The neurotoxic potential of microplastics (MPs) is an emerging environmental health crisis. However, the majority of environmental MPs are unable to penetrate the blood-brain barrier (BBB), leaving their mechanism of neurotoxicity largely unknown. Here, we show that oral exposure to pristine polystyrene MPs (which do not translocate to the brain) induces hippocampal-dependent cognitive deficits, impaired neurogenesis, and synaptic loss in mice, without detectable brain particle accumulation. This neurotoxicity is mediated by gut-brain axis disruption, characterized by gut microbiota dysbiosis, altered tryptophan metabolism, and increased permeability of both the intestinal barrier and the BBB. Crucially, hippocampal microglia exhibited a sustained pro-inflammatory shift (M1↑/M2↓) accompanied by defective autophagy. Fecal microbiota transplantation from healthy donors rescued the cognitive impairments and microglial dysfunction, establishing a causal role for the gut microbiota. Integrated multi-omics and correlation analyses identified the commensal bacterium Alloprevotella and the tryptophan-kynurenine metabolite 3-hydroxyanthranilic acid (3-HAA) as key mediators. In vitro, treatment of microglia with fecal supernatant from MPs-exposed mice recapitulated the M1/M2 imbalance, suppressed autophagy, and impaired brain-derived neurotrophic factor (BDNF) maturation. Remarkably, supplementation with 3-HAA restored autophagy in microglia, which in turn rebalanced their phenotypic polarization and rescued BDNF maturation. Our findings delineate a complete pathway from oral non-BBB-penetrable MPs exposure to cognitive dysfunction, orchestrated through the disruption of gut microbiota-3-HAA-microglial autophagy axis. This work unveils a fundamental indirect mechanism for the neurotoxicity of non-brain-penetrant environmental pollutants and identifies novel microbiota- and metabolite-centric targets for intervention.

In the present study, the taxonomic positions of Robertmurraya yapensis, Bacillus yapensis, Pseudonocardia saturnea, and Pseudonocardia autotrophica were evaluated. The 16S rRNA gene sequence similarity, phylogenetic, phylogenomic and genome relatedness using average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) were analysed. The 16S rRNA gene sequences extracted from the genomes of the strains Robertmurraya yapensis CLA-AA-H227T and Bacillus yapensis XXST-01ᵀ and Pseudonocardia saturnea NBRC 14499T and Pseudonocardia autotrophica NBRC 12743T showed 100

Objective Considering the traditional female nature of the nursing field, male nursing students often experience a strong urge to leave the profession. A robust professional identity (PI) is crucial for male nurses, as it can alleviate professional stress and enhance their willingness to remain in the field. Among full-time nursing vocational education programs, the consecutive secondary and higher vocational nursing (CSAHVN) stands out for offering comprehensive and advanced professional education, leading to the cultivation of highly skilled nurses. Nevertheless, the predictive factors influencing male nursing students’ PI during their CSAHVN education remain poorly understood. Methods Convenience sampling was used to recruit male students in the CSAHVN education from two vocational schools. Data on PI, self-consistency and congruence, perceived social support and psychological resilience were collected using questionnaires. Results The average score for male nursing students’ PI was 3.85 (SD = 0.68). The total scores and sub-dimensions of self-consistency and congruence, perceived social support, and psychological resilience demonstrated significant correlations with PI. Multivariate analyses identified motivation and interest in nursing profession, along with sub-dimensions of self-consistency and congruence (self-flexibility), psychological resilience (tenacity), and perceived social support (family support) ( p < 0.01) as principal predictors of the PI among male CSAHVN students, with three-dimensional scatter plots demonstrating superior predictive capacity of tenacity and self-flexibility. Conclusion Our findings underscore the necessity for systemic interventions in educational innovations that strengthen professional commitment and foster family-school collaboration to enhance tenacity and self-flexibility, which are essential to counteract gender stereotypes and thereby increase the PI of male students in CSAHVN education.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV) which results in a high mortality rate and poses a public health threat. Gene variation of SFTSV is one of the major forces driving its persistence and widespread prevalence. However, how genetic variations affect virus invasion is not yet fully understood. In this study, we evaluated the adaptive advantage of three stable high-frequency substitutions D170N, I323V, and K619R located on the envelope glycoprotein of SFTSV based on 1041 M segments of their genomes. The result demonstrated that single mutation of D170N, or K619R reduced infectivity of mutant. However, the combined presence of both D170N, and K619R mutation enhanced infectivity of mutants. Structure model and SPR assay studies indicated that the substitution at the 170 site reduced the binding affinity between Gn glycoprotein and host C-C motif chemokine receptor 2 (CCR2). Additionally, neutralization assay showed I323/K619R mutant exhibited completely resistance to neutralizing antibodies pressure. This study reveals that SFTSV balances its entry ability by gene variation of different loci on its glycoprotein via a trade-off between Gn and Gc. In addition, a weakened invasion strategy facilitated by site mutations benefits its immune evasion. The findings provide mechanistic insights into its prevalence, thereby enabling early warnings for potential future outbreaks.

In the present study, the taxonomic position of Bacillus yapensis was evaluated using phylogenetic, amino acid identity (AAI) and average nucleotide identity (ANI) values. In the phylogenetic tree, Bacillus yapensis clustered with Robertmurraya species. The AAI value between Bacillus yapensis XXST-01T and Robertmurraya species was above the cut-off level (65

Background: SHP1 has been documented as a tumor suppressor and it was thought to play an antagonistic role in the pathogenesis of Helicobacter pylori infection. In this study, the exact mechanism of this antagonistic action was studied. Materials and methods: AGS, MGC803, and GES-1 cells were infected with H. pylori, intracellular distribution changes of SHP1 were first detected by immunofluorescence. SHP1 overexpression and knockdown were then constructed in these cells to investigate its antagonistic roles in H. pylori infection. Migration and invasion of infected cells were detected by transwell assay, secretion of IL-8 was examined via ELISA, the cells with hummingbird-like alteration were determined by microexamination, and activation of JAK2/STAT3, PI3K/Akt, and ERK pathways were detected by immunoblotting. Mice infection model was established and gastric pathological changes were evaluated. Finally, the SHP1 activator sorafenib was used to analyze the attenuating effect of SHP1 activation on H. pylori pathogenesis in vitro and in vivo. Results: The sub-localization of SHP1 changed after H. pylori infection, specifically that the majority of the cytoplasmic SHP1 was transferred to the cell membrane. SHP1 inhibited H. pylori-induced activation of JAK2/STAT3 pathway, PI3K/Akt pathway, nuclear translocation of NF-kappa B, and then reduced EMT, migration, invasion, and IL-8 secretion. In addition, SHP1 inhibited the formation of CagA-SHP2 complex by dephosphorylating phosphorylated CagA, reduced ERK phosphorylation and the formation of CagA-dependent hummingbird-like cells. In the mice infection model, gastric pathological changes were observed and increased IL-8 secretion, indicators of cell proliferation and EMT progression were also detected. By activating SHP1 with sorafenib, a significant curative effect against H. pylori infection was obtained in vitro and in vivo. Conclusions: SHP1 plays an antagonistic role in H. pylori pathogenesis by inhibiting JAK2/STAT3 and PI3K/Akt pathways, NF-kappa B nuclear translocation, and CagA phosphorylation, thereby reducing cell EMT, migration, invasion, IL-8 secretion, and hummingbird-like changes.

目的 研究不同类型信号肽对新布尼亚病毒(SFTSV)包膜蛋白Gn表达的影响.方法 以SFTSV(SD4毒株)M段为模板PCR扩增Gn基因,双酶切后分别连接至A16H和pHL表达载体,连接产物转染293T细胞,收集细胞和上清进行Western blot、免疫荧光以及质谱检测,分析Gn重组蛋白的表达情况;ELISA检测Gn重组蛋白的结合活性.结果 成功构建缺失载体信号肽的pA16H-Gn质粒和包含信号肽的sp-pA16H-Gn质粒,以及携带另一种载体信号肽的pHL-Fc-Gn质粒.缺失载体信号肽的pA16H-Gn质粒在细胞内外均不表达Gn重组蛋白(rGn-Fc),包含A16H载体信号肽的sp-pA16H-Gn质粒在细胞内表达Gn重组蛋白(rGn-Fc),但不能分泌表达,包含pHL载体信号肽的pHL-Fc-Gn质粒可将Gn重组蛋白(rGn-Fc)分泌表达到胞外,且具有结合活性.结论 载体本身携带的信号肽会影响SFTSV Gn重组蛋白的表达,不同信号肽影响重组蛋白的表达定位.该研究为SFTSV Gn重组蛋白的开发奠定了基础,同时也为SFTSV重组疫苗的研究提供了新思路.

Our study indicated that the gut microbiota contributes to spatial learning and memory dysfunction after chronic METH exposure, in which microglial phenotype status plays an intermediary role. The elucidated “specific microbiota taxa-microglial M1/M2 phenotypes-spatial learning and memory impairment” pathway would provide a novel mechanism and elucidate potential gut microbiota taxon targets for the no-drug treatment of cognitive deterioration after chronic METH exposure.

BACKGROUND:Schistosomiasis is a prevalent infectious disease caused by the parasitic trematodes of the genus Schistosoma. Praziquantel (PZQ), a safe and affordable drug, is the recommended oral treatment for schistosomiasis. The main pathologic manifestation of schistosomiasis is liver injury. However, the role and interactions of various RNA molecules in the effect of PZQ on the liver after S. japonicum infection have not been elucidated.RESULTS:In this study, C57BL/6 mice were randomly divided into the control group, infection group, and PZQ treatment group. Total RNA was extracted from the livers of the mice. High-throughput whole transcriptome sequencing was performed to detect the RNA expression profiles in the three groups. A co-expression gene-interaction network was established based on the significant differentially expressed genes in the PZQ treatment group; messenger RNA (mRNA) Cyp4a14 was identified as a critical hub gene. Furthermore, competitive endogenous RNA networks were constructed by predicting the specific binding relations between mRNA and long noncoding (lnc) RNA and between lncRNA and microRNA (miRNA) of Cyp4a14, suggesting the involvement of the H19/miR-130b-3p/Cyp4a14 regulatory axis. Dual luciferase reporter assay result proved the specific binding of miR-130b-3p with Cyp4a14 3'UTR.CONCLUSIONS:Our findings indicate the involvement of the H19/miR-130b-3p/Cyp4a14 axis in the effect of PZQ on the liver after S. japonicum infection. Moreover, the expression of mRNA Cyp4a14 could be regulated by the bonding of miR-130b-3p with 3'UTR of Cyp4a14. The findings of this study could provide a novel perspective to understand the host response to PZQ against S. japonicum in the future.

目的:以产肠毒素大肠杆菌(enterotoxigenic Escherichia coli,ETEC)诱导肠道菌群失调性腹泻模型,分析益生菌嗜黏蛋白阿克曼氏菌(Akkermansia muciniphila,A.muciniphila)对ETEC诱导腹泻的改善效果.方法:用ETEC诱导小鼠腹泻模型.实验小鼠随机分为PBS组、模型组、干预组.干预组给予灌服A.muciniphila菌液(浓度为1×109CFU/mL)0.2mL/d,连续5 d,模型组口腔灌服ETEC菌液(浓度为1×109CFU/mL)0.5 mL/d.记录小鼠身体状况、体重、腹泻率和死亡率的变化;HE染色观察结肠组织病理变化;ELISA检测血清白细胞介素(interleukin,IL)IL-1β、IL-6、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的含量;RT-PCR检测结肠组织IL-1、TNF-α、IL-6 mRNA的表达;收取小鼠粪便进行16S rRNA高通量测序并进行统计分析.结果:干预组与模型组相比,身体状况明显改善,腹泻率降低了 66％,死亡率降低了 30％;血清IL-1β、IL-6和TNF-α含量明显降低(P＜0.05).结肠组织IL-1、IL-6、TNF-α mRNA含量明显降低(P＜0.05).结肠组织病理变化显著改善.16SrRNA测序显示干预组物种相对丰度明显增加,肠道菌群α多样性与菌群组成发生明显改变,在干预组中,多种益生菌丰度增加.结论:益生菌A.muciniphila通过增加肠道菌群多样性、保护结肠黏膜组织和降低炎症因子的表达,减轻ETEC引起的腹泻.

Growing evidence has demonstrated that hypertension was associated with dysbiosis of intestinal flora. Since intestinal microbes could critically regulate neurofunction via the intestinal–brain axis, the study aimed to reveal the role and prediction value of intestinal flora alteration in hypertension-associated cognitive impairment. A cohort of 97 participants included 63 hypertension patients and 34 healthy controls. The structure of intestinal flora was analyzed by V3–V4 16S rRNA amplicon sequencing. The cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and 31 patients were considered to have cognitive impairment (MoCA < 26). Patients with cognitive impairment had considerable alterations in intestinal flora structure, composition, and function compared with normal-cognitive patients. In particular, the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia–Shigella) and SCFA-producing taxon (Prevotella) significantly changed in cognition-impaired patients. Tax4Fun predication results showed downregulation of glycan biosynthesis and metabolism in hypertension patients with cognitive impairment. Additionally, the pathway was demonstrated to be significantly correlated with LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia–Shigella) and SCFA-producing taxon Prevotella. Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). The current study revealed the involvement of intestinal microbiota dysbiosis in cognition-impaired hypertension patients and provided an objective predictive index for this cognition disorder.

Acetaminophen (APAP) overdose is one of the most common causes of acute liver injury (ALI) in Western countries. Many studies have shown that the gut microbiota plays an important role in liver injury. Currently, the only approved treatment for APAP-induced ALI is N-acetylcysteine; therefore, it is essential to develop new therapeutic agents and explore the underlying mechanisms. We developed a novel monoclonal anti-Toll-like receptor 4 (TLR4) antibody (ATAB) and hypothesized that it has therapeutic effects on APAP-induced ALI and that the gut microbiota may be involved in the underlying mechanism of ATAB treatment. Male C57BL/6 mice were treated with APAP and ATAB, which produced a therapeutic effect on ALI and altered the members of the gut microbiota and their metabolic pathways, such as Roseburia, Lactobacillus, Akkermansia, and the fatty acid pathway, etc. Furthermore, we verified that purified short-chain fatty acids (SCFAs) could alleviate ALI. Moreover, a separate group of mice that received feces from the ATAB group showed less severe liver injury than mice that received feces from the APAP group. ATAB therapy also improved gut barrier functions in mice and reduced the expression of the protein zonulin. Our results revealed that the gut microbiota plays an important role in the therapeutic effect of ATAB on APAP-induced ALI. IMPORTANCE In this study, we found that a monoclonal anti-Toll-like receptor 4 antibody can alleviate APAP-induced acute liver injury through changes in the gut microbiota, metabolic pathways, and gut barrier function. This work suggested that the gut microbiota can be a therapeutic target of APAP-induced acute liver injury, and we performed foundation for further research.

We sincerely appreciate the letter from you asking for more information about our work. Dr. Jaeschke and Dr. Ramachandran asked some questions which are useful for us to address. We will answer the questions as follows.

Background Severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) is a tick-borne virus that causes severe communicable fever with thrombocytopenia syndrome (SFTS) with an average case fatality rate of 10%. In the study, we aimed to identify the cross-neutralizing antibody (nAb) against different genotype strains from sera of SFTSV infected patients. Methods Firstly the genotype of SFTSV was identified by constructing a phylogenetic tree based on the M segments epidemic in the Jiaodong area of Shandong province, then different sera of subjects cross reactive with recombinant Gn (rGn-Fc) or recombinant Gc (rGc-Fc) of 0921 strain were examined. The levels of polyclonal nAbs from sera of 25 convalescents were measured by a pseudovirus-based neutralizing experiment. Results We found local endemic strains were mainly C2 and C3 isolates of SFTSV. 14 of 15 sera from donors reacted with 0921 rGn-Fc, and 9 of 15 sera from donors reacted with 0921 rGc-Fc. Cross nAbs were produced by 10 of 25 sera from donors during the period of 2019–2021. Among these, five nAbs (A2, A4, A5, L9, and L10) neutralized the pseudoviruses of HB29, Gangwon, HN13, HN20, SPL030A, and SD4 strains. Conclusion Our data suggested that epidemic strains showed relatively stable heredity. Some blood sources from patients produced cross nAbs that could neutralize all of the strains examined. These findings highlight the important role played by humoral immunity in combatting SFTSV.

目的:研究该院2016～2020年血培养病原菌的分布特点及耐药性,为临床治疗及合理选择抗菌药物提供依据.方法:分析该院2016～2020年期间临床血培养分离的999株病原菌的药敏结果,按照CLSI2019年标准,使用WHONET5.6软件进行数据分析.结果:革兰阴性菌分离率最高,共670株(67.1％),其次是革兰阳性菌,共317株(31.7％),真菌共12株(1.2％).血培养分离前五位的细菌分别是大肠埃希菌449株(44.9％),肺炎克雷伯菌97株(9.7％),人葡萄球菌69株(6.9％),金黄色葡萄球菌53株(5.3％),表皮葡萄球菌52株(5.2％).革兰阴性杆菌中大肠埃希菌和肺炎克雷伯菌对哌拉西林/他唑巴坦、头孢哌酮/舒巴坦、头孢替坦、厄他培南、亚胺培南、美罗培南、阿米卡星的耐药率低均低于5％.耐碳青霉烯类肠杆菌科细菌(CRE)共检出8株(0.8％),其中耐碳青霉烯类的大肠埃希菌(CR-eco)6株,耐碳青霉烯类的肺炎克雷伯菌(CR-kpn)2株,CRE对大多数临床常用抗菌药物呈高度耐药,对阿米卡星、替加环素有较高敏感性.鲍曼不动杆菌对大多数抗菌药物的耐药率均较高,对碳青霉烯类药物耐药率为66.7％,铜绿假单胞菌对多数抗菌药物敏感.耐甲氧西林金黄色葡萄球菌(MRSA)的检出率为45.3％,未发现对万古霉素耐药的葡萄球菌和肺炎链球菌.结论:该院血培养以革兰阴性菌为主,不同病原菌对抗生素的耐药性有一定差异.应充分利用药敏结果进行感染控制,合理选择抗菌药物,减少耐药菌的出现.

The ability of Helicobacter pylori to manipulate host autophagy is an important pathogenic mechanism. We found an inverse correlation between the expression of ILK and the autophagy marker protein LC3B in H. pylori-positive human samples, H. pylori-infected mice models and H. pylori-infected GES-1 cell lines. When the ILK-knockdown GES-1 cells were infected by H. pylori, CagA were significantly degraded, autophagosomes accumulation and autolysosomes formation were significantly increased, and LC3B protein levels and ratio of LC3BII to LC3BI were also remarkably upregulated. And chloroquine treatment increased LC3B levels in ILK-knockdown GES-1 cells. The expression levels of both Rac1 and RhoA were downregulated in GES-1 cells after H. pylori infection and were decreased in ILK-knockdown GES-1 cells. The mRNA and protein levels of PAK1, MLC, and LIMK were significantly decreased and cofilin mRNA and protein levels were significantly increased in GES-1 cells treated with the Rac1 inhibitor NSC 23766. The mRNA and protein levels of ROCK1, ROCK2, MLC, and LIMK1 were significantly reduced and cofilin mRNA and protein levels were significantly increased in GES-1 cells treated with the RhoA inhibitor CCG-1423. F-actin was significantly reduced in Rac1- or RhoA-inhibited GES-1 cells. F-actin depolymerization induced autophagosomes accumulation, autolysosomes formation, and the increase of LC3B levels in GES-1 cells. Therefore, these findings revealed that ILK could serve as a novel regulator to affect Rac1/ PAK1 and RhoA/ROCKs signaling pathways, thereby influencing H. pylori-induced autophagy.

With the widespread use of plastics and nanotechnology products, nanoplastics (NPs) have become a potential threat to human health. It is of great practical significance to study and evaluate the distribution of NPs in mice as mammal models and their entry, transport, and cytotoxicity in human cell lines. In this study, we detected the tissue distribution of fluorescent polystyrene nanoplastics (PS-NPs) in mice and assessed their endocytosis, transport pathways, and cytotoxic effects in GES-1 cells. We found that PS-NPs were clearly visible in gastric, intestine, and liver tissues of mice and in GES-1 cells treated with PS-NPs. Entry of PS-NPs into GES-1 cells decreased with the inhibition of caveolae-mediated endocytosis (nystatin), clathrin-mediated endocytosis (chlorpromazine HCl), micropinocytosis (ethyl-isopropyl amiloride), RhoA (CCG-1423), and F-actin polymerization (lantrunculin A). Rac1 inhibitors (NSC 23766) had no significant effect on PS-NPs entering GES-1 cells. F-actin levels significantly decreased in CCG-1423-pretreated GES-1 cells exposed to PS-NPs. GES-1 cell ultrastructural features indicated that internalized PS-NPs can be encapsulated in vesicles, autophagosomes, lysosomes, and lysosomal residues. RhoA, F-actin, RAB7, and LAMP1 levels in PS-NPs-treated GES-1 cells were remarkably up-regulated and the Rab5 level was significantly down-regulated compared to levels in untreated cells. PS-NPs treatment decreased cell proliferation rates and increased cell apoptosis. The formation of autophagosomes and autolysosomes and levels of LC3II increased with the length of PS-NPs treatment. The results indicated that cells regulated endocytosis in response to PS-NPs through the RhoA/F-actin signaling pathway and internalized PS-NPs in the cytoplasm, autophagosomes, or lysosomes produced cytotoxicity. These results illustrate the potential threat of NPs pollution to human health.

Background Despite the substantial burden of caring schizophrenic patients, primary caregivers can also experience posttraumatic growth (PTG) which may buffer their negative experience. Influencing factors of PTG and their functional pathways among primary caregivers of schizophrenic patients remain unclear. This study is designed to test the simple and serial mediating roles of coping styles and resilience in the relationship between perceived social support and PTG among those primary caregivers. Methods A cross-sectional study was conducted from October 2018 to January 2019, and 365 primary caregivers (self-reported) of schizophrenic patients were analyzed. Measures used to assess their perceived social support, coping styles, resilience, and PTG were the Perceived Social Support Scale, the Simplified Coping Style Questionnaire, the Connor-Davidson Resilience Scale, and the Posttraumatic Growth Inventory, respectively. Structural equation modeling was used to run the analysis. Results The average scores of PTG (range: 0–5), perceived social support (range: 1–7), positive coping style (range: 0–3), negative coping style (range: 0–3), resilience (range: 0–4) reported by primary caregivers was (2.91 ± 0.99), (4.80 ± 1.26), (1.79 ± 0.65), (1.49 ± 0.56), and (2.46 ± 0.66), respectively. The fitness indices of measurement and structural models were satisfactory. Three indirect pathways totally explained 55.56% variance of the PTG. The indirect effect of positive coping style between perceived social support and PTG was 0.20 [95% confidence interval (CI) 0.05 to 0.37], and this simple mediation pathway explained 27.78% variance of PTG. The indirect effect of resilience between perceived social support and PTG was 0.11 [95% CI 0.01 to 0.20], and this simple mediation pathway explained 15.28% variance of PTG. The indirect effect of positive coping style and then resilience between perceived social support and PTG was 0.09 [95% CI 0.01 to 0.17], and this serial mediation pathway explained 12.50% variance of PTG. Conclusions Both simple and serial mediation roles of positive coping style and resilience are established in the relationship between perceived social support and PTG among primary caregivers of schizophrenic patients. Positive coping style and resilience are two important targets for future interventional studies, and interventions on them may bring the synergistic effect on improving PTG.

目的:了解淄博市南部地区肠杆菌科细菌耐药现状,为临床合理应用抗生素提供理论依据.方法:收集淄博市第一医院2019年1月1日～2019年12月31日期间分离的门诊病人及住院病人细菌,采用VITEK 2 Compact全自动微生物分析仪进行鉴定及药敏实验,K-B法和E-test对药敏结果进行复核.结果:共收集门诊病人及住院病人细菌1849株,其中肠杆菌科细菌679株,其标本来源主要为痰和尿,分布较多的科室主要为儿科和重症监护室.结论:淄博市南部地区肠杆菌科细菌在致病菌中占有较高比例,且出现了多重耐药菌株,应该及时采取措施,提高对抗菌药物合理应用的重视程度.

AbstractBackgroundCD4+T helper (Th) cells play critical roles in both host humoral and cellular immunity against parasitic infection and in the immunopathology of schistosomiasis. T follicular helper (Tfh) cells are a specialized subset of Th cells involved in immunity against infectious diseases. However, the role of Tfh cells in schistosome infection is not fully understood. In this study, the dynamics and roles of Tfh cell regulation were examined. We demonstrated that granulocytic myeloid-derived suppressor cells (G-MDSC) can suppress the proliferation of Tfh cells.MethodsThe levels of Tfh cells and two other Th cells (Th1, Th2) were quantitated at differentSchistosoma japonicuminfection times (0,3, 5, 8, 13 weeks) using flow cytometry. The proliferation of Tfh cells stimulated by soluble egg antigen (SEA) and soluble worm antigen (SWA) in vivo and in vitro were analyzed. Tfh cells were co-cultured with MDSC to detect the proliferation of Tfh cells labelled by 5(6)-carboxyfluorescein diacetateN-succinimidyl ester. We dynamically monitored the expression of programmed cell death protein 1 (PD-1) on the surface of Tfh cells and programmed cell death ligand 1 (PD-L1) on the surface of MDSC at different infection times (0, 3, 5, 8 weeks). Naïve CD4+T cells (in Tfh cell differentiation) were co-cultured with G-MDSC or monocytic MDSC in the presence, or in the absence, of PD-L1 blocking antibody.ResultsThe proportion of Tfh cells among CD4+T cells increased gradually with time ofS. japonicuminfection, reaching a peak at 8 weeks, after which it decreased gradually. Both SEA and SWA caused an increase in Tfh cells in vitro and in vivo. It was found that MDSC can suppress the proliferation of Tfh cells. The expression of PD-1 on Tfh cells and PD-L1 from MDSC cells increased with prolongation of the infection cycle. G-MDSC might regulate Tfh cells through the PD-1/PD-L1 pathway.ConclusionsThe reported study not only reveals the dynamics of Tfh cell regulation duringS. japonicuminfection,but also provides evidence that G-MDSC may regulate Tfh cells by PD-1/PD-L1. This study provides strong evidence for the important role of Tfh cells in the immune response toS. japonicuminfection.Graphical abstract