Intestinal stem cells(ISCs)initiate intestinal epithelial regeneration and tumorigenesis,and they experi-ence rapid refilling upon various injuries for epithelial repair as well as tumor reoccurrence.It is crucial to ...Intestinal stem cells(ISCs)initiate intestinal epithelial regeneration and tumorigenesis,and they experi-ence rapid refilling upon various injuries for epithelial repair as well as tumor reoccurrence.It is crucial to reveal the mechanism underlying such plasticity for intestinal health.Recent studies have found that metabolic pathways control stem cell fate in homeostasis,but the role of metabolism in the regeneration of ISCs after damage has not been clarified.Here,we find that in a human colorectal cancer dataset,miR-29a and b(miR-29a/b)are metabolic regulators highly associated with intestinal tumorigenesis and worse prognostic value of radiotherapy.We also show that these two microRNAs are required for intesti-nal stemness maintenance in mice,and their expression is induced in regenerated ISCs after irradiation injury,resulting in skewed ISC fate from differentiation towards self-renewal.This upregulation of miR-29a/b expression in ISCs leads to suppression of fatty acid oxidation(FAO)and depression of oxidative phosphorylation,which in turn controls the balance between self-renewal and differentiation of ISCs.Deletion of miR-29a/b prevents these effects and thus impairs ISC-mediated epithelial recovery.Finally,we filter the potential targets of miR-29a/b and identify Hnf4g,a transcription factor,that drives this metabolic reprogramming through regulating FAO-related enzymes.Our work discovers an impor-tant metabolic mechanism of ISC-mediated regeneration and potentially pave the way for more targeted and effective therapeutic strategies for intestinal repair as well as tumor treatment.展开更多
Background:The prevalence of type 2 diabetes mellitus(T2DM)has been rapidly growing in Chinese populations in recent decades,and the shift in eating habits is a key contributing factor to this increase.Eating out of h...Background:The prevalence of type 2 diabetes mellitus(T2DM)has been rapidly growing in Chinese populations in recent decades,and the shift in eating habits is a key contributing factor to this increase.Eating out of home(EOH)is one of the major shifts in eating habits during this period.However,the influence of EOH on the incidence of T2DM among Chinese urban workers is unknown.Methods:The cross-sectional study involved an analysis of 13,904 urban workers recruited from 11 health examination centers in the major cities of China to explore the relationship between EOH and T2DM between 2013 September and 2016 March.Results:Average weekly EOH frequency≥10 times was positively associated with increased incidence of T2DM in the sampled population(OR:1.31[1.11-1.54],p<0.01),most notably in participants≤45 years old(OR:1.41[1.11-1.80],p<0.01])and in males(OR:1.26[1.06-1.51],p<0.01).An EOH frequency of 5 times/week appears as a threshold for a significant increase in the odds of T2DM.Weekly EOH frequency≥5 times was associated with increased odds of T2DM in a dose-response manner in the total population and almost all subgroups(poverall association<0.05 andpnonlinearity≤0.05).Conclusion:This study showed that a frequency of EOH(≥5 times/week)was associated with a frequency-dependent increase in the odds of T2DM urban workers in China.More nutrition promotion is needed to improve the eating behavior of Chinese urban workers to reduce T2DM risk.展开更多
BACKGROUND Long noncoding RNA(lncRNA)ZNFX1-AS1(ZFAS1)is a newly discovered lncRNA,but its diagnostic value in gastric cancer is unclear.AIM To investigate the potential role of ZFAS1 in gastric cancer and to evaluate ...BACKGROUND Long noncoding RNA(lncRNA)ZNFX1-AS1(ZFAS1)is a newly discovered lncRNA,but its diagnostic value in gastric cancer is unclear.AIM To investigate the potential role of ZFAS1 in gastric cancer and to evaluate the clinical significance of ZFAS1 as a biomarker for gastric cancer screening.METHODS Quantitative real-time polymerase chain reaction(qRT-PCR)was used to screen for gastric cancer-associated lncRNAs in gastric cancer patients,gastric stromal tumor patients,gastritis or gastric ulcer patients,and healthy controls.Correlations between ZFAS1 expression and clinicopathological features were analyzed.The biological effects of ZFAS1 on the proliferation,migration,and invasion of gastric cancer cells were studied by MTT,colony formation,and transwell migration assays.The potential mechanism of ZFAS1 was demonstrated using enzyme-linked immunosorbent assay and qRT-PCR.The relationship between ZFAS1 and tumorigenesis was demonstrated using in vivo tumor formation assays.RESULTS The plasma level of lncRNA ZFAS1 was significantly higher in preoperative patients with gastric cancer than in individuals in the other 4 groups.Increased expression of ZFAS1 was significantly associated with lymph node metastasis,advanced TNM stage,and poor prognosis.ZFAS1 regulated the proliferation,migration,and invasion of gastric cancer cells and regulated the growth of gastric cancer cells in vivo.LIN28 and CAPRIN1 were identified as key downstream mediators of ZFAS1 in gastric cancer cells.CONCLUSION LncRNA ZFAS1 promoted the invasion and proliferation of gastric cancer cells by modulating LIN28 and CAPRIN1 expression,suggesting that ZFAS1 can be used as a potential diagnostic and prognostic biomarker in gastric cancer.展开更多
Exosomes,a type of extracellular vesicles(EVs),were first discovered in sheep reticulocytes in 1983[1],and after four years,the name‘exosome’was officially given to them.A variety of cells secrete exosomes under bot...Exosomes,a type of extracellular vesicles(EVs),were first discovered in sheep reticulocytes in 1983[1],and after four years,the name‘exosome’was officially given to them.A variety of cells secrete exosomes under both normal and pathological conditions.Exosomes are mainly products of themultivesicular body formed by intracellular lysosomal invagi nation,and released into the extracellular space by fusion of the outer membrane of the multivesicular body with the cell membrane.展开更多
Endothelial progenitor cells (EPC) are the precursors of mature endothelial cells and are involved in neovascularization and reendothelization. Previous studies have shown that oxidative stress can induce EPC senescen...Endothelial progenitor cells (EPC) are the precursors of mature endothelial cells and are involved in neovascularization and reendothelization. Previous studies have shown that oxidative stress can induce EPC senescence. However,the potential molecular mechanisms involved are still not clearly elucidated.展开更多
Glucagon-like peptide-1(GLP-1),a signal peptide hormone produced by enteroendocrine L cells from the distal small intestine and colon,is a crucial regulator of glycemic control,gastric emptying,satiety,and body weight...Glucagon-like peptide-1(GLP-1),a signal peptide hormone produced by enteroendocrine L cells from the distal small intestine and colon,is a crucial regulator of glycemic control,gastric emptying,satiety,and body weight.Recent advancements in understanding the dietary modulation of GLP-1 through enteroendocrine L-cells have highlighted the potential of various nutrients in enhancing its endogenous secretion.This review summarizes the current knowledge on food-derived molecules,including macronutrients,polyphenols,other chemicals,and bacterial products,that can modulate GLP-1 production.It explores the efficacy and impact of various treatments and the involved signaling pathways,aiming to contribute to developing innovative strategies for enhancing endogenous GLP-1 release.展开更多
Adolescent depressive symptoms represent a significant public health concern,with negative life events and dysfunctional attitudes playing pivotal roles in theirdevelopment.A cross-sectional study by Yu et al assessed...Adolescent depressive symptoms represent a significant public health concern,with negative life events and dysfunctional attitudes playing pivotal roles in theirdevelopment.A cross-sectional study by Yu et al assessed the interplay betweendysfunctional attitudes,social support,and depressive symptoms in 795 Chineseadolescents(49.9%male,mean age 15.2±1.8 years,age range 11-18 years)fromfive middle schools in Shandong Province.Using the Dysfunctional AttitudesScale,Adolescent Life Events Scale,Beck Depression Inventory,and SocialSupport Rating Scale,the study identified that dysfunctional attitudes,particularlyover-autonomy and over-perfectionism,mediate the relationship betweennegative life events and depressive symptoms.Social support moderated thisrelationship,significantly reducing depressive symptoms.These findingsunderscore the need for preventive and therapeutic strategies targeting dysfunctionalattitudes and enhancing social support to address adolescent depressivesymptoms.In this article,we extend their findings to highlight the significance ofculturally tailored interventions that incorporate familial and communitydynamics in mitigating depressive symptoms,particularly in collectivist societies.展开更多
Background The genes encoding adiponectin receptor 1 (ADIPOR1) and small ubiquitin-like modifier 4 (SUM04) have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two g...Background The genes encoding adiponectin receptor 1 (ADIPOR1) and small ubiquitin-like modifier 4 (SUM04) have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two genes, acting separately or interacting, affect risk of coronary artery disease (CAD) without diabetes. Methods We genotyped 200 CAD patients without diabetes and 200 controls without CAD or diabetes at three single-nucleotide polymorphisms (SNPs) in ADIPOR1 and one SNP in SUM04, which were chosen based on previous studies. Potential associations were also explored between these SNPs and clinical characteristics of CAD without diabetes. Results Risk alleles at three SNPs inADIPOR1 (rs7539542-G, rs7514221-C and rs3737884-G) and the G allele at SNP rs237025 in SUM04 significantly increased risk of CAD without diabetes, with ORs ranging from 1.79 to 4.44. Carriers of any of these four risk alleles showed similar adverse clinical characteristics. Compared with individuals with a CC or GC genotype, those with a GG genotype at rs3737884 were at significantly higher risk of CAD that affected the left anterior descending coronary artery (OR: 6.77, P = 0.009), the right coronary artery (OR: 4.81, P = 0.028) or a relatively large number of vessels (P = 0.04). Individuals carrying a risk allele at one or more of the three SNPs in ADIPOR1 as well as a risk allele at the SNP in SUM04 were at significantly higher risk of CAD without diabetes than individuals not carrying any risk alleles (OR: 5.82, 95% CI: 1.23-27.7, P= 0.013). Conelusions SNPs in ADIPORl and SUMO4 are associated with elevated risk of CAD without diabetes, and SNPs in the two genes may interact to jointly affect disease risk.展开更多
BACKGROUND Shigella flexneri(S.flexneri)is a major pathogen causing acute intestinal infection,but the systematic oxidative damage incurred during the course of infection has not been investigated.AIM To investigate t...BACKGROUND Shigella flexneri(S.flexneri)is a major pathogen causing acute intestinal infection,but the systematic oxidative damage incurred during the course of infection has not been investigated.AIM To investigate the incurred systemic RNA oxidative damage and the diagnostic value of RNA oxidative metabolites during S.flexneri-induced intestinal infection.METHODS In this study,a Sprague-Dawley rat model of acute intestinal infection was established by oral gavage with S.flexneri strains.The changes in white blood cells(WBCs)and cytokine levels in blood and the inflammatory response in the colon were investigated.We also detected the RNA and DNA oxidation in urine and tissues.RESULTS S.flexneri infection induced an increase in WBCs,C-reactive protein,interleukin(IL)-6,IL-10,IL-1β,IL-4,IL-17a,IL-10,and tumor necrosis factorα(TNF-α)in blood.Of note,a significant increase in urinary 8-oxo-7,8-dihydroguanosine(8-oxo-Gsn),an important marker of total RNA oxidation,was detected after intestinal infection(P=0.03).The urinary 8-oxo-Gsn level returned to the baseline level after recovery from infection.In addition,the results of a correlation analysis showed that urinary 8-oxo-Gsn was positively correlated with the WBC count and the cytokines IL-6,TNF-α,IL-10,IL-1β,and IL-17α.Further detection of the oxidation in different tissues showed that S.flexneri infection induced RNA oxidative damage in the colon,ileum,liver,spleen,and brain.CONCLUSION Acute infection induced by S.flexneri causes increased RNA oxidative damage in various tissues(liver,spleen,and brain)and an increase of 8-oxo-Gsn,a urinary metabolite.Urinary 8-oxo-Gsn may be useful as a biomarker for evaluating the severity and prognosis of infection.展开更多
Aim To explore the mechanisms of microRNA 200a in hepatic insulin resistance induced by interleukin-6(IL-6),specifically to in-vestigate the role of microRNA 200a in hepatic glucogen and insulin signal pathway transdu...Aim To explore the mechanisms of microRNA 200a in hepatic insulin resistance induced by interleukin-6(IL-6),specifically to in-vestigate the role of microRNA 200a in hepatic glucogen and insulin signal pathway transduction.Methods The cell model forhepatic insulin resistance was induced by IL-6(10μg/L) for 24 hours in NCTC1469 cell.The level of glucogen was reduced.The expression of microRNA 200a was tested by q-PCR.The level of glucogen was quantified in NCTC 1469 transfected with microRNA200a mimics.The target gene of microRNA200a was predicted by bio-information software.The protein level of the target gene wastested by Western Blotting.Results The level of glucogen and the insulin signal pathway was inhibited in NCTC 1469 cells treated by IL-6.The expression of microRNA 200a was decreased in NCTC 1469 cell induced by IL-6.The level of glucogen and theinsulin signal pathway were stimulated in NCTC 1469 cell transfected by microRNA 200a mimics.The protein level of Pten was decreased by overexpression of microRNA200a.Conclusions IL-6 downregulates the expression of microRNA200a in hepatic insulin resistant NCTC 1469 cells.The microRNA 200a stimulates biosynthesis of glucogen as well as insulin signal pathway accompanied by down-regulating the expression of Pten.展开更多
BACKGROUND As of June 1,2020,over 370000 coronavirus disease 2019(COVID-19)deaths have been reported to the World Health Organization.However,the risk factors for patients with moderate-to-severe or severe-to-critical...BACKGROUND As of June 1,2020,over 370000 coronavirus disease 2019(COVID-19)deaths have been reported to the World Health Organization.However,the risk factors for patients with moderate-to-severe or severe-to-critical COVID-19 remain unclear.AIM To explore the characteristics and predictive markers of severely and critically ill patients with COVID-19.METHODS A retrospective study was conducted at the B11 Zhongfaxincheng campus and E1-3 Guanggu campus of Tongji Hospital affiliated with Huazhong University of Science and Technology in Wuhan.Patients with COVID-19 admitted from 1st February 2020 to 8th March 2020 were enrolled and categorized into 3 groups:The moderate group,severe group and critically ill group.Epidemiological data,demographic data,clinical symptoms and outcomes,complications,laboratory tests and radiographic examinations were collected retrospectively from the hospital information system and then compared between groups.RESULTS A total of 126 patients were enrolled.There were 59 in the moderate group,49 in the severe group,and 18 in the critically ill group.Multivariate logistic regression analysis showed that age[odd ratio(OR)=1.055,95%(confidence interval)CI:1.099-1.104],elevated neutrophil-to-lymphocyte ratios(OR=4.019,95%CI:1.045-15.467)and elevated high-sensitivity cardiac troponin I(OR=10.126,95%CI:1.088-94.247)were high-risk factors.CONCLUSION The following indicators can help clinicians identify patients with severe COVID-19 at an early stage:age,an elevated neutrophil-to-lymphocyte ratio and high sensitivity cardiac troponin I.展开更多
Objective VATER/VACTERL-like association is associated with adverse pregnancy outcomes.Genetic evidence of this disorder is sporadic.In this study,we aimed to provide genetic insights to improve the diagnosis of VACTE...Objective VATER/VACTERL-like association is associated with adverse pregnancy outcomes.Genetic evidence of this disorder is sporadic.In this study,we aimed to provide genetic insights to improve the diagnosis of VACTERL.Methods We have described a Chinese family in which four members were affected by renal defects or agenesis,anal atresia,and anovaginal fistula,which is consistent with the diagnosis of a VACTERL-like association.Pedigree and genetic analyses were conducted using genome and exome sequencing.Results Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals,harboring a 196–380 kb microdeletion on Xq27.1,which was identified by familial exome sequencing.Genome sequencing was performed on the affected male,confirming a-196 kb microdeletion in Xq27.1,which included a 28%loss of the CDR-1 gene.Four family members were included in the co-segregation analysis,and only VACTERL-like cases with microdeletions were reported in X27.1.Conclusion These results suggest that the 196–380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like association.However,further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.展开更多
MicroRNAs(miRNAs) are key regulators involved in various tumors. They regulate cell cycle, apoptosis and cancer stemness, metastasis and chemoresistance by controlling their target gene expressions. Here, we mainly di...MicroRNAs(miRNAs) are key regulators involved in various tumors. They regulate cell cycle, apoptosis and cancer stemness, metastasis and chemoresistance by controlling their target gene expressions. Here, we mainly discuss the potential uses of miR NAs in colorectal cancer(CRC) diagnosis. We also shed light on the important corresponding miR NA targets and on the major regulators of miR NAs. Furthermore, we discuss miR NA activity in assessing the prognosis and recurrence of CRC as well as in modulating responsiveness to chemotherapy. Based on the various pro-oncogenic/anti-oncogenic roles of miR NAs, the advantages of a therapeutic strategy based on the delivery of miR NA mimics are also mentioned. Together, mi RNA seems to be an excellent tool for effectively monitoring and targeting CRC.展开更多
The immunologically mediated disease is a big family which affects many people in the world, since the cures are not yet available for most immune diseases, the patients face a lifetime of illness and treatment. Chine...The immunologically mediated disease is a big family which affects many people in the world, since the cures are not yet available for most immune diseases, the patients face a lifetime of illness and treatment. Chinese medicine inspires us to develop new methods for the treatment of immune diseases. Previous researches of immune system have revealed that an immune network exists. The immune system is like a complex highway; if we travel on these highways, we must have a map to avoid travelling in the wrong direction. Drawing the map of immune network will provide new tools for us to look directly at the basis of the immune system.展开更多
Current contraceptive methods come with a number of drawbacks,including low efficacy,in the case of commercial contraceptive gels,and a reduction in the quality of sexual intercourse,in the case of condoms.Adding phar...Current contraceptive methods come with a number of drawbacks,including low efficacy,in the case of commercial contraceptive gels,and a reduction in the quality of sexual intercourse,in the case of condoms.Adding pharmacologically-active agents to contraceptive gels holds the potential to improve sexual experience,and hardbor safety and hygiene.In this study,we fabricated a carbomer-based contraceptive gel consisting of three agents:tenofovir,gossypol acetate,and nitroglycerin(TGN),with pH adjusted to 4.5(to be compatible with the vagina).In vitro,the gossypol component of the contraceptive gel proved to be an effective spermicide.When the concentration of gossypol acetate was 10 mg/ml,the spermicidal ability reached 100%after 30 s.In addition,tenofovir in the gel significantly inhibited lentiviral transfection efficiency in cell-containing media.In 6 pairs of rats,the gel successfully prevented all females from conceiving after successful mating.Moreover,increased sexual frequency and enhanced erection,which were promoted by the nitroglycerin in the components,were observed in male rats that had the gel applied to their penises.This novel TGN contraceptive gel yielded a higher contraceptive success rate than that of the commercial contraceptive gel(Contragel®).In addition,it has the added benefits to prevent sexually transmitted diseases and improve male libido and erectile function during sexual intercourse.Combining three FDA-approved and marketed agents together,our trifunctional TGN gel has a great potential for further translation and commercialization.展开更多
Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia,and increases the risk of many aging-related metabolic diseases.Here,we report phenotypic and single-nucleus transcriptomic analyses o...Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia,and increases the risk of many aging-related metabolic diseases.Here,we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging.A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types,indicating a higher susceptibility of skeletal muscle fiber to aging.We found a downregulation of Foxo3 in aged primate skeletal muscle,and identi-fied FOxo3 as a hub transcription factor maintaining skeletal muscle homeostasis.Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model,we revealed that silence of Foxo3 accelerates human myotube senescence,whereas genetic activation of endogenous FOxO3 alleviates human myotube aging.Altogether,based on a combination of monkey skeletal muscle and human myotube aging research models,we unraveled the pivotal role of the FOxO3 in safeguarding primate skeletal muscle from aging,providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-relateddisorders.展开更多
Introduction:The treatment of elderly‐onset rheumatoid arthritis(RA)pursues the same objectives as in younger patients:to control the symptoms,to prevent structural damage,to preserve function,and to decrease excess ...Introduction:The treatment of elderly‐onset rheumatoid arthritis(RA)pursues the same objectives as in younger patients:to control the symptoms,to prevent structural damage,to preserve function,and to decrease excess mortality.The presence of co‐morbidities is more specific in elderly patients with RA,which raises therapeutic challenges for physicians.Comprehensive geriatric assessment(CGA)is an essential tool that examines factors affecting the course of disease and the outcome of treatment.CGA includes the patient's functional,physical,mental,emotional,pharmacotherapeutic,and socioeconomic status.This article aims to present CGA in the evaluation and management of frail elderly patient with RA.Patient&Result:A case study of an 80‐year‐old man with RA and ILD is presented to describe the process of CGA and provides nutritional supplement therapy,patient education,and rehabilitation guidance to help patient progress from frailty to non‐frailty.Discussion:The case revealed that CGA provides physicians with information on the reversible area of frailty and the leading cause of deterioration in EORA.展开更多
Objective:Few studies have been conducted to establish animal models of left bundle branch block by using three-dimensional mapping systems.This research was aimed at creating a canine left bundle branch block model b...Objective:Few studies have been conducted to establish animal models of left bundle branch block by using three-dimensional mapping systems.This research was aimed at creating a canine left bundle branch block model by using a three-dimensional mapping system.Materials and Methods:We used a three-dimensional mapping system to map and ablate the left bundle branch in beagles.Results:Ten canines underwent radiofrequency ablation,among which left bundle branch block was successfully es-tablished in eight,one experienced ventricular fibrillation,and one developed third-degree atrioventricular block.The maximum HV interval measured within the left ventricle was 29.00±2.93 ms,and the LBP-V interval at the ablation site was 20.63±2.77 ms.The LBP-V interval at the ablation target was 71.08%of the maximum HV interval.Conclusion:This three-dimensional mapping system is a reliable and effective guide for ablation of the left bundle branch in dogs.展开更多
The gut microbiome is emerging as a pivotal player in the pathogenesis and development of autoimmune diseases(ADs)[1].A comprehensive understanding of the interaction among gut microbiota,drug metabolism,and host immu...The gut microbiome is emerging as a pivotal player in the pathogenesis and development of autoimmune diseases(ADs)[1].A comprehensive understanding of the interaction among gut microbiota,drug metabolism,and host immune reaction will shed light on the development of precision medicine for ADs.Microbiota-based interventions,such as specific diet,probiotics/prebiotics,or restricted consortium transplantation,have shown promising preventive and therapeutic potentials in pre-clinical and clinical trials[2].展开更多
Accumulating evidence suggests an essential role of disturbed gut microbiota in the etiopathogenesis of systemic lupus erythematosus(SLE),but it remains unclear as to gut virome.In this study,fecal virus-like particle...Accumulating evidence suggests an essential role of disturbed gut microbiota in the etiopathogenesis of systemic lupus erythematosus(SLE),but it remains unclear as to gut virome.In this study,fecal virus-like particles(VLPs)isolated from 76 non-treated SLE patients and 75 healthy controls were subjected to gut virome profiling.The proportion of bacteriophages was significantly elevated in the SLE gut,and the altered viral taxa were correlated with clinical parameters.Gut virome and bacteriome were closely associated with each other in SLE patients.The combination of gut viral and bacterial markers displayed better performance in distinguishing SLE patients from healthy controls.Further,VLPs from non-treated SLE patients promoted interferon-a production in an epithelial cell line and human immune cells.Intriguingly,the interferon-stimulatory capacity diminished in VLPs from post-treated SLE patients.Our findings may shed novel insights into SLE pathogenesis.Further in-depth understanding of gut virome might help develop future biomarkers and therapeutics for SLE patients.展开更多
基金supported by the National Natural Science Foundation of China(32372247)the National Key Research and Development Program of China(2023YFF1104501)to Huiyuan Guo.
文摘Intestinal stem cells(ISCs)initiate intestinal epithelial regeneration and tumorigenesis,and they experi-ence rapid refilling upon various injuries for epithelial repair as well as tumor reoccurrence.It is crucial to reveal the mechanism underlying such plasticity for intestinal health.Recent studies have found that metabolic pathways control stem cell fate in homeostasis,but the role of metabolism in the regeneration of ISCs after damage has not been clarified.Here,we find that in a human colorectal cancer dataset,miR-29a and b(miR-29a/b)are metabolic regulators highly associated with intestinal tumorigenesis and worse prognostic value of radiotherapy.We also show that these two microRNAs are required for intesti-nal stemness maintenance in mice,and their expression is induced in regenerated ISCs after irradiation injury,resulting in skewed ISC fate from differentiation towards self-renewal.This upregulation of miR-29a/b expression in ISCs leads to suppression of fatty acid oxidation(FAO)and depression of oxidative phosphorylation,which in turn controls the balance between self-renewal and differentiation of ISCs.Deletion of miR-29a/b prevents these effects and thus impairs ISC-mediated epithelial recovery.Finally,we filter the potential targets of miR-29a/b and identify Hnf4g,a transcription factor,that drives this metabolic reprogramming through regulating FAO-related enzymes.Our work discovers an impor-tant metabolic mechanism of ISC-mediated regeneration and potentially pave the way for more targeted and effective therapeutic strategies for intestinal repair as well as tumor treatment.
基金National Nutrition Science Research Grant(Grant/Award Number:CNS-NNSRG2019-234)Chinese National Key Research and Development Program during the 13th Five-year Plan Period(Grant/Award Number:2022YFC2010106)+2 种基金Disciplines Construction Project of Peking Union Medical College(Grant/Award Number:PUMC,201920202102)National Natural Science Foundation of China(Grant/Award Number:81971316)National High Level Hospital Clinical Research Funding(Grant/Award Number:bj-2023-72)。
文摘Background:The prevalence of type 2 diabetes mellitus(T2DM)has been rapidly growing in Chinese populations in recent decades,and the shift in eating habits is a key contributing factor to this increase.Eating out of home(EOH)is one of the major shifts in eating habits during this period.However,the influence of EOH on the incidence of T2DM among Chinese urban workers is unknown.Methods:The cross-sectional study involved an analysis of 13,904 urban workers recruited from 11 health examination centers in the major cities of China to explore the relationship between EOH and T2DM between 2013 September and 2016 March.Results:Average weekly EOH frequency≥10 times was positively associated with increased incidence of T2DM in the sampled population(OR:1.31[1.11-1.54],p<0.01),most notably in participants≤45 years old(OR:1.41[1.11-1.80],p<0.01])and in males(OR:1.26[1.06-1.51],p<0.01).An EOH frequency of 5 times/week appears as a threshold for a significant increase in the odds of T2DM.Weekly EOH frequency≥5 times was associated with increased odds of T2DM in a dose-response manner in the total population and almost all subgroups(poverall association<0.05 andpnonlinearity≤0.05).Conclusion:This study showed that a frequency of EOH(≥5 times/week)was associated with a frequency-dependent increase in the odds of T2DM urban workers in China.More nutrition promotion is needed to improve the eating behavior of Chinese urban workers to reduce T2DM risk.
基金Supported by Beijing Natural Science Foundation,No.7172225
文摘BACKGROUND Long noncoding RNA(lncRNA)ZNFX1-AS1(ZFAS1)is a newly discovered lncRNA,but its diagnostic value in gastric cancer is unclear.AIM To investigate the potential role of ZFAS1 in gastric cancer and to evaluate the clinical significance of ZFAS1 as a biomarker for gastric cancer screening.METHODS Quantitative real-time polymerase chain reaction(qRT-PCR)was used to screen for gastric cancer-associated lncRNAs in gastric cancer patients,gastric stromal tumor patients,gastritis or gastric ulcer patients,and healthy controls.Correlations between ZFAS1 expression and clinicopathological features were analyzed.The biological effects of ZFAS1 on the proliferation,migration,and invasion of gastric cancer cells were studied by MTT,colony formation,and transwell migration assays.The potential mechanism of ZFAS1 was demonstrated using enzyme-linked immunosorbent assay and qRT-PCR.The relationship between ZFAS1 and tumorigenesis was demonstrated using in vivo tumor formation assays.RESULTS The plasma level of lncRNA ZFAS1 was significantly higher in preoperative patients with gastric cancer than in individuals in the other 4 groups.Increased expression of ZFAS1 was significantly associated with lymph node metastasis,advanced TNM stage,and poor prognosis.ZFAS1 regulated the proliferation,migration,and invasion of gastric cancer cells and regulated the growth of gastric cancer cells in vivo.LIN28 and CAPRIN1 were identified as key downstream mediators of ZFAS1 in gastric cancer cells.CONCLUSION LncRNA ZFAS1 promoted the invasion and proliferation of gastric cancer cells by modulating LIN28 and CAPRIN1 expression,suggesting that ZFAS1 can be used as a potential diagnostic and prognostic biomarker in gastric cancer.
基金the National Natural Science Foundation of China[No.81970739,81471071,and 81270948]Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry[SRF for ROCS,SEM][No.2013-693]。
文摘Exosomes,a type of extracellular vesicles(EVs),were first discovered in sheep reticulocytes in 1983[1],and after four years,the name‘exosome’was officially given to them.A variety of cells secrete exosomes under both normal and pathological conditions.Exosomes are mainly products of themultivesicular body formed by intracellular lysosomal invagi nation,and released into the extracellular space by fusion of the outer membrane of the multivesicular body with the cell membrane.
基金supported by research grants from National basic research program of china (2006CB503910)Chinese National Natural Science Foundation (30440065,30572082)Beijing Natural Science Foundation(7052059)
文摘Endothelial progenitor cells (EPC) are the precursors of mature endothelial cells and are involved in neovascularization and reendothelization. Previous studies have shown that oxidative stress can induce EPC senescence. However,the potential molecular mechanisms involved are still not clearly elucidated.
基金This work was supported in part by grants from National Key Research&Development Program of China(No.2022YFC3602102)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(No.2021-1-I2M-050)+1 种基金National Natural Science Foundation of China(No.82170856)China Postdoctoral Science Foundation(No.2022M710456).
文摘Glucagon-like peptide-1(GLP-1),a signal peptide hormone produced by enteroendocrine L cells from the distal small intestine and colon,is a crucial regulator of glycemic control,gastric emptying,satiety,and body weight.Recent advancements in understanding the dietary modulation of GLP-1 through enteroendocrine L-cells have highlighted the potential of various nutrients in enhancing its endogenous secretion.This review summarizes the current knowledge on food-derived molecules,including macronutrients,polyphenols,other chemicals,and bacterial products,that can modulate GLP-1 production.It explores the efficacy and impact of various treatments and the involved signaling pathways,aiming to contribute to developing innovative strategies for enhancing endogenous GLP-1 release.
基金Supported by National High Level Hospital Clinical Research Funding Project,No.BJ-2023-206.
文摘Adolescent depressive symptoms represent a significant public health concern,with negative life events and dysfunctional attitudes playing pivotal roles in theirdevelopment.A cross-sectional study by Yu et al assessed the interplay betweendysfunctional attitudes,social support,and depressive symptoms in 795 Chineseadolescents(49.9%male,mean age 15.2±1.8 years,age range 11-18 years)fromfive middle schools in Shandong Province.Using the Dysfunctional AttitudesScale,Adolescent Life Events Scale,Beck Depression Inventory,and SocialSupport Rating Scale,the study identified that dysfunctional attitudes,particularlyover-autonomy and over-perfectionism,mediate the relationship betweennegative life events and depressive symptoms.Social support moderated thisrelationship,significantly reducing depressive symptoms.These findingsunderscore the need for preventive and therapeutic strategies targeting dysfunctionalattitudes and enhancing social support to address adolescent depressivesymptoms.In this article,we extend their findings to highlight the significance ofculturally tailored interventions that incorporate familial and communitydynamics in mitigating depressive symptoms,particularly in collectivist societies.
基金Acknowledgments This study was funded by the National Natural Science Foundation of China (81570323, 30972709, 81061120527, 81241082) and the 12th Five-Year National Program of the Ministry of Scientific Technology (2012BAI10B01). We thank Liu M and Zhou L from Beijing Hospital for providing experimental data, the nurses from Beijing Anzhen Hospital for collecting specimens, and the study volunteers.
文摘Background The genes encoding adiponectin receptor 1 (ADIPOR1) and small ubiquitin-like modifier 4 (SUM04) have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two genes, acting separately or interacting, affect risk of coronary artery disease (CAD) without diabetes. Methods We genotyped 200 CAD patients without diabetes and 200 controls without CAD or diabetes at three single-nucleotide polymorphisms (SNPs) in ADIPOR1 and one SNP in SUM04, which were chosen based on previous studies. Potential associations were also explored between these SNPs and clinical characteristics of CAD without diabetes. Results Risk alleles at three SNPs inADIPOR1 (rs7539542-G, rs7514221-C and rs3737884-G) and the G allele at SNP rs237025 in SUM04 significantly increased risk of CAD without diabetes, with ORs ranging from 1.79 to 4.44. Carriers of any of these four risk alleles showed similar adverse clinical characteristics. Compared with individuals with a CC or GC genotype, those with a GG genotype at rs3737884 were at significantly higher risk of CAD that affected the left anterior descending coronary artery (OR: 6.77, P = 0.009), the right coronary artery (OR: 4.81, P = 0.028) or a relatively large number of vessels (P = 0.04). Individuals carrying a risk allele at one or more of the three SNPs in ADIPOR1 as well as a risk allele at the SNP in SUM04 were at significantly higher risk of CAD without diabetes than individuals not carrying any risk alleles (OR: 5.82, 95% CI: 1.23-27.7, P= 0.013). Conelusions SNPs in ADIPORl and SUMO4 are associated with elevated risk of CAD without diabetes, and SNPs in the two genes may interact to jointly affect disease risk.
基金Supported by the National Key R&D Program of China,No.2018YFC2000300and CAMS Innovation Fund for Medical Sciences,No.2018-I2M-1-002.
文摘BACKGROUND Shigella flexneri(S.flexneri)is a major pathogen causing acute intestinal infection,but the systematic oxidative damage incurred during the course of infection has not been investigated.AIM To investigate the incurred systemic RNA oxidative damage and the diagnostic value of RNA oxidative metabolites during S.flexneri-induced intestinal infection.METHODS In this study,a Sprague-Dawley rat model of acute intestinal infection was established by oral gavage with S.flexneri strains.The changes in white blood cells(WBCs)and cytokine levels in blood and the inflammatory response in the colon were investigated.We also detected the RNA and DNA oxidation in urine and tissues.RESULTS S.flexneri infection induced an increase in WBCs,C-reactive protein,interleukin(IL)-6,IL-10,IL-1β,IL-4,IL-17a,IL-10,and tumor necrosis factorα(TNF-α)in blood.Of note,a significant increase in urinary 8-oxo-7,8-dihydroguanosine(8-oxo-Gsn),an important marker of total RNA oxidation,was detected after intestinal infection(P=0.03).The urinary 8-oxo-Gsn level returned to the baseline level after recovery from infection.In addition,the results of a correlation analysis showed that urinary 8-oxo-Gsn was positively correlated with the WBC count and the cytokines IL-6,TNF-α,IL-10,IL-1β,and IL-17α.Further detection of the oxidation in different tissues showed that S.flexneri infection induced RNA oxidative damage in the colon,ileum,liver,spleen,and brain.CONCLUSION Acute infection induced by S.flexneri causes increased RNA oxidative damage in various tissues(liver,spleen,and brain)and an increase of 8-oxo-Gsn,a urinary metabolite.Urinary 8-oxo-Gsn may be useful as a biomarker for evaluating the severity and prognosis of infection.
文摘Aim To explore the mechanisms of microRNA 200a in hepatic insulin resistance induced by interleukin-6(IL-6),specifically to in-vestigate the role of microRNA 200a in hepatic glucogen and insulin signal pathway transduction.Methods The cell model forhepatic insulin resistance was induced by IL-6(10μg/L) for 24 hours in NCTC1469 cell.The level of glucogen was reduced.The expression of microRNA 200a was tested by q-PCR.The level of glucogen was quantified in NCTC 1469 transfected with microRNA200a mimics.The target gene of microRNA200a was predicted by bio-information software.The protein level of the target gene wastested by Western Blotting.Results The level of glucogen and the insulin signal pathway was inhibited in NCTC 1469 cells treated by IL-6.The expression of microRNA 200a was decreased in NCTC 1469 cell induced by IL-6.The level of glucogen and theinsulin signal pathway were stimulated in NCTC 1469 cell transfected by microRNA 200a mimics.The protein level of Pten was decreased by overexpression of microRNA200a.Conclusions IL-6 downregulates the expression of microRNA200a in hepatic insulin resistant NCTC 1469 cells.The microRNA 200a stimulates biosynthesis of glucogen as well as insulin signal pathway accompanied by down-regulating the expression of Pten.
基金Supported by Disciplines Construction Project of Peking Union Medical College,No.201920202102.
文摘BACKGROUND As of June 1,2020,over 370000 coronavirus disease 2019(COVID-19)deaths have been reported to the World Health Organization.However,the risk factors for patients with moderate-to-severe or severe-to-critical COVID-19 remain unclear.AIM To explore the characteristics and predictive markers of severely and critically ill patients with COVID-19.METHODS A retrospective study was conducted at the B11 Zhongfaxincheng campus and E1-3 Guanggu campus of Tongji Hospital affiliated with Huazhong University of Science and Technology in Wuhan.Patients with COVID-19 admitted from 1st February 2020 to 8th March 2020 were enrolled and categorized into 3 groups:The moderate group,severe group and critically ill group.Epidemiological data,demographic data,clinical symptoms and outcomes,complications,laboratory tests and radiographic examinations were collected retrospectively from the hospital information system and then compared between groups.RESULTS A total of 126 patients were enrolled.There were 59 in the moderate group,49 in the severe group,and 18 in the critically ill group.Multivariate logistic regression analysis showed that age[odd ratio(OR)=1.055,95%(confidence interval)CI:1.099-1.104],elevated neutrophil-to-lymphocyte ratios(OR=4.019,95%CI:1.045-15.467)and elevated high-sensitivity cardiac troponin I(OR=10.126,95%CI:1.088-94.247)were high-risk factors.CONCLUSION The following indicators can help clinicians identify patients with severe COVID-19 at an early stage:age,an elevated neutrophil-to-lymphocyte ratio and high sensitivity cardiac troponin I.
基金National High Level Hospital Clinical Research Funding(BJ-2018-204,BJ-2023-112)。
文摘Objective VATER/VACTERL-like association is associated with adverse pregnancy outcomes.Genetic evidence of this disorder is sporadic.In this study,we aimed to provide genetic insights to improve the diagnosis of VACTERL.Methods We have described a Chinese family in which four members were affected by renal defects or agenesis,anal atresia,and anovaginal fistula,which is consistent with the diagnosis of a VACTERL-like association.Pedigree and genetic analyses were conducted using genome and exome sequencing.Results Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals,harboring a 196–380 kb microdeletion on Xq27.1,which was identified by familial exome sequencing.Genome sequencing was performed on the affected male,confirming a-196 kb microdeletion in Xq27.1,which included a 28%loss of the CDR-1 gene.Four family members were included in the co-segregation analysis,and only VACTERL-like cases with microdeletions were reported in X27.1.Conclusion These results suggest that the 196–380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like association.However,further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.
基金Supported by Municipal Natural Science Foundation of Beijing of China, No.5102039National Natural Science Foundation of China, Nos.81101859, 81270379, 81070231
文摘MicroRNAs(miRNAs) are key regulators involved in various tumors. They regulate cell cycle, apoptosis and cancer stemness, metastasis and chemoresistance by controlling their target gene expressions. Here, we mainly discuss the potential uses of miR NAs in colorectal cancer(CRC) diagnosis. We also shed light on the important corresponding miR NA targets and on the major regulators of miR NAs. Furthermore, we discuss miR NA activity in assessing the prognosis and recurrence of CRC as well as in modulating responsiveness to chemotherapy. Based on the various pro-oncogenic/anti-oncogenic roles of miR NAs, the advantages of a therapeutic strategy based on the delivery of miR NA mimics are also mentioned. Together, mi RNA seems to be an excellent tool for effectively monitoring and targeting CRC.
文摘The immunologically mediated disease is a big family which affects many people in the world, since the cures are not yet available for most immune diseases, the patients face a lifetime of illness and treatment. Chinese medicine inspires us to develop new methods for the treatment of immune diseases. Previous researches of immune system have revealed that an immune network exists. The immune system is like a complex highway; if we travel on these highways, we must have a map to avoid travelling in the wrong direction. Drawing the map of immune network will provide new tools for us to look directly at the basis of the immune system.
文摘Current contraceptive methods come with a number of drawbacks,including low efficacy,in the case of commercial contraceptive gels,and a reduction in the quality of sexual intercourse,in the case of condoms.Adding pharmacologically-active agents to contraceptive gels holds the potential to improve sexual experience,and hardbor safety and hygiene.In this study,we fabricated a carbomer-based contraceptive gel consisting of three agents:tenofovir,gossypol acetate,and nitroglycerin(TGN),with pH adjusted to 4.5(to be compatible with the vagina).In vitro,the gossypol component of the contraceptive gel proved to be an effective spermicide.When the concentration of gossypol acetate was 10 mg/ml,the spermicidal ability reached 100%after 30 s.In addition,tenofovir in the gel significantly inhibited lentiviral transfection efficiency in cell-containing media.In 6 pairs of rats,the gel successfully prevented all females from conceiving after successful mating.Moreover,increased sexual frequency and enhanced erection,which were promoted by the nitroglycerin in the components,were observed in male rats that had the gel applied to their penises.This novel TGN contraceptive gel yielded a higher contraceptive success rate than that of the commercial contraceptive gel(Contragel®).In addition,it has the added benefits to prevent sexually transmitted diseases and improve male libido and erectile function during sexual intercourse.Combining three FDA-approved and marketed agents together,our trifunctional TGN gel has a great potential for further translation and commercialization.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA16000000)the National Natural Science Foundation of China(Nos.82071588,81921006,82125011,92149301,92168201,92049116,32121001,82192863,91949209,92049304,82122024,82001477,31900523,81861168034,32000500,82271600,82201714)+10 种基金the National Key Research and Development Program of China(Nos.2018YFC2000100,2020YFA0804000,2018YFA0107203,2020YFA0112200,2021YFF1201005,2021ZD0202401,2018YFC2000400,2020YFA0113400,2021YFE0111800,2022YFA1103700)the Program of the Beijing Natural Science Foundation(No.Z190019)K.C.Wong Education Foundation(Nos.GJTD-2019-06,GJTD-2019-08)Beijing Medical Research(2021-8)the Pilot Project for Public Welfare Development and Reform of Beijing-affliated Medical Research Institutes(No.11000022T000000461062)Young Elite Scientists Sponsorship Program by CAST(Nos.YESS20200012,YESS20210002)CAS Project for Young Scientists in Basic Research(No.YSBR-076,YSBR-012,YSBR-036)Youth Innovation Promotion Association of CAS(Nos.E1CAZW0401,2020085,2022083)the Informatization Plan of Chinese Academy of Sciences(Nos.CAS-WX2022SDC-XK14,CASWX2021SF-0301,CAS-WX2021SF-0101)the Tencent Foundation(No.2021-1045),CAMS Innovation Fund for Medical Sciences(No.2021-12M-1-050)the Fellowship of China Postdoctoral Science Foundation(2022M712216).
文摘Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia,and increases the risk of many aging-related metabolic diseases.Here,we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging.A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types,indicating a higher susceptibility of skeletal muscle fiber to aging.We found a downregulation of Foxo3 in aged primate skeletal muscle,and identi-fied FOxo3 as a hub transcription factor maintaining skeletal muscle homeostasis.Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model,we revealed that silence of Foxo3 accelerates human myotube senescence,whereas genetic activation of endogenous FOxO3 alleviates human myotube aging.Altogether,based on a combination of monkey skeletal muscle and human myotube aging research models,we unraveled the pivotal role of the FOxO3 in safeguarding primate skeletal muscle from aging,providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-relateddisorders.
文摘Introduction:The treatment of elderly‐onset rheumatoid arthritis(RA)pursues the same objectives as in younger patients:to control the symptoms,to prevent structural damage,to preserve function,and to decrease excess mortality.The presence of co‐morbidities is more specific in elderly patients with RA,which raises therapeutic challenges for physicians.Comprehensive geriatric assessment(CGA)is an essential tool that examines factors affecting the course of disease and the outcome of treatment.CGA includes the patient's functional,physical,mental,emotional,pharmacotherapeutic,and socioeconomic status.This article aims to present CGA in the evaluation and management of frail elderly patient with RA.Patient&Result:A case study of an 80‐year‐old man with RA and ILD is presented to describe the process of CGA and provides nutritional supplement therapy,patient education,and rehabilitation guidance to help patient progress from frailty to non‐frailty.Discussion:The case revealed that CGA provides physicians with information on the reversible area of frailty and the leading cause of deterioration in EORA.
基金This work was supported by the National Science Foundation for Young Researchers of China(grant Nos:82000315,82000325 and 82100325).
文摘Objective:Few studies have been conducted to establish animal models of left bundle branch block by using three-dimensional mapping systems.This research was aimed at creating a canine left bundle branch block model by using a three-dimensional mapping system.Materials and Methods:We used a three-dimensional mapping system to map and ablate the left bundle branch in beagles.Results:Ten canines underwent radiofrequency ablation,among which left bundle branch block was successfully es-tablished in eight,one experienced ventricular fibrillation,and one developed third-degree atrioventricular block.The maximum HV interval measured within the left ventricle was 29.00±2.93 ms,and the LBP-V interval at the ablation site was 20.63±2.77 ms.The LBP-V interval at the ablation target was 71.08%of the maximum HV interval.Conclusion:This three-dimensional mapping system is a reliable and effective guide for ablation of the left bundle branch in dogs.
基金supported by the National Natural Science Foundation of China(81788101,81630044,82071840,81771763,82171798,and 81801635)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-017,2021-I2M-1-047,2021-I2M-1040,2021-I2M-1-016,2021-I2M-1-026,and 2020-I2M-C&T-B013)Beijing Capital Health Development Fund(2020-2-4019)。
文摘The gut microbiome is emerging as a pivotal player in the pathogenesis and development of autoimmune diseases(ADs)[1].A comprehensive understanding of the interaction among gut microbiota,drug metabolism,and host immune reaction will shed light on the development of precision medicine for ADs.Microbiota-based interventions,such as specific diet,probiotics/prebiotics,or restricted consortium transplantation,have shown promising preventive and therapeutic potentials in pre-clinical and clinical trials[2].
基金supported by the Key R&D Plan of the Ministry of Science and Technology(2022YFC3602000)the National Natural Science Foundation of China(82230060,81788101,82201978,32141004,and 82171798)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29020000)the Chinese Academy of Medical Science Innovation Fund for Medical Sciences(CIFMS)(2021-1-I2M-017,2021-1-I2M-047,2021-1-I2M-040,2021-1-I2M-016,and 2021-1-I2M-026)the Capital’s Funds for Health Improvement and Research(2020-2-4019).
文摘Accumulating evidence suggests an essential role of disturbed gut microbiota in the etiopathogenesis of systemic lupus erythematosus(SLE),but it remains unclear as to gut virome.In this study,fecal virus-like particles(VLPs)isolated from 76 non-treated SLE patients and 75 healthy controls were subjected to gut virome profiling.The proportion of bacteriophages was significantly elevated in the SLE gut,and the altered viral taxa were correlated with clinical parameters.Gut virome and bacteriome were closely associated with each other in SLE patients.The combination of gut viral and bacterial markers displayed better performance in distinguishing SLE patients from healthy controls.Further,VLPs from non-treated SLE patients promoted interferon-a production in an epithelial cell line and human immune cells.Intriguingly,the interferon-stimulatory capacity diminished in VLPs from post-treated SLE patients.Our findings may shed novel insights into SLE pathogenesis.Further in-depth understanding of gut virome might help develop future biomarkers and therapeutics for SLE patients.