Explore the vast range of titles available.

Diabetic nephropathy (DN), one of the most common and severe microvascular complications of diabetes mellitus (DM), is an important risk factor for DM patient’s death. Nowadays, DN has become the leading cause of end-stage renal disease (ESRD) in most countries without effective therapeutic methods. Recently, the renoprotective effects mediated by vitamin D (VD) and vitamin D receptor (VDR) have been evidenced. VD, a kind of steroid with the active form 1,25(OH)2D3, has been known for the crucial roles in the modulation of serum calcium and phosphorus concentrations. It exerts important functions by binding with its receptor VDR.VDR, a transcription factor located at chromosome 12 containing 9 exons, is one of the nonsteroid nuclear hormone receptor superfamily, which participates in transcriptional regulation of genes in tissue- and cell-specific ways. Increasing evidences have demonstrated that VD/VDR signaling pathway possesses a variety of kidney-protective effects in DN patients, such as antiproteinuria, antifibrosis, anti-inflammatory, and preventing podocyte damage. Although there are many studies on the role of the VD/VDR signaling pathway in DN, the effects and mechanisms still need to be further explained. This review summarized the multiple roles of VD/VDR in podocyte injury, tubule lesions, interstitial fibrosis, and inflammation, as well as the clinical applications about DN to explore much more and effective therapeutic methods for DN.

This paper reviews the recent achievements in the enhanced production of volatile fatty acids (VFAs) from waste activated sludge (WAS). The enhanced strategies are divided into two approaches. The first strategy focuses on the regulation of carbon-to-nitrogen (C/N) ratio by co-digestion of WAS with carbon-rich substrates, including municipal solid wastes (MSW), marine algae, agricultural residues, and animal manures. The other strategy is to enhance the solubilization and hydrolysis of WAS or inhibit the methanogenesis by applying various pretreatments, such as mechanical, chemical, enzymatic, and thermal pretreatment. Finally, the applications of WAS-derived VFAs are discussed. The future researches in enhancing VFAs production and wide application of the VFAs from both technical and economic perspectives are proposed.

Gastrodia elata Blume (G. elata) is a valuable Traditional Chinese Medicine (TCM) with a wide range of clinical applications. G. elata polysaccharides, as one of the main active ingredients of G. elata, have interesting extraction, purification, qualitative analysis, quantitative analysis, derivatization, and pharmacological activity aspects, yet a review of G. elata polysaccharides has not yet been published. Based on this, this article summarizes the progress of G. elata polysaccharides in terms of the above aspects to provide a basis for their further research and development.

Metabolism, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and other metabolic pathways, impacts the phenotypes and functions of immune cells. The metabolic regulation of the immune system is important in the pathogenesis and progression of numerous diseases, such as cancers, autoimmune diseases and metabolic diseases. The concept of immunometabolism was introduced over a decade ago to elucidate the intricate interplay between metabolism and immunity. The definition of immunometabolism has expanded from chronic low-grade inflammation in metabolic diseases to metabolic reprogramming of immune cells in various diseases. With immunometabolism being proposed and developed, the metabolic regulation of the immune system can be gradually summarized and becomes more and more clearer. In the context of many diseases including cancer, autoimmune diseases, metabolic diseases, and many other disease, metabolic reprogramming occurs in immune cells inducing proinflammatory or anti-inflammatory effects. The phenotypic and functional changes of immune cells caused by metabolic regulation further affect and development of diseases. Based on experimental results, targeting cellular metabolism of immune cells becomes a promising therapy. In this review, we focus on immune cells to introduce their metabolic pathways and metabolic reprogramming, and summarize how these metabolic pathways affect immune effects in the context of diseases. We thoroughly explore targets and treatments based on immunometabolism in existing studies. The challenges of translating experimental results into clinical applications in the field of immunometabolism are also summarized. We believe that a better understanding of immune regulation in health and diseases will improve the management of most diseases.

BackgroundOur aim was to validate the American Joint Committee on Cancer (AJCC) 8th edition stage system for gastric cancer in the Western world and to compare several modifications between the 7th and 8th edition systems.MethodsEligible patients having undergone surgical resection of gastric cancer during 2004–2011 from the Surveillance, Epidemiology, and End Results (SEER) database were included in the current study. Survival differences were assessed by Kaplan–Meier curve and log-rank tests. The discriminative power of the AJCC 8th and 7th editions was compared by Harrell’s concordance index (c-index).ResultsPatients with pN3a and pN3b presented distinct survival outcomes, especially for cases in which more than 15 lymph nodes were examined. The overall (OS) and cancer-specific survival (CSS) c-indices for the 8th edition were largely comparable with c-indices for the 7th edition throughout the cohort. Notably, the new edition improved the power of discrimination slightly in OS and CSS (c-indices: 0.717, 0.744) compared with the 7th edition (c-indices: 0.712, 0.739) for patients for whom 15 or more lymph nodes were examined. The analysis of stage migration in the new edition revealed nonhomogeneous survival outcomes in stages IIIB and IIIC.ConclusionThe AJCC 8th stage system for gastric cancer performs as well as the AJCC 7th edition in the United States (USA). Importantly, when more than 15 lymph nodes are examined, the discriminatory performance of the new edition is improved.

Background This study aimed to investigate the association between dietary fiber intake and long-term cardiovascular disease (CVD) risk based on the National Health and Nutrition Examination Survey (NHANES) database. Methods A total of 14,947 participants aged 20–79 from the NHANES database were included in this study between 2009 and 2018. The atherosclerotic cardiovascular disease (ASCVD) score was utilized to predict the 10-year risk of CVD in individuals (low, borderline, intermediate, and high risk). Weighted univariate and multinomial multivariate logistic regression analyses were used to analyze the association between dietary fiber intake and long-term CVD risk. Results Higher dietary fiber density may be associated with a reduced ASCVD risk in participants with intermediate risk [odds ratio (OR) = 0.76; 95% confidence interval (CI), 0.61–0.94] and high risk (OR = 0.60; 95%CI, 0.45–0.81) compared with those in the group with low risk. Higher total dietary fiber intake may also reduce ASCVD risk in participants with high risk (OR = 0.84; 95%CI, 0.75–0.95). Subgroup analyses showed that higher dietary fiber density may be related to reduced ASCVD risk in intermediate-risk participants aged 20–39 (OR = 0.62; 95%CI, 0.43–0.89) and 40–59 (OR = 0.67; 95%CI, 0.49–0.94). In high-risk participants, higher dietary fiber density may reduce ASCVD risk in 20–39-year-old (OR = 0.38; 95%CI, 0.19–0.77), 40–59-year-old (OR = 0.37; 95%CI, 0.20–0.70), male (OR = 0.47; 95%CI, 0.23–0.97) and female (OR = 0.57; 95%CI, 0.38–0.86) participants. Conclusion Higher dietary fiber density and total dietary fiber intake were associated with a lower long-term CVD risk, especially in the 20–39 and 40–59 age groups, where the reduction was most significant.

Background: One of the typical symptoms of diabetes mellitus patients was memory impairment, which was followed by gradual cognitive deterioration and for which there is no efficient treatment. The anti-diabetic incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were demonstrated to have highly neuroprotective benefits in animal models of AD. We wanted to find out how the GLP-1/GIP dual agonist tirzepatide affected diabetes’s impairment of spatial learning memory. Methods: High fat diet and streptozotocin injection-induced diabetic rats were injected intraperitoneally with Tirzepatide (1.35 mg/kg) once a week. The protective effects were assessed using the Morris water maze test, immunofluorescence, and Western blot analysis. Golgi staining was adopted for quantified dendritic spines. Results: Tirzepatide significantly improved impaired glucose tolerance, fasting blood glucose level, and insulin level in diabetic rats. Then, tirzepatide dramatically alleviated spatial learning and memory impairment, inhibited Aβ accumulation, prevented structural damage, boosted the synthesis of synaptic proteins and increased dendritic spines formation in diabetic hippocampus. Furthermore, some aberrant changes in signal molecules concerning inflammation signaling pathways were normalized after tirzepatide treatment in diabetic rats. Finally, PI3K/Akt/GSK3β signaling pathway was restored by tirzepatide. Conclusion: Tirzepatide obviously exerts a protective effect against spatial learning and memory impairment, potentially through regulating abnormal insulin resistance and inflammatory responses.

Trehalose is a nonreducing disaccharide, and it plays an intracellular protective role in organisms under various stress conditions. In this study, the trehalose synthesis and its protective role in Pleurotus ostreatus were investigated. As a signal in metabolic regulation, reactive oxygen species (ROS) accumulated in the mycelia of P. ostreatus under heat stress (HS). Furthermore, mycelial growth was significantly inhibited, and the malondialdehyde (MDA) level significantly increased under HS. First, exogenous addition of H 2 O 2 inhibited mycelial growth and elevated the MDA level, while N -acetyl cysteine (NAC) and vitamin C (VC) reduced the MDA level and recovered mycelial growth under HS by scavenging ROS. These results indicated that the mycelial radial growth defect under HS might be partly caused by ROS accumulation. Second, adding NAC and VC to the media resulted in rescued trehalose accumulation, which indicated that ROS has an effect on inducing trehalose synthesis. Third, the mycelial growth was recovered by addition of trehalose to the media after HS, and the MDA level was reduced. This effect was further verified by the overexpression of genes for trehalose-6-phosphate synthase ( TPS ) and neutral trehalase ( NTH ), which led to increased and reduced trehalose content, respectively. In addition, adding validamycin A (NTH inhibitor) to the media promoted trehalose accumulation and the recovered mycelial growth after HS. In conclusion, trehalose production was partly induced by ROS accumulation in the mycelia under HS, and the accumulated trehalose could promote the recovery of growth after HS, partly by reducing the MDA level in the mycelia.

Background Being the most common type of arrhythmia, atrial fibrillation (AF) is progressively increasing with an annual rate of 5 million new cases. Recent guidelines highlight the importance of using collaborative multidisciplinary teams in order to improve outcomes during management of patients with AF. A nurse-led program including a nurse-directed education, counselling and intervention has shown to improve patients’ outcomes in candidates with AF. In this analysis, we aimed to systematically compare the clinical outcomes observed in patients with AF who were assigned to a nurse-led interventional program versus a usual care group. Methods EMBASE, MEDLINE, Http://www.ClinicalTrials.gov , Web of Science; Google Scholar and Cochrane databases were the data sources. The clinical outcomes were considered as the endpoints in this study. This is a meta-analysis, and the statistical analysis was conducted by the RevMan software (version 5.4). Risk ratios (RR) with 95% confidence intervals (CI) were used to represent the data after statistical analysis. Results Six studies with a total number 2916 participants were included whereby 1434 participants were assigned to a nurse-led intervention and 1482 participants were assigned to the usual care group. Our results showed that participants with AF who were assigned to the nurse-led interventional group had a significantly lower risk of composite endpoints (RR: 0.82, 95% CI: 0.70–0.96; P  = 0.01), heart failure (RR: 0.66, 95% CI: 0.47–0.92; P  = 0.02), atrial fibrillation (RR: 0.77, 95% CI: 0.63–0.94; P  = 0.01) and re-admission (RR: 0.78, 95% CI: 0.62–0.99; P  = 0.04). However, the risks of all-cause mortality (RR: 0.86, 95% CI: 0.68–1.09; P  = 0.21), cardiac death (RR: 0.67, 95% CI: 0.33–1.39; P  = 0.28), myocardial infarction (RR: 0.70, 95% CI: 0.35–1.42; P  = 0.33), stroke (RR: 0.75, 95% CI: 0.44–1.26; P  = 0.28), all bleeding events (RR: 1.11, 95% CI: 0.81–1.53; P  = 0.51) and major bleeding events (RR: 0.91, 95% CI: 0.56–1.49; P  = 0.71) were not significantly different. Conclusions The nurse-led interventional program significantly improved composite endpoints including heart failure and the recurrence of AF, resulting in a significantly lower admission rate compared to the usual care group. However, nurse-led interventional program did not affect mortality, stroke, myocardial infarction and bleeding events. Based on our current results, a nurse-led interventional programs apparently could be beneficial in patients with AF. Future larger trials would be able to confirm this hypothesis.

A specific bone vessel subtype, strongly positive for CD31 and endomucin (CD31 hi Emcn hi ), is identified as coupling angiogenesis and osteogenesis. The abundance of type CD31 hi Emcn hi vessels decrease during ageing. Here we show that expression of the miR-497∼195 cluster is high in CD31 hi Emcn hi endothelium but gradually decreases during ageing. Mice with depletion of miR-497∼195 in endothelial cells show fewer CD31 hi Emcn hi vessels and lower bone mass. Conversely, transgenic overexpression of miR-497∼195 in murine endothelium alleviates age-related reduction of type CD31 hi Emcn hi vessels and bone loss. miR-497∼195 cluster maintains the endothelial Notch activity and HIF-1α stability via targeting F-box and WD-40 domain protein (Fbxw7) and Prolyl 4-hydroxylase possessing a transmembrane domain (P4HTM) respectively. Notably, endothelialium-specific activation of miR-195 by intravenous injection of aptamer-agomiR-195 stimulates CD31 hi Emcn hi vessel and bone formation in aged mice. Together, our study indicates that miR-497∼195 regulates angiogenesis coupled with osteogenesis and may represent a potential therapeutic target for age-related osteoporosis. H-type endothelium, defined by the high expression of CD31 and endomucin, is found in the bone where it promotes angiogenesis and osteogensis. Here Yang et al . show that the miR-497∼195 cluster regulates the generation and maintenance of the H-type endothelium by controlling the levels of Notch regulator Fbxw7 and the HIF regulator P4HTM.