the Shanghai Center for Disease Control and Prevention.Environmental data on air pollutants,meteorological variables,and greenspace exposure were obtained from the National Tibetan Plateau Data Center.We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases.Results Increased TB risk was linked to PM_(2.5),PM_(10),and rainfall,whereas NO_(2),SO_(2),and air pressure were associated with a reduced risk.Specifically,the strongest cumulative effects occurred at various lags:PM_(2.5)(RR=1.166,95%CI:1.026–1.325)at 0–19 weeks;PM_(10)(RR=1.167,95%CI:1.028–1.324)at 0–18 weeks;NO_(2)(RR=0.968,95%CI:0.938–0.999)at 0–1 weeks;SO_(2)(RR=0.945,95%CI:0.894–0.999)at 0–2 weeks;air pressure(RR=0.604,95%CI:0.447–0.816)at 0–8 weeks;and rainfall(RR=1.404,95%CI:1.076–1.833)at 0–22 weeks.Green space exposure did not significantly impact TB cases.Additionally,low temperatures amplified the effect of PM_(2.5)on TB.Conclusion Exposure to PM_(2.5),PM_(10),and rainfall increased the risk of TB,highlighting the need to address air pollutants for the prevention of TB in Shanghai.展开更多
Objective To investigate the associations between eight serum per-and polyfluoroalkyl substances(PFASs)and regional fat depots,we analyzed the data from the National Health and Nutrition Examination Survey(NHANES)2011...Objective To investigate the associations between eight serum per-and polyfluoroalkyl substances(PFASs)and regional fat depots,we analyzed the data from the National Health and Nutrition Examination Survey(NHANES)2011-2018 cycles.Methods Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions.The associations between structurally grouped PFASs and fat distribution were assessed,and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk.Results Among females aged 39-59 years,trunk fat mass was positively associated with perfluorooctane sulfonate(PFOS).Higher concentrations of PFOS,perfluorohexane sulfonate(PFHxS),perfluorodecanoate(PFDeA),perfluorononanoate(PFNA),and n-perfluorooctanoate(n-PFOA)were linked to greater visceral adipose tissue in this group.In men,exposure to total perfluoroalkane sulfonates(PFSAs)and long-chain PFSAs was associated with reductions in abdominal fat,while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs.The prediction model demonstrated high accuracy,with an area under the curve(AUC)of 0.9925 for predicting obesity risk.Conclusion PFAS exposure is associated with regional fat distribution,with varying effects based on age,sex,and PFAS structure.The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk,with significant implications for public health.The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.展开更多
Pu-erh tea,a traditional Chinese beverage,performs an anti-obesity function,but the correlation between its components and efficacy remains unknown.Here,we screened two Pu-erh teas with significant anti-obesity effica...Pu-erh tea,a traditional Chinese beverage,performs an anti-obesity function,but the correlation between its components and efficacy remains unknown.Here,we screened two Pu-erh teas with significant anti-obesity efficacies from 11 teas.In vitro experiments revealed that lipid accumulation in L02 cells and lipid synthesis in 3T3-L1 cells were significantly better inhibited by Tea-B than Tea-A.Further in vivo experiments using model mice revealed that the differences in chemical components generated two pathways in the anti-obesity efficacy and mechanism of Pu-erh teas.Tea-A changes the histomorphology of brown adipose tissue(BAT)and increases the abundance of Coriobacteriaceae_UCG_002 and cyclic AMP in guts through high chemical contents of cyclopentasiloxane,decamethyl,tridecane and 1,2,3-trimethoxybenzene,eventually increasing BAT activation and fat browning gene expression;the high content of hexadecane and 1,2-dimethoxybenzene in Tea-B reduces white adipose tissue(WAT)accumulation and the process of fatty liver,increases the abundance of Odoribacter and sphinganine 1-phosphate,inhibits the expression of lipid synthesis and transport genes.These mechanistic findings on the association of the representative bioactive components in Pu-erh teas with the anti-obesity phenotypes,gut microbes,gut metabolite structure and anti-obesity pathways,which were obtained for the first time,provide foundations for developing functional Pu-erh tea.展开更多
As a major subunit of the exocyst complex,members of the EXO70 family have mainly been shown to play roles in cell polarity and morphogenesis in Arabidopsis,but their roles in plant endosymbiosis,such as with arbuscul...As a major subunit of the exocyst complex,members of the EXO70 family have mainly been shown to play roles in cell polarity and morphogenesis in Arabidopsis,but their roles in plant endosymbiosis,such as with arbuscular mycorrhizal fungi(AMF),have rarely been reported.Here,using knockout and overexpression lines,we show that OsEXO70L2,which encodes a divergent EXO70 protein in rice,controls the number of primary roots and is essential for large lateral root formation.Furthermore,the OsEXO70L2 mutant sr1 displayed rare internal AMF hyphaeand no arbuscules.We also found that AMF sporulation can occur in roots despite low colonization and that AMF colonization and sporulation are modulated by photoperiod and co-culture with clover.Finally,genes related to auxin homeostasis were found to be affected in the OsEXO70L2 knockout or overexpression lines,suggesting that auxin is at least partly responsible for the phenotypes.This study provides new perspectives on the role of the exocyst complex during root development and AM in rice.展开更多
Severe traumatic bone healing relies on the involvement of growth factors.However,excessive supplementation of growth factors can lead to ectopic ossification and inflammation.In this study,utilizing the neural regula...Severe traumatic bone healing relies on the involvement of growth factors.However,excessive supplementation of growth factors can lead to ectopic ossification and inflammation.In this study,utilizing the neural regulatory mechanism of bone regeneration,we have developed a multifunctional three dimensions(3D)printed scaffold containing both vasoactive intestinal peptide(VIP)and nerve growth factor(NGF)as an effective new method for achieving bone defect regeneration.The scaffold is provided by a controlled biodegradable and biomechanically matched poly(lactide-ethylene glycol-trimethylene carbonate)(PLTG),providing long-term support for the bone healing cycle.Factor loading is provided by peptide fiber-reinforced biomimetic antimicrobial extracellular matrix(ECM)(B-ECM)hydrogels with different release kinetics,the hydrogel guides rapid bone growth and resists bacterial infection at the early stage of healing.Physical and chemical characterization indicates that the scaffold has good structural stability and mechanical properties,providing an ideal 3D microenvironment for bone reconstruction.In the skull defect model,compared to releasing VIP or NGF alone,this drug delivery system can simulate a natural healing cascade of controllable release factors,significantly accelerating nerve/vascular bone regeneration.In conclusion,this study provides a promising strategy for implanting materials to repair bone defects by utilizing neuroregulatory mechanisms during bone regeneration.展开更多
Traditional Chinese medicine(TCM)can help prevent or treat diseases;however,there are few studies on the active substances of TCM.For example,Lycium barbarum L.has been proven to be effective in treating osteoporosis ...Traditional Chinese medicine(TCM)can help prevent or treat diseases;however,there are few studies on the active substances of TCM.For example,Lycium barbarum L.has been proven to be effective in treating osteoporosis for thousands of years,but its active substance remains to be unknown.Prompted by the efforts to modernize TCM,the present study focused on the novel active substance of Lycium barbarum L.to reinforce kidney essence to produce bone marrow.Illumina deep sequencing analysis and stemloop polymerase chain reaction(PCR)assay revealed that miR162a,a Lycium barbarum L.-derived microRNA,can pass through the gastrointestinal tract to target the bone marrow in mice.Immunofluorescence staining showed that miR162a was absorbed through systemic RNA interference defective transmembrane family member 1(SIDT1)in the stomach.Bioinformatics prediction and luciferase reporter assay identified that miR162a targeted nuclear receptor corepressor(NcoR).Alizarin red staining and micro-computed tomography(microCT)confirmed that miR162a promoted osteogenic differentiation in bone marrow mesenchymal stem cells,zebrafish,and a mouse model of osteoporosis.In addition,transgenic Nicotiana benthamiana(N.benthamiana)leaves overexpressing miR162a were developed by agrobacterium infiltration method.microCT and tartrate-resistant acid phosphatase staining confirmed that transgenic N.benthamiana leaves effectively protected against osteoporosis in mice.Our study mechanistically explains how Lycium barbarum L.improves osteoporosis and supports that Lycium barbarum L.reinforces kidney essence,thereby strengthening the bone.miR162a expressed by transgenic plants may represent a novel and safe treatment for human osteoporosis.展开更多
BACKGROUND Probiotic Acetobacter pasteurianus is used to treat diabetes,but its specific hypoglycemic substances and mechanisms remain unclear.AIM To investigate the components for lipid metabolism of A.pasteurianus a...BACKGROUND Probiotic Acetobacter pasteurianus is used to treat diabetes,but its specific hypoglycemic substances and mechanisms remain unclear.AIM To investigate the components for lipid metabolism of A.pasteurianus and its hypoglycemic effects,providing a basis for its broader application.METHODS The lipid metabolism of A.pasteurianus under different growth conditions was analyzed using lipidomics.Neutral lipid staining in A.pasteurianus cells and the formation of lipid droplet-like structures were observed using a confocal laser scanning microscope.The neutral lipid components were also analyzed using thin layer chromato-graphy.A diabetic mouse model was established to evaluate the hypoglycemic effects of the main lipid components of A.pasteurianus and their role in repairing tissues such as the pancreas.RESULTS After comparing the effects of three culture media,namely,brain heart infusion(BHI)medium with 2%glucose,chromium-rich and zinc-rich medium,and mineral salt medium,A.pasteurianus grew well in BHI containing 2%glucose and produced the most lipids.A total of 583 lipid metabolic products was identified,with higher levels of coenzyme Q9(CoQ9),oleic acid(OA),and wax ester,but no triacylglycerol was observed.It was found that the components that affected lipid metabolism in A.pasteurianus were mainly CoQ9 and OA.They exhibited hypoglycemic effects comparable to metformin in diabetic mice,repaired damaged pancreatic tissues,and did not cause damage to the liver and spleen.CONCLUSION Under high-nutrient growth conditions,A.pasteurianus contains abundant lipid components,such as CoQ9 and OA,with good hypoglycemic effects.展开更多
BACKGROUND Helicobacter pylori(H.pylori),a globally prevalent pathogen,is exhibiting increasing rates of antimicrobial resistance.However,clinical implementation of pre-treatment susceptibility testing remains limited...BACKGROUND Helicobacter pylori(H.pylori),a globally prevalent pathogen,is exhibiting increasing rates of antimicrobial resistance.However,clinical implementation of pre-treatment susceptibility testing remains limited due to the organism’s fastidious growth requirements and prolonged culture time.AIM To propose a novel detection method utilizing antibiotic-supplemented media to inhibit susceptible strains,while resistant isolates were identified through urease-mediated hydrolysis of urea,inducing a phenol red color change for visual confirmation.METHODS Colombia agar was supplemented with urea,phenol red,and nickel chloride,and the final pH was adjusted to 7.35.Antibiotic-selective media were prepared by incorporating amoxicillin(0.5μg/mL),clarithromycin(2μg/mL),metronidazole(8μg/mL),or levofloxacin(2μg/mL)into separate batches.Gastric antral biopsies were homogenized and inoculated at 1.0×105 CFU onto the media,and then incubated under microaerobic conditions at 37°C for 28-36 hours.Resistance was determined based on a color change from yellow to pink,and the results were validated via broth microdilution according to Clinical and Laboratory Standards Institute guidelines.RESULTS After 28-36 hours of incubation,the drug-resistant H.pylori isolates induced a light red color change in the medium.Conversely,susceptible strains(H.pylori 26695 and G27)produced no visible color change.Compared with the conventional 11-day protocol,the novel method significantly reduced detection time.Among 201 clinical isolates,182 were successfully evaluated using the new method,resulting in a 90.5%detection rate.This was consistent with the 95.5%agreement rate observed when compared with microdilution-based susceptibility testing.The success rate of the novel approach was significantly higher than that of the comparative method(P<0.01).The accuracy of the new method was comparable to that of the dilution method.CONCLUSION The novel detection method can rapidly detect H.pylori drug resistance within 28-36 hours.With its operational simplicity and high diagnostic performance,it holds strong potential for clinical application in the management of H.pylori antimicrobial resistance.展开更多
The microbial consortium within an organism is crucial for its development and immune status.Alteration of the host microbiome by antibiotics or antinutritional factors may contribute to increased disease susceptibili...The microbial consortium within an organism is crucial for its development and immune status.Alteration of the host microbiome by antibiotics or antinutritional factors may contribute to increased disease susceptibility.Here,we investigated whether exposure to different microbes could influence zebrafish larval microbiota composition and modulate their immune response towards a saponin challenge.Adult zebrafish were exposed to the antibiotic oxytetracycline(OxyT)or control tank water and their intestinal content was harvested after 30h(24h exposure,6h wash-out).Subsequently,zebrafish embryos were exposed to either OxyT-treated content or non-treated content from 3 to 6 days post fertilization(dpf).At 6 dpf part of the group received a saponin challenge until 8 dpf.Zebrafish larvae exposed to OxyT-treated adult gut content(3–6 dpf)showed an altered microbiota composition compared to controls.Interestingly,larvae exposed to saponin-treated OxyT-content showed fewer macrophages(as visualized by fluorescent microscopy using mpx:GFP114;mpeg:mCherry transgenic fish)in the overall fish as well as around the gut area than saponin-treated control-exposed larvae.Fewer macrophages were associated with a decreased expression of interleukin 22(il22)in larvae exposed to saponin-treated OxyT-content compared to controls.Overall,this study shows that exposure to different microbial environments early in life might affect disease susceptibility of larval zebrafish.展开更多
The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary...The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads,as it is one of the DNA viruses with the largest genome and the most AT-biased,and has a significant number of tandem repeats.Here we evaluated the performance of metagenomic and amplicon sequencing techniques,and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland.We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens.Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes.Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences.Besides,several intra-host single nucleotide variations were identified in the first imported mpox case.This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens.The findings of this study will significantly enhance the surveillance of MPXV.展开更多
Two new dihydropyrones,rhytismatones C(1)and D(2),and a known compound,penicillenol A1(3),were isolated from the co-culture broth of the deep-sea-derived fungus Penicillium crustosum PRB-2 and Suaeda salsa-derived end...Two new dihydropyrones,rhytismatones C(1)and D(2),and a known compound,penicillenol A1(3),were isolated from the co-culture broth of the deep-sea-derived fungus Penicillium crustosum PRB-2 and Suaeda salsa-derived endophytic fungus Peni-cillium citrinum HDN11-186.Their structures were elucidated through comprehensive analysis of nuclear magnetic resonance(NMR)spectra and mass spectra.The absolute configurations of new compounds were determined by calculating the electronic circular di-chroism(ECD)spectrum.UPLC-MS data showed that compounds 1–3 could only be detected in the media of co-culture,suggesting new biosynthetic pathways were activated in the co-cultured fungi.Compound 1 showed obvious antibacterial activities against Pro-teus sp.MMBC-1002 and Bacillus subtilis MMBC-1004 with minimum inhibitory concentration(MIC)both at 25μmolL^(-1).展开更多
To fight against invasion by pathogens,plants have evolved an elaborate innate immune system,of which the nucleotide-binding domain leucine-rich repeat-containing receptor(NLR)acts as the sensor and immune executor.Po...To fight against invasion by pathogens,plants have evolved an elaborate innate immune system,of which the nucleotide-binding domain leucine-rich repeat-containing receptor(NLR)acts as the sensor and immune executor.Potyviruses,comprising one of the largest genera of plant viruses,cause severe crop yield losses worldwide.Inherited crop resistance to potyviruses can be used in breeding and plant transgenesis to control disease development.This review summarizes achievements in mapping and cloning NLR genes conferring dominant resistance against potyvirus in the families Fabaceae,Solanaceae,Brassicaceae,and Cucurbitaceae.It compares mechanisms of potyviral protein recognition and downstream signaling employed by NLRs and discusses strategies for exploiting NLRs to better control diseases caused by potyviruses.展开更多
Haptophytes(Eukaryota,Hacrobia)play a crucial role in the energy budget and element cycling of diverse aquatic ecosystems due to their ability to engage in both phototrophic and mixotrophic nutritional modes.Neverthel...Haptophytes(Eukaryota,Hacrobia)play a crucial role in the energy budget and element cycling of diverse aquatic ecosystems due to their ability to engage in both phototrophic and mixotrophic nutritional modes.Nevertheless,there is a significant lack of knowledge regarding the short-term variations,such as diel dynamics,of their ecological features.During a short time frame in the summer of 2018,samples were collected from three distinct water layers in the South China Sea,including surface water,the deep chlorophyll maximum(DCM)layer,and 200 m depth.Fluorescence in situ hybridization coupled with tyramide signal amplification was used to quantify haptophyte cell abundance.Most haptophyte communities in all three water layers were composed of cells 2-5μm in size,while the proportion of cells<2μm increased with water depth.High-throughput sequencing of the V4 hypervariable regions of the SSU rRNA revealed that Chrysochromulina and Phaeocystis predominated the community,and the former was more abundant in the surface water and 200 m depth and the latter was more abundant in the DCM layer.Higher abundance of small cells(<2μm and 2-5μm)during the night was found compared to the day time,whereas large cells(5-10μm and 10-20μm)were more prevalent during the day time.The results of correlation analyses showed that haptophyte abundance was possibly impacted by both environmental biotic(heterotrophic nanoflagellates,heterotrophic bacteria,and viruses)and abiotic(temperature,salinity,and nutrients)factors.展开更多
Bacterial biofilms present a significant challenge in treating drug-resistant infections,necessitating the development of innovative nanomedicines.In this study,we introduce triclosan-conjugated,lipase-responsive poly...Bacterial biofilms present a significant challenge in treating drug-resistant infections,necessitating the development of innovative nanomedicines.In this study,we introduce triclosan-conjugated,lipase-responsive polymeric micelles designed to exploit biofilm properties and serve as a responsive drug delivery platform.The micelles were created using an amphiphilic block polymer synthesized via ring-opening polymerization ofε-caprolactone(CL)and triclosan-containing cyclic trimethylene carbonate(MTC-Tri).Poly(ethylene glycol)(PEG-OH)acted as the macro-initiator,resulting in micelles with a PEG shell that facilitated their penetration into bacterial biofilms.An important advantage of our micelles lies in their interaction with local bacterial lipases within biofilms.These lipases triggered rapid micelle degradation,releasing triclosan in a controlled manner.This liberated triclosan effectively eliminated bacteria embedded in the biofilms.Notably,the triclosan-conjugated micelles displayed minimal toxicity to murine fibroblasts,indicating their biocompatibility and safety.This finding emphasizes the potential application of these micelles in combatting drug resistance observed in bacterial biofilms.Our triclosan-conjugated,lipase-responsive polymeric micelles exhibit promising characteristics for addressing drug resistance in bacterial biofilms.By harnessing biofilm properties and implementing a responsive drug delivery system,we seek to provide an effective solution in the fight against drug-resistant bacteria.展开更多
BACKGROUND The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host.Although selenium is closely related to pathogenicity as an environmental factor,the specific correlat...BACKGROUND The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host.Although selenium is closely related to pathogenicity as an environmental factor,the specific correlation between them remains unclear.AIM To investigate how selenium acts on virulence factors and reduces their toxicity.METHODS H.pylori strains were induced by sodium selenite.The expression of cytotoxin-associated protein A(CagA)and vacuolating cytotoxin gene A(VacA)was determined by quantitative PCR and Western blotting.Transcriptomics was used to analyze CagA,CagM,CagE,Cag1,Cag3,and CagT.C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction,and H.pylori colonization,inflammatory reactions,and the cell adhesion ability of H.pylori were assessed.RESULTS CagA and VacA expression was upregulated at first and then downregulated in the H.pylori strains after sodium selenite treatment.Their expression was significantly and steadily downregulated after the 5th cycle(10 d).Transcriptome analysis revealed that sodium selenite altered the levels affect H.pylori virulence factors such as CagA,CagM,CagE,Cag1,Cag3,and CagT.Of these factors,CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite.Moreover,CagT expression was upregulated before the 3rd cycle(6 d)and significantly downregulated after the 5th cycle.Cag1 and Cag3 expression was upregulated and downregulated,respectively,but no significant change was observed by the 5th cycle.C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction.The extent of H.pylori colonization in the stomach increased;however,sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H.pylori-infected mice,and the cell adhesion ability of H.pylori was significantly weakened.CONCLUSION These results demonstrate that H.pylori displayed virulence attenuation after the 10th d of sodium selenite treatment.Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H.pylori,thus mitigating the inflammatory damage to the gastric mucosa.展开更多
The SARS-CoV-2 virus,particularly the Omicron BA.2 variant,led to a significant surge in Shanghai,2022.However,the viral load dynamic in Omicron infections with varying clinical severities remain unclear.This prospect...The SARS-CoV-2 virus,particularly the Omicron BA.2 variant,led to a significant surge in Shanghai,2022.However,the viral load dynamic in Omicron infections with varying clinical severities remain unclear.This prospective cohort included 48,830 hospitalized coronavirus disease 2019(COVID-19)patients across three hospitals in Shanghai,China,between 23 March and 15 May,2022.Systematic nucleic acid testing was performed using RT-PCR Cycle threshold(Ct)value as a proxy of viral load.We analyzed the kinetic characteristics of viral shedding by clinical severity and identified associated risk factors.The study comprised 31.06%asymptomatic cases,67.66%mild-moderate cases,1.00%severe cases,0.29%critical and fatal cases.Upon admission,57%of patients tested positive,with peak viral load observed at 4 days(median Ct value 27.5),followed by a decrease and an average viral shedding time(VST)of 6.1 days(Interquartile range,4.0–8.8 days).Although viral load exhibited variation by age and clinical severity,peak Ct values occurred at similar times.Unvaccinated status,age exceeding 60,and comorbidities including hypertension,renal issues kidney dialysis and kidney transplantation,neurological disorders,rheumatism,and psychotic conditions were found to correlate with elevated peak viral load and extended VST.Asymptomatic cases demonstrated a 40%likelihood of contagiousness within 6 days of detection,while mild-moderate and severe cases exhibited post-symptom resolution infectious probabilities of 27%and over 50%,respectively.These findings revealed that the initial Ct values serve as a predictive indicator of severe outcomes.Unvaccinated elderly individuals with particular comorbidities are at high-risk for elevated viral load and prolonged VST.展开更多
The prevalence of metabolic-dysfunction-associated steatotic liver disease(MASLD)is alarmingly high;it is estimated to affect up to a quarter of the global population,making it the most common liver disorder worldwide...The prevalence of metabolic-dysfunction-associated steatotic liver disease(MASLD)is alarmingly high;it is estimated to affect up to a quarter of the global population,making it the most common liver disorder worldwide.MASLD is characterized by excessive hepatic fat accumulation and is commonly associated with comorbidities such as obesity,dyslipidemia,and insulin resistance;however,it can also manifest in lean individuals.Therefore,it is crucial to develop effective therapies for this complex condition.Currently,there are no approved medications for MASLD treatment,so there is a pressing need to investigate alternative approaches.Extensive research has characterized MASLD as a multifaceted disease,frequently linked to metabolic disorders that stem from dietary habits.Evidence suggests that changes in the gut microbiome play a fundamental role in the development and progression of MASLD from simple steatosis to steatohepatitis and even hepatocellular carcinoma(HCC).In this review,we critically examine the literature on the emerging field of gut-microbiota-based therapies for MASLD and metabolicdysfunction-associated steatohepatitis(MASH),including interventions such as fecal microbiota transplantation(FMT),probiotics,prebiotics,short-chain fatty acids,antibiotics,metabolic pathway targeting,and immune checkpoint kinase blockade.展开更多
BACKGROUND Modern pharmacological studies have confirmed that plant-derived compounds from Puerariae flos(PF)has significant biological activities against liver damage,tumors and inflammation.Kakkatin is an isoflavone...BACKGROUND Modern pharmacological studies have confirmed that plant-derived compounds from Puerariae flos(PF)has significant biological activities against liver damage,tumors and inflammation.Kakkatin is an isoflavone polyphenolic compound isolated from PF flower.However,the effect of kakkatin and its derivatives on anti-tumor has not been well explored.AIM To design and synthesize a kakkatin derivative[6-(hept-6-yn-1-yloxy)-3-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one(HK)]to explore its anti-tumor biological activity.METHODS Hept-6-yn-1-yl ethanesulfonate was introduced to replace hydrogen at the hydroxyl position of kakkatin phenol,and the derivative of kakkatin was prepared;the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to detect cell viability,a clone formation assay was adopted to detect cell proliferation,apoptosis,necrosis,and cell cycles were analyzed by Annexin V/propidium iodide staining and flow cytometry.Cell migration and invasion ability were evaluated by cell scratch assay and transwell assay.The potential mechanism of HK on hepatocellular carcinoma(HCC)SMMC-7721 cells was explored through network pharmacology and molecular docking,and finally real-time PCR assays was used to verify the potential targets and evaluate the biological activity of HK.RESULTS Compared with kakkatin,the modified HK did not significantly increase the inhibitory activity of gastric cancer MGC803 cells,but the inhibitory activity of HCC SMMC-7721 cells was increased by about 30 times,with an IC50 value of 2.5μM,and the tumor inhibition effect was better than cisplatin,which could significantly inhibit the cloning,invasion and metastasis of HCC SMMC-7721 cells,and induce apoptosis and G2/M cycle arrest.Its mechanism of action is mainly related to the upregulation of PDE3B and NFKB1 target proteins in the cAMP pathway.CONCLUSION HK have a significant inhibitory effect on HCC SMMC-7721 cells,and the targets of their action may be PDE3B and NFKB1 proteins in the cAMP pathway,making it a good lead drug for the treatment of HCC.展开更多
基金Supported by Guangxi Science and Technology Major Projects,No.2023AA20009National Natural Science Foundation of China,No.32360035 and No.32060018.
文摘BACKGROUND Skin wounds are highly common in diabetic patients,and with increasing types of pathogenic bacteria and antibiotic resistance,wounds and infections in diabetic patients are difficult to treat and heal.AIM To explore the effects of betaine ointment(BO)in promoting the healing of skin wounds and reducing the inflammation and apoptosis of skin cells in microbially infected diabetic mice.METHODS By detecting the minimum inhibitory concentrations(MICs)of betaine and plant monomer components such as psoralen,we prepared BO with betaine as the main ingredient,blended it with traditional Chinese medicines such as gromwell root and psoralen,and evaluated its antibacterial effects and safety in vitro and in vivo.The skin infection wound models of ordinary mice and diabetic mice were constructed,and the OTC drugs mupirocin ointment and Zicao ointment were used as controls to evaluate the antibacterial effects in vivo and the anti-inflammatory and anti-apoptotic effects of BO.RESULTS The MICs of betaine against microorganisms such as Staphylococcus aureus(S.aureus),Candida albicans and Cryptococcus neoformans ranged from 4 to 32μg/mL.Gromwell root and psoralea,both of which contain antimicrobial components,mixed to prepare BO with MICs ranging from 16 to 64μg/mL,which is 32-256 times lower than those of Zicao ointment,although the MIC is greater than that of betaine.After 15 days of treatment with BO for USA300-infected ordinary mice,the wound scab removal rates were 83.3%,while those of mupirocin ointment and Zicao ointment were 66.7%and 0%,respectively,and the differences were statistically significant.In diabetic mice,the wound scab removal rate of BO and mupirolacin ointment was 80.0%,but BO reduced wound inflammation and the apoptosis of skin cells and facilitated wound healing.CONCLUSION The ointment prepared by mixing betaine and traditional Chinese medicine can effectively inhibit common skin microorganisms and has a strong effect on the skin wounds of sensitive or drug-resistant S.aureus-infected ordinary mice and diabetic mice.
基金supported by the S&T Program of Hebei,China(23567601H)the Hebei Provincial Central Leading Local Science and Technology Development Fund Project,China(236Z6508G)+1 种基金the Basic Research Funds for Provincial Universities in Hebei Province,China(KY2022037 and KY2021042)the Natural Science Foundation of Hebei Province,China(C2023204100 and C2021204136)。
文摘LysM proteins contain the lysin domain(LysM),bind chitin and are found in various organisms including fungi.In phytopathogenic fungi,certain LysM proteins act as effectors to inhibit host immunity,thus increasing fungal virulence.However,our understanding of the LysM protein family in Setosphaeria turcica is limited.In this study,eight StLysM genes are identified and designated as StLysM1 to StLysM8.The analysis of sequence features indicates that five proteins(StLysM1,StLysM2,StLysM5,StLysM6,and StLysM7)are potential effectors.Phylogenetic analysis suggests that the StLysMs are divided into fungal/bacterial and fungus-specific subclasses.Domain architecture analysis reveals that the five StLysM effectors exclusively harbor the LysM domain,whereas the other three StLysM proteins contain additional functional domains.Sequence conservation analysis shows that the fungal-specific LysM domain sequences share the ^(8)GDxTC^(12) and ^(29)WNP^(31) motifs as well as three highly conserved cysteine residues.Conversely,the LysM domain sequences from the bacterial/fungal branch have few conserved sites.Moreover,expression profiling analysis shows that the StLysM1 gene is significantly upregulated during the infection of maize.Yeast secretion assays and transient expression experiments demonstrate that StLysM1 is a secreted protein that can suppress BAX/INF1-induced programmed cell death in Nicotiana benthamiana.Further functional analysis suggests that St Lys M1 cannot interact with itself but it can bind chitin.The transient expression of StLysM1 inhibits the chitin-triggered plant immune response,increasing susceptibility to the phytopathogenic fungus Botrytis cinerea in N.benthamiana.This study reveals that the S.turcica LySM protein family consists of eight members,highlighting the significance of StLysM1 as a vital effector in regulating plant immunity.The results provide insight into StLysMs and establish a foundation for understanding the roles of StLysM proteins in the pathogenic process of S.turcica.
基金supported by the National Key Research and Development Program of China[2023YFC2307305]Shenzhen Medical Research Fund[B2303003]+3 种基金the Zhujiang Innovation and Entrepreneurship Talents Program[2021ZT09Y544]the Shenzhen Science and Technology Program[ZDSYS20230626091203007]Shanghai CDC(Shanghai three-year(2023–2025)action plan to strengthen the public health system[GWVI–11.1–05])Top Young Talents in Shanghai。
文摘Objective To assess the independent and combined effects of air pollutants,meteorological factors,and greenspace exposure on new tuberculosis(TB)cases.Methods TB case data from Shanghai(2013–2018)were obtained from the Shanghai Center for Disease Control and Prevention.Environmental data on air pollutants,meteorological variables,and greenspace exposure were obtained from the National Tibetan Plateau Data Center.We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases.Results Increased TB risk was linked to PM_(2.5),PM_(10),and rainfall,whereas NO_(2),SO_(2),and air pressure were associated with a reduced risk.Specifically,the strongest cumulative effects occurred at various lags:PM_(2.5)(RR=1.166,95%CI:1.026–1.325)at 0–19 weeks;PM_(10)(RR=1.167,95%CI:1.028–1.324)at 0–18 weeks;NO_(2)(RR=0.968,95%CI:0.938–0.999)at 0–1 weeks;SO_(2)(RR=0.945,95%CI:0.894–0.999)at 0–2 weeks;air pressure(RR=0.604,95%CI:0.447–0.816)at 0–8 weeks;and rainfall(RR=1.404,95%CI:1.076–1.833)at 0–22 weeks.Green space exposure did not significantly impact TB cases.Additionally,low temperatures amplified the effect of PM_(2.5)on TB.Conclusion Exposure to PM_(2.5),PM_(10),and rainfall increased the risk of TB,highlighting the need to address air pollutants for the prevention of TB in Shanghai.
基金supported by the National Key R&D Program of China(No.2021YFC2700605)the National Natural Science Foundation of China(82071700 and 82101679)+4 种基金333 High-level Talent Training Project of the Jiangsu Province((2022)3-16-425)the Natural Science Foundation of Jiangsu Province(BK20220317)Jiangsu Funding Program for Excellent Postdoctoral Talent(2022ZB414)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(22KJB330001)China Postdoctoral Science Foundation(2022M711673).
文摘Objective To investigate the associations between eight serum per-and polyfluoroalkyl substances(PFASs)and regional fat depots,we analyzed the data from the National Health and Nutrition Examination Survey(NHANES)2011-2018 cycles.Methods Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions.The associations between structurally grouped PFASs and fat distribution were assessed,and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk.Results Among females aged 39-59 years,trunk fat mass was positively associated with perfluorooctane sulfonate(PFOS).Higher concentrations of PFOS,perfluorohexane sulfonate(PFHxS),perfluorodecanoate(PFDeA),perfluorononanoate(PFNA),and n-perfluorooctanoate(n-PFOA)were linked to greater visceral adipose tissue in this group.In men,exposure to total perfluoroalkane sulfonates(PFSAs)and long-chain PFSAs was associated with reductions in abdominal fat,while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs.The prediction model demonstrated high accuracy,with an area under the curve(AUC)of 0.9925 for predicting obesity risk.Conclusion PFAS exposure is associated with regional fat distribution,with varying effects based on age,sex,and PFAS structure.The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk,with significant implications for public health.The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
基金The financial support received from the Shenzhen Science and Technology Innovation Commission(KCXFZ20201221173207022,WDZC20200821141349001)Shenzhen Bay Laboratory Startup Fund(21310041,S234602003)。
文摘Pu-erh tea,a traditional Chinese beverage,performs an anti-obesity function,but the correlation between its components and efficacy remains unknown.Here,we screened two Pu-erh teas with significant anti-obesity efficacies from 11 teas.In vitro experiments revealed that lipid accumulation in L02 cells and lipid synthesis in 3T3-L1 cells were significantly better inhibited by Tea-B than Tea-A.Further in vivo experiments using model mice revealed that the differences in chemical components generated two pathways in the anti-obesity efficacy and mechanism of Pu-erh teas.Tea-A changes the histomorphology of brown adipose tissue(BAT)and increases the abundance of Coriobacteriaceae_UCG_002 and cyclic AMP in guts through high chemical contents of cyclopentasiloxane,decamethyl,tridecane and 1,2,3-trimethoxybenzene,eventually increasing BAT activation and fat browning gene expression;the high content of hexadecane and 1,2-dimethoxybenzene in Tea-B reduces white adipose tissue(WAT)accumulation and the process of fatty liver,increases the abundance of Odoribacter and sphinganine 1-phosphate,inhibits the expression of lipid synthesis and transport genes.These mechanistic findings on the association of the representative bioactive components in Pu-erh teas with the anti-obesity phenotypes,gut microbes,gut metabolite structure and anti-obesity pathways,which were obtained for the first time,provide foundations for developing functional Pu-erh tea.
基金supported by the National Natural Science Foundation of China(32171970)the Chongqing Talent Program,China(cstc2022ycjh-bgzxm0073)+1 种基金the Natural Science Foundation of Chongqing,China(cstc2021jcyjcxtt X0004)the Rice Innovative Research Team of Chongqing Modern Agricultural Industrial Technology System,China(CQMAITS202301)。
文摘As a major subunit of the exocyst complex,members of the EXO70 family have mainly been shown to play roles in cell polarity and morphogenesis in Arabidopsis,but their roles in plant endosymbiosis,such as with arbuscular mycorrhizal fungi(AMF),have rarely been reported.Here,using knockout and overexpression lines,we show that OsEXO70L2,which encodes a divergent EXO70 protein in rice,controls the number of primary roots and is essential for large lateral root formation.Furthermore,the OsEXO70L2 mutant sr1 displayed rare internal AMF hyphaeand no arbuscules.We also found that AMF sporulation can occur in roots despite low colonization and that AMF colonization and sporulation are modulated by photoperiod and co-culture with clover.Finally,genes related to auxin homeostasis were found to be affected in the OsEXO70L2 knockout or overexpression lines,suggesting that auxin is at least partly responsible for the phenotypes.This study provides new perspectives on the role of the exocyst complex during root development and AM in rice.
基金supported by the Laboratory Open Fund of Key Technology and Materials in Minimally Invasive Spine Surgery(No.2024JZWC-YBA06)Medical and Industrial Cross Research Fundation of"Star of Jiaotong University"Program of Shanghai Jiao Tong University(Nos.YG2022ZD030,YG2021ZD34)+3 种基金Shanghai Jiao Tong University Institute of Minimally Invasive Surgery on Spine(No.2021JCPT03)Tongren Hospital Introduces the Talented Person Scientific Research Start Funds Subsidization Project(No.TR2022rc07)Tongren Hospital Top Priority Subject Project(No.tr2023xk01),Youth Innovation Promotion Association of CAS(No.2021264)Shanghai Natural Science Foundation(No.22ZR1469800).
文摘Severe traumatic bone healing relies on the involvement of growth factors.However,excessive supplementation of growth factors can lead to ectopic ossification and inflammation.In this study,utilizing the neural regulatory mechanism of bone regeneration,we have developed a multifunctional three dimensions(3D)printed scaffold containing both vasoactive intestinal peptide(VIP)and nerve growth factor(NGF)as an effective new method for achieving bone defect regeneration.The scaffold is provided by a controlled biodegradable and biomechanically matched poly(lactide-ethylene glycol-trimethylene carbonate)(PLTG),providing long-term support for the bone healing cycle.Factor loading is provided by peptide fiber-reinforced biomimetic antimicrobial extracellular matrix(ECM)(B-ECM)hydrogels with different release kinetics,the hydrogel guides rapid bone growth and resists bacterial infection at the early stage of healing.Physical and chemical characterization indicates that the scaffold has good structural stability and mechanical properties,providing an ideal 3D microenvironment for bone reconstruction.In the skull defect model,compared to releasing VIP or NGF alone,this drug delivery system can simulate a natural healing cascade of controllable release factors,significantly accelerating nerve/vascular bone regeneration.In conclusion,this study provides a promising strategy for implanting materials to repair bone defects by utilizing neuroregulatory mechanisms during bone regeneration.
基金supported by Key Project of Jiangsu Province’s Administration of Traditional Chinese Medicine(ZD202203)Jiangsu Province’s Innovation Program(JSSCTD202142)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(traditional Chinese medicine).
文摘Traditional Chinese medicine(TCM)can help prevent or treat diseases;however,there are few studies on the active substances of TCM.For example,Lycium barbarum L.has been proven to be effective in treating osteoporosis for thousands of years,but its active substance remains to be unknown.Prompted by the efforts to modernize TCM,the present study focused on the novel active substance of Lycium barbarum L.to reinforce kidney essence to produce bone marrow.Illumina deep sequencing analysis and stemloop polymerase chain reaction(PCR)assay revealed that miR162a,a Lycium barbarum L.-derived microRNA,can pass through the gastrointestinal tract to target the bone marrow in mice.Immunofluorescence staining showed that miR162a was absorbed through systemic RNA interference defective transmembrane family member 1(SIDT1)in the stomach.Bioinformatics prediction and luciferase reporter assay identified that miR162a targeted nuclear receptor corepressor(NcoR).Alizarin red staining and micro-computed tomography(microCT)confirmed that miR162a promoted osteogenic differentiation in bone marrow mesenchymal stem cells,zebrafish,and a mouse model of osteoporosis.In addition,transgenic Nicotiana benthamiana(N.benthamiana)leaves overexpressing miR162a were developed by agrobacterium infiltration method.microCT and tartrate-resistant acid phosphatase staining confirmed that transgenic N.benthamiana leaves effectively protected against osteoporosis in mice.Our study mechanistically explains how Lycium barbarum L.improves osteoporosis and supports that Lycium barbarum L.reinforces kidney essence,thereby strengthening the bone.miR162a expressed by transgenic plants may represent a novel and safe treatment for human osteoporosis.
基金Supported by the Guangxi Science and Technology Major Projects,No.AA23073012the National Natural Science Foundation of China,No.32360035 and No.32060018.
文摘BACKGROUND Probiotic Acetobacter pasteurianus is used to treat diabetes,but its specific hypoglycemic substances and mechanisms remain unclear.AIM To investigate the components for lipid metabolism of A.pasteurianus and its hypoglycemic effects,providing a basis for its broader application.METHODS The lipid metabolism of A.pasteurianus under different growth conditions was analyzed using lipidomics.Neutral lipid staining in A.pasteurianus cells and the formation of lipid droplet-like structures were observed using a confocal laser scanning microscope.The neutral lipid components were also analyzed using thin layer chromato-graphy.A diabetic mouse model was established to evaluate the hypoglycemic effects of the main lipid components of A.pasteurianus and their role in repairing tissues such as the pancreas.RESULTS After comparing the effects of three culture media,namely,brain heart infusion(BHI)medium with 2%glucose,chromium-rich and zinc-rich medium,and mineral salt medium,A.pasteurianus grew well in BHI containing 2%glucose and produced the most lipids.A total of 583 lipid metabolic products was identified,with higher levels of coenzyme Q9(CoQ9),oleic acid(OA),and wax ester,but no triacylglycerol was observed.It was found that the components that affected lipid metabolism in A.pasteurianus were mainly CoQ9 and OA.They exhibited hypoglycemic effects comparable to metformin in diabetic mice,repaired damaged pancreatic tissues,and did not cause damage to the liver and spleen.CONCLUSION Under high-nutrient growth conditions,A.pasteurianus contains abundant lipid components,such as CoQ9 and OA,with good hypoglycemic effects.
基金Supported by the Guangxi Science and Technology Major Projects,No.AA23073012the National Natural Science Foundation of China,No.32360035 and No.32060018。
文摘BACKGROUND Helicobacter pylori(H.pylori),a globally prevalent pathogen,is exhibiting increasing rates of antimicrobial resistance.However,clinical implementation of pre-treatment susceptibility testing remains limited due to the organism’s fastidious growth requirements and prolonged culture time.AIM To propose a novel detection method utilizing antibiotic-supplemented media to inhibit susceptible strains,while resistant isolates were identified through urease-mediated hydrolysis of urea,inducing a phenol red color change for visual confirmation.METHODS Colombia agar was supplemented with urea,phenol red,and nickel chloride,and the final pH was adjusted to 7.35.Antibiotic-selective media were prepared by incorporating amoxicillin(0.5μg/mL),clarithromycin(2μg/mL),metronidazole(8μg/mL),or levofloxacin(2μg/mL)into separate batches.Gastric antral biopsies were homogenized and inoculated at 1.0×105 CFU onto the media,and then incubated under microaerobic conditions at 37°C for 28-36 hours.Resistance was determined based on a color change from yellow to pink,and the results were validated via broth microdilution according to Clinical and Laboratory Standards Institute guidelines.RESULTS After 28-36 hours of incubation,the drug-resistant H.pylori isolates induced a light red color change in the medium.Conversely,susceptible strains(H.pylori 26695 and G27)produced no visible color change.Compared with the conventional 11-day protocol,the novel method significantly reduced detection time.Among 201 clinical isolates,182 were successfully evaluated using the new method,resulting in a 90.5%detection rate.This was consistent with the 95.5%agreement rate observed when compared with microdilution-based susceptibility testing.The success rate of the novel approach was significantly higher than that of the comparative method(P<0.01).The accuracy of the new method was comparable to that of the dilution method.CONCLUSION The novel detection method can rapidly detect H.pylori drug resistance within 28-36 hours.With its operational simplicity and high diagnostic performance,it holds strong potential for clinical application in the management of H.pylori antimicrobial resistance.
文摘The microbial consortium within an organism is crucial for its development and immune status.Alteration of the host microbiome by antibiotics or antinutritional factors may contribute to increased disease susceptibility.Here,we investigated whether exposure to different microbes could influence zebrafish larval microbiota composition and modulate their immune response towards a saponin challenge.Adult zebrafish were exposed to the antibiotic oxytetracycline(OxyT)or control tank water and their intestinal content was harvested after 30h(24h exposure,6h wash-out).Subsequently,zebrafish embryos were exposed to either OxyT-treated content or non-treated content from 3 to 6 days post fertilization(dpf).At 6 dpf part of the group received a saponin challenge until 8 dpf.Zebrafish larvae exposed to OxyT-treated adult gut content(3–6 dpf)showed an altered microbiota composition compared to controls.Interestingly,larvae exposed to saponin-treated OxyT-content showed fewer macrophages(as visualized by fluorescent microscopy using mpx:GFP114;mpeg:mCherry transgenic fish)in the overall fish as well as around the gut area than saponin-treated control-exposed larvae.Fewer macrophages were associated with a decreased expression of interleukin 22(il22)in larvae exposed to saponin-treated OxyT-content compared to controls.Overall,this study shows that exposure to different microbial environments early in life might affect disease susceptibility of larval zebrafish.
基金supported by the National Key Research and Development Program of China(2022YFC2303401,2022YFC2304100,2016YFD0500301,2021YFC0863300)the Beijing Science and Technology Plan(Z211100002521017)the National Natural Science Foundation of China(82241080)。
文摘The monkeypox virus(MPXV)has triggered a current outbreak globally.Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control.It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads,as it is one of the DNA viruses with the largest genome and the most AT-biased,and has a significant number of tandem repeats.Here we evaluated the performance of metagenomic and amplicon sequencing techniques,and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland.We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens.Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes.Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences.Besides,several intra-host single nucleotide variations were identified in the first imported mpox case.This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens.The findings of this study will significantly enhance the surveillance of MPXV.
基金supported by the National Natural Science Foundation of China(No.41806167)the High-Level Talents Research Fund of Qingdao Agricultural University(No.665/1120034)+4 种基金the NSFC-Shandong Joint Fund(No.U1906212)the Major Project of the 14th Five-Year Plan(No.2022QNLM030003-1)the Natural Science Foundation of Shandong Province(No.ZR2021ZD28)the Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City(No.2021CXLH0012)the Youth Innovation Plan of Shandong Province(No.2019KJM004).
文摘Two new dihydropyrones,rhytismatones C(1)and D(2),and a known compound,penicillenol A1(3),were isolated from the co-culture broth of the deep-sea-derived fungus Penicillium crustosum PRB-2 and Suaeda salsa-derived endophytic fungus Peni-cillium citrinum HDN11-186.Their structures were elucidated through comprehensive analysis of nuclear magnetic resonance(NMR)spectra and mass spectra.The absolute configurations of new compounds were determined by calculating the electronic circular di-chroism(ECD)spectrum.UPLC-MS data showed that compounds 1–3 could only be detected in the media of co-culture,suggesting new biosynthetic pathways were activated in the co-cultured fungi.Compound 1 showed obvious antibacterial activities against Pro-teus sp.MMBC-1002 and Bacillus subtilis MMBC-1004 with minimum inhibitory concentration(MIC)both at 25μmolL^(-1).
基金supported by the National Natural Science Foundation of China(31770164)Jiangsu Province’s Innovation Program(JSSCTD202142).
文摘To fight against invasion by pathogens,plants have evolved an elaborate innate immune system,of which the nucleotide-binding domain leucine-rich repeat-containing receptor(NLR)acts as the sensor and immune executor.Potyviruses,comprising one of the largest genera of plant viruses,cause severe crop yield losses worldwide.Inherited crop resistance to potyviruses can be used in breeding and plant transgenesis to control disease development.This review summarizes achievements in mapping and cloning NLR genes conferring dominant resistance against potyvirus in the families Fabaceae,Solanaceae,Brassicaceae,and Cucurbitaceae.It compares mechanisms of potyviral protein recognition and downstream signaling employed by NLRs and discusses strategies for exploiting NLRs to better control diseases caused by potyviruses.
基金supported by the National Natural Science Foundation of China(Nos.42276095,42188102,42141003,and U20A20103)the Open Innovation Fund for Undergraduate Students of Xiamen University,and Ocean Negative Carbon Emissions(ONCE)program。
文摘Haptophytes(Eukaryota,Hacrobia)play a crucial role in the energy budget and element cycling of diverse aquatic ecosystems due to their ability to engage in both phototrophic and mixotrophic nutritional modes.Nevertheless,there is a significant lack of knowledge regarding the short-term variations,such as diel dynamics,of their ecological features.During a short time frame in the summer of 2018,samples were collected from three distinct water layers in the South China Sea,including surface water,the deep chlorophyll maximum(DCM)layer,and 200 m depth.Fluorescence in situ hybridization coupled with tyramide signal amplification was used to quantify haptophyte cell abundance.Most haptophyte communities in all three water layers were composed of cells 2-5μm in size,while the proportion of cells<2μm increased with water depth.High-throughput sequencing of the V4 hypervariable regions of the SSU rRNA revealed that Chrysochromulina and Phaeocystis predominated the community,and the former was more abundant in the surface water and 200 m depth and the latter was more abundant in the DCM layer.Higher abundance of small cells(<2μm and 2-5μm)during the night was found compared to the day time,whereas large cells(5-10μm and 10-20μm)were more prevalent during the day time.The results of correlation analyses showed that haptophyte abundance was possibly impacted by both environmental biotic(heterotrophic nanoflagellates,heterotrophic bacteria,and viruses)and abiotic(temperature,salinity,and nutrients)factors.
基金supported by the National Natural Science Foundation of China(Nos.22275043,52203184,52293380 and 52293383)Startup Fund of Wenzhou Institute,University of Chinese Academy of Sciences(Nos.WIUCASQD2021022 and WIUCASQD2021019).
文摘Bacterial biofilms present a significant challenge in treating drug-resistant infections,necessitating the development of innovative nanomedicines.In this study,we introduce triclosan-conjugated,lipase-responsive polymeric micelles designed to exploit biofilm properties and serve as a responsive drug delivery platform.The micelles were created using an amphiphilic block polymer synthesized via ring-opening polymerization ofε-caprolactone(CL)and triclosan-containing cyclic trimethylene carbonate(MTC-Tri).Poly(ethylene glycol)(PEG-OH)acted as the macro-initiator,resulting in micelles with a PEG shell that facilitated their penetration into bacterial biofilms.An important advantage of our micelles lies in their interaction with local bacterial lipases within biofilms.These lipases triggered rapid micelle degradation,releasing triclosan in a controlled manner.This liberated triclosan effectively eliminated bacteria embedded in the biofilms.Notably,the triclosan-conjugated micelles displayed minimal toxicity to murine fibroblasts,indicating their biocompatibility and safety.This finding emphasizes the potential application of these micelles in combatting drug resistance observed in bacterial biofilms.Our triclosan-conjugated,lipase-responsive polymeric micelles exhibit promising characteristics for addressing drug resistance in bacterial biofilms.By harnessing biofilm properties and implementing a responsive drug delivery system,we seek to provide an effective solution in the fight against drug-resistant bacteria.
基金National Natural Science Foundation of China,No.32060018 and No.32360035Through Special Fund Projects for Guide Local Science and Technology Development by the China Government,No.GUIKEZY20198004+2 种基金Anhui Provincial Natural Science Foundation,No.2308085QH245the Natural Science Foundation of the Anhui Higher Education Institutions of China,No.2023AH040261Changzhou Science and Technology Project Fund,No.CJ20210012.
文摘BACKGROUND The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host.Although selenium is closely related to pathogenicity as an environmental factor,the specific correlation between them remains unclear.AIM To investigate how selenium acts on virulence factors and reduces their toxicity.METHODS H.pylori strains were induced by sodium selenite.The expression of cytotoxin-associated protein A(CagA)and vacuolating cytotoxin gene A(VacA)was determined by quantitative PCR and Western blotting.Transcriptomics was used to analyze CagA,CagM,CagE,Cag1,Cag3,and CagT.C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction,and H.pylori colonization,inflammatory reactions,and the cell adhesion ability of H.pylori were assessed.RESULTS CagA and VacA expression was upregulated at first and then downregulated in the H.pylori strains after sodium selenite treatment.Their expression was significantly and steadily downregulated after the 5th cycle(10 d).Transcriptome analysis revealed that sodium selenite altered the levels affect H.pylori virulence factors such as CagA,CagM,CagE,Cag1,Cag3,and CagT.Of these factors,CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite.Moreover,CagT expression was upregulated before the 3rd cycle(6 d)and significantly downregulated after the 5th cycle.Cag1 and Cag3 expression was upregulated and downregulated,respectively,but no significant change was observed by the 5th cycle.C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction.The extent of H.pylori colonization in the stomach increased;however,sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H.pylori-infected mice,and the cell adhesion ability of H.pylori was significantly weakened.CONCLUSION These results demonstrate that H.pylori displayed virulence attenuation after the 10th d of sodium selenite treatment.Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H.pylori,thus mitigating the inflammatory damage to the gastric mucosa.
基金financial support from the Key Program of the National Natural Science Foundation of China(82130093)Wenhong Zhang,Juanjuan Zhang acknowledge financial support from Shanghai Municipal Science and Technology Major Project(HS2021SHZX001)+2 种基金Wenhong Zhang acknowledges financial support from the Key Program of the National Natural Science Foundation of China(82161138018 and 82041010)Shanghai Science and Technology Committee(20dz2260100,20Z11901100)Shanghai Hospital Development Center(SHDC2020 CR5010-002).
文摘The SARS-CoV-2 virus,particularly the Omicron BA.2 variant,led to a significant surge in Shanghai,2022.However,the viral load dynamic in Omicron infections with varying clinical severities remain unclear.This prospective cohort included 48,830 hospitalized coronavirus disease 2019(COVID-19)patients across three hospitals in Shanghai,China,between 23 March and 15 May,2022.Systematic nucleic acid testing was performed using RT-PCR Cycle threshold(Ct)value as a proxy of viral load.We analyzed the kinetic characteristics of viral shedding by clinical severity and identified associated risk factors.The study comprised 31.06%asymptomatic cases,67.66%mild-moderate cases,1.00%severe cases,0.29%critical and fatal cases.Upon admission,57%of patients tested positive,with peak viral load observed at 4 days(median Ct value 27.5),followed by a decrease and an average viral shedding time(VST)of 6.1 days(Interquartile range,4.0–8.8 days).Although viral load exhibited variation by age and clinical severity,peak Ct values occurred at similar times.Unvaccinated status,age exceeding 60,and comorbidities including hypertension,renal issues kidney dialysis and kidney transplantation,neurological disorders,rheumatism,and psychotic conditions were found to correlate with elevated peak viral load and extended VST.Asymptomatic cases demonstrated a 40%likelihood of contagiousness within 6 days of detection,while mild-moderate and severe cases exhibited post-symptom resolution infectious probabilities of 27%and over 50%,respectively.These findings revealed that the initial Ct values serve as a predictive indicator of severe outcomes.Unvaccinated elderly individuals with particular comorbidities are at high-risk for elevated viral load and prolonged VST.
基金Federal Ministry of Education and Research(Q-HCC,01KD2214)the Sino-German Center for Research Promotion(GZ-1546 and C-0012)+5 种基金the State Ministry of Baden-Wuerttemberg for Sciences,Research and Arts supporting the Clinical Cooperation Unit Healthy Metabolism at the Center for Preventive Medicine and Digital Health(CCU Healthy Metabolism)the Baden-Wuerttemberg Center for Digital Early Disease Detection and Prevention(BW-ZDFP)the Foundation for Biomedical Alcohol Research,Schriesheim,Germanyfunded by the Federal Ministry of Education and Research(BMBF)the Ministry of Culture and Science of the German State of North Rhine-Westphalia(MKW)(NRW Rueckkehrprogramm)under the Excellence Strategy of the Federal Government and the Länderthe German Research Foundation(DFG,403224013-SFB1382,gut-liver axis).
文摘The prevalence of metabolic-dysfunction-associated steatotic liver disease(MASLD)is alarmingly high;it is estimated to affect up to a quarter of the global population,making it the most common liver disorder worldwide.MASLD is characterized by excessive hepatic fat accumulation and is commonly associated with comorbidities such as obesity,dyslipidemia,and insulin resistance;however,it can also manifest in lean individuals.Therefore,it is crucial to develop effective therapies for this complex condition.Currently,there are no approved medications for MASLD treatment,so there is a pressing need to investigate alternative approaches.Extensive research has characterized MASLD as a multifaceted disease,frequently linked to metabolic disorders that stem from dietary habits.Evidence suggests that changes in the gut microbiome play a fundamental role in the development and progression of MASLD from simple steatosis to steatohepatitis and even hepatocellular carcinoma(HCC).In this review,we critically examine the literature on the emerging field of gut-microbiota-based therapies for MASLD and metabolicdysfunction-associated steatohepatitis(MASH),including interventions such as fecal microbiota transplantation(FMT),probiotics,prebiotics,short-chain fatty acids,antibiotics,metabolic pathway targeting,and immune checkpoint kinase blockade.
文摘BACKGROUND Modern pharmacological studies have confirmed that plant-derived compounds from Puerariae flos(PF)has significant biological activities against liver damage,tumors and inflammation.Kakkatin is an isoflavone polyphenolic compound isolated from PF flower.However,the effect of kakkatin and its derivatives on anti-tumor has not been well explored.AIM To design and synthesize a kakkatin derivative[6-(hept-6-yn-1-yloxy)-3-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one(HK)]to explore its anti-tumor biological activity.METHODS Hept-6-yn-1-yl ethanesulfonate was introduced to replace hydrogen at the hydroxyl position of kakkatin phenol,and the derivative of kakkatin was prepared;the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to detect cell viability,a clone formation assay was adopted to detect cell proliferation,apoptosis,necrosis,and cell cycles were analyzed by Annexin V/propidium iodide staining and flow cytometry.Cell migration and invasion ability were evaluated by cell scratch assay and transwell assay.The potential mechanism of HK on hepatocellular carcinoma(HCC)SMMC-7721 cells was explored through network pharmacology and molecular docking,and finally real-time PCR assays was used to verify the potential targets and evaluate the biological activity of HK.RESULTS Compared with kakkatin,the modified HK did not significantly increase the inhibitory activity of gastric cancer MGC803 cells,but the inhibitory activity of HCC SMMC-7721 cells was increased by about 30 times,with an IC50 value of 2.5μM,and the tumor inhibition effect was better than cisplatin,which could significantly inhibit the cloning,invasion and metastasis of HCC SMMC-7721 cells,and induce apoptosis and G2/M cycle arrest.Its mechanism of action is mainly related to the upregulation of PDE3B and NFKB1 target proteins in the cAMP pathway.CONCLUSION HK have a significant inhibitory effect on HCC SMMC-7721 cells,and the targets of their action may be PDE3B and NFKB1 proteins in the cAMP pathway,making it a good lead drug for the treatment of HCC.
