Spread of plasmids carrying antibiotic resistance genes in soil-lettuce-snail food chain.

Fertilization can change the composition of antibiotic resistance genes(ARGs) and their host bacteria in agricultural fields, while complex microbial activities help ARGs into crops and transmit them to humans through agricultural products.Therefore, this study constructed a farmland food chain with soil-lettuce-snail as a typical structure, added genetically engineered Pseudomonas fluorescens containing multidrug-resistant plasmid RP4 to track its spread in the farmland food chain, and used different fertilization methods to explore its influence on the spread and diffusion of ARGs and intl1 in the farmland food chain. It was found that exogenous Pseudomonas can enter plants from soil and pass into snails' intestines, and there is horizontal gene transfer phenomenon of RP4 plasmid in bacteria. At different interfaces of the constructed food chain, the addition of exogenous drug-resistant bacteria had different effects on the total abundance of ARGs and intl1. Fertilization, especially manure, not only promoted the spread of Pseudomonas aeruginosa and the transfer of RP4 plasmid levels, but also significantly increased the total abundance of ARGs and intl1 at all interfaces of the constructed food chain. The main ARGs host bacteria in the constructed food chain include Proteobacteria, Bacteroides, and Firmicutes, while Flavobacterium of Bacteroides is the unique potential host bacteria of RP4 plasmid. In conclusion, this study provides a reference for the risk assessment of ARGs transmitted to the human body through the food chain, and has important practical significance to reduce the antibiotic resistance contamination of agricultural products and ensure the safety of vegetable basket.

Visible-light-induced N-alkylation of anilines with 4-hydroxybutan-2-one.

The synthesis of amines through N-alkylation is particularly attractive. Herein, a strategy for visible-light-induced N-alkylation of anilines with 4-hydroxybutan-2-one was developed in the presence of NH4Br, which avoid the use of metals, bases and ligands. In addition, gram-scale experiments proved that the system has the potential to be scaled.

Systematic review and meta-analysis: multimodal functional and anatomical neural alterations in autism spectrum disorder.

BACKGROUND: This meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the functional and structural brain alterations in individuals with autism spectrum disorder (ASD). METHODS: A whole-brain voxel-wise meta-analysis was conducted to compare the differences in the intrinsic functional activity and gray matter volume (GMV) between individuals with ASD and typically developing individuals (TDs) using Seed-based d Mapping software. RESULTS: A total of 23 functional imaging studies (786 ASD, 710 TDs) and 52 VBM studies (1728 ASD, 1747 TDs) were included. Compared with TDs, individuals with ASD displayed resting-state functional decreases in the left insula (extending to left superior temporal gyrus [STG]), bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), left angular gyrus and right inferior temporal gyrus, as well as increases in the right supplementary motor area and precuneus. For VBM meta-analysis, individuals with ASD displayed decreased GMV in the ACC/mPFC and left cerebellum, and increased GMV in the left middle temporal gyrus (extending to the left insula and STG), bilateral olfactory cortex, and right precentral gyrus. Further, individuals with ASD displayed decreased resting-state functional activity and increased GMV in the left insula after overlapping the functional and structural differences. CONCLUSIONS: The present multimodal meta-analysis demonstrated that ASD exhibited similar alterations in both function and structure of the insula and ACC/mPFC, and functional or structural alterations in the default mode network (DMN), primary motor and sensory regions. These findings contribute to further understanding of the pathophysiology of ASD.

Activation of the IL-6/STAT3 pathway contributes to the pathogenesis of membranous nephropathy and is a target for Mahuang Fuzi and Shenzhuo Decoction (MFSD) to repair podocyte damage.

BACKGROUND: Primary membranous nephropathy (PMN) is an autoimmune glomerular disease. IL-6 is a potential therapeutic target for PMN. Previous clinical studies have demonstrated the effectiveness of Mahuang Fuzi and Shenzhuo Decoction (MFSD) in treating membranous nephropathy. However, the mechanism of action of MFSD remains unclear. METHODS: Serum IL-6 levels were measured in patients with PMN and healthy subjects. The passive Heymann nephritis (PHN) rat model was established, and high and low doses of MFSD were used for intervention to observe the repair effect of MFSD on renal pathological changes and podocyte injury. RNA-seq was used to screen the possible targets of MFSD, and the effect of MFSD targeting IL-6/STAT3 was further verified by combining the experimental results. Finally, the efficacy of tocilizumab in PHN rats was observed. RESULTS: Serum IL-6 levels were significantly higher in PMN patients than in healthy subjects. These levels significantly decreased in patients in remission after MFSD treatment. MFSD treatment improved laboratory indicators in PHN rats, as well as glomerular filtration barrier damage and podocyte marker protein expression. Renal transcriptome changes showed that MFSD-targeted differential genes were enriched in JAK/STAT and cytokine-related pathways. MFSD inhibits the IL6/STAT3 pathway in podocytes. Additionally, MFSD significantly reduced serum levels of IL-6 and other cytokines in PHN rats. However, treatment of PHN with tocilizumab did not achieve the expected effect. CONCLUSION: The IL-6/STAT3 signaling pathway is activated in podocytes of experimental membranous nephropathy. MFSD alleviates podocyte damage by inhibiting the IL-6/STAT3 pathway.

Metal-Free Nitrogen-Doped Mesoporous Carbons for the Mild and Selective Synthesis of Pyrroles from Nitroarenes via Cascade Reaction.

The cascade synthesis of pyrroles from nitroarenes is an attractive alternative strategy. However, metal catalysts and relatively high temperatures cover the existing reported catalytic systems for this strategy. The development of nonmetallic heterogeneous catalytic systems for the one-pot synthesis of pyrrole from nitroarenes under mild conditions is both worthwhile and challenging. Herein, we describe an exceptionally efficient method for the synthesis of N-substituted pyrroles by the reductive coupling of nitroarenes and diketones over heterogeneous metal-free catalysts under mild conditions. Nonmetallic NC-X catalysts with high activity were prepared from the pyrolysis of well-defined ligands via simple sacrificing hard template methods. Hydrazine hydrate, formic acid, and molecular hydrogen can all be used as reducing agents in the hydrogenation/Paal-Knorr reaction sequence to efficiently synthesize various N-substituted pyrroles, including drugs and bioactive molecules. The catalytic system was featured with good tolerance to sensitive functional groups and no side reactions such as dehalogenation and aromatics hydrogenation. Hammett correlation studies have shown that the electron-donating substituents are beneficial for the one-pot synthesis of N-substituted pyrroles. The results established that the outstanding performance of the catalyst is mainly attributed to the contribution of graphitic N in the catalyst as well as the promotion effect of the mesoporous structure on the reaction.

Transcriptional regulation of SARS-CoV-2 receptor ACE2 by SP1.

Angiotensin-converting enzyme 2 (ACE2) is a major cell entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The induction of ACE2 expression may serve as a strategy by SARS-CoV-2 to facilitate its propagation. However, the regulatory mechanisms of ACE2 expression after viral infection remain largely unknown. Using 45 different luciferase reporters, the transcription factors SP1 and HNF4α were found to positively and negatively regulate ACE2 expression, respectively, at the transcriptional level in human lung epithelial cells (HPAEpiCs). SARS-CoV-2 infection increased the transcriptional activity of SP1 while inhibiting that of HNF4α. The PI3K/AKT signaling pathway, activated by SARS-CoV-2 infection, served as a crucial regulatory node, inducing ACE2 expression by enhancing SP1 phosphorylation-a marker of its activity-and reducing the nuclear localization of HNF4α. However, colchicine treatment inhibited the PI3K/AKT signaling pathway, thereby suppressing ACE2 expression. In Syrian hamsters (Mesocricetus auratus) infected with SARS-CoV-2, inhibition of SP1 by either mithramycin A or colchicine resulted in reduced viral replication and tissue injury. In summary, our study uncovers a novel function of SP1 in the regulation of ACE2 expression and identifies SP1 as a potential target to reduce SARS-CoV-2 infection.

A Multimodal Meta-Analytical Evidence of Functional and Structural Brain Abnormalities Across Alzheimer's Disease Spectrum.

BACKGROUND: Numerous neuroimaging studies have reported that Alzheimer's disease (AD) spectrum have been linked to alterations in intrinsic functional activity and cortical thickness (CT) of some brain areas. However, the findings have been inconsistent and the correlation with the transcriptional profile and neurotransmitter systems remain largely unknown. METHODS: We conducted a meta-analysis to identify multimodal differences in the amplitude of low-frequency fluctuation (ALFF)/fractional ALFF (fALFF) and CT in patients with AD and preclinical AD compared to healthy controls (HCs), using the Seed-based d Mapping with Permutation of Subject Images software. Transcriptional data were retrieved from the Allen Human Brain Atlas. The atlas-based nuclear imaging-derived neurotransmitter maps were investigated by JuSpace toolbox. RESULTS: We included 26 ALFF/fALFF studies comprising 884 patients with AD and 1,020 controls, along with 52 studies comprising 2,046 patients with preclinical AD and 2,336 controls. For CT, we included 11 studies comprising 353 patients with AD and 330 controls. Overall, compared to HCs, patients with AD showed decreased ALFF/fALFF in the bilateral posterior cingulate gyrus (PCC)/precuneus and right angular gyrus, as well as increased ALFF/fALFF in the bilateral parahippocampal gyrus (PHG). Patients with peclinical AD showed decreased ALFF/fALFF in the left precuneus. Additionally, patients with AD displayed decreased CT in the bilateral PHG, left PCC, bilateral orbitofrontal cortex, sensorimotor areas and temporal lobe. Furthermore, gene sets related to brain structural and functional changes in AD and preclincal AD were enriched for G protein-coupled receptor signaling pathway, ion gated channel activity, and components of biological membrane. Functional and structural alterations in AD and preclinical AD were spatially associated with dopaminergic, serotonergic, and GABAergic neurotransmitter systems. CONCLUSIONS: The multimodal meta-analysis demonstrated that patients with AD exhibited convergent functional and structural alterations in the PCC/precuneus and PHG, as well as cortical thinning in the primary sensory and motor areas. Furthermore, patients with preclinical AD showed reduced functional activity in the precuneus. AD and preclinical AD showed genetic modulations/neurotransmitter deficits of brain functional and structural impairments. These findings may provide new insights into the pathophysiology of the AD spectrum.

MACC: a visual interactive knowledgebase of metabolite-associated cell communications.

Metabolite-associated cell communications play critical roles in maintaining the normal biological function of human through coordinating cells, organs and physiological systems. Though substantial information of MACCs has been continuously reported, no relevant database has become available so far. To address this gap, we here developed the first knowledgebase (MACC), to comprehensively describe human metabolite-associated cell communications through curation of experimental literatures. MACC currently contains: (a) 4206 carefully curated metabolite-associated cell communications pairs involving 244 human endogenous metabolites and reported biological effects in vivo and in vitro; (b) 226 comprehensive cell subtypes and 296 disease states, such as cancers, autoimmune diseases, and pathogenic infections; (c) 4508 metabolite-related enzymes and transporters, involving 542 pathways; (d) an interactive tool with user-friendly interface to visualize networks of multiple metabolite-cell interactions. (e) overall expression landscape of metabolite-associated gene sets derived from over 1500 single-cell expression profiles to infer metabolites variations across different cells in the sample. Also, MACC enables cross-links to well-known databases, such as HMDB, DrugBank, TTD and PubMed etc. In complement to ligand-receptor databases, MACC may give new perspectives of alternative communication between cells via metabolite secretion and adsorption, together with the resulting biological functions. MACC is publicly accessible at: http://macc.badd-cao.net/.

Experimental models for elderly patients with membranous nephropathy: Application and advancements.

Membranous nephropathy (MN) occurs predominantly in middle-aged and elderly individuals and ranks among the most prevalent etiologies of elderly nephrotic syndrome. As an autoimmune glomerular disorder characterized by glomerular basement membrane thickening and immune complex deposition, conventional MN animal models, including the Heymann nephritis rat model and the c-BSA mouse model, have laid a foundation for MN pathogenesis research. However, differences in target antigens between rodents and humans have impeded this work. In recent years, researchers have created antigen-specific MN animal models, primarily centered on PLA2R1 and THSD7A, employing diverse techniques that provide innovative in vivo research platforms for MN. Furthermore, significant advancements have been made in the development of in vitro podocyte models relevant to MN. This review compiles recent antigen-specific MN animal models and podocyte models, elucidates their immune responses and pathological characteristics, and offers insights into the future of MN experimental model development. Our aim is to provide a comprehensive resource for research into the pathogenesis of MN and the development of targeted therapies for older patients with MN to prolong lifespan and improve quality of life.

Advances in the correlation between digital eye strain and sleep quality in adolescents / 中国学校卫生

Abstract@#Digital eye strain can affect not only adolescents visual health, but also sleep quality. In order to provide a reference for safeguarding adolescents visual health and physical health, the paper reviews the direct correlation, feedback correlation, mediating role and the mechanisms between their digital eye strain and sleep quality, as well as proposes some strategies to reduce digital eye strain and improve sleep quality, such as screen time limits, adjusting the brightness and contrast of electronic screen devices, maintaining correct posture and viewing distance, increasing eye nutrition and protection, establishing a regular sleep routine, avoiding the use of electronic screen devices before bedtime, creating a comfortable and quiet sleep environment, and paying attention to the effects of diet and exercise.

Neutrophils are involved in early bone formation during midpalatal expansion.

OBJECTIVE: Midpalatal expansion (MPE) is routinely employed to treat transverse maxillary arch deficiency. Neutrophils are indispensable for recruiting bone marrow stromal cells (BMSCs) at the initial stage of bone regeneration. This study aimed to explore whether neutrophils participate in MPE and how they function during bone formation under mechanical stretching. MATERIALS AND METHODS: The presence and phenotype of neutrophils in the midpalatal suture during expansion were detected by flow cytometry and immunofluorescence staining. The possible mechanism of neutrophil recruitment and polarization was explored in vitro by exposing vascular endothelial cells (VECs) to cyclic tensile strain. RESULTS: The number of neutrophils in the distracted suture peaked on Day 3, and N2-type neutrophils significantly increased on Day 5 after force application. The depletion of circulatory neutrophils reduced bone volume by 43.6% after 7-day expansion. The stretched VECs recruited neutrophils via a CXCR2 mechanism in vitro, which then promoted BMSC osteogenic differentiation through the VEGFA/VEGFR2 axis. Consistently, these neutrophils showed higher expression of canonical N2 phenotype genes, including CD206 and Arg1. CONCLUSIONS: These results suggested that neutrophils participated in early bone formation during MPE. Based on these findings, we propose that stretched VECs recruited and polarized neutrophils, which, in turn, induced BMSC osteogenic differentiation.

Formulation of a Stable Oil-in-Water Microemulsion of Torreya grandis cv. Merrillii Aril Essential Oil and Its Application in Loquat Fruit Preservation.

Loquat is a nutrient-rich fruit with juicy and sweet pulp, but it is vulnerable to rot and deterioration without proper postharvest preservation measures. This study aimed to improve the postharvest quality of loquat by developing a microemulsion system based on an essential oil extracted from the Torreya grandis cv. Merrillii aril (TaEO), which has antimicrobial and antioxidant properties. An optimal TaEO microemulsion (TaEO-ME) was formulated, using a mixture of Tween-40 and Tween-80 as the surfactant, 1-butanol as the co-surfactant, and TaEO as the oil phase, with mass ratios of 9:1, 3:1, and 6:1, respectively. Two TaEO-ME formulations with 60% and 70% water contents were stable for 180 days at room temperature, with a mean droplet size below 12 nm and polydispersity index less than 0.24. They also exhibited higher stability and enhanced biological activities compared to free TaEO. Loquat fruit treated with TaEO-ME displayed a reduced decay index and lower membrane lipid peroxidation after 15 days of storage at 15 °C, as indicated by the lower malondialdehyde content and higher peroxidase activity. Moreover, the TaEO-ME treatment preserved the nutrient quality by maintaining the total phenolic compounds and ascorbic acid content. Our findings suggested that TaEO-ME can be used as a substitute for chemical preservatives to keep fruits fresh.

Isolation, Identification and Antimicrobial Resistance Analysis of Canine Oral and Intestinal Escherichia coli Resistant to Colistin.

In recent years, the antimicrobial resistance in Escherichia coli has gradually developed into a global problem. These resistant bacteria could be transmitted to humans through animal feces in the environment or direct contact with pets, leading to a problem in bacterial treatment for humans and animals. Now, the antibiotic resistance of oral and intestinal microbiota from dog origins remains unclear in China. Therefore, this study first analyzed the current colistin resistance of oral and intestinal microbiota from dog origins in mainland China. A total of 536 samples were collected from dogs in mainland China and, respectively, cultured on the SS and MacConkey agar plate containing colistin (4 µg/mL) to obtain bacteria, and the antibiotic-resistance phenotype of Escherichia coli was investigated for nine antibiotics. Results showed that a total of 2259 colistin-resistant bacteria were isolated from samples and identified, and among them, the isolated rate of Escherichia coli (34.01%, 769/2259) was relatively higher than that of other bacteria. Subsequently, it was found that the resistance of these Escherichia coli was very severe by exploring its resistance to different antibiotics, particularly to three common antibiotics in a clinic which were ceftriaxone, ampicillin and trimethoprim/sulfamethoxazole, with the resistance rates of 60.60% (466/769), 57.22% (440/769), and 53.06% (408/769), respectively. Moreover, the simultaneous resistance of Escherichia coli to one or more antibiotics was determined, and 69.96% (538/769) strains have defined the resistance to both two or more antibiotics, and even 13 of Escherichia coli strains that were resistant to all nine antibiotics, indicating that the Escherichia coli from dog origins has severe antibiotic resistance in the clinic. In conclusion, this study guided the use of antibiotics and could draw attention to antibiotic resistance in veterinary clinical treatment for animals in the future.

Prognosis and adjuvant chemotherapy for patients with malignant peritoneal cytology in early-stage non-endometrioid endometrial cancer.

OBJECTIVE: To investigate the influence of malignant peritoneal cytology (MPC) on the prognosis of early-stage patients with endometrial clear cell carcinoma(CCC) and serous carcinoma(SC), and the value of chemotherapy in their treatment. METHODS: A retrospective observational cohort study was conducted by querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2010 to 2019. Women with early-stage CCC and SC with available peritoneal cytology results were enrolled. Propensity score matching(PSM) and propensity score inverse probability of treatment weighting (IPTW) was used to balance the measured covariates in each sub-cohort. RESULTS: A total of 3,616 eligible patients were included, and 368 patients had MPC (10.2%). Women with MPC were more likely to receive postoperative chemotherapy (OR 2.033; 95%CI 1.589-2.602). In PSM model, MPC had worse overall survival(OS) and cancer-specific survival (CSS) (All,p < 0.001). The 5-year OS rates were 56.5% for women with MPC and 74.4% for those with negative peritoneal cytology, and the 5-year CSS rates were 60.8% versus 80.0%(All, p < 0.0001). In the subgroup analyses, MPC was associated with decreased OS and CSS in serous, clear cell histology group, and stage IA cases(All,p < 0.001), but not for stage IB or stage II disease. In multivariate analysis, chemotherapy improved the prognosis of patients with MPC(OS:p = 0.005; CSS:p = 0.010). Additionally, in stage IA subgroup, chemotherapy improved survival outcomes in patients with MPC(OS:P = 0.025; CSS:P = 0.038), in NPC patients, however, chemotherapy was a good prognostic factor for OS (P = 0.001) but not for CSS(P = 0.300). CONCLUSION: MPC was a prognostic factor for decreased survival in early-stage endometrial CCC and SC, and those with MPC could further benefit from chemotherapy.

In situfabrication of Cu-Mn-O nanostructure catalysts on Ti mesh and their catalytic property optimization for low-temperature and stable CO oxidation.

A series of interlaced 'tripe-shaped' nanoflake catalysts made of CuMn2O4werein situprepared on Ti mesh substrate through the associated methods of plasma electrolyte oxidation and hydrothermal technique. The surface morphology, elemental distribution and chemical state, phase composition and microstructure of CuMn2O4nanostructures prepared under different conditions were systemically investigated. To evaluate the catalytic activity, the CO oxidation as a probe reaction was used, and the results showed that 12h-Cu1Mn2-300 (hydrothermal reaction at 150 °C for 12 h, Cu/Mn = 1/2 in initial precursor, heat treatment temperature at 300 °C) exhibited the best CO oxidation capability withT100= 150 °C owe to the formation of uniform CuMn2O4nanosheet layersin situgrown on flexible Ti mesh and the synergistic effect of Cu and Mn species in spinel CuMn2O4, which makes it more active towards CO oxidation than pure copper/manganese oxides.

The role of TCGA molecular classification in clear cell endometrial carcinoma.

Clear cell endometrial carcinoma (CCEC) represents a relatively rare and heterogeneous entity. Based on The Cancer Genome Atlas (TCGA) molecular classification, the risk stratification and management of endometrial cancer (EC) have been improved. Although the relationship of CCEC with the TCGA classification is less well understood, data has emerged to suggest that molecular classification plays an important role in the prognosis and management of CCEC. Most of patients with CCEC are characterized by p53abn or NSMP type and the prognosis of these patients is poor, whereas those with MMRd or POLEmut seem to have a favorable prognosis. Adjuvant therapy is recommended in CCEC with p53abn and NSMP. Advanced/recurrent CCEC with MMRd benefit much more from immune checkpoint inhibitors after the failure of platinum-based chemotherapy. In addition, bevacizumab plus chemotherapy upfront seems to improve outcomes of advanced/recurrent patients whose tumors harbored mutated TP53, including CCECs with p53abn. Further studies which exclusively recruit CCEC are urgently needed to better understand the role of molecular classification in CCEC. This review will provide an overview of our current understanding of TCGA classification in CCEC.

Matrix mechanics regulate the polarization state of bone marrow-derived neutrophils through the JAK1/STAT3 signaling pathway.

Matrix mechanics regulate essential cell behaviors through mechanotransduction, and as one of its most important elements, substrate stiffness was reported to regulate cell functions such as viability, communication, migration, and differentiation. Neutrophils (Neus) predominate the early inflammatory response and initiate regeneration. The activation of Neus can be regulated by physical cues; however, the functional alterations of Neus by substrate stiffness remain unknown, which is critical in determining the outcomes of engineered tissue mimics. Herein, a three-dimensional (3D) culture system made of hydrogels was developed to explore the effects of varying stiffnesses (1.5, 2.6, and 5.7 kPa) on the states of Neus. Neus showed better cell integrity and viability in the 3D system. Moreover, it was shown that the stiffer matrix tended to induce Neus toward an anti-inflammatory phenotype (N2) with less adhesion molecule expression, less reactive oxygen species (ROS) production, and more anti-inflammatory cytokine secretion. Additionally, the aortic ring assay indicated that Neus cultured in a stiffer matrix significantly increased vascular sprouting. RNA sequencing showed that a stiffer matrix could significantly activate JAK1/STAT3 signaling in Neus and the inhibition of JAK1 ablated the stiffness-dependent increase in the expression of CD182 (an N2 marker). Taken together, these results demonstrate that a stiffer matrix promotes Neus to shift to the N2 phenotype, which was regulated by JAK1/STAT3 pathway. This study lays the groundwork for further research on fabricating engineered tissue mimics, which may provide more treatment options for ischemic diseases and bone defects. STATEMENT OF SIGNIFICANCE.

Fecal antibiotic resistance genes were transferred through the distribution of soil-lettuce-snail food chain.

Massive antibiotic resistance genes (ARG) were detected in the soil modified by manure, which may affect human life safety through the food chain. However, the transmission of ARGs through the soil-plant-animal food chain is still unclear. Therefore, this study used high-throughput quantitative PCR technology to explore the effects of pig manure application on ARGs and bacterial communities in soil, lettuce phyllosphere, and snail excrement. The results showed that a total of 384 ARGs and 48 MEGs were detected in all samples after 75 days of incubation. The diversity of ARGs and MGEs in soil components increased significantly by 87.04% and 40% with the addition of pig manure. The absolute abundance of ARGs in the phyllosphere of lettuce was significantly higher than that of the control group, with a growth rate of 212.5%. Six common ARGs were detected between the three components of the fertilization group, indicating that there was internal transmission of fecal ARGs between the trophic levels of the food chain. Firmicutes and Proteobacteria were identified as the dominant host bacteria in the food chain system, which were more likely to be used as carriers of ARGs to promote the spread of resistance in the food chain. The results were used to assess the potential ecological risks of livestock and poultry manure. It provides theoretical basis and scientific support for the formulation of ARG prevention and control policies.

A study on the correlation between intrauterine microbiota and uterine pyogenesis in dogs.

Pyometra is a common and high-incidence reproductive system disease in female dogs, and its development involves both hormonal and bacterial factors. Characterization of the endometrial microbiome in healthy dogs and diseased dogs with pyometra remains unclear at present, however. In this study, dogs with pyometra were identified based on the clinical examinations, hematology examinations, vaginal smears and uterine histopathology. The endometrial samples of healthy dogs (n = 30) and diseased dogs (n = 41) were then collected and sequenced by 16S rRNA high-throughput sequencing technology. Dogs with pyometra suffered from inflammation, and their endometrial microbial diversity (ACE and Chao 1 indices) was significantly lower than that of healthy dogs (P < 0.05). The endometrial samples of both groups were enriched in four phyla (Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria), with a greater abundance of Firmicutes in diseased dogs (P < 0.05). At the genus level, the most prevalent microbes in diseased dogs belonged to Pseudomonas, Escherichia-Shigella, Mycoplasma, Enterococcus, Haemophilus, Vibrio and Ralstonia, with lower levels of Mycoplasma, Enterococcus and Haemophilus in the healthy control. Principal co-ordinates analysis and non-metric multi-dimensional scaling showed that the endometrial microbiome of diseased dogs clustered separately from that of the healthy controls (P < 0.05). In the LDA effect size analysis, 18 members of the endometrial microbiome were screened. Of these, the bacterial species Pseudomonas_aeruginosa and microbes within the genera Mycoplasma, Enterococcus and Haemophilus were found to be enriched in the uteruses of diseased dogs. Furthermore, the Random Forests model further confirmed that Mycoplasma and Haemophilus could be considered as biomarkers of diseased endometrium. In conclusion, this study provided a theoretical basis for the development of probiotic preparation in the future.

Cytokines network in primary membranous nephropathy.

There have been extensive studies on the immunological mechanism of primary membranous nephropathy (PMN). Autoantibodies, being the end product of humoral auto-immunity, matter much in diagnosis, therapy and prediction. Although PMN has been thought of as oligoinflammatory glomerulopathy, autoimmune diseases usually involve inflammation and it may be long-lasting. Cytokines are key mediators and effector molecules of inflammatory and humoral immune responses. Their function and network are helpful to understand the immune mechanism of PMN, but there is a lack of systematic summary. Accordingly, this review explores the advance of cytokines in PMN, and clarifies whether inflammation involves in the pathological process of PMN, based on which certain cytokines are proposed as potential biomarkers or therapeutic targets, and the importance of updating existing therapy regimens is highlighted.