TG-rich lipoprotein (TRL)-related biomarkers, including TRL-cholesterol (TRL-C), remnant-like lipoprotein particle-cholesterol (RLP-C), and apoC-III have been associated with atherosclerosis. ...However, their prognostic values have not been fully determined, especially in patients with previous CAD. This study aimed to examine the associations of TRL-C, RLP-C, and apoC-III with incident cardiovascular events (CVEs) in the setting of secondary prevention of CAD. Plasma TRL-C, RLP-C, and total apoC-III were directly measured. A total of 4,355 participants with angiographically confirmed CAD were followed up for the occurrence of CVEs. During a median follow-up period of 5.1 years (interquartile range: 3.9–6.4 years), 543 (12.5%) events occurred. Patients with incident CVEs had significantly higher levels of TRL-C, RLP-C, and apoC-III than those without events. Multivariable Cox analysis indicated that a log unit increase in TRL-C, RLP-C, and apoC-III increased the risk of CVEs by 49% (95% CI: 1.16–1.93), 21% (95% CI: 1.09–1.35), and 40% (95% CI: 1.11–1.77), respectively. High TRL-C, RLP-C, and apoC-III were also independent predictors of CVEs in individuals with LDL-C levels ≤1.8 mmol/l (n = 1,068). The addition of RLP-C level to a prediction model resulted in a significant increase in discrimination, and all three TRL biomarkers improved risk reclassification. Thus, TRL-C, RLP-C, and apoC-III levels were independently associated with incident CVEs in Chinese CAD patients undergoing statin therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Post-weaning diarrhea due to enterotoxigenic
(ETEC) is a common disease of piglets and causes great economic loss for the swine industry. Over the past few decades, decreasing effectiveness of ...conventional antibiotics has caused serious problems because of the growing emergence of multidrug-resistant (MDR) pathogens. Various studies have indicated that antimicrobial peptides (AMPs) have potential to serve as an alternative to antibiotics owing to rapid killing action and highly selective toxicity. Our previous studies have shown that AMP GW-Q4 and its derivatives possess effective antibacterial activities against the Gram-negative bacteria. Hence, in the current study, we evaluated the antibacterial efficacy of GW-Q4 and its derivatives against MDR ETEC and their minimal inhibition concentration (MIC) values were determined to be around 2~32 μg/mL. Among them, AMP Q4-15a-1 with the second lowest MIC (4 μg/mL) and the highest minimal hemolysis concentration (MHC, 256 μg/mL), thus showing the greatest selectivity (MHC/MIC = 64) was selected for further investigations. Moreover, Q4-15a-1 showed dose-dependent bactericidal activity against MDR ETEC in time-kill curve assays. According to the cellular localization and membrane integrity analyses using confocal microscopy, Q4-15a-1 can rapidly interact with the bacterial surface, disrupt the membrane and enter cytosol in less than 30 min. Minimum biofilm eradication concentration (MBEC) of Q4-15a-1 is 4× MIC (16 μg/mL), indicating that Q4-15a-1 is effective against MDR ETEC biofilm. Besides, we established an MDR ETEC infection model with intestinal porcine epithelial cell-1 (IPEC-1). In this infection model, 32 μg/mL Q4-15a-1 can completely inhibit ETEC adhesion onto IPEC-1. Overall, these results suggested that Q4-15a-1 may be a promising antibacterial candidate for treatment of weaned piglets infected by MDR ETEC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Atherosclerosis (AS) is a chronic progressive disease caused by injury and functional changes in vascular smooth muscle cells (VSMCs). Long non‑coding RNAs (lncRNAs) are pivotal regulators in AS ...development. The present study aimed to explore the roles and molecular mechanisms of lncRNA CTBP1‑AS2 in AS progression. A dual‑luciferase reporter assay confirmed that miR‑195‑5p is a downstream target miRNA of lncRNA CTBP1‑AS2 and miR‑195‑5p was increased in AS. The expression levels of miR‑195‑5p and CTBP1‑AS2 in the serums of patients with AS and human aorta vascular smooth muscle cells was increased or decreased, respectively, following treatment with oxidized low‑density lipoprotein (ox‑LDL). Functional experiments showed that the overexpression of lncRNA CTBP1‑AS2 inhibited the proliferation of HA‑VSMCs and promoted their autophagy following ox‑LDL treatment. This effect could be reversed by treatment with ROC‑325, the inhibitor of autophagy, or miR‑195‑5p mimics. Autophagy related 14 (ATG14) was identified to be a target of miR‑195‑5p, and lncRNA CTBP1‑AS2 promoted ATG14 expression by serving as a competing endogenous RNA of miR‑195‑5p. The present study revealed that lncRNA CTBP1‑AS2 may serve a role in AS by inhibiting the proliferation and promoting the autophagy of VSMCs through ATG14 modulation via miR‑195‑5p. These data may provide a novel therapeutic target for AS.
Diabetes is a risk factor for Alzheimer's disease (AD), a chronic neurodegenerative disease. We and others have shown prediabetes, including hyperglycemia and obesity induced by high fat and high ...sucrose diets, is associated with exacerbated amyloid beta (Aβ) accumulation and cognitive impairment in AD transgenic mice. However, whether hyperglycemia reduce glial clearance of oligomeric amyloid-β (oAβ), the most neurotoxic Aβ aggregate, remains unclear. Mixed glial cultures simulating the coexistence of astrocytes and microglia in the neural microenvironment were established to investigate glial clearance of oAβ under normoglycemia and chronic hyperglycemia. Ramified microglia and low IL-1β release were observed in mixed glia cultures. In contrast, amoeboid-like microglia and higher IL-1β release were observed in primary microglia cultures. APPswe/PS1dE9 transgenic mice are a commonly used AD mouse model. Microglia close to senile plaques in APPswe/PS1dE9 transgenic mice exposed to normoglycemia or chronic hyperglycemia exhibited an amoeboid-like morphology; other microglia were ramified. Therefore, mixed glia cultures reproduce the in vivo ramified microglial morphology. To investigate the impact of sustained high-glucose conditions on glial oAβ clearance, mixed glia were cultured in media containing 5.5 mM glucose (normal glucose, NG) or 25 mM glucose (high glucose, HG) for 16 days. Compared to NG, HG reduced the steady-state level of oAβ puncta internalized by microglia and astrocytes and decreased oAβ degradation kinetics. Furthermore, the lysosomal acidification and lysosomal hydrolysis activity of microglia and astrocytes were lower in HG with and without oAβ treatment than NG. Moreover, HG reduced mitochondrial membrane potential and ATP levels in mixed glia, which can lead to reduced lysosomal function. Overall, continuous high glucose reduces microglial and astrocytic ATP production and lysosome activity which may lead to decreased glial oAβ degradation. Our study reveals diabetes-induced hyperglycemia hinders glial oAβ clearance and contributes to oAβ accumulation in AD pathogenesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Renal fibrosis is an inevitable outcome of various manifestations of progressive chronic kidney diseases (CKD). The need for efficacious treatment regimen against renal fibrosis can therefore not be ...overemphasized. Here we show a novel protective role of Bacteroides fragilis (B. fragilis) in renal fibrosis in mice. We demonstrate decreased abundance of B. fragilis in the feces of CKD patients and unilateral ureteral obstruction (UUO) mice. Oral administration of live B. fragilis attenuates renal fibrosis in UUO and adenine mice models. Increased lipopolysaccharide (LPS) levels are decreased after B. fragilis administration. Results of metabolomics and proteomics studies show decreased level of 1,5-anhydroglucitol (1,5-AG), a substrate of SGLT2, which increases after B. fragilis administration via enhancement of renal SGLT2 expression. 1,5-AG is an agonist of TGR5 that attenuates renal fibrosis by inhibiting oxidative stress and inflammation. Madecassoside, a natural product found via in vitro screening promotes B. fragilis growth and remarkably ameliorates renal fibrosis. Our findings reveal the ameliorative role of B. fragilis in renal fibrosis via decreasing LPS and increasing 1,5-AG levels.
Soil has been used to generate electrical power in microbial fuel cells (MFCs) and exhibited several potential applications. This study aimed to reveal the effect of soil properties on the generated ...electricity and the diversity of soil source exoelectrogenic bacteria. Seven soil samples were collected across China and packed into air-cathode MFCs to generate electricity over a 270 days period. The Fe(III)-reducing bacteria in soil were enriched and sequenced by Illumina pyrosequencing. Culturable strains of Fe(III)-reducing bacteria were isolated and identified phylogenetically. Their exoelectrogenic ability was evaluated by polarization measurement. The results showed that soils with higher organic carbon (OC) content but lower soil pH generated higher peak voltage and charge. The sequencing of Fe(III)-reducing bacteria showed that
were dominant in all soil samples. At the family level,
Family XI incertae sedis were dominant in soils with lower OC content but higher pH (>8), while
, and
were dominant in soils with higher OC content but lower pH. The isolated culturable strains were allied phylogenetically to 15 different species, of which 11 were
. The others were
, and
. The maximum power density generated by the isolates in the MFCs ranged from 16.4 to 28.6 mW m
. We concluded that soil OC content had the most important effect on power generation and that the
were the dominant exoelectrogenic bacterial group in soil. This study might lead to the discovery of more soil source exoelectrogenic bacteria species.
The accurate diagnosis and treatment of oral squamous cell carcinoma (OSCC) requires an understanding of its genomic alterations. Liquid biopsies, especially cell-free DNA (cfDNA) analysis, are a ...minimally invasive technique used for genomic profiling. We conducted comprehensive whole-exome sequencing (WES) of 50 paired OSCC cell-free plasma with whole blood samples using multiple mutation calling pipelines and filtering criteria. Integrative Genomics Viewer (IGV) was used to validate somatic mutations. Mutation burden and mutant genes were correlated to clinico-pathological parameters. The plasma mutation burden of cfDNA was significantly associated with clinical staging and distant metastasis status. The genes
,
,
, and
were most frequently mutated in OSCC, and known driver genes, including
,
,
and
, were also significantly and frequently mutated. Additionally, the novel mutated genes
,
, and
were significantly and frequently present in patients with OSCC. The mutated genes most frequently found in patients with metastatic OSCC were
,
, and
Further analysis revealed that branched-chain amino acid (BCAA) catabolism, extracellular matrix-receptor interaction, and the hypoxia-related pathway were associated with OSCC prognosis. Choline metabolism in cancer, O-glycan biosynthesis, and protein processing in the endoplasmic reticulum pathway were associated with distant metastatic status. About 20% of tumors carried at least one aberrant event in BCAA catabolism signaling that could possibly be targeted by an approved therapeutic agent. We identified molecular-level OSCC that were correlated with etiology and prognosis while defining the landscape of major altered events of the OSCC plasma genome. These findings will be useful in the design of clinical trials for targeted therapies and the stratification of patients with OSCC according to therapeutic efficacy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The principle of prepared zirconia-COF shell composite for sensing water.
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•Fluorescent MOF@COF-derived composite was prepared.•The composite showed excellent stability and dual ...emission only in water.•A ratiometric method for sensing water with ultralow background was developed.
A ratiometric sensor with ultralow background is highly desired due to its low environmental influence and high sensitivity. Herein, inspired by the solubility difference of carboxylate in aqueous and organic solvents, we prepared a core–shell structure porous zirconia–covalent organic framework (COF) composite through thermal hydrolysis of UiO-66-COF precursors in organic alkali solution. The ligand 2-aminoterephthalic acids (H2BDC-NH2) of UiO-66 were transformed into 2-aminoterephthalate salts (ATA salts) that existed in zirconium-oxo clusters building units. The composites emitted only yellow emission (597 nm) from the COF in organic solvent due to the insolubility of ATA salts that induce aggregation-caused quenching (ACQ) and the protection of the COF shell. Contrarily, when water was added into mixture, the ATA salts were released into solution and its fluorescence recovered at 446 nm, while the fluorescence of COF was quenched due to the blockage of the intramolecular charge transfer (ICT) process by water. Thus, a high-sensitivity ratiometric fluorescence method is obtained with ultralow background signal and fast response (less than 1 min) for sensing water in organic solvent. We believe that the proposed ratiometric fluorescence sensor based on the zirconia–COF composite will provide the guidance for detection with wide applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A model incorporates factors that may drive and hinder B2B firms to adopt the SE.Both motivations and constraints significantly affect B2B SE adoption.Reciprocal benefits have emerged as an important ...motivating factor.Top management support mediates the effect of motivations on B2B SE adoption.The findings contribute to a better understanding of SE adoption in the B2B context.
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The birth of the sharing economy (SE) has been linked to a paradigm shift towards sustainable consumption, resulting from economic, environmental, and societal pressure. As a disruptive innovation, the SE presents both opportunities and challenges to businesses. However, prior studies on the SE have predominantly focused on the business-to-consumer (B2C) domain. To examine the factors that influence business-to-business (B2B) SE adoption, we developed a research model based on the diffusion of innovation theory, the Technology-Organization-Environment framework, and the social exchange theory. We empirically analyzed a sample of 127 Chinese companies by applying partial least squares-structural equation modeling (PLS-SEM) and fuzzy-set qualitative comparative analysis (fsQCA). The results from the PLS-SEM indicate that motivations affect a firm's intention to adopt the SE indirectly through top management support, whereas constraints affect a firm's adoption intention directly. It also suggests that reciprocity benefits are a salient motivating factor. The fSQCA findings reveal that there are three causal conditions that lead to high adoption intention.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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