No causal association between plasma cystatin C and cardiovascular diseases: Mendelian randomization analyses in UK biobank

BackgroundWe aimed to determine whether the plasma cystatin C is a causal risk factor for cardiovascular events, stroke, myocardial infarction (MI), and cardiovascular disease (CVD) mortality by conducting Mendelian randomization (MR) designs.MethodsOur study included 277,057 individuals free of CVDs or cancer at baseline in the UK Biobank. The genetic scores of plasma cystatin C comprising 67 single-nucleotide polymorphisms were calculated on the basis of data from a large genome-wide association study. By stratifying the genetic score, we conducted cox regression to assess the relationship between plasma cystatin C and CVDs. In this study, linear MR analysis was used to estimate the causal association between plasma cystatin C and CVDs.ResultsObservational analyses showed that plasma cystatin C concentrations were associated with the risk of CVDs [hazard ratios (HR) per standard deviation (SD) 1.09, 95% confidence interval (CI); 1.07–1.10] and CVD mortality (1.14, 1.11–1.17). Among CVDs, plasma cystatin C were associated with stroke (1.10, 1.08–1.11) and MI (1.08, 1.07–1.10). Linear MR analysis did not provide evidence of a causal association between plasma cystatin C and the risk of CVDs [odds ratio (OR) per SD 0.96, 95% CI;0.90–1.03], stroke (0.96, 0.93–1.01), MI (0.97, 0.91–1.03), and CVD mortality (0.98, 0.96–1.01), with consistent estimates from sensitivity analyses.ConclusionObservational findings indicated that higher plasma cystatin C is associated with a higher risk of CVDs; According to MR studies, there is no causal association between plasma cystatin C and the risk of CVDs and CVD mortality

CloudBrain-MRS: An Intelligent Cloud Computing Platform for in vivo Magnetic Resonance Spectroscopy Preprocessing, Quantification, and Analysis

Magnetic resonance spectroscopy (MRS) is an important clinical imaging method for diagnosis of diseases. MRS spectrum is used to observe the signal intensity of metabolites or further infer their concentrations. Although the magnetic resonance vendors commonly provide basic functions of spectra plots and metabolite quantification, the widespread clinical research of MRS is still limited due to the lack of easy-to-use processing software or platform. To address this issue, we have developed CloudBrain-MRS, a cloud-based online platform that provides powerful hardware and advanced algorithms. The platform can be accessed simply through a web browser, without the need of any program installation on the user side. CloudBrain-MRS also integrates the classic LCModel and advanced artificial intelligence algorithms and supports batch preprocessing, quantification, and analysis of MRS data from different vendors. Additionally, the platform offers useful functions: 1) Automatically statistical analysis to find biomarkers for diseases; 2) Consistency verification between the classic and artificial intelligence quantification algorithms; 3) Colorful three-dimensional visualization for easy observation of individual metabolite spectrum. Last, both healthy and mild cognitive impairment patient data are used to demonstrate the functions of the platform. To the best of our knowledge, this is the first cloud computing platform for in vivo MRS with artificial intelligence processing. We have shared our cloud platform at MRSHub, providing free access and service for two years. Please visit https://mrshub.org/software_all/#CloudBrain-MRS or https://csrc.xmu.edu.cn/CloudBrain.html.Comment: 11 pages, 12 figure

Insight Into the Superlubricity and Self-Assembly of Liquid Crystals

Liquid crystals are promising molecular materials in the application of lubrication. Herein, the microscale solid superlubricity is accomplished by the construction of uniform and ordered self-assembly of several liquid crystals. The self-assembly structures on a highly oriented pyrolytic graphite (HOPG) surface are explicitly revealed by using scanning tunneling microscopy (STM). Meanwhile, the nanotribological performance of the self-assemblies are measured by using atomic force microscopy (AFM), revealing ultralow friction coefficients lower than 0.01. The interaction energies are calculated by density functional theory (DFT) method, indicating the positive correlation between friction coefficients and interaction strength. The effort on the self-assembly and superlubricity of liquid crystals could enhance the understanding of the nanotribological mechanism and benefit the further application of liquid crystals as lubricants

Assessment of the Wind Resource at the Grace Pacific Quarry site in Kapolei, Oahu

The goal of this research project is to determine the feasibility of building a wind farm at Grace Pacific Quarry (GPQ) in Kapolei. This location was chosen because wind maps for Oahu suggest that the location of GPQ has a sufficient wind resource for a wind farm. Meteorological data from Grace Pacific Wind Towers were used to analyze the quality of the wind resource at GPQ. The people who work at First Wind in Hawaii were interviewed, and the wind resource at their wind farms was compared with that at GPQ. Finally, the thesis discusses local and political considerations and environmental impact studies needed to assess the feasibility of constructing a wind farm in Hawaii

Evaluation of Effectiveness and Safety of Microcin C7 in Weaned Piglets

The effects and safety of dietary supplementation with Microcin C7 (C7) were evaluated in 216 weaned piglets. The pigs were given a control corn–soybean meal basal diet or C7 diet (control diet supplemented with 250, 500, 750, 1000, or 5000 mg C7/kg diets). Compared with the control group, the 500 mg/kg C7 supplementation group had better intestinal morphological indicators (p p p p p p < 0.05). Compared with the control diet, 5000 mg/kg C7 supplementation had no significant adverse effect on all parameters. Overall, the 250–500 mg/kg dose had the best effect, and the highest dose (5000 mg/kg) posed no toxicity risk. Therefore, C7 appears safe for use as an alternative to antibiotic growth promoters in weaned piglets

Microbiota Transplantation in an Antibiotic-Induced Bacterial Depletion Mouse Model: Reproducible Establishment, Analysis, and Application

The fecal bacteria transplantation (FMT) technique is indispensable when exploring the pathogenesis and potential treatments for microbiota-related diseases. For FMT clinical treatments, there are already systematic guidelines for donor selection, fecal bacterial separation, FMT frequency, and infusion methods. However, only a few studies have demonstrated the use of standardized FMT procedures for animal models used in theoretical research, creating difficulties for many new researchers in this field. In the present paper, we provide a brief overview of FMT and discuss its contribution to the current understanding of disease mechanisms that relate to microbiota. This protocol can be used to generate a commonly used FMT mouse model and provides a literature reference of customizable steps

Compromised Hindgut Microbial Digestion, Rather Than Chemical Digestion in the Foregut, Leads to Decreased Nutrient Digestibility in Pigs Fed Low-Protein Diets

Background: Reduced nutrient digestibility due to low-protein (LP) diets occurring in the foregut or hindgut of pigs remains unclear. Methods: Growing barrows (21.7 &plusmn; 1.7 kg) were allotted into LP and high-protein (HP) diet treatments. Ileal digesta and feces were collected for in vitro cross-fermentation and microbial sequencing, and cross-feeding assessed nutrient digestibility. Results: No difference in foregut digesta flora and nutrient digestibility between treatments was observed. LP diet caused decreased total tract digestibility of dry matter (DM), organic matter (OM), gross energy (GE), neutral detergent fiber (NDF), and acid detergent fiber (ADF) compared with the HP diet (p &lt; 0.05). The fermentation broth from LP diet-fed pigs induced less full fermentation digestion of DM, OM, crude protein, and GE than HP broth (p &lt; 0.05). Additionally, LP broth fermentation presented lower fermentation gas and short-chain fatty acids (SCFAs) generation than HP group (p &lt; 0.05). This situation above may be related to decreased abundances of Lachnospiraceae, Eubacterium_eligens_group, Roseburia, and Ruminococcaceae_UCG-009, which can efficiently ferment nutrients to produce SCFA. Conclusions: Change in the flora caused compromise in hindgut microbial fermentation digestion leads to decreased total tract nutrient digestibility in pigs fed an LP diet

Schaftoside ameliorates oxygen glucose deprivation-induced inflammation associated with the TLR4/Myd88/Drp1-related mitochondrial fission in BV2 microglia cells

Background: Neuroinflammation plays a major role in the development of ischemic stroke, and regulation of the proinflammatory TLR4 signaling pathway in microglia stands to be a promising therapeutic strategy for stroke intervention. Recently, the homeostasis of mitochondrial dynamics has also been raised as a vital component in maintaining neuronal health, but its relevance in microglia hasn't been investigated. Schaftoside, a natural flavonoid compound and a promising treatment for inflammation, has demonstrated potency against LPS-induced lung inflammation in mice; however, its action on TLR4-induced neuroinflammation and mitochondrial dynamics in microglia is still unknown. Methods: The effects of schaftoside in regulating inflammation and mitochondrial dynamics were investigated in vitro in oxygen glucose deprivation (OGD)-stimulated BV2 microglia cells. Results: Schaftoside inhibited mRNA and protein expressions of proinflammatory cytokines (IL-1β, TNF-α, and IL-6) after 4 h in OGD-stimulated BV2 microglia cells, similar to the effect of TAK242, an inhibitor of TLR4. TLR4/Myd88 signaling pathway was effectively suppressed by schaftoside. In addition, both schaftoside and TAK242 treatments significantly decreased Drp1 expression, phosphorylation, translocation and mitochondrial fission in OGD-stimulated BV2 cells. Conclusions: Our study suggested that schaftoside was able to reduce neuroinflammation, which is mediated in part by reducing TLR4/Myd88/Drp1-related mitochondrial fission in BV2 microglia cells. Keywords: Mitochondrial fission, Microglia, TLR4, Stroke, Schaftosid

The Cold-Adapted, Temperature-Sensitive SARS-CoV-2 Strain TS11 Is Attenuated in Syrian Hamsters and a Candidate Attenuated Vaccine

Live attenuated vaccines (LAVs) replicate in the respiratory/oral mucosa, mimic natural infection, and can induce mucosal and systemic immune responses to the full repertoire of SARS-CoV-2 structural/nonstructural proteins. Generally, LAVs produce broader and more durable protection than current COVID-19 vaccines. We generated a temperature-sensitive (TS) SARS-CoV-2 mutant TS11 via cold-adaptation of the WA1 strain in Vero E6 cells. TS11 replicated at >4 Log10-higher titers at 32 °C than at 39 °C. TS11 has multiple mutations, including those in nsp3, a 12-amino acid-deletion spanning the furin cleavage site of the S protein and a 371-nucleotide-deletion spanning the ORF7b-ORF8 genes. We tested the pathogenicity and protective efficacy of TS11 against challenge with a heterologous virulent SARS-CoV-2 D614G strain 14B in Syrian hamsters. Hamsters were randomly assigned to mock immunization-challenge (Mock-C) and TS11 immunization-challenge (TS11-C) groups. Like the mock group, TS11-vaccinated hamsters did not show any clinical signs and continuously gained body weight. TS11 replicated well in the nasal cavity but poorly in the lungs and caused only mild lesions in the lungs. After challenge, hamsters in the Mock-C group lost weight. In contrast, the animals in the TS11-C group continued gaining weight. The virus titers in the nasal turbinates and lungs of the TS11-C group were significantly lower than those in the Mock-C group, confirming the protective effects of TS11 immunization of hamsters. Histopathological examination demonstrated that animals in the Mock-C group had severe pulmonary lesions and large amounts of viral antigens in the lungs post-challenge; however, the TS11-C group had minimal pathological changes and few viral antigen-positive cells. In summary, the TS11 mutant was attenuated and induced protection against disease after a heterologous SARS-CoV-2 challenge in Syrian hamsters