Kunduan Yimu Decoction affected Th17/Treg balance through microRNA-124 to improve rheumatoid arthritis pathology.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune condition characterized by inflammation and the deterioration of joints. Current treatments often have side effects, highlighting the need for safer options. This study investigates the therapeutic effects of Kunduan Yimu Decoction (KDYMD) on RA, focusing on the role of miR-124 in regulating Th17/Treg differentiation. METHODS: PBMCs from RA patients were analyzed before and after KDYMD treatment. RT-qPCR was used to measure the miR-124 expressions. Flow cytometry was used to assess the ratios of Th17 to Treg cells. ELISA was used to quantify the cytokine concentrations. The effects of KDYMD on JAK2/STAT3 signaling were evaluated by western blot analysis. A CIA mouse model was used to validate the in vivo effects of KDYMD. RESULTS: MiR-124 expression was significantly upregulated in PBMCs of RA patients after KDYMD treatment. This upregulation was associated with increased Tip60 and Foxp3 expression and decreased RORγt expression. In the cytokine analysis, IL-1, IL-6, and IL-17A were decreased, and IL-10 and TGF- were increased after treatment. Flow cytometry showed a restoration of the Th17/Treg balance, with a decrease in Th17 and an increase in Treg cells. In vivo, KDYMD treatment ameliorated ankle swelling and arthritis index in CIA mice, comparable to methotrexate (MTX). In addition, KDYMD modulated JAK2/STAT3 signaling and enhanced anti-inflammatory responses. CONCLUSIONS: KDYMD exerts significant anti-inflammatory effects in RA by upregulating miR-124, which in turn regulates Th17/Treg differentiation and modulates JAK2/STAT3 signaling. A novel mechanism involving miR-124 and immune cell balance suggests KDYMD could be a promising therapeutic agent for RA.

Allopurinol is Associated with an Increased Risk of Cerebral Infarction: A Two-Sample Mendelian Randomization Study.

OBJECTIVE: Previous studies have reported that the inappropriate use of allopurinol may increase the risk of cerebrovascular accidents, but some studies have also confirmed that allopurinol is a protective factor against stroke. To clarify whether there is a relevant causal relationship between allopurinol and cerebral infarction, we conducted a two-sample Mendelian randomization (MR) study. METHODS: Data on single nucleotide polymorphisms (SNPs) associated with allopurinol and genome-wide association studies of cerebral infarction were obtained from the genome-wide association study (GWAS) web site. Five basic MR analyses were performed using MR-Egger regression, weighted median (WM1), inverse variance weighting (IVW), weighted mode (WM2), and simple mode. Sensitivity analysis was subsequently performed to detect horizontal pleiotropy, heterogeneity, and potential outliers. The final analysis results were mainly based on the IVW estimates. RESULTS: A total of 10 SNPs were used as instrumental variables (IVs). MR analysis [(IVW: odds ratio (OR) = 1.053, 95% confidence interval (CI): 1.019-1.088, P = 0.002), (WM1: OR = 1.053, 95% CI: 1.009-1.098, P = 0.017), (WM2: OR = 1.050, 95% CI: 1.008-1.095, P = 0.044), (MR Egger: Q = 4.285, P = 0.830)] showed a positive causal association between allopurinol and the risk of cerebral infarction. Sensitivity analysis such as horizontal pleiotropy and heterogeneity increased the reliability of this result. CONCLUSION: The results of this study provide direct evidence that there is a causal relationship between allopurinol and cerebral infarction and that allopurinol may increase the risk of cerebral infarction.

Salinity-induced variations in bacterial composition and co-occurrence patterns within Salicornia-based constructed wetlands in mariculture.

Constructed wetlands use vegetation and microorganisms to remove contaminants like nitrogen and phosphorus from water. For mariculture, the impact of salinity on the efficiency of wastewater treatment of wetlands is unneglectable. However, little is known about their impact on the microbiome in constructed wetlands. Here, we set four salinity levels (15, 22, 29, and 36) in Salicornia constructed wetlands, and the experiment was conducted for a period of 72 days. The 15 group exhibited the highest removal rates of nitrogen compounds and phosphate, compared to the other salinity groups, the nosZ gene exhibited significantly higher expression in the 22 group (p < 0.05), indicated that microorganisms in 22 salinity have higher denitrification abilities. The three dominant phyla identified within the microbiomes were Proteobacteria, known for their diverse metabolic capabilities; Cyanobacteria, important for photosynthesis and nitrogen fixation; and Firmicutes, which include many fermenters. The ecological network analysis revealed a 'small world' model, characterized by high interconnectivity and short path lengths between microbial species, and had higher co-occurrence (45.13%) observed in this study comparing to the Erdös-Réyni random one (32.35%). The genus Microbulbifer emerged as the sole connector taxon, pivotal for integrating different microbial communities involved in nitrogen removal. A negative correlation was observed between salinity levels and network complexity, as assessed by the number of connections and diversity of interactions within the microbial community. Collectively, these findings underscore the critical role of microbial community interactions in optimizing nitrogen removal in constructed wetlands, with potential applications in the design and management of such systems for improved wastewater treatment in mariculture.

Risk of dyslipidemia and major adverse cardiac events with tofacitinib versus adalimumab in rheumatoid arthritis: a real-world cohort study from 7580 patients.

Objective: To compare the effects of tofacitinib and adalimumab on the risk of adverse lipidaemia outcomes in patients with newly diagnosed rheumatoid arthritis (RA). Methods: Data of adult patients newly diagnosed with RA who were treated with tofacitinib or adalimumab at least twice during a 3-year period from 1 January 2018 to 31 December 2020, were enrolled in the TriNetX US Collaborative Network. Patient demographics, comorbidities, medications, and laboratory data were matched by propensity score at baseline. Outcome measurements include incidental risk of dyslipidemia, major adverse cardiac events (MACE) and all-cause mortality. Results: A total of 7,580 newly diagnosed patients with RA (1998 receiving tofacitinib, 5,582 receiving adalimumab) were screened. After propensity score matching, the risk of dyslipidaemia outcomes were higher in the tofacitinib cohort, compared with adalimumab cohort (hazard ratio [HR] with 95% confidence interval [CI], 1.250 [1.076-1.453]). However, there is no statistically significant differences between two cohorts on MACE (HR, 0.995 [0.760-1.303]) and all-cause mortality (HR, 1.402 [0.887-2.215]). Conclusion: Tofacitinib use in patients with RA may increase the risk of dyslipidaemia to some extent compared to adalimumab. However, there is no differences on MACE and all-cause mortality.

Serum 25-hydroxyvitamin D levels and dermatomyositis: A 2-sample mendelian randomization study.

BACKGROUND: Previous studies have reported low serum 25-hydroxyvitamin D [25(OH)D] levels in dermatomyositis (DM) patients, but the exact causal relationship between them remains elusive. Our aim is to confirm the causal relationship between 25(OH)D and DM risk through a Mendelian randomization study. METHODS: Retrieve genome-wide association study (GWAS) data on 25(OH)D (n = 441 291) and DM (n cases = 201, n controls = 172 834) from the GWAS database (https://gwas.mrcieu.ac.uk/). Select single-nucleotide polymorphisms (SNPs) strongly correlated with 25(OH)D as instrumental variables (IVs). The primary analytical approach involves the use of the inverse-variance weighted method (IVW), supplemented by MR-Egger regression and weighted median methods to enhance the reliability of the results. Heterogeneity and sensitivity analyses were conducted using Cochran's Q and leave-one-out approaches, respectively. RESULTS: The IVW analysis confirmed a positive causal relationship between genetic variation in 25(OH)D levels and DM (OR = 2.36, 95% CI = 1.01-5.52, p = .048). Although not statistically significant (all p > .05), the other methods also suggested a protective effect of 25(OH)D on DM. Based on MR-Egger intercepts and Cochran's Q analysis, the selected SNPs showed no horizontal pleiotropy and heterogeneity. Sensitivity analysis demonstrated the robustness of the results against individual SNPs. CONCLUSION: We provide the first evidence of a causal relationship between 25(OH)D levels and DM. Our findings support the importance of measuring serum 25(OH)D levels and considering vitamin D supplementation in clinical practice for patients with DM.

Bibliometric and visual analysis on oxidative stress in gynecological and reproductive diseases: A systematic review.

BACKGROUND: The imbalance between the generation and elimination of reactive oxygen species (ROS) is defined as oxidative stress (OS). Elevated levels of OS are implicated in various diseases, especially in gynecological and reproductive disorders. The abundance of recent literature makes it challenging to assimilate all available information. This bibliometric analysis seeks to depict the research landscape of OS in gynecological and reproductive diseases and to identify future hotspots and trends. METHODS: The Web of Science Core Collection served as the source for articles related to OS in gynecological and reproductive diseases. CtieSpace and VOSviewer software were utilized to analyzed countries/regions, institutions, journals, authors, and keywords of all eligible articles. RESULTS: A total of 1423 articles were included. There was a gradual increase in the number of publications in this field. The USA maintained the highest number of publications, with 372 articles. Cleveland Clinic was the leading institution in terms of publication volume, contributing 67 articles. In total, 6925 authors were identified. Agarwal A as the most frequently co-cited author, received 812 citations across 43 publications. The predominant clusters included "placenta," "polycystic ovary syndrome," "male infertility," and "oocyte quality." Notably, "oocyte quality'" was identified as a current key research topic. CONCLUSION: There was an uptrend in the number of articles addressing OS in gynecological and reproductive diseases. However, international collaboration and exchange were limited. The topic of male infertility had remained a consistent area of interest, and research on oocyte quality is poised to become a potential focal point in the future.

Methotrexate and the Risk of Dementia: A Two-Sample Mendelian Randomization Study.

INTRODUCTION: Recent studies have suggested a potential association between methotrexate use and an increased risk of dementia. However, the causal relationship between methotrexate and dementia remains unclear. This study aims to investigate the potential causal effect of methotrexate use on the risk of dementia using a two-sample Mendelian randomization (TSMR) approach. METHODS: We conducted a TSMR study using summary statistics from genome-wide association studies (GWAS) of methotrexate use and dementia. We obtained genetic instruments for methotrexate use from a large-scale GWAS meta-analysis and genetic instruments for dementia from a separate GWAS meta-analysis. We performed several statistical analyses, including inverse-variance weighted (IVW), weighted median (WM1), weighted mode (WM2), and MR-Egger regression methods, to estimate the causal effect of methotrexate on dementia risk. RESULTS: Our TSMR analysis showed a significant positive association between genetic predisposition to methotrexate use and dementia risk. The IVW method estimated a causal odds ratio (OR) of 0.476 [95% confidence interval (CI) 0.362-0.626] per unit increase in the log odds ratio of methotrexate use. WM1, WM2, and MR-Egger methods provided consistent results. CONCLUSION: The findings of this mendelian randomization (MR) study suggest a potential causal effect of methotrexate use on the risk of dementia. However, further research is needed to validate these findings and explore the underlying mechanisms. Since methotrexate is widely prescribed for various autoimmune diseases, a better understanding of its potential impact on dementia risk is crucial for optimizing treatment strategies and addressing potential adverse effects.

Peripheral nerve injury associated with JEV infection in high endemic regions, 2016-2020: a multicenter retrospective study in China.

Previously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016-2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

Aggregation-induced emission of TTCPy-3: A novel approach for eradicating Nocardia seriolae infections in aquatic fishes.

Aquatic fishes are threatened by the strong pathogenic bacterium Nocardia seriolae, which challenges the current prevention and treatment approaches. This study introduces luminogens with aggregation-induced emission (AIE) as an innovative and non-antibiotic therapy for N. seriolae. Specifically, the AIE photosensitizer, TTCPy-3 is employed against N. seriolae. We evaluated the antibacterial activity of TTCPy-3 and investigated the killing mechanism against N. seriolae, emphasizing its ability to aggregate within the bacterium and produce reactive oxygen species (ROS). TTCPy-3 could effectively aggregate in N. seriolae, generate ROS, and perform real-time imaging of the bacteria. A bactericidal efficiency of 100% was observed while concentrations exceeding 4 µM in the presence of white light irradiation for 10 min. In vivo, evaluation on zebrafish (Danio rerio) confirmed the superior therapeutic efficacy induced by TTCPy-3 to fight against N. seriolae infections. TTCPy-3 offers a promising strategy for treating nocardiosis of fish, paving the way for alternative treatments beyond traditional antibiotics and potentially addressing antibiotic resistance.

A bibliometric analysis of the research status and trends in studies on polymyositis and dermatomyositis with interstitial lung disease from 2000 to 2022 using Web of Science.

BACKGROUND: The main subtypes of idiopathic inflammatory myopathies (IIMs)-polymyositis (PM) and dermatomyositis (DM)-are often presented as interstitial lung disease (ILD) in clinical practice; therefore, many researchers have combined the three studies into PM/DM with ILD. METHODS: Using bibliometrics, the research status, progress, and hotspots of PM/DM with ILD between 2000 and 2022 were studied. Literature data on PM/DM with ILD were retrieved from the Web of Science (WoS) database for the research period. Visualization software, including VOSviewer, Pajek, CiteSpace, and Scimago Graphica were used for bibliometric analysis. RESULTS: A total of 1555 relevant articles were obtained, and the overall research in this field showed an increasing trend. Regarding contributing countries and venues, Japan published the most articles while Rheumatology was the most prolific journal. Regarding authors, the most published article was by Wang Guochun from Changchun University of Technology in China. Keyword analysis and cocited literature cluster analysis showed that diagnosis, classification, autoantibodies, antibodies, prognosis, complications, and treatment of PM/DM with ILD have been hot topics in this field recently. Moreover, our study shows that anti-mda5 antibody, mortality, gene 5 antibody, IIMs, double-blind, and prognostic factors, among others, may be new hot topics. CONCLUSION: This study found that research on PM/DM with ILD has increased over time, and scholars are paying more attention to this field. The development of new drugs for the management, treatment, and prevention of PM/DM with ILD is the primary task of researchers and a direction for future research in this field.

Leonurine alleviates rheumatoid arthritis by regulating the Hippo signaling pathway.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause joint inflammation and damage. Leonurine (LE) is an alkaloid found in Leonurus heterophyllus. It has anti-inflammatory effects. HYPOTHESIS/PURPOSE: The molecular mechanisms by which LE acts in RA are unclear and further investigation is required. METHODS: Mice with collagen-induced arthritis (CIA), and RA-fibroblast-like synoviocytes (FLSs) isolated from them were used as in vivo and in vitro models of RA, respectively. The therapeutic effects of LE on CIA-induced joint injury were investigated by micro-computed tomography, and staining with hematoxylin and eosin and Safranin-O/Fast Green. Cell Counting Kit-8, a Transwell® chamber, enzyme-linked immunosorbent assays, RT-qPCR, and western blotting were used to investigate the effects of LE on RA-FLS viability, migratory capacity, inflammation, microRNA-21 (miR-21) levels, the Hippo signaling pathway, and the effects and intrinsic mechanisms of related proteins. Dual luciferase was used to investigate the binding of miR-21 to YOD1 deubiquitinase (YOD1) and yes-associated protein (YAP). Immunofluorescence was used to investigate the localization of YAP within the nucleus and cytoplasm. RESULTS: Treatment with LE significantly inhibited joint swelling, bone damage, synovial inflammation, and proteoglycan loss in the CIA mice. It also reduced the proliferation, cell colonization, migration/invasion, and inflammation levels of RA-FLSs, and promoted miR-21 expression in vitro. The effects of LE on RA-FLSs were enhanced by an miR-21 mimic and reversed by an miR-21 inhibitor. The dual luciferase investigation confirmed that both YOD1 and YAP are direct targets of miR-21. Treatment with LE activated the Hippo signaling pathway, and promoted the downregulation and dephosphorylation of MST1 and LATS1 in RA, while inhibiting the activation of YOD1 and YAP. Regulation of the therapeutic effects of LE by miR-21 was counteracted by YOD1 overexpression, which caused the phosphorylation of YAP and prevented its nuclear ectopic position, thereby reducing LE effect on pro-proliferation-inhibiting apoptosis target genes. CONCLUSION: LE regulates the Hippo signaling pathway through the miR-21/YOD1/YAP axis to reduce joint inflammation and bone destruction in CIA mice, thereby inhibiting the growth and inflammation of RA-FLSs. LE has potential for the treatment of RA.

Whole-Genome Resequencing Reveals the Diversity of Patchouli Germplasm.

As an important medicinal and aromatic plant, patchouli is distributed throughout most of Asia. However, current research on patchouli's genetic diversity is limited and lacks genome-wide studies. Here, we have collected seven representative patchouli accessions from different localities and performed whole-genome resequencing on them. In total, 402,650 single nucleotide polymorphisms (SNPs) and 153,233 insertions/deletions (INDELs) were detected. Based on these abundant genetic variants, patchouli accessions were primarily classified into the Chinese group and the Southeast Asian group. However, the accession SP (Shipai) collected from China formed a distinct subgroup within the Southeast Asian group. As SP has been used as a genuine herb in traditional Chinese medicine, its unique molecular markers have been subsequently screened and verified. For 26,144 specific SNPs and 16,289 specific INDELs in SP, 10 of them were validated using Polymerase Chain Reaction (PCR) following three different approaches. Further, we analyzed the effects of total genetic variants on genes involved in the sesquiterpene synthesis pathway, which produce the primary phytochemical compounds found in patchouli. Eight genes were ultimately investigated and a gene encoding nerolidol synthetase (PatNES) was chosen and confirmed through biochemical assay. In accession YN, genetic variants in PatNES led to a loss of synthetase activity. Our results provide valuable information for understanding the diversity of patchouli germplasm resources.

Proton pump inhibitor use associated with an increased risk of gout: A population-based case-control study.

OBJECTIVES: In previous reports, proton pump inhibitor (PPI) use increased the risk of gout. However, there is no epidemiological study investigating this association. We aimed to examine the potential impact of PPI treatment on the risk of developing gout. METHODS: A population-based case-control study was performed using a Longitudinal Health Insurance Database 2000 from Taiwan (population 23 million). We identified gout cases and non-gout controls through propensity score matching at 1:1, which was matched by sex and age. We used a conditional logistic regression model to estimate an odds ratio and 95% confidence intervals (CI) for gout population versus controls. RESULTS: Esomeprazole increased the risk of gout after adjusting confounding variables (adjusted odds ratio [aOR] 1.3; 95% CI 1.0-1.6). The risk of gout was highest within 30 days of PPI treatment (aOR 1.7; 95% CI 1.4-1.9) and attenuated thereafter. The risk of gout was increased among female users of PPI compared with male users (aOR 2.2; 95% CI 1.7-2.8). The aOR of gout in people with PPI use was higher in middle-aged individuals (41-60 years: aOR 2.1; 95% CI 1.7-2.7) than in the older group (≥60 years: aOR 1.8; 95% CI 1.5-2.2). CONCLUSIONS: Our findings provide population-level evidence for the hypothesis that PPI treatment is positively associated with the risk of developing gout. Further research on the mechanism underlying this association is warranted.

Induced neural stem cells suppressed neuroinflammation by inhibiting the microglial pyroptotic pathway in intracerebral hemorrhage rats.

Intracerebral hemorrhage usually manifests as strong neuroinflammation and neurological deficits. There is an urgent need to explore effective methods for the treatment of intracerebral hemorrhage. The therapeutic effect and the possible mechanism of induced neural stem cell transplantation in an intracerebral hemorrhage rat model are still unclear. Our results showed that transplantation of induced neural stem cells could improve neurological deficits by inhibiting inflammation in an intracerebral hemorrhage rat model. Additionally, induced neural stem cell treatment could effectively suppress microglial pyroptosis, which might occur through inhibiting the NF-κB signaling pathway. Induced neural stem cells could also regulate the polarization of microglia and promote the transition of microglia from pro-inflammatory phenotypes to anti-inflammatory phenotypes to exert their anti-inflammatory effects. Overall, induced neural stem cells may be a promising tool for the treatment of intracerebral hemorrhage and other neuroinflammatory diseases.

Novel in vivo endometriotic models associated eutopic endometrium by implanting menstrual blood-derived stromal cells from patients with endometriosis.

The eutopic endometrium provides novel insights into endometriotic pathophysiology and treatment. However, no in vivo models currently available are suitable for eutopic endometrium in endometriosis. In this study, we present new endometriotic in vivo models associated with eutopic endometrium using menstrual blood-derived stromal cells (MenSCs). First, we isolated endometriotic MenSCs (E-MenSCs) and healthy MenSCs (H-MenSCs) from the menstrual blood of patients with endometriosis (n = 6) and healthy volunteers (n = 6). Then, we identified MenSCs' endometrial stromal cell properties using adipogenic and osteogenic differentiation. A cell counting kit-8 and wound healing assay were used to compare the proliferation and migration capability between E-MenSCs and H-MenSCs. Seventy female nude mice were used to prepare endometriotic models related to eutopic endometrium by implanting E-MenSCs relying on three approaches, including surgical implantation using scaffolds seeded with MenSCs, and subcutaneous injection of MenSCs in the abdomen and the back (n = 10). H-MenSCs or scaffolds only were implanted in control groups (n = 10). One month after the surgical implantation and 1 week after the subcutaneous injection, we evaluated modeling by hematoxylin-eosin (H&E) and immunofluorescent staining of human leukocyte antigen α (HLAA). Fibroblast morphology, lipid droplets, and calcium nodules in E-MenSCs and H-MenSCs identified their endometrial stromal cell properties. We noticed that the proliferation and migration of E-MenSCs were considerably enhanced compared to H-MenSCs (P < 0.05). E-MenSCs implanted in nude mice formed ectopic lesions using three approaches (n = 10; lesions formation rate: 90%, 115%, and 80%; average volumes: 123.60, 27.37, and 29.56 mm3), while H-MenSCs in the nude mice shaped nothing at the implantation sites. Endometrial glands, stroma, and HLAA expression in these lesions further verified the success and applicability of the proposed endometriotic modeling. Findings provide in vitro and in vivo models and paired controls associated with eutopic endometrium in women with endometriosis using E-MenSCs and H-MenSCs. The approach of subcutaneous injection of MenSCs in the abdomen is highlighted due to non-invasive, simple, and safe steps, a short modeling period (1 week), and an excellent modeling success rate (115%), which could improve the repeats and success of endometriotic nude mice model and shorten the modeling period. These novel models could nearly intimate human eutopic endometrial mesenchymal stromal cells in the progress of endometriosis, opening a new path for disease pathology and treatment.

Efficient nitrogen removal of a novel Pseudomonas chengduensis strain BF6 mainly through assimilation in the recirculating aquaculture systems.

Biological nitrogen removal has received increasing attention in wastewater treatment. A bacterium with excellent nitrogen removal performance was isolated from biofilters of recirculating aquaculture systems (RAS) and identified as Pseudomonas chengduensis BF6. It was indicated that inorganic nitrogen is transformed into gaseous and biological nitrogen by the metabolic pathways of denitrification, anammox, and assimilation, which is the main nitrogen removal pathway of strain BF6. The strain BF6 could effectively remove nitrogen within 24 h under the conditions of ammonia, nitrate, nitrite, and mixed nitrogen sources with maximum total nitrogen removal efficiencies reaching 97.00 %, 61.40 %, 79.10 %, and 84.98 %, respectively. The strain BF6 exhibited total nitrogen removal efficiency of 91.14 %, altered the microbial diversity and enhanced the relative abundance of Pseudomonas in the RAS biofilter. These findings demonstrate that Pseudomonas sp. BF6 is a highly efficient nitrogen-removing bacterium with great potential for application in aquaculture wastewater remediation.

Placental mesenchymal stem cells ameliorate NLRP3 inflammasome-induced ovarian insufficiency by modulating macrophage M2 polarization.

BACKGROUND: Premature ovarian insufficiency (POI) is a common clinical problem, however, there are currently no effective therapies. Pyroptosis induced by the NLRP3 inflammasome is considered a possible mechanism of POI. Placental mesenchymal stem cells (PMSCs) have excellent immunomodulatory potential and offer a promising method for treating POI. METHODS: Female Sprague-Dawley rats were randomly divided into four treatment groups: control (no POI), POI with no PMSCs, POI with PMSCs transplant, and POI with hormones (estrogen + progesterone) as positive control. POI was induced by exposure to 4-vinylcyclohexene diepoxide (VCD) for 15 days. After four weeks, all animals were euthanized and examined for pathology. Hormone levels were measured and ovarian function was evaluated in relation to the estrous cycle. Levels of NLRP3 inflammasome pathway proteins were determined by immunohistochemistry and western blot. RESULTS: VCD significantly damaged rat follicles at different estrous stages. Injection of human PMSCs improved ovarian function and reproductive ability of POI rats compared to the sham and hormone groups. Our data also showed that PMSCs markedly suppress cell pyroptosis via downregulation of the NLRP3 inflammasome, caspase-1, IL-1ß and IL-18 compared to the other two groups. The human PMSCs increased the expression of IL-4 and IL-10 and decreased pro-inflammatory factors by phenotypic changes in macrophages. CONCLUSIONS: Our findings revealed a novel mechanism of follicular dysfunction and ovarian fibrosis via activation of the NLRP3 inflammasome followed by secretion of pro-inflammatory factors. Transplantation of PMSCs into POI rats suppressed pro-inflammatory factor production, NLRP3 inflammasome formation and pyroptosis, and improved ovarian function.

Study on the interaction mechanism between Crocus sativus and Fusarium oxysporum based on dual RNA-seq.

KEY MESSAGE: The saffron phenylpropane synthesis pathway and Fusarium oxysporum cell wall-degrading enzymes play key roles in their early interactions. Saffron (Crocus sativus) is a highly important crop with diverse medicinal properties. F. oxysporum is a widely-distributed soil-borne fungus, causing the serious saffron rot disease. Currently, there is no effective management strategy to control this disease because of no resistant cultivars and limited information about the resistance and pathogenic mechanisms. In this study, we first characterized the infection process and physiological responses of saffron infected by F. oxysporum. The molecular mechanism of these infection interactions was revealed by dual RNA-seq analysis. On the 3rd day of infection, the hyphae completely entered, colonized and spread in the corm cells; while on the 6th day of infection, hyphae had appeared in the xylem cells, blocking these vessels. Transcriptome results indicate that within the host, phenylpropanoid metabolism, plant hormone signal transduction and plant pathogen interaction pathways were activated during infection. These pathways were conducive to the enhancement of cell wall, the occurrence of hypersensitivity, and the accumulation of various antibacterial proteins and phytoantitoxins. Meanwhile, in the fungus, many up-regulated genes were related to F. oxysporum cell wall degrading enzymes, toxin synthesis and pathogenicity gene, showing its strong pathogenicity. This study provides new ideas for the control of saffron corm rot, and also provides a theoretical basis for mining the key functional genes.

Erbu Zhuyu decoction improves endometrial angiogenesis via uterine natural killer cells and the PI3K/Akt/eNOS pathway a mouse model of embryo implantation dysfunction.

BACKGROUND: We investigated the effect of Erbu Zhuyu decoction (EBZY) on angiogenesis via uterine natural killer (uNK) cells and the PI3K/Akt/eNOS pathway in embryo implantation dysfunction (EID) mice. METHODS: Pregnant mice were randomly divided into blank, model, EBZY, progynova, and aspirin groups. Uteri were excised on the 5th day of pregnancy for analysis. RESULTS: Mice in the model group showed pale uteri, a reduced implantation rate, and lower expression levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), endothelial nitric oxide synthase (eNOS) and nitric oxide (NO). Compared to the model group, implantation rates in the medium-dose and high-dose groups of EBZY were significantly higher (P < .05), PI3K and Akt mRNA expression levels in the low-dose group were significantly higher (P < .05, P < .01), and the expression of p-PI3K, p-Akt, and p-eNOS proteins in all treatment groups were significantly increased (P < .01, P < .05). The expression of NO was significantly increased in the low-dose and high-dose groups (P < .01, P < .05, respectively). The level of p-Akt protein in the high-dose group was significantly higher than those in the other treatment groups (P < .01, P < .05). There was no significant difference in the density of uNK cells (P > .05). CONCLUSIONS: EBZY facilitated embryo implantation in EID mice by enhancing endometrial angiogenesis via activation of the PI3K/Akt/eNOS pathway, at least in part. There was no evidence to indicate that EBZY could adjust the expression of uNK.