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Adenosine, a nucleoside, regulates various systems, such as the cardiovascular, immune, and nervous systems, by binding to Adenosine receptors. To elucidate the role of Adenosine in Osteoporosis, this study employed an experimental approach involving the stimulation of bone formation in osteoporotic zebrafish and the reduction of reactive oxygen levels in a glucocorticoid-induced zebrafish model of Osteoporosis with oxidative stress. Adenosine significantly promoted the proliferation of MC3T3-E1 cells and increased the activity of alkaline phosphatase (ALP). It also elevated nitric oxide, glutathione, and superoxide dismutase levels while decreasing malondialdehyde. The target of Adenosine’s impact on Osteoporosis with oxidative stress was elucidated through network pharmacology, revealing the PI3K/Akt pathway, a finding corroborated through RT-qPCR analysis. Hence, we present the mechanism through which Adenosine can be utilized to prevent and manage Osteoporosis accompanied by oxidative stress, distinct from the previously identified mode of action of Adenosine in osteoporosis treatment.

Introduction: The industrial processing of corn (Zeamays L.) generates by-products such as corn silk, straw peels, and straw core, which contribute to adverse environmental impacts. Our study aimed to investigate sustainable approaches for mitigating these effects by evaluating the hypoglycemic potential and mechanisms of ethyl acetate fractions derived from these corn derivatives.Methods: We employed glucose consumption assays, high glucose stress tests, UPLC-QE-Orbitrap-MS analysis, molecular docking, and simulations to assess their components and efficacy. Antioxidant capacities were evaluated using DPPH, FRAP, ABTS, and •OH scavenging assays.Results: Notably, the ethyl acetate fraction extracted from straw peels (SPE) exhibited a high concentration of flavonoids and phenolic compounds along with pronounced hypoglycemic activity and antioxidant capacity. SPE significantly enhanced glucose consumption in insulin-resistant HepG2 cells while protecting HUVECs against damage caused by high glucose levels. Molecular docking analyses confirmed the interaction between active compounds and α-glucosidase as well as α-amylase, while molecular dynamic simulations indicated stability at their binding sites.Discussion: In conclusion, the hypoglycemic and antioxidative properties observed in corn by-products such as straw peels, corn silk, and straw core can be attributed to the inhibition of α-glucosidase and α-amylase activities, coupled with their rich phenolic and flavonoid content. These findings highlight the potential of these by-products for applications in healthcare management and their sustainable utilization, demonstrating significant value in the use of agricultural residues.

Abstract Extracellular matrix (ECM) assembly/disassembly is a critical regulator for airway epithelial development and remodeling. Airway organoid is widely used in respiratory research, yet there is limited study to indicate the roles and mechanisms of ECM organization in epithelial growth and differentiation by using in vitro organoid system. Moreover, most of current Matrigel-based airway organoids are in basal-out orientation where accessing the apical surface is challenging. We present a human apical-out airway organoid using a biochemically defined hybrid hydrogel system. During human nasal epithelial progenitor cells (hNEPCs) differentiation, the gel gradually degrade, leading to the organoid apical surfaces facing outward. The expression and activity of ECM-degrading enzymes, matrix metalloproteinases (MMP7, MMP9, MMP10 and MMP13) increases during organoid differentiation, where inhibition of MMPs significantly suppresses the normal ciliation, resulting in increased goblet cell proportion. Moreover, a decrease of MMPs is found in goblet cell hyperplastic epithelium in inflammatory mucosa. This system reveals essential roles of epithelial-derived MMPs on epithelial cell fate determination, and provides an applicable platform enabling further study for ECM in regulating airway development in health and diseases.

Background and Aims: Perioperative intravenous (IV) infusions of lidocaine and esketamine reduce postoperative pain, but there are few studies on the quality of recovery and patients' emotional states postoperatively. We aimed to explore the effects of perioperative IV lidocaine and esketamine on the quality of recovery and emotional state after thyroidectomy. Methods: In this randomised trial, 137 patients undergoing thyroidectomy were randomly assigned to three groups: a lidocaine group (Group L), an esketamine group (Group E) and a normal saline placebo group (Group C). The primary outcome was the Quality of Recovery 40 (QoR-40) on postoperative days (PODs) 1 and 2. The secondary outcomes included Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) scores on days 1 and 2 after surgery, pain scores, opioid consumption and incidence of postoperative nausea and vomiting (PONV). Statistical analysis was performed using the one-way analysis of variance (ANOVA), the Kruskal-Wallis and Chi-square tests. Results: The global QoR-40 scores in groups L and E on POD 1 and POD 2 were significantly higher than in group C (P < 0.001). The SAS and SDS scores on POD 1 and POD 2 in groups L and E were significantly lower than in group C (P < 0.05). There were statistically significant differences in Numerical Rating Scale (NRS) scores among the three groups at 1 h, 2 h, 6 h and 12 h (P < 0.05). Conclusion: Perioperative IV lidocaine and esketamine improve the quality of postoperative recovery and the emotional state of patients undergoing thyroidectomy.

Background and Aims: Recent studies have found that ultrasound-guided (USG) bilateral superficial cervical plexus block (BSCPB) and intravenous infusion of lidocaine (IVL) have the potential to improve the quality of postoperative recovery. This study aimed to investigate and compare their effects on postoperative quality of recovery in patients undergoing thyroidectomy. Methods: A total of 135 patients were randomised to Group N: BSCPB with 10 mL 0.75% ropivacaine on each side, Group L: intravenous lidocaine (1.5 mg/kg for 10 min, followed by 1.5 mg/kg/h) and Group C: intravenous saline combined with BSCPB saline. The primary objective was quality of recovery-40 (QoR-40). Other parameters compared were numeric rating pain scale (NRS) score, haemodynamic data, opioid dosage and incidence of adverse effects. Statistical analysis was performed using the one-way analysis of variance (ANOVA), the Kruskal-Wallis test and the Chi-square test. Results: Compared to Group C, both groups N and L had higher QoR-40 total scores as well as scores indicating physical comfort, emotional state and pain dimensions on postoperative day (POD) 1 and POD2 (P < 0.001). The QoR-40 total and pain dimension scores in Group N were higher on POD1 and POD2 (P < 0.05). The NRS scores and the change in haemodynamics were lower in Group N compared to groups L and C (P < 0.05). The results of other parameters were lower in groups N and L than in Group C (P < 0.05). Conclusion: USG BSCPB and IVL are comparable in improving the quality of postoperative recovery in patients undergoing thyroidectomy.

Acicular ferrite (AF) has been regarded as the optimal microstructure in steel welds and heat affect zones (HAZs), because of its superior combination of strength and toughness. Although various aspects of AF have been investigated, the crystallographic characteristics of AF, including orientation relationship, variant selection and variant pairing, are still not fully studied. In this research, a Ti-deoxidized high strength low alloy steel was prepared and subjected to HAZ thermal cycle simulation tests to attain AF microstructure. Optical micrographs were obtained and EBSD mappings of AF microstructures were conducted. Through crystallographic analysis, the orientation relationship between AF and austenite was found close to that of bainite transformed at a high temperature (580 °C). In the AF microstructure, all 24 variants are formed and variant selection is nearly random. Compared with bainite, the variant pairing of AF is more random despite the slight favour of certain variant pairs. Most of the adjacent AF laths are from different close-packed plane (CP) groups, leading to the classic interlocking morphology. Meanwhile, a large number of neighbouring AF laths belong to different Bain groups, resulting in a high density of high angle grain boundaries (HAGBs). Intragranular nucleation of primary AF laths on inclusions contributes both to the high HAGB density and to the interlocking morphology of AF, while the sympathetic nucleation of secondary AF laths only contributes to the latter. These results suggest that to increase the HAGB density in AF, promoting the intragranular nucleation on inclusions is more important than enhancing the sympathetic nucleation.

IntroductionGrassland-livestock balance is an important principle of sustainable development of grassland livestock production and grassland ecosystem health. Grassland degradation becomes more serious at global scales and especially at the area that is sensitive to climate change and human activities. Decreases in pasture biomass and shifts in plant community composition in degraded grasslands can largely affect grazing behaviors of livestock. Up to date, however, it is unclear that whether livestock behaviors change across spatial and temporal scales and what key factors are to shape observed behavioral patterns of livestock.MethodsHere, yak behaviors including grazing, rumination and walking on the eastern Qinghai-Tibetan Plateau (QTP) were monitored by a continuous visual observation, to investigate temporal and spatial variations of grazing behavior of yaks (Bos grunniens); based on the data from public database in the past 18 years, a meta-analysis was conducted to examine the main factors that affect grazing behaviors and intake of yaks.ResultsWe showed that grazing behaviors of yaks differed significantly within hours, among hours of each day and among days as well as across different observation sites. Intake rate of yaks was higher in the morning than in the afternoon, but walking speed showed an inverse trend compared with intake rate. Resting, altitude, the mean annual precipitation (MAP), the mean annual temperature (MAT), forage ash, yak age and season were the main predictors for yak intake, and forage and yak individual characteristics had direct effects on grazing behaviors and intake of yaks.DiscussionThe findings confirm that grazing behaviors of yaks can vary even at small temporal scales and regional scales, which is closely related to the shift in forage quality and biomass caused by environmental changes. The study suggests that multiple factors can be responsible for the variation in livestock behaviors and shifts in behavioral patterns may consequently lead to positive or negative feedback to grassland ecosystems through plant-animal interactions.

Background: Hepatitis B virus associated-glomerulonephritis (HBV-GN) is one of the major secondary renal diseases in China, and microRNAs (miRNAs) in bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo) can attenuate HBV-X protein (HBx)-induced ferroptosis in renal podocytes, but the exact mechanism remains unclear. This study aimed to investigate the protective mechanism of miR-223-3p in BMSC-Exo in HBx-induced ferroptosis in podocytes.Methods: The study employed human renal podocyte cells (HPCs), bone marrow-derived mesenchymal stem cells (BMSCs), as well as kidney tissue from C57BL/6 mice and HBx transgenic mice. Initially, the correlation between STAT3 phosphorylation and ferroptosis was authenticated through the administration of signal transducer and activator of transcription 3 (STAT3) phosphorylation inhibitors in both in vivo and in vitro settings. Furthermore, the effect of HDAC2 overexpression on STAT3 phosphorylation was examined. Subsequently, the association between BMSC-Exo carrying miR-223-3p, HDAC2, and the phosphorylation of STAT3 in HPCs ferroptosis and injury induced by HBx was assessed. The interaction between miR-223-3p and HDAC2 was confirmed via RNA immunoprecipitation assay. Various techniques such as cell counting kit-8 assay, western blot, RT-qPCR, immunofluorescence, flow cytometry, lipid peroxidation assay kit, iron assay kit, transmission electron microscopy, and hematoxylin-eosin staining were employed to visualize the extent of HBx-induced podocyte injury and ferroptosis in both in vivo and in vitro.Results: The attenuation of podocyte ferroptosis can be achieved by inhibiting the phosphorylation of STAT3 in podocytes induced by HBx. Conversely, the upregulation of HDAC2 can enhance STAT3 phosphorylation, thereby promoting podocyte ferroptosis. MiR-223-3p was capable of directly exerting negative regulation on HDAC2 expression. BMSC-Exo carrying miR-223-3p can effectively suppress the expression of HDAC2, ultimately leading to reduce HBx-induced ferroptosis in podocytes by targeting HDAC2 with miR-223-3p and downregulating STAT3 phosphorylation.Conclusion: This study evidences the potential of BMSC-Exo mediated delivery of miR-223-3p in mitigating HBx-induced ferroptosis in podocytes, thereby offering a novel therapeutic target and approach for treating HBV-GN and alleviating renal injury.

BackgroundType 2 diabetes mellitus (T2DM) is a chronic and progressive condition defined by hyperglycemia caused by abnormalities in insulin production, insulin receptor sensitivity, or both. Several studies have revealed that higher body mass index (BMI) is associated with increasing risk of developing diabetes. In this study, we perform a protocol for systematic review to explore metabolite biomarkers that could be used to identify T2DM in obese subjects.MethodsThe protocol of this review was registered in PROSPERO (CRD42023405518). Three databases, EMBASE, PubMed, and Web of Science were selected to collect potential literature from their inceptions to July December 2023. Data for collection will include title, authors, study subjects, publication date, sample size, detection and analytical platforms, participant characteristics, biological samples, confounding factors, methods of statistical analysis, the frequency and directions of changes in potential metabolic biomarkers, and major findings. Pathway analysis of differential metabolites will be performed with MetaboAnalyst 5.0 based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Human Metabolome Database.ResultsThe results of this systematic review will be published in a peer-reviewed journal.ConclusionThis systematic review will summarize the potential biomarkers and metabolic pathways to provide a new reference for the prevention and treatment of T2DM in obese subjects.

Abstract Polymyxin resistance is conferred by MCR‐1 (mobile colistin resistance 1)‐induced lipopolysaccharide (LPS) modification of G− bacteria. However, the peptide MSI‐1 exerts potent antimicrobial activity against mcr‐1‐carrying bacteria. To further investigate the potential role of MCR‐1 in improving bacterial virulence and facilitating immune evasion, and the immunomodulatory effect of peptide MSI‐1, we first explored outer membrane vesicle (OMV) alterations of mcr‐1‐carrying bacteria in the presence and absence of sub‐MIC MSI‐1, and host immune activation during bacterial infection and OMV stimulation. Our results demonstrated that LPS remodelling induced by MCR‐1 negatively affected OMV formation and protein cargo by E. coli. In addition, MCR‐1 diminished LPS‐stimulated pyroptosis but facilitated mitochondrial dysfunction, further aggravating apoptosis in macrophages induced by OMVs of E. coli. Similarly, TLR4‐mediated NF‐κB activation was markedly alleviated once LPS was modified by MCR‐1. However, peptide MSI‐1 at the sub‐MIC level inhibited the expression of MCR‐1, further partly rescuing OMV alteration and attenuation of immune responses in the presence of MCR‐1 during both infection and OMV stimulation, which can be exploited for anti‐infective therapy.

Acinetobacter baumannii has developed multiple drug resistances, posing a significant threat to antibiotic efficacy. LysECD7, an endolysin derived from phages, could be a promising therapeutic agent against multi-drug resistance A. baumannii. In this study, in order to further enhance the antibacterial efficiency of the engineered LysECD7, a few lipopolysaccharide-interacting peptides (Li5, MSI594 and Li5-MSI) were genetically fused with LysECD7. Based on in vitro antibacterial activity, the fusion protein Lys-Li5-MSI was selected for further modifications aimed at extending its half-life. A cysteine residue was introduced into Lys-Li5-MSI through mutation (Lys-Li5-MSIV12C), followed by conjugation with a C16 fatty acid chain via a protonation substitution reaction(V12C-C16). The pharmacokinetic profile of V12C-C16 exhibited a more favorable characteristic in comparison to Lys-Li5-MSI, thereby resulting in enhanced therapeutic efficacy against lethal A. baumannii infection in mice. The study provides valuable insights for the development of novel endolysin therapeutics and proposes an alternative therapeutic strategy for combating A. baumannii infections.

IntroductionSoil microorganisms are essential for crop growth and production as part of soil health. However, our current knowledge of microbial communities in tobacco soils and their impact factors is limited.MethodsIn this study, we compared the characterization of bacterial and fungal communities in tobacco soils and their response to regional and rootstock disease differences.Results and discussionThe results showed that the diversity and composition of bacterial and fungal communities responded more strongly to regional differences than to rootstock diseases, while bacterial niche breadth was more sensitive than fungi to regional differences. Similarly, the core bacterial and fungal taxa shared by the three regions accounted for 21.73% and 20.62% of all OTUs, respectively, which was much lower than that shared by RD and NRD in each region, ranging from 44.87% to 62.14%. Meanwhile, the differences in topological characteristics, connectivity, and stability of microbial networks in different regions also verified the high responsiveness of microbial communities to regions. However, rootstock diseases had a more direct effect on fungal communities than regional differences.ConclusionThis provided insight into the interactions between microbial communities, regional differences, and rootstock diseases, with important implications for maintaining soil health and improving tobacco yield and quality.

AbstractIntroduction Hepatitis B virus-associated glomerulonephritis (HBV-GN) is one of the main types of secondary glomerular diseases, and podocyte injury is an important pathogenic mechanism of HBV-GN, participating in the occurrence and development of HBV-GN. However, the specific mechanism of podocyte injury remains to be studied.Methods Human renal podocytes cultured in vitro were divided into six groups. The podocyte morphology was observed under a transmission electron microscope, and the expression of M-type phospholipase A2 receptor (M-PLA2R) on the podocyte membrane was observed by indirect immunofluorescence staining under a fluorescence microscope. The pyroptosis rate and reactive oxygen species (ROS) of podocytes were assessed by FLICA/PI double staining and flow cytometry. Western blot (WB) and quantitative real-time PCR (qPCR) were used to determine the expression of PLA2R, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing card (ASC), caspase-1, IL-1β, and IL-18.Results Hepatitis B virus X (HBx) transfected into human renal podocytes in vitro induced the overexpression of PLA2R. Moreover, the overexpressed PLA2R combined with secretory phospholipase A2 group IB (sPLA2-IB) aggravated podocyte injury and increased the pyroptosis rate. In addition, the expression of ROS, the NLRP3 inflammasome and downstream inflammatory factors was increased. In contrast, after inhibiting the expression of PLA2R and ROS, podocyte damage was alleviated, and the pyroptosis rate and the expression of genes related to the ROS-NLRP3 signaling pathway were decreased.Conclusion HBx-induced PLA2R overexpression on the podocyte membrane can significantly upregulate the ROS-NLRP3 signaling pathway, thereby mediating podocyte pyroptosis.

IntroductionDiabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide. Therefore, efforts to understand DKD pathophysiology and prevent its development at the early phase are highly warranted.MethodsHere, we analyzed kidneys from healthy mice, diabetic mice, and diabetic mice treated with the sodium-glucose cotransporter 2 inhibitor dapagliflozin using ATAC and RNA sequencing. The findings were verified at the protein levels and in cultured cells.ResultsOur combined method of ATAC and RNA sequencing revealed Csf2rb, Btla, and Isg15 as the key candidate genes associated with hyperglycemia, azotemia, and albuminuria. Their protein levels were altered together with multiple other inflammatory cytokines in the diabetic kidney, which was alleviated by dapagliflozin treatment. Cell culture of immortalized renal tubular cells and macrophages unraveled that dapagliflozin could directly effect on these cells in vitro as an anti-inflammatory agent independent of glucose concentrations. We further proved that dapagliflozin attenuated ischemia/reperfusion-induced chronic kidney injury and renal inflammation in mice.DiscussionOverall, our data emphasize the importance of inflammatory factors to the pathogenesis of DKD, and provide valuable mechanistic insights into the renoprotective role of dapagliflozin.

Abstract Background Impaired renal function was not a recognized indication for renal biopsy. The effects of receiving renal biopsy on the renal functional prognosis for chronic kidney disease (CKD) patients with impaired renal function need to be explored. Methods This study retrospectively enrolled 300 renal function impaired CKD patients in Renji Hospital from January 2015 to December 2017, 150 of them received percutaneous renal biopsy while the others did not. The endpoint was ≥ 50% estimated glomerular filtration rate (eGFR) decline from baseline or development of end-stage renal disease (ESRD). Kaplan-Meier analysis with log-rank test was performed to compare the renal survival probability between patients receiving renal biopsy or not. Univariate and multivariate analysis with Cox regression were conducted with predictors of poor renal outcomes in the study cohort. Results The median follow-up period was 37.6 months. During the follow-up period, the eGFR of the biopsy group increased from 52.2 ± 14.4 to 67.4 ± 37.8 ml/min/1.73 m², but decreased from 55.3 ± 17.1 to 29.8 ± 19.1 ml/min/1.73 m² in the non-biopsy group. Patients who received renal biopsy had significantly higher renal survival probability (P

While a significant number of studies have focused on elucidating the functioning mechanisms of the Hepatocellular carcinoma (HCC) microenvironment, the intercellular crosstalk between multiple cells in the tumor microenvironment remains unclear. Here we co-cultured spheroids of HCC cells, hepatic stellate cells (HSCs), and hepatocytes in a biomimetic composite hydrogel to construct a 3D model of the HCC microenvironment in vitro. The model reproduced the major cellular components of early HCC in a biomimetic 3D microenvironment, realizing the visualization of the cellular interplay between cells and the microenvironment. Using this model, we showed that the HSCs were activated when co-cultured with HCC cells and deposed collagen to remodel the microenvironment, which in turn triggered higher EMT levels in HCC cells. The hepatocytes also responded to the existence of HCC cells and the activation of HSCs in co-culture, showing the downregulated expression level of ALB, AFP, and HNF4A. This model recapitulated the activation of HSCs in the HCC microenvironment and enabled visualization of multicellular interplay in 3D, providing a biomimetic platform to investigate mechanisms of HCC and related hepatic fibrosis.

Rural microcredit plays an important role in promoting rural economic development and increasing farmers’ income. However, traditional credit risk assessment models may have insufficient adaptability in rural areas. This study is based on the improved Long Short Term Memory (LSTM) algorithm using self organizing method, aiming to design an optimized evaluation model for rural microcredit risk. The improved LSTM algorithm can better capture the long-term dependence between the borrower’s historical behavior and risk factors with its advantages in sequential data modeling. The experimental results show that the rural microcredit risk assessment model based on the self organizing LSTM algorithm has higher accuracy and stability compared to traditional models, and can effectively control credit default risk, providing more comprehensive risk management support for financial institutions. In addition, the model also has real-time monitoring and warning functions, which helps financial institutions adjust their decisions in a timely manner and reduce credit losses. The practical application of this study is expected to promote the stable development of rural economy and the advancement of financial technology. However, future work needs to further validate the practical application effectiveness and interpretability of the model, taking into account the special circumstances of different rural areas, in order to achieve sustainable application of the model in the rural microcredit market.

During a survey of soil fungi collected from Yunnan Province, China, two new species of Exophiala, E. yunnanensis and E. yuxiensis, were isolated from the soil of karst rocky desertification (KRD). The DNA sequences of these respective strains, including internal transcribed spacers (ITS), large subunit nuclear ribosomal RNA (LSU rRNA), partial small subunit (SSU) and β-tubulin (tub2) were sequenced and compared with those from species closely-related to Exophiala. Exophiala yunnanensis differs from the phylogenetically closely related E. nagquensis and E. brunnea by its smaller aseptate conidia. Exophiala yuxiensis is phylogenetically related to E. lecanii-corni, E. lavatrina and E. mali, but can be distinguished from them by its larger conidia. Full descriptions, illustrations and phylogenetic positions of E. yunnanensis and E. yuxiensis were provided.

Abstract Obesity is a global epidemic elevating the risk of various metabolic disorders. As there is a lack of effective drugs to treat obesity, we combined bioinformatics and reverse network pharmacology in this study to identify effective herbs to treat obesity. We identified 1011 differentially expressed genes (DEGs) of adipose tissue after weight loss by analyzing five expression profiles (GSE103766, GSE35411, GSE112307, GSE43471, and GSE35710) from the Gene Expression Omnibus (GEO) database. We identified 27 hub genes from the protein–protein interaction (PPI) network by performing MCODE using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that these hub genes have roles in the extracellular matrix–receptor interaction, cholesterol metabolism, PI3K-Akt signaling pathway, etc. Ten herbs (Aloe, Portulacae Herba, Mori Follum, Silybum Marianum, Phyllanthi Fructus, Pollen Typhae, Ginkgo Semen, Leonuri Herba, Eriobotryae Folium, and Litseae Fructus) targeting the nine hub genes (COL1A1, MMP2, MMP9, SPP1, DNMT3B, MMP7, CETP, COL1A2, and MUC1) using six ingredients were identified as the key herbs. Quercetin and (-)-epigallocatechin-3-gallate were determined to be the key ingredients. Lastly, Ingredients-Targets, Herbs-Ingredients-Targets, and Herbs-Taste-Meridian Tropism networks were constructed using Cytoscape to elucidate this complex relationship. This study could help identify promising therapeutic targets and drugs to treat obesity.

Abstract Primary Sjögren's syndrome (pSS) patients with hypertension (pSS‐HT) have a significantly increased risk of cardio‐cerebrovascular events. Serum uric acid (SUA), a potential inflammatory substance, is considered to be closely related to hypertension in the general population. Our aim is to assess the association between SUA and pSS‐HT. This is a retrospective cohort study. The diagnosis of pSS is based on the American European Consensus Classification criteria. Primary outcome was incident hypertension in pSS patients. Cox regression model was used to estimate the hazard ratios (HR) and 95% CI of SUA in pSS‐HT. The authors also plotted Kaplan–Meier plots to assess the cumulative risk of first hypertension in patients with hyperuricemia and normal uric acid. In addition, the dose‐response curve was also used to discuss the relationship between SUA and pSS‐HT. Finally, three hundred and fifty‐one pSS patients were enrolled from May 2011 to May 2020, of which 166 cases developed hypertension within a mean follow‐up of 3.91 years. Univariate Cox regression demonstrated that SUA was associated with the onset of hypertension in pSS (HR: 1.005 95%Cl: 1.002–1.009). After adjusting for the potential risk factors, the relationship remained unchanged (HR: 1.003, 95%Cl: 1.001–1.005). Kaplan‐Meier survival analysis showed a statistically significant difference of hypertension risk between hyperuricemia patients and normal uric acid patients (P = .026). There was also a significant dose‐effect relationship between SUA and hypertension in pSS in dose‐response model. In this study, the authors find that SUA may be closely associated with the development of hypertension in pSS, which is also confirmed by our dose‐response model. Therefore, SUA could be considered in the management of pSS‐HT.

Introduction Hepatitis B virus-associated glomerulonephritis (HBV-GN) is a common secondary kidney disease in China, the pathogenesis of which is not completely clear, and there is still a lack of effective treatment. Methods The mechanism of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) was investigated by using HBx-transfected human renal podocytes. Cell viability was detected by CCK8 assay. Iron and malondialdehyde (MDA) contents were detected by using commercial kits. Reactive oxygen species (ROS) levels were measured by flow cytometry analysis. The expression of ferroptosis related molecules was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. The effect of miR-223-3p transferred by BMSC-derived exosomes on HBx-overexpressing podocytes was proved by using miR-223-3p inhibitor. Results The cell viability of podocytes reduced at 72 h or 96 h after the transfection of lentivirus overexpressing HBx protein (p < 0.05). Ferroptosis-related proteins, including glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were down-regulated upon HBx overexpression, while acyl-CoA synthetase long-chain family member 4 (ACSL4) was up-regulated (p < 0.05). Intracellular levels of iron, MDA, and ROS were also enhanced (p < 0.05). BMSC-derived exosomes protected against ferroptosis induced by HBx overexpression in podocytes. miR-223-3p was enriched in BMSC-derived exosomes. Application of miR-223-3p inhibitor reversed the protective effect of BMSC-derived exosomes on HBx-induced ferroptosis in podocytes. Conclusion BMSC-derived exosomes inhibit HBx-induced podocyte ferroptosis by transferring miR-223-3p.

With the increase in cadmium (Cd) release into the environment, it is necessary to find appropriate solutions to reduce soil Cd pollution. Microorganisms are a green and effective means for the remediation of Cd-contaminated soil. In this study, in a Cd-contaminated farmland, we screened and identified novel Cd-resistant strains, Paenarthrobactor nitroguajacolicus, Lysinibacillus fusiformis, Bacillus licheniformis, and Methyllobacium brachiatum, with minimum inhibitory concentrations of 100, 100, 50, and 50 mg/L, respectively, and added them each to pots containing Cd-contaminated rape plants to explore their remediation ability. The results showed that treatment with each of the four strains significantly increased the abundance of Nitrospirae, Firmicutes, Verrucomicrobia, and Patescibacterium in the rhizosphere soil of the plants. This led to changes in soil physical and chemical indices; pH; and available phosphorus, urease, and catalase activities, which were significantly negatively correlated with bioavailable Cd, reducing 28.74–58.82 % Cd enrichment to plants and 23.72–43.79 % Cd transport within plants, and reducing 5.52–10.68 % available cadmium in soil, effectively reducing the biotoxicity of Cd. Thus, this study suggests microbial remediation as a reliable option, forming a basis for the remediation of Cd-contaminated soil.

Phosphodiesterase-4 (PDE4) functions as a catalyzing enzyme targeting hydrolyzation of intracellular cyclic adenosine monophosphate (cAMP) and inhibition of PDE4 has been proven to be a competitive strategy for dermatological and pulmonary inflammation. However, the pathological role of PDE4 and the therapeutic feasibility of PDE4 inhibitors in chronic ulcerative colitis (UC) are less clearly understood. This study introduced apremilast, a breakthrough in discovery of PDE4 inhibitors, to explore the therapeutic capacity in dextran sulfate sodium (DSS)-induced experimental murine chronic UC. In the inflamed tissues, overexpression of PDE4 isoforms and defective cAMP-mediating pathway were firstly identified in chronic UC patients. Therapeutically, inhibition of PDE4 by apremilast modulated cAMP-predominant protein kinase A (PKA)–cAMP-response element binding protein (CREB) signaling and ameliorated the clinical symptoms of chronic UC, as evidenced by improvements on mucosal ulcerations, tissue fibrosis, and inflammatory infiltrations. Consequently, apremilast maintained a normal intestinal physical and chemical barrier function and rebuilt the mucosal homeostasis by interfering with the cross-talk between human epithelial cells and immune cells. Furthermore, we found that apremilast could remap the landscape of gut microbiota and exert regulatory effects on antimicrobial responses and the function of mucus in the gut microenvironment. Taken together, the present study revealed that intervene of PDE4 provided an infusive therapeutic strategy for patients with chronic and relapsing UC.

Objective(s): This study was designed to investigate whether HBx-induced podocyte injury is related to the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and the specific mechanism of the oxidative stress pathway in hepatitis B virus-associated glomerulonephritis (HBV-GN).Materials and Methods: The HBx gene was overexpressed in renal podocytes to mimic HBV-GN. Podocyte morphology was observed under a scanning electron microscope. Reactive oxygen species (ROS) generation was detected by dichlorodihydrofluorescein diacetate (DCFH-DA) assay. The podocytes in each group were treated with Hoechst 33342 and subjected to immunofluorescence staining. Caspase-1 activity and LDH levels were assessed with a Caspase-1 Activity Assay Kit and an LDH ELISA Kit, respectively. The expression of all pyroptosis-related proteins was examined by Western blot analysis.Results: Pyroptosis-related proteins, including NLRP3, apoptosis-associated speck-like protein containing card (ASC), caspase-1, IL-1β, and IL-18 (P

Abstract Cardiac involvement is an important cause of morbidity and mortality in patients with idiopathic inflammatory myopathies (IIMs). Hypertension, an important cardiovascular risk factor for the general population, has a crucial role in heart involvement. However, few studies have focused on the hypertension associated with IIMs. This study aimed to develop and assess the prediction model for incident hypertension in patients with IIMs. A retrospective cohort study was performed on 362 patients with IIMs, of whom 54 (14.9%) were given a diagnosis of new‐onset hypertension from January 2008 to December 2018. The predictors of hypertension in IIMs were selected by least absolute shrinkage and selection operator (LASSO) regression, multivariable logistic regression, and clinically relevance, and then these predictors were used to draw the nomogram. Discrimination, calibration and clinical usefulness of the model were evaluated using the C‐index, calibration plot, and decision curve analysis, respectively. The predicting model was validated by the bootstrapping validation. The nomogram mainly included predictors such as age, diabetes mellitus, triglyceride, low‐density lipoprotein‐cholesterol (LDL‐C), antinuclear antibodies (ANA), and smoking. This prediction model demonstrated good discrimination with a C‐index of 0.754 (95%CI, 0.684 to 0.824) and good calibration. The C‐index of internal validation was 0.728, and decision curve analysis demonstrated that this nomogram was clinically useful. Clinicians can use this prediction model to assess the risk of hypertension in IIMs patients, and early preventive measures should be taken to reduce the incidence of hypertension in high‐risk patients.

Intestinal barrier disruption due to the intestinal epithelial cells’ (IECs) death is one of the critical pathological features of inflammatory bowel diseases (IBDs). SM934, an artemisinin analog, has previously been proven to ameliorate colitis induced by dextran sulfate sodium (DSS) in mice by suppressing inflammation response. In this study, we investigated the protective effects of SM934 on the epithelial barrier and the underlying mechanism in trinitrobenzene sulfonic acid (TNBS)-induced colitis mice. We demonstrated that SM934 restored the body weight and colon length, and improved the intestine pathology. Furthermore, SM934 treatment preserved the intestinal barrier function via decreasing the intestinal permeability, maintaining epithelial tight junction (TJ) protein expressions, and preventing apoptosis of epithelial cells, which were observed both in the colon tissue and the tumor necrosis factor-α (TNF-α)-induced human colonic epithelial cell line HT-29. Specifically, SM934 reduced the pyroptosis of IECs exposed to pathogenic signaling and inhibited pyroptosis-related factors such as NOD-like receptor family pyrin domain containing 3 (NLRP3), adapter apoptosis-associated speck-like protein (ASC), cysteine protease-1 (caspase-1), gasdermin (GSDMD), interleukin-18 (IL-18), and high-mobility group box 1 (HMGB1) both in colon tissue and lipopolysaccharide (LPS) and adenosine triphosphate (ATP) co-stimulated HT-29 cells in vitro. Moreover, SM934 interdicted pyroptosis via blocking the transduction of mitogen-activated protein kinase (MAPK) and nuclear factor-kB (NF-kB) signaling pathways. In conclusion, SM934 protected TNBS-induced colitis against intestinal barrier disruption by inhibiting the apoptosis and pyroptosis of epithelial cells via the NLRP3/NF-κB/MAPK signal axis, and intestinal barrier protection in company with an anti-inflammatory strategy might yield greater benefits in IBD treatment.

Aberrant microbe-immune cell interaction is a predisposing factor in inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Cortex Periplocae is a famous traditional Chinese medicine with putative anti-rheumatoid arthritis and anti-dyspepsia effects. Here, we show that the Periploca sepium periplosides (PePs), a cardiac glycosides-free pregnane glycosides extract from root bark of Cortex Periplocae, alleviates colon inflammation, improves intestinal epithelial barrier function, and prevents colitis-associated tumorigenesis in mice with colitis and CAC. Mechanistically, PePs treatment modulates abnormal gut microbiota composition in model mice, especially enriches an anti-inflammatory commensal bacterium A. muciniphila BAA-835. We further demonstrate that the altered gut microbiota following PePs treatment plays an important role in modulation of intestinal Type 17 immunity in both colitis and CAC mouse model. Our results indicate that PePs may be used as a potential gut microbiota modulator to treat IBD and CAC.

Objectives:It is well-established that the association between atherosclerotic cardiovascular diseases (ASCVD) and connective tissue diseases (CTDs), but the relationship between coronary heart disease (CHD) and idiopathic inflammatory myopathies (IIMs) remains controversial yet. The aim of this meta-analysis is to systematically evaluate the risk of CHD in IIMs patients. In addition, we explore differences in traditional cardiovascular risk factors between IIMs patients and controls.Methods:We searched Pubmed, EMBASE and Cochrane databases to identify relevant observational studies published in English up to August 2021. Pooled relative risk (RR) and 95% confidence interval (CI) was calculated using the generic inverse variance method for the risk of CHD. A meta-proportion analysis was conducted to assess differences in cardiovascular risk factors between two groups.Results:A total of 15 studies met inclusion criteria: seven studies focused on CHD and nine studies focused on traditional cardiovascular risk factors. The results demonstrated that IIMs patients had a higher risk of CHD (RR = 2.19, 95% CI: 1.40–3.42). Hypertension (OR = 1.44, 95% CI: 1.28–1.61), diabetes mellitus (OR = 1.67, 95% CI: 1.55–1.81) and dyslipidemia (OR = 1.48, 95% CI: 1.19–1.84) were more prevalent in IIMs patients compared with controls. However, there was a significant heterogeneity among studies assessing the risk of CHD and hypertension. Subgroup analysis demonstrated that definition of CHD, country and sample size may be potential sources of heterogeneity.Conclusions:IIMs patients were at increased risk of CHD, and traditional cardiovascular risk factors appeared more prevalent in IIMs patients. This systemic review offers the proof that early appropriate interventions could reduce cardiovascular-associated morbidity and mortality in IIMs patients.

BackgroundAs an indispensable marker of complement cascades activation, C4d was confirmed of its crucial role in the pathogenesis of both lupus nephritis (LN) and IgA nephropathy (IgAN). While the studies directly comparing the diagnostic value, and outcomes predicting function of C4d between LN and IgAN are still absent.MethodsA cohort of 120 LN patients, 120 IgAN patients who were diagnosed by renal biopsy between January 2015 and December 2017 and 24 healthy age matched controls were prospectively analyzed. The patients were followed till December 2020. The outcomes were adverse disease treatment response (disease relapse) and kidney disease progression event (decline of estimated glomerular filtration rate by more than 20% or end-stage kidney disease). The renal C4d deposition proportion and pattern were compared between IgAN and LN patients. In addition, the relationship between renal C4d deposition and disease subtypes, disease relapse as well as disease progression for LN and IgAN patients were also analyzed.ResultsThe LN, IgAN patients and healthy controls were well matched in ages. The follow-up period was 38.5 (30.3–60.8) months for LN patients and 45.0 (30.5–57.0) months for IgAN patients. 78 patients (65.0%) with LN had renal C4d deposition, compared with only 39 IgAN patients (32.5%) with C4d deposition in renal tissues (P < 0.001). The LN patients shared different renal C4d distribution patterns with IgAN patients. Compared with IgAN patients, the C4d deposition in LN patients was significantly more in renal glomerulus (P < 0.001) and less in renal tubules (P = 0.003). For disease subtypes, renal C4d deposition was especially strong in class V membranous LN and IgAN with tubulointerstitial fibrosis (T1/T2) lesions. Renal C4d deposition was independently correlated with the disease relapse of LN patients (HR = 1.007, P = 0.040), and acted as an independent predictor of disease progression during the follow-up period for IgAN patients (HR = 1.821, P = 0.040).ConclusionsRenal C4d distribution proportion and pattern differed between LN and IgAN patients. The presence of C4d in renal tissue acted as an independent predictor of relapse for LN patients and disease progression for IgAN patients.

Abstract Background Our previous studies showed the expression of herpes virus entry mediator (HVEM) is high in ovarian cancer samples and correlated to the patient clinic pathological features. As we all know, the hypoxic environment is the main feature of tumor. In this work, we explored the role of HVEM in hypoxic ovarian cancer cells and its effects on HIF-1α, a transcription factor responding to hypoxia. Methods The expression of HVEM, HIF-1α and apoptosis-related genes was detected by qRT-PCR and western blot. The proliferation and apoptosis of the ovarian cancer cells were determined with the Cell Counting Kit-8 assay and AnnexinV-FITC/PI-stained flow cytometry assay, respectively. Results The expression of HVEM was positively correlated to that of HIF-1α. The expression of HVEM and HIF-1α under hypoxic conditions was higher than that under normoxic conditions, which suggested that the level of HVEM and HIF-1α correlates with prolonged periods of hypoxia in ovarian cancer. The overexpression of HVEM promoted cell proliferation and inhibited cell apoptosis under hypoxic condition. HVEM overexpression elevated the expression of HIF-1α and Bcl-2 (anti-apoptotic protein), and reduced the expression of Bax (pro-apoptotic protein). In addition, overexpression of HVEM activated the AKT/mTOR signaling. Moreover, knockdown of HVEM had the completely opposite effects. Conclusion These data indicated that HVEM signaling might promote HIF-1α activity via AKT/mTOR signaling pathway and thus to regulate tumor growth in ovarian cancer under the hypoxic conditions. Furthermore, these findings indicate that this molecular mechanism could represent a therapeutic target for ovarian cancer.

Ulcerative colitis (UC) manifests as an etiologically complicated and relapsing gastrointestinal disease. The enteric nervous system (ENS) plays a pivotal role in rectifying and orchestrating the inflammatory responses in gut tract. Berberine, an isoquinoline alkaloid, is known as its anti-inflammatory and therapeutic effects in experimental colitis. However, little research focused on its regulatory function on ENS. Therefore, we set out to explore the pathological role of neurogenic inflammation in UC and the modulating effects of berberine on neuro–immune interactions. Functional defects of enteric glial cells (EGCs), with decreased glial fibrillary acidic protein (GFAP) and increased substance P expression, were observed in DSS-induced murine UC. Administration of berberine can obviously ameliorate the disease severity and restore the mucosal barrier homeostasis of UC, closely accompanying by maintaining the residence of EGCs and attenuating inflammatory infiltrations and immune cells overactivation. In vitro, berberine showed direct protective effects on monoculture of EGCs, bone marrow-derived dendritic cells (BMDCs), T cells, and intestinal epithelial cells (IECs) in the simulated inflammatory conditions. Furthermore, berberine could modulate gut EGCs–IECs–immune cell interactions in the co-culture systems. In summary, our study indicated the EGCs–IECs–immune cell interactions might function as a crucial paradigm in mucosal inflammation and provided an infusive mechanism of berberine in regulating enteric neurogenic inflammation. Keywords: Ulcerative colitis, Berberine, Mucosal inflammation, Enteric glial cells, Enteric nervous system

Abstract Background One major etiology of hepatic sinusoidal obstruction syndrome (HSOS) in China is the intake of pyrrolizidine alkaloids (PAs). Since PAs-induced HSOS is a rare disease that has not been clearly characterized until now, the aim of this study was to investigate clinical characteristics, CT features, and pathological findings of PA-induced HSOS. Methods This retrospective cohort study included 116 patients with PAs-induced HSOS and 68 patients with Budd-Chiari syndrome from Jan 2006 to Sep 2016. We collected medical records of the patients, and reviewed image features of CT, and analyzed pathological findings. Results Common clinical manifestations of PAs-induced HSOS were abdominal distention (98.26%), ascites (100%), jaundice (52.94%), abdominal pain (36.36%). Abnormal liver function was observed in most of PAs-induced HSOS. On CT scan, common findings included: ascites, hepatomegaly, the thickening of gallbladder wall, pleural effusion, patchy liver enhancement, and heterogeneous hypoattenuation. Most of the patients had a low ascitic total protein (

Abstract Background The LDL-C lowering effect of ezetimibe has been attributed primarily to increased catabolism of LDL-C via up-regulation of LDL receptor (LDLR) and decreased cholesterol absorption. Recently, ezetimibe has been demonstrated to have reverse cholesterol transport (RCT) promoting effects in mice, hamsters and humans. However, the underlying mechanisms are still not clear. The aim of this study is to investigate whether ezetimibe improves RCT-related protein expression in LDLR −/− hamsters. Methods A high-fat diet was used to induce a human-like hyperlipidemia in LDLR −/− hamsters. Lipid profiles were assayed by commercially available kits, and the effects of ezetimibe on lipid metabolism-related protein expression were carried out via western blot. Results Our data demonstrated that ezetimibe administration significantly reduced plasma total cholesterol (~ 51.6% reduction, P

Nitrogen (N) is one of the most crucial elements for plant growth and development. However, little is known about the metabolic regulation of trees under conditions of N deficiency. In this investigation, gas chromatography-mass spectrometry (GC-MS) was used to determine global changes in metabolites and regulatory pathways in Populus tomentosa. Thirty metabolites were found to be changed significantly under conditions of low-N stress. N deficiency resulted in increased levels of carbohydrates and decreases in amino acids and some alcohols, as well as some secondary metabolites. Furthermore, an RNA-sequencing (RNA-Seq) analysis was performed to characterize the transcriptomic profiles, and 1,662 differentially expressed genes were identified in P. tomentosa. Intriguingly, four pathways related to carbohydrate metabolism were enriched. Genes involved in the gibberellic acid and indole-3-acetic acid pathways were found to be responsive to low-N stress, and the contents of hormones were then validated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Coordinated metabolomics and transcriptomics analysis revealed a pattern of co-expression of five pairs of metabolites and unigenes. Overall, our investigation showed that metabolism directly related to N deficiency was depressed, while some components of energy metabolism were increased. These observations provided insights into the metabolic and molecular mechanisms underlying the interactions of N and carbon in poplar.

DNA methylation plays crucial roles in responses to environmental stimuli. Modification of DNA methylation during development and abiotic stress responses has been confirmed in increasing numbers of plants, mainly annual plants. However, the epigenetic regulation mechanism underlying the immune response to pathogens remains largely unknown in plants, especially trees. To investigate whether DNA methylation is involved in the response to infection process or is related to the resistance differences among poplars, we performed comprehensive whole-genome bisulfite sequencing of the infected stem of the susceptible type Populus × euramerican ‘74/76’ and resistant type Populus tomentosa ‘henan’ upon Lonsdalea populi infection. The results revealed that DNA methylation changed dynamically in poplars during the infection process with a remarkable decrease seen in the DNA methylation ratio. Intriguingly, the resistant P. tomentosa ‘henan’ had a much lower basal DNA methylation ratio than the susceptible P. × euramerican ‘74/76’. Compared to mock-inoculation, both poplar types underwent post-inoculation CHH hypomethylation; however, significant decreases in mC and mCHH proportions were found in resistant poplar. In addition, most differentially CHH-hypomethylated regions were distributed in repeat and promoter regions. Based on comparison of DNA methylation modification with the expression profiles of genes, DNA methylation occurred in resistance genes, pathogenesis-related genes, and phytohormone genes in poplars during pathogen infection. Additionally, transcript levels of genes encoding methylation-related enzymes changed during pathogen infection. Interestingly, small-regulator miRNAs were subject to DNA methylation in poplars experiencing pathogen infection. This investigation highlights the critical role of DNA methylation in the poplar immune response to pathogen infection and provides new insights into epigenetic regulation in perennial plants in response to biotic stress.

Summary: Chronic kidney disease (CKD) is associated with substantial morbidity and mortality. We developed a mouse model that mimics human CKD with inflammation, extracellular matrix deposition, tubulointerstitial fibrosis, increased proteinuria, and associated reduction in glomerular filtration rate over time. Using this model, we show that genetic deficiency of SMOC2 or therapeutic silencing of SMOC2 with small interfering RNAs (siRNAs) after disease onset significantly ameliorates inflammation, fibrosis, and kidney function loss. Mechanistically, we found that SMOC2 promotes fibroblast to myofibroblast differentiation by activation of diverse cellular signaling pathways including MAPKs, Smad, and Akt. Thus, targeting SMOC2 therapeutically offers an approach to prevent fibrosis progression and CKD after injury.

(1) Background: Astragaloside IV (AS-IV) is derived from Astragalus membranous (AM), which is used to treat kidney disease. Macrophages significantly affect the whole process of renal ischemia-reperfusion (I/R). The regulation of macrophage polarization in kidneys by AS-IV was the focus. (2) Methods: Renal tubular injury and fibrosis in mice were detected by Hematoxylin and Eosin staining and Masson Trichrome Staining, separately. An ELISA and quantitative real-time polymerase chain reaction were used to explore the cytokine and mRNA expression. Western blot was used to determine protein expression and siRNA technology was used to reveal the crosstalk of signal pathways in RAW 264.7 under hypoxia. (3) Results: In the early stages of I/R injury, AS-IV reduced renal damage and macrophage infiltration. M1-associated markers were decreased, while M2 biomarkers were increased. The NF-κB (p65)/Hif-1α pathway was suppressed by AS-IV in M1. Moreover, p65 dominated the expression of Hif-1α. In the late stages of I/R injury, renal fibrosis was alleviated, and M2 infiltration also decreased after AS-IV treatment. Hif-1α expression was reduced by AS-IV, while Smad7 expression was enhanced. Hif-1α interferes with the expression of Smad7 in M2. (4) Conclusions: AS-IV promoted the differentiation of M1 to M2, relieving the proinflammatory response to alleviate the kidney injury during the early stages. AS-IV attenuated M2 macrophage infiltration to prevent kidney fibrosis during the later stages.

Ulva meridionalis is one of the causal green macroalgae for green tides in Japan and exists in coastal areas of China. In the present study, complete chloroplast (cp) genome sequence of Ulva meridionalis was reported, and the total length of this species was 88,653 bp (GenBank accession number MN889540). The overall base composition of cp genome was A (37.1%), T (39.0%), C (11.4%) and G (12.5%), similar to other Ulva macroalgae within cp genome, and the percentage of A + T (76.1%) was higher than C + G (23.9%). U. meridionalis cp genome encoded 113 genes, including 80 protein-coding genes, 27 transfer RNAs genes and 6 ribosomal RNAs genes. The maximum likelihood phylogenetic analysis shows that Ulva linza is the closest sister species of U. meridionalis.

Non-coding RNAs (ncRNAs) play essential roles in plants by modulating the expression of genes at the transcriptional or post-transcriptional level. In recent years, ncRNAs have been recognized as crucial regulators for growth and development in forest trees, and ncRNAs that respond to various abiotic stresses are now under intense study. In this review, we summarized recent advances in the understanding of abiotic stress-responsive microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in forest trees. Furthermore, we analyzed the intersection of miRNAs, and epigenetic modified ncRNAs of forest trees in response to abiotic stress. In particular, the abiotic stress-related lncRNA/circRNA–miRNA–mRNA regulatory network of forest trees was explored.

Abstract Background Although vaginal repair has been conducted to manage caesarean scar diverticula, most studies evaluated only the gynaecological outcomes post-surgery, and their obstetrical outcomes were unknown. This study aimed to evaluate the obstetrical outcomes in vaginal repair-treated caesarean scar diverticula patients. Methods A series of 51 symptomatic women with caesarean scar defects or a thickness of the remaining muscular layer of less than 3 mm according to transvaginal ultrasound were included. We retrospectively evaluated the gynaecological and obstetrical outcomes after vaginal repair and histologically analysed the defect. Results Transvaginal ultrasound revealed that the thickness of the remaining muscular layer significantly increased from 2.24 ± 0.81 mm to 6.10 ± 1.43 mm 3 months after vaginal repair. The duration of menstruation significantly decreased from 14.29 ± 3.13 days to 8.31 ± 2.14 days post-vaginal repair. Notably, 26 of the 51 (50.98%) women who were followed for more than 15.04 months post-surgery achieved pregnancy. A total of 6 of the 26 pregnancies (23.08%) resulted in miscarriages, including 5 early miscarriages and 1 late miscarriage. Among the 20 women who achieved pregnancy without miscarriage, 18 had term deliveries, 2 had preterm birth, and none reported uterine rupture. Histological analysis was performed in all 51 cases. Muscle fibre density was significantly lower in the scar than in the myometrium adjacent to the scar and collagen expression was markedly increased in the scar tissue. Conclusion Satisfactory gynaecological and subsequent obstetrical outcomes can be achieved in vaginal repair-treated caesarean scar diverticula patients.

The front retaining wall (FRW) is an effective facility of selective withdrawal. Previous research has not estimated the effect of FRWs on the thermal regimes of reservoirs and outflow temperature, which are crucial to reservoir ecology. For this purpose, taking the Dongqing Reservoir as a case study, a two-dimensional hydrodynamic CE-QUAL-W2 model was configured for the typical channel-type reservoir in the southwestern Guizhou Province, to better understand the influence of FRWs on the thermal structure and outflow temperature. The simulated data from January to September 2017 showed that FRWs can change the vertical temperature distribution during the stratification period, accelerate the upper warmer water release and thus decrease the strength of thermal stratification. The stratification structure changed from a single thermocline to double thermoclines in August. An FRW resulted in an average 11.8 m increase in the thickness of the hypolimnion and a 1.2°C decrease in the thickness of the thermocline layer. An FRW increased the outflow temperature by 0.4°C and raised the withdrawal elevation by 16 m on average. The longitudinal velocity increased compared with the non-FRW condition, while the maximum velocity position moved up. In addition, FRWs can continuously obtain surface warmer water without manual operation and have low investment and good construction conditions. This study can provide an available selective withdrawal idea for reservoirs with similar hydraulic conditions.

(1) Background: The EndoSequence BC Sealer HiFlow (Brasseler, Savannah, GA, USA) has recently been introduced in clinical applications. Thus, the aims of the present study are to determine its biocompatibility in vivo and to examine its ability to drive macrophage polarization in vitro and in vivo. (2) Methods: HiFlow was implanted into rat connective tissue for 7, 30 and 150 days. The microstructures and elemental compositions were determined by scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX). Hematoxylin–eosin, immunofluorescence, RT–qPCR and flow cytometry were used to elucidate the effects on inflammatory responses and macrophage polarization. (3) Results: SEM-EDX revealed the formation of surface hydroxyapatite crystal layers. Histological evaluation showed that HiFlow exhibited long-term biocompatibility because it decreased inflammatory responses and reduced the number of macrophages over time; however, tissue necrosis was observed in all the groups. RT–qPCR verified that HiFlow regulated the expression of inflammatory factors to inhibit the inflammatory response. Immunofluorescence analysis performed on in vivo samples revealed that HiFlow promoted M2-like macrophage polarization, and these results were confirmed by flow cytometry in vitro. (4) Conclusion: After 150 days of investigation, HiFlow was considered biologically acceptable, and the formation of apatite crystal layers and the promotion of M2-like macrophage polarization may contribute to its favorable biocompatibility.

BackgroundBased on 122 cases reported in China, data mining indicated that Sini Powder (SNP) and the Zuojin Pill (ZJP) are both widely used as the basic recipe for treating Gastroesophageal Reflux Disease (GERD).ObjectivesTo evaluate the intervention effects of Sini Zuojin Decoction (SNZJD) in patients with GERD.MethodsA comprehensive collection of randomized controlled trials (RCTs) using SNZJD in patients with GERD that were published in domestic and foreign journals was made by computer retrieval. RevMan 5.3 software was used for meta-analysis and bias risk assessment, Stata 14.0 software was used for sensitivity analysis, GRADE profiler 3.6 was used to evaluate the level of evidence, and trial sequential analysis (TSA), employed to control for random errors, was performed to assess the main outcomes. Network pharmacology analysis was applied to preliminarily study the mechanisms of action of SNZJD on GERD.ResultsThirteen articles were eventually included, covering a total of 966 patients. Meta-analysis indicated that: ① the SNZJD plus traditional stomach medicines (SPTSM) group was more effective than the traditional stomach medicines (TSM) group (RR = 1.16, 95% CI [1.04, 1.29], P = 0.009); ② the experimental group with SNZJD was significantly better than TSM controls in improving heartburn, substernal chest pain, acid regurgitation, and food regurgitation symptoms (P < 0.0001); ③ SPTSM could significantly decrease total symptom scores with substantial effectiveness (P < 0.00001). The recurrence rate and adverse effects of SNZJD treatment were significantly reduced (P < 0.05). TSA showed that the effective rate of meta-analysis might be reliable, but the recurrence and safety results were still uncertain. According to the evaluation by the GRADE method, the quality of evidence was low. Besides, SNZJD might treat GERD by acting on related targets and pathways such as inflammation, hormone regulation, and so on.ConclusionsSNZJD might be useful in the treatment of GERD, but its long-term effects and specific clinical mechanisms are unclear. Due to the poor quality of the evidence, more samples and high-quality clinical studies should be tested and verified in the future.

Abstract Background The effect of pretransplant peritoneal dialysis (PD) or hemodialysis (HD) modality on outcomes of kidney transplantation (KT) for end-stage renal disease (ESRD) is debatable. We evaluated the outcomes these modalities in KT from donor after cardiac death (DCD). Methods A cohort of 251 patients on HD, PD or pre-emptive who underwent first KT from DCD between January 2014 and December 2016 were prospectively analyzed to compare for outcomes on recovery of renal function, complications as well as patient and graft survival. The patients were followed till August 2017. Data on 104 HD and 98 PD were available for final comparative outcome analysis, 5 pre-emptive were analyzed as the control group. Results Both HD and PD group patients were well matched for demographic and baseline characteristics. The follow-up period was 12.5 (3.0, 22.0) months in HD and 12.0 (6.0, 20.0) months in PD patients. Post-transplant renal functions between the two groups showed no differences. Among PD patients, 16 (16.3%) suffered delayed graft function, versus 19 (18.3%) in HD, with no statistical differences (p = 0.715). Complications of acute rejection, infections were comparable between the groups. The patient survival, graft survival and death-censored graft survival were similar for HD and PD after adjusting for other multiple risk factors. Conclusions Our results indicate that outcome of first KT from DCD is not affected by pretransplant dialysis modality of PD or HD in aspects of recovery of renal function, complications as well as patient and graft survival.

Sea cucumber is a functional food in Asia countries. This study was designed to investigate whether the fucoidan from sea cucumber A. japonicus has an anti-inflammatory effect in the liver of lipopolysaccharide (LPS)-challenged mice. Our results demonstrated for the first time that the fucoidan reduced the pathologic changes and levels of pro-inflammatory cytokines, such as, TNF-α, IL-1β and IL-6. RT-PCR and western blot results demonstrated that this fucoidan significantly reduced the expression of iNOS and the phosphorylation of NF-κB P65, P38 and ERK1/2, but not JNK compared to the model group. Furthermore, this fucoidan significantly suppressed the phosphorylation of AKT, mTOR, p70S6K, RPS6 and GSK3β, but not GSK3α. These results demonstrated this fucoidan has a powerful anti-inflammatory effect in the liver of LPS-challenged mice via down-regulating MAPK/NF-κB and AKT/mTOR pathways, and the expression of iNOS. Collectively, food intake of sea cucumber may have a potential effect against inflammation.

Ulva meridionalis, a green macroalgae, is one of the causal species for green tides in Japan and spread into the coast of China. During this research, we sequenced the complete mitochondrial genome of U. meridionalis. The mitogenome is 62,887 bp in length, including 28 encoding genes and 29 tRNA genes. Compared with the Ulva species from mitogenome, the gene order and organization of this mitogenome are similar to most of other determined Ulva mitogenomes, with the nucleotide base composition of A 33.6%, T 32.2%, C 16.2%, and G 18.0%. Phylogenetic analysis shows U. meridionalis is closely related to Ulva flexuosa.

The data presented in this article describe characteristics of the polysaccharides, designated as CM1 and CMS, isolated from the fruiting body of C. militaris. Fourier transform infrared spectrometry analysis was used to identify the basic characteristics of the polysaccharides and the completeness of methylation. Gas chromatography-tandem mass spectrometry and nuclear magnetic resonance spectroscopy were carried out to reveal the glycosidic linkages of CM1 and CMS. Further interpretation and discussion could be found at our research article entitled “Structural characterisation and cholesterol efflux improving capacity of the novel polysaccharides from Cordyceps militaris” (Hu et al., 2019; https://doi.org/10.1016/j.ijbiomac.2019.03.078) [1]. Keywords: Polysaccharide, Mushroom, GC-MS, FTIR spectrum, Methylation analysis, NMR