Differential gene expression and miRNA regulatory network in coronary slow flow.

Coronary slow flow (CSF) is characterized by slow progression of coronary angiography without epicardial stenosis. The aim of this study was to explore the potential biomarkers and regulatory mechanism for CSF. Peripheral blood mononuclear cells from 3 cases of CSF and 3 healthy controls were collected for high-throughput sequencing of mRNA and miRNA, respectively. The differentially expressed mRNAs (DE-mRNAs) and miRNAs (DE-miRNAs) was identified. A total of 117 DE-mRNAs and 32 DE-miRNAs were obtained and they were mainly enriched in immune and inflammatory responses. Twenty-six DE-mRNAs were the predicted target genes for miRNAs by RAID, and then the regulatory network of 15 miRNAs were constructed. In addition, through the PPI network, we identified the three genes (FPR1, FPR2 and CXCR4) with larger degrees as hub genes. Among them, FPR1 was regulated by hsa-miR-342-3p, hsa-let-7c-5p and hsa-miR-197-3p and participated in the immune response. Finally, we validated the differential expression of hub genes and key miRNAs between 20 CSF and 20 control. Moreover, we found that miR-342-3p has a targeted regulatory relationship with FPR1, and their expression is negatively correlated. Then we established a hypoxia/reoxygenation (H/R) HUVEC model and detected FPR1, cell proliferation and apoptosis. Transfection with miR-342-3p mimics can significantly promote the proliferation of HUVEC under H/R conditions. FPR1 were associated with CSF as a biomarker and may be regulated by miR-342-3p potential biomarkers.

The oncogenic role and regulatory mechanism of ACAA2 in human ovarian cancer.

Acetyl-CoAacyltransferase2 (ACAA2) is a key enzyme in the fatty acid oxidation pathway that catalyzes the final step of mitochondrial ß oxidation, which plays an important role in fatty acid metabolism. The expression of ACAA2 is closely related to the occurrence and malignant progression of tumors. However, the function of ACAA2 in ovarian cancer is unclear. The expression level and prognostic value of ACAA2 were analyzed by databases. Gain and loss of function were carried out to explore the function of ACAA2 in ovarian cancer. RNA-seq and bioinformatics methods were applied to illustrate the regulatory mechanism of ACAA2. ACAA2 overexpression promoted the growth, proliferation, migration, and invasion of ovarian cancer, and ACAA2 knockdown inhibited the malignant progression of ovarian cancer as well as the ability of subcutaneous tumor formation in nude mice. At the same time, we found that OGT can induce glycosylation modification of ACAA2 and regulate the karyoplasmic distribution of ACAA2. OGT plays a vital role in ovarian cancer as a function of oncogenes. In addition, through RNA-seq sequencing, we found that ACAA2 regulates the expression of DIXDC1. ACAA2 regulated the malignant progression of ovarian cancer through the WNT/ß-Catenin signaling pathway probably. ACAA2 is an oncogene in ovarian cancer and has the potential to be a target for ovarian cancer therapy.

Wogonoside alleviates microglia-mediated neuroinflammation via TLR4/MyD88/NF-κB signaling axis after spinal cord injury.

Wogonoside (WG) is a natural flavonoid extracted from Scutellariae Radix, recognized for its established anti-inflammatory properties. However, the role of WG in the context of neuroinflammation after spinal cord injury (SCI) remains inadequately elucidated. This study employed in silico, in vitro, and in vivo methodologies to investigate the impact of WG on microglia-mediated neuroinflammation after SCI. In the in silico experiment, we identified 15 potential target genes of WG associated with SCI. These genes were linked to the regulation of inflammatory response and immune defense. Molecular docking maps revealed toll-like receptor 4 as a molecular target for WG, demonstrating binding through a hydrogen bond (Lys263, Ser120). In lipopolysaccharide-stimulated BV2 cells and SCI mice, WG significantly attenuated microglial activation and facilitated a phenotype shift from M1 to M2. This was evidenced by the reversal of the increased expressions of Iba1, GFAP, and iNOS, as well as the decreased expression of Arg1. WG also suppressed the production of pro-inflammatory mediators (NO, TNF-α, IL-6, IL-1α, IL-1ß, C1q). WG exerted these effects by suppressing the TLR4/MyD88/NF-κB signaling axis in microglia. Furthermore, by reducing levels of TNF-α, IL-1α, and C1q in supernatant of LPS-induced microglia, WG indirectly induced astrocytes change to A2 phenotype, evidenced by transcriptome sequencing result of primary mouse astrocytes. All these events above collectively created a favorable microenvironment, contributing to a significant alleviation of weight loss and neuronal damage at the lesion site of SCI mice. Our findings substantiate the efficacy of WG in mitigating neuroinflammation after SCI, thereby warranting further exploration.

Polyphonic sound event localization and detection based on Multiple Attention Fusion ResNet.

Sound event localization and detection have been applied in various fields. Due to the polyphony and noise interference, it becomes challenging to accurately predict the sound event and their occurrence locations. Aiming at this problem, we propose a Multiple Attention Fusion ResNet, which uses ResNet34 as the base network. Given the situation that the sound duration is not fixed, and there are multiple polyphonic and noise, we introduce the Gated Channel Transform to enhance the residual basic block. This enables the model to capture contextual information, evaluate channel weights, and reduce the interference caused by polyphony and noise. Furthermore, Split Attention is introduced to the model for capturing cross-channel information, which enhances the ability to distinguish the polyphony. Finally, Coordinate Attention is introduced to the model so that the model can focus on both the channel information and spatial location information of sound events. Experiments were conducted on two different datasets, TAU-NIGENS Spatial Sound Events 2020, and TAU-NIGENS Spatial Sound Events 2021. The results demonstrate that the proposed model significantly outperforms state-of-the-art methods under multiple polyphonic and noise-directional interference environments and it achieves competitive performance under a single polyphonic environment.

The prognostic values of estimating intraperitoneal pressure in the occurrence of abdominal wall complications in peritoneal dialysis patients.

BACKGROUND: Increased intraperitoneal pressure is associated with abdominal wall complications and technical failure of peritoneal dialysis (PD). Several equations have been developed to estimate intraperitoneal pressure. We aimed to assess the prognostic yield of the intraperitoneal pressure as estimated by current equations on the occurrence of abdominal wall complications in peritoneal dialysis patients. METHODS: This is a retrospective analysis of data from a prospective cohort which recruited 1207 incident PD patients. Estimated intraperitoneal pressure was calculated using four available equations (according to Sigogne, Castellanos, Scanziani and de Jesus Ventura). Abdominal wall complications were recorded during follow-up. Univariate analysis and multivariate analysis with competing risk regression were used to assess the predictive power of the estimates of intraperitoneal pressure in the occurrence of abdominal wall complications. RESULTS: During a median follow-up of 30 months, 66 (5.5%) patients (1.6/100 patient-years) developed abdominal wall complications. The median time to the occurrence of abdominal wall complications was 5.7 months. Only the estimated intraperitoneal pressure by the de Jesus Ventura equation significantly predicted abdominal wall complications by using univariate analyses. Associations between estimated intraperitoneal pressure by the de Jesus Ventura equation and the occurrence of abdominal wall complications disappeared after adjusting for significant clinical factors. CONCLUSIONS: We verified the prognostic value of estimation of intraperitoneal pressure by four available equations in predicting abdominal wall complications in our single-center PD cohort. Due to a low diagnostic yield, a novel equation for estimating the intraperitoneal pressure is urgently needed.

High preseason temperature variability drives convergence of xylem phenology in the Northern Hemisphere conifers.

Wood growth is key to understanding the feedback of forest ecosystems to the ongoing climate warming. An increase in spatial synchrony (i.e., coincident changes in distant populations) of spring phenology is one of the most prominent climate responses of forest trees. However, whether temperature variability contributes to an increase in the spatial synchrony of spring phenology and its underlying mechanisms remains largely unknown. Here, we analyzed an extensive dataset of xylem phenology observations of 20 conifer species from 75 sites over the Northern Hemisphere. Along the gradient of increase in temperature variability in the 75 sites, we observed a convergence in the onset of cell enlargement roughly toward the 5th of June, with a convergence in the onset of cell wall thickening toward the summer solstice. The increase in rainfall since the 5th of June is favorable for cell division and expansion, and as the most hours of sunlight are received around the summer solstice, it allows the optimization of carbon assimilation for cell wall thickening. Hence, the convergences can be considered as the result of matching xylem phenological activities to favorable conditions in regions with high temperature variability. Yet, forest trees relying on such consistent seasonal cues for xylem growth could constrain their ability to respond to climate warming, with consequences for the potential growing season length and, ultimately, forest productivity and survival in the future.

Interguild fungal competition in litter and soil inversely modulate microbial necromass accumulation during Loess Plateau forest succession.

Microbial interactions determine ecosystem carbon (C) and nutrient cycling, yet it remains unclear how interguild fungal interactions modulate microbial residue contribution to soil C pools (SOC) during forest succession. Here, we present a region-wide investigation of the relative dominance of saprophytic versus symbiotic fungi in litter and soil compartments, exploring their linkages to soil microbial residue pools and potential drivers along a chronosequence of secondary Chinese pine (Pinus tabulaeformis) forests on the Loess Plateau. Despite minor changes in C and nitrogen (N) stocks in the litter or soil layers across successional stages, we found significantly lower soil phosphorus (P) stocks, higher ratios of soil C: N, soil N: P and soil C: P but lower ratios of litter C: N and litter C: P in old (>75 years) than young stands (<30 years). Pine stand development altered the saprotroph: symbiotroph ratios of fungal communities to favor the soil symbiotrophs versus the litter saprotrophs. The dominance of saprotrophs in litter is positively related to microbial necromass contribution to SOC, which is negatively related to the dominance of symbiotrophs in soils. Antagonistic interguild fungal competition in litter and soil layers, in conjunction with increased fungal but decreased bacterial necromass contribution to SOC, jointly contribute to unchanged total necromass contribution to SOC with stand development. The saprotroph: symbiotroph ratios in litter and soil layers are mainly driven by soil P stocks and stand parameters (e.g., stand age and slope), respectively, while substrate stoichiometries primarily regulate microbial necromass accumulation and fungal: bacterial necromass ratios. These results provide novel insights into how microbial interactions at local spatial scales modulate temporal changes in SOC pools, with management implications for mitigating regional land degradation.

The transcription factor Ofi1 is critical for white-opaque switching in natural MTLa/α isolates of Candida albicans.

Candida albicans, an opportunistic fungal pathogen, is able to switch between two distinct cell types: white and opaque. While white-to-opaque switching is typically repressed by the a1/α2 heterodimer in MTLa/α cells, it was recently reported that switching can also occur in some natural MTLa/α strains under certain environmental conditions. However, the regulatory program governing white-opaque switching in MTLa/α cells is not fully understood. Here, we collected 90 clinical isolates of C. albicans, 16 of which possess the ability to form opaque colonies. Among the known regulators implicated in white-opaque switching, only OFI1 exhibited significantly higher expression in these 16 strains compared to the reference strain SC5314. Importantly, ectopic expression of OFI1 in both clinical isolates and laboratory strains promoted switching frequency even in the absence of N-acetylglucosamine and high CO2 , the optimal condition for white-to-opaque switching in MTLa/α strains. Deleting OFI1 resulted in a reduction in opaque-formation frequency and the stability of the opaque cell in MTLa/α cells. Ofi1 binds to the promoters of WOR1 and WOR3 to induce their expression, which facilitates white-to-opaque switching. Ofi1 is conserved across the CTG species. Altogether, our study reported the identification of a transcription factor Ofi1 as the critical regulator that promotes white-to-opaque switching in natural MTLa/α isolates of C. albicans.

Dietary fatty acids intake and all-cause and cardiovascular mortality in patients on peritoneal dialysis.

BACKGROUND & AIMS: The relationship between dietary fatty acids (FA) and clinical outcomes are relatively lacking in non-dialyzed and dialyzed chronic kidney disease (CKD) population, resulting in insufficient guide about the dietary FA intake in this population. In this study, we aimed to observe the association between the intake of total or different types of FA and all-cause and cardiovascular (CV) mortality in patients undergoing peritoneal dialysis (PD). METHODS: This is a prospective cohort study with data retrospectively analyzed in 881 patients undergoing PD. Dietary FA intake measured by 3-day dietary records. The outcomes were defined as all-cause and CV death. Baseline FA intake and time-averaged FA intake were categorized by tertiles based on the distribution among the study population. We used univariate and multivariate Cox proportional regression models to determine the association between amounts and types of FA and all-cause and CV mortality. RESULTS: During a median follow up of 45 months, 93 patients were still being maintained on PD, 467 had died, including 189 (40.5%) attributable to CV death. Compared to patients in the low tertile of total FA (TFA) intake at baseline group, the middle or/and high tertile groups were more likely to be male, younger, well-educated and better nutritional status (P < 0.05). At the baseline, no association was found between all-cause and CV death in either total or different types of FA after adjusting for nutritional variables. As for time-averaged analyses, the associations of TFA, saturated FA (SFA), monounsaturated FA (MUFA), ω-3 and ω-6 polyunsaturated FA (PUFA) and all-cause mortality were weakened after adjustment for laboratory and nutrients variables. However, PUFA independently reduced 5% of mortality even after adjustment for laboratory and nutrients variables [HR 0.95 (0.91, 0.99), P = 0.023], and the ratio of MUFA/PUFA was positively associated with the risk for all-cause mortality [HR 1.05 (1.01, 1.09), P = 0.008]. Furthermore, each 10% increase of the ratio of ω-6/ω-3 was only weakly associated with the risk for all-cause mortality [HR 1.02 (1.00, 1.04), P = 0.034]. As for CVD mortality, the impacts of total and each type of FA disappeared after adjustment for laboratory or nutrients variables. CONCLUSIONS: Time-averaged PUFA intake was independently associated with a lower risk for all-cause mortality in our PD cohort, while the higher ratio of MUFA/PUFA and ω-6/ω-3 increased all-cause mortality. More observational and interventional researches are needed to determine these associations.

S1PR1 regulates ovarian cancer cell senescence through the PDK1-LATS1/2-YAP pathway.

Cell senescence deters the activation of various oncogenes. Induction of senescence is, therefore, a potentially effective strategy to interfere with vital processes in tumor cells. Sphingosine-1-phosphate receptor 1 (S1PR1) has been implicated in various cancer types, including ovarian cancer. The mechanism by which S1PR1 regulates ovarian cancer cell senescence is currently elusive. In this study, we demonstrate that S1PR1 was highly expressed in human ovarian cancer tissues and cell lines. S1PR1 deletion inhibited the proliferation and migration of ovarian cancer cells. S1PR1 deletion promoted ovarian cancer cell senescence and sensitized ovarian cancer cells to cisplatin chemotherapy. Exposure of ovarian cancer cells to sphingosine-1-phosphate (S1P) increased the expression of 3-phosphatidylinositol-dependent protein kinase 1 (PDK1), decreased the expression of large tumor suppressor 1/2 (LATS1/2), and induced phosphorylation of Yes-associated protein (p-YAP). Opposite results were obtained in S1PR1 knockout cells following pharmacological inhibition. After silencing LATS1/2 in S1PR1-deficient ovarian cancer cells, senescence was suppressed and S1PR1 expression was increased concomitantly with YAP expression. Transcriptional regulation of S1PR1 by YAP was confirmed by chromatin immunoprecipitation. Accordingly, the S1PR1-PDK1-LATS1/2-YAP pathway regulates ovarian cancer cell senescence and does so through a YAP-mediated feedback loop. S1PR1 constitutes a druggable target for the induction of senescence in ovarian cancer cells. Pharmacological intervention in the S1PR1-PDK1-LATS1/2-YAP signaling axis may augment the efficacy of standard chemotherapy.

Comprehensive metabolome and transcriptome analyses demonstrate divergent anthocyanin and carotenoid accumulation in fruits of wild and cultivated loquats.

Eriobotrya is an evergreen fruit tree native to South-West China and adjacent countries. There are more than 26 loquat species known in this genus, while E. japonica is the only species yet domesticated to produce fresh fruits from late spring to early summer. Fruits of cultivated loquat are usually orange colored, in contrast to the red color of fruits of wild E. henryi (EH). However, the mechanisms of fruit pigment formation during loquat evolution are yet to be elucidated. To understand these, targeted carotenoid and anthocyanin metabolomics as well as transcriptomics analyses were carried out in this study. The results showed that ß-carotene, violaxanthin palmitate and rubixanthin laurate, totally accounted for over 60% of the colored carotenoids, were the major carotenoids in peel of the orange colored 'Jiefangzhong' (JFZ) fruits. Total carotenoids content in JFZ is about 10 times to that of EH, and the expression levels of PSY, ZDS and ZEP in JFZ were 10.69 to 23.26 folds to that in EH at ripen stage. Cyanidin-3-O-galactoside and pelargonidin-3-O-galactoside were the predominant anthocyanins enriched in EH peel. On the contrary, both of them were almost undetectable in JFZ, and the transcript levels of F3H, F3'H, ANS, CHS and CHI in EH were 4.39 to 73.12 folds higher than that in JFZ during fruit pigmentation. In summary, abundant carotenoid deposition in JFZ peel is well correlated with the strong expression of PSY, ZDS and ZEP, while the accumulation of anthocyanin metabolites in EH peel is tightly associated with the notably upregulated expressions of F3H, F3'H, ANS, CHS and CHI. This study was the first to demonstrate the metabolic background of how fruit pigmentations evolved from wild to cultivated loquat species, and provided gene targets for further breeding of more colorful loquat fruits via manipulation of carotenoids and anthocyanin biosynthesis.

Strain-tunable magnetism and topological states in layered VBi2Te4.

Similar to the magnetic topological insulator of MnBi2Te4, recent studies have demonstrated that VBi2Te4 is also an ideal candidate to explore many intriguing quantum states. Different from the strong interlayer antiferromagnetic (AFM) coupling in layered MnBi2Te4, based on first-principles calculations, we find that the energy difference between AFM and ferromagnetic (FM) orders in layered VBi2Te4 is much smaller than that of MnBi2Te4. Specifically, it is found that the interlayer FM coupling can be readily achieved by applying strain. Further electronic band structures reveal that the VBi2Te4 bilayer is a time-reversal symmetry broken quantum spin Hall insulator with a spin Chern number of CS = 1, which is essentially different from the QAH state with a Chern number of C = 1 in the MnBi2Te4 bilayer. Most strikingly, the topological states of the magnetic VBi2Te4 bilayer can be well tuned by strain, whose topological phase diagram is mapped out as a function of strain by employing continuum model analyses. All of these results indicate that the layered VBi2Te4 not only enriches the family of magnetic topological materials, but also provides a promising platform to explore more exotic quantum phenomena.

Novel equations for estimating intraperitoneal pressure among peritoneal dialysis patients.

Background: Increased intraperitoneal pressure (IPP) is associated with abdominal wall complications and technical failure in peritoneal dialysis (PD). Since the standard measurement of IPP is limited due to its cumbersome procedures, we aimed to develop and validate equations for estimating IPP. Methods: We performed a cross-sectional study with a total of 200 prevalent PD patients who were divided into development and validation datasets after random sampling matched by body mass index. The IPPs were measured using the Durand method, with whole-body and abdominal anthropometry indices collected. Equations with 2.0-L and 1.5-L fill volumes were generated by stepwise linear regression modelling. The bias, accuracy and precision of the estimated IPP (eIPP) with 2-L and 1.5-L fill volumes were compared with actual IPPs by the Durand method. The eIPP for the 2-L fill volume was also compared with other existing equations. Results: Two new equations incorporating waist circumference and height from the decubitus plane to mid-axillary line were generated. The eIPPs exhibited small biases in relation to the Durand method , with median differences of -0.24 cmH2O and -0.10 cmH2O for 2 L and 1.5 L, respectively. The precisions evaluated by the standard deviation of the absolute value of the differences were 2.59 cmH2O and 2.50 cmH2O, respectively. The accuracies evaluated by the value of the percentage of estimates that differed by >20% for the eIPP were 26% for 2.0 L and 27% for 1.5 L. Better bias, precision and accuracy were observed for the eIPP equation compared with other existing equations for the 2.0-L fill volume. Conclusions: We provided two new equations developed from abdominal anthropometry indices to accurately estimate the IPP in the PD population.

Bi2Te3-intercalated MnBi2Te4: ideal candidate to explore intrinsic Chern insulator and high-temperature quantum anomalous Hall effect.

The recently discovered magnetic topological insulator of MnBi2Te4(MBT), has been demonstrated to realize the quantum anomalous Hall (QAH) effect, while the naturally antiferromagnetic (AFM) interlayer coupling in MBT results in that the QAH effect can only be realized in odd-layered systems and at low temperature. Using first-principles calculations, we find that intercalating Bi2Te3(BT) layers into MBT by forming MBT/(BT)n/MBT (n= 1-6) heterostructures can induce magnetic phase transition from AFM to ferromagnetic (FM) interlayer coupling whenn⩾ 3. Specifically, MBT/(BT)3/MBT and MBT/(BT)4/MBT respectively host Curie temperaturesTcof 14 K and 11 K, which fits well the experimentally measuredTcof 12 K. Detailed band structure calculations and topological identification show that the QAH phases are well preserved for all FM heterostructures. And the topological mechanism of MBT/(BT)n/MBT as a function ofnis revealed by employing continuum model analysis. Most importantly, the FM MBT/(BT)4/MBT has already been experimentally fabricated. Thus, our work provides a practical guideline to explore high-temperature QAH effect in MBT family of materials.

Engineering topological states in a two-dimensional honeycomb lattice.

In this work, we use first-principles calculations to determine the interplay between spin-orbit coupling (SOC) and magnetism which can not only generate a quantum anomalous Hall state but can also result in topologically trivial states although some honeycomb systems host large band gaps. By employing tight-binding model analysis, we have summarized two types of topologically trivial states: one is due to the coexistence of quadratic non-Dirac and linear Dirac bands in the same spin channel that act together destructively in magnetic materials (such as, CrBr3, CrCl3, and VBr3 monolayers); the other one is caused by the destructive coupling effect between two different spin channels due to small magnetic spin splitting in heavy-metal-based materials, such as, BaTe(111)-supported plumbene. Further investigations reveal that topologically nontrivial states can be realized by removing the Dirac band dispersion of the magnetic monolayers for the former case (such as in alkali metal doped CrBr3), while separating the two different spin channels from each other by enhancing the magnetic spin splitting for the latter case (such as in half-iodinated silicene). Thus, our work provides a theoretical guideline to manipulate the topological states in a two-dimensional honeycomb lattice.

Quality of evidence supporting the role of acupuncture for breast cancer-related lymphoedema: an overview of systematic reviews and meta-analyses.

BACKGROUND: Breast cancer-related lymphedema (BCRL) may benefit from acupuncture as a therapeutic. However, the findings of systematic reviews (SRs) and meta-analyses (MAs) are inconsistent and their quality needs to be evaluated critically. We aimed to provide an overview of the methodological quality, risk of bias, quality of reporting, and quality of evidence for SRs/MAs of acupuncture for BCRL. METHODS: Publications were retrieved from four Chinese databases and four English databases. The methodological quality, risk of bias, reporting quality, and evidence quality of the included SRs/MAs were assessed by two independent researchers using the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2), Risk of Bias in Systematic Reviews (ROBIS), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and Grading of Recommendations, Assessment, Development and Evaluation (GRADE), respectively. RESULTS: There were a total of 8 SRs/MAs included. By AMSTAR-2, all SRs/MAs were graded as having low or very low methodological quality. By ROBIS, all SRs/MAs in phase 1, domain 1, and domain 4 of phase 2 were at low risk, while in domain 2 were at high risk. By PRISMA, reporting weaknesses in protocol and registration, as well as search method, were identified. By GRADE, the level of evidence quality was "low" to "very low", and the most commonly downgraded factor was the risk of bias. CONCLUSIONS: Acupuncture may be beneficial in improving BCRL. However, due to the identified limitations and conflicting findings, further more prescriptive and rigorous SRs/MAs are required to give strong evidence for final judgments.

The role of total antioxidant capacity and malondialdehyde of seminal plasma in the association between air pollution and sperm quality.

Accumulating evidence has suggested that men exposed to air pollution are associated with decreased sperm quality, and seminal plasma plays a pivotal role in maintaining sperm viability. However, the role of seminal plasma in air pollution related sperm quality decline remain unestablished. In current study, we recruited 524 participants from couples who underwent in vitro fertilization treatment due to female factors at a fertility clinic in China from March to August 2020. Conventional sperm parameters, total antioxidant capacity (T-AOC), malondialdehyde (MDA) and testosterone were measured using semen samples. The six main air pollutants (PM2.5, PM10, NO2, SO2, CO, O3) during four key periods of sperm development (meiotic stage, spermiogenesis stage, epididymal stage and total sperm cycle period) were estimated using inverse distance weighting method. Multiple linear regression models were employed to investigate the exposure-outcome relationships. And we found that PM10 exposures were negatively related to sperm total motility and the exposures of PM2.5 and PM10 were inversely associated with sperm progressive motility during epididymal stage. Furthermore, PM2.5 and PM10 exposures were positively associated with seminal plasma MDA and PM10 was negatively related to seminal plasma T-AOC during epididymal stage. PM2.5, PM10 and CO exposures during total sperm cycle period might relate to increased seminal plasma testosterone. Mediation analysis indicated seminal plasma MDA and T-AOC partially mediated PM10 associated reduction of sperm motility during epididymal stage. Our study suggested MDA and T-AOC of seminal plasma played a role in air pollution associated decline of sperm motility.

Exercise-induced irisin improves follicular dysfunction by inhibiting IRE1α-TXNIP/ROS-NLRP3 pathway in PCOS.

BACKGROUND: Excessive production of androgen drives oxidative stress (OS) and inflammasome activation in ovarian granulosa cells (GCs). Therefore, the induced follicular developmental disorder is the major cause of infertility in women with polycystic ovary syndrome (PCOS). Exercise-induced upregulation of irisin is capable of regulating metabolism by reducing OS and inflammation. Exercise has been shown to alleviate a range of PCOS symptoms, including maintaining a normal menstrual cycle, in several clinical trials. METHODS: Female Sprague-Dawley (SD) rats and primary ovarian cells were treated with two different androgens, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT), to simulate a hyperandrogenic environment, followed by eight weeks of exercise training and irisin intervention. The levels of reactive oxygen species (ROS), tissue inflammation and fibrosis were examined using hematoxylin and eosin (H&E) staining, western blot, quantitative real-time PCR (qRT-PCR), dichlorofluorescein diacetate (DCF-DA) probe detection, immunofluorescence staining, immunohistochemistry, and Sirius red staining. RESULTS: Exercise for eight weeks improved polycystic ovarian morphology and decreased the levels of inflammation, OS, and fibrosis in PCOS rats. Hyperandrogen increased ROS production in ovarian cells by inducing endoplasmic reticulum stress (ERS) and activating the inositol-requiring enzyme 1α (IRE1α)-thioredoxin-interacting protein (TXNIP)/ROS-NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathway, further enhancing the levels of inflammation. Irisin suppressed the expression of IRE1α and its downstream targets, thus improving the ovarian dysfunction of PCOS rats induced by hyperandrogen. CONCLUSION: Exercise can alleviate various phenotypes of PCOS rats induced by DHEA, and its therapeutic effect may be mediated by secreting beneficial myokines. IRE1α may be an important target of irisin for reducing OS and inflammation, thereby improving ovarian fibrosis.

Mechanism of Gynostemmae Pentaphylli Herba in the treatment of ischemic stroke based on network pharmacology and molecular docking.

OBJECTIVES: To analyze the mechanism of Gynostemmae Pentaphylli Herba in the treatment of ischemic stroke based on network pharmacology and molecular docking. METHODS: We used various databases and software, including Cytoscape, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Pubchem, Swiss Target Prediction, GenCards, String, and WebGestalt to identify the active components and targets of Gynostemmae Pentaphylli Herba, as well as the targets associated with ischemic stroke. The mechanism of Gynostemmae Pentaphylli Herba in treating ischemic stroke was analyzed from the perspective of protein-protein interaction (PPI) co-expression, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and AutoDock was used for molecular docking. RESULTS: A total of 12 active components were identified, and 276 potential targets of Gynostemmae Pentaphylli Herba were obtained. There were 3151 disease targets associated with ischemic stroke. The top 5 active components of Gynostemmae Pentaphylli Herba were Ruvoside_qt, quercetin, 3'-methyleriodictyol, Spinasterol, and Cholesterin (CLR) according to the node degree value. There were 186 common targets between the disease targets of cerebral ischemic stroke and drug targets of Gynostemmae Pentaphylli Herba, with 21 key targets obtained by PPI network analysis. KEGG analysis revealed enrichment in 45 signaling pathways. Biological process increased 139 biological processes. Molecular function enriched 17 cell functions. Cellular component enriched 20 cell components. Molecular docking found that the binding energy of other protein molecules to ligand small molecules was less than -5 kal·mol-1, except that the binding energy of AKT1 to 3'-methyleriodictyol was greater than -5 kal·mol-1. CONCLUSIONS: Gynostemmae Pentaphylli Herba may play a role in treating ischemic stroke by affecting various pathways through its active ingredients such as Ruvoside_qt, quercetin, 3'-methyleriodictyol, Spinasterol and CLR.

Research Progress of Cordyceps sinensis and Its Fermented Mycelium Products on Ameliorating Renal Fibrosis by Reducing Epithelial-to-Mesenchymal Transition.

Renal fibrosis is a hallmark and common outcome of various chronic kidney diseases (CKDs) and manifests pathologically as accumulation and deposition of extracellular matrix (ECM) in the kidney. Epithelial-to-mesenchymal transition (EMT) has been shown to be an important mechanism involved in renal fibrosis. Cordyceps sinensis, a traditional Chinese medicine, has long been used for the treatment of renal fibrosis. As research on the mycelium of C. sinensis progressed, a variety of medicines developed from fermented mycelium were used to treat CKD. However, their efficacies and mechanisms have not been fully summarized. In this review, five medicines developed from fermented mycelium of C. sinensis are presented. The pharmacodynamic effects of C. sinensis on different animal models of renal fibrosis are summarized. The in vitro studies and related mechanisms of C. sinensis on renal cells are detailed. Finally, the application and efficacy of these five commercial medicines that meet national standards in different types of CKD are summarized. From this review, it can be concluded that C. sinensis can alleviate various causes of renal fibrosis to some extent, and its mechanism is related to TGF-ß1 dependent signaling, inhibition of inflammation, and improvement of renal function. Further research on rigorously designed, large-sample, clinically randomized controlled trial studies and detailed mechanisms should be conducted.