Mannose-Modificated Polyethylenimine: A Specific and Effective Antibacterial Agent against <i>Escherichia coli</i>

Poly­ethyl­en­imine (PEI) has antimicrobial activity against Gram-positive (<i>Staphylococcus aureus</i>, <i>S. aureus</i>) and Gram-negative (<i>Escherichia coli</i>, <i>E. coli</i>), bacteria but is highly cytotoxic, and the selective antimicrobial activity against <i>S. aureus</i> is obviously better than that against <i>E. coli</i>. To reduce the cytotoxicity and improve the antibacterial activity against <i>E. coli</i>, we modified PEI with d-mannose through nucleophilic addition between primary amine and aldehyde groups to get mannose-modified poly­ethyl­en­imine copolymer particles (Man-PEI CPs). The use of mannose may provide good targeting ability toward <i>E. coli</i> pili. The antibacterial activity of Man-PEI CPs was investigated. Man-PEI CPs shows specific and very strong killing capability against <i>E. coli</i> at a concentration of 10 μg/mL, which is the highest antimicrobial efficiency compared to that of unmodified PEI (220 μg/mL). The antibacterial mechanism demonstrated that the enhancement in antibacterial activity is due to specific recognition of the mannose and destroying the cell wall of the bacteria by PEIs. Importantly, the Man-PEI CPs show less cytotoxicity and excellent biocompatibility. The results indicate that Man-PEI CPs have great potential as novel antimicrobial materials to prevent bacterial infections and provide specific applications for killing <i>E. coli</i>

Additional file 1: of Qcorp: an annotated classification corpus of Chinese health questions

A brief introduction of the data source websites. This additional file is in PDF format. It contains a table that gives a brief introduction of the data source websites, including their abbreviation, Chinese name, English names, and description. (PDF 58 kb

Bioinspired Hierarchical Nanofibrous Silver-Nanoparticle/Anatase–Rutile-Titania Composite as an Anode Material for Lithium-Ion Batteries

A new bioinspired hierarchical nanofibrous silver-nanoparticle/anatase–rutile-titania (Ag-NP/A–R-titania) composite was fabricated by employing a natural cellulose substance (e.g., commercial laboratory cellulose filter paper) as the structural scaffold template, which was composed of anatase-phase titania (A-titania) nanotubes with rutile-phase titania (R-titania) nanoneedles grown on the surfaces and further silver nanoparticles (AgNPs) immobilized thereon. As it was employed as an anode material for lithium-ion batteries (LIBs), high reversible capacity, enhanced rate performance, and excellent cycling stability were achieved as compared with those of the corresponding cellulose-substance-derived nanotubular A-titania, R-titania, heterogeneous anatase/rutile titania (A–R-titania) composite, and commercial P25 powder. This benefited from its unique porous cross-linked three-dimensional structure inherited from the initial cellulose substance scaffold, which enhances the sufficient electrode/electrolyte contact, relieves the severe volume change upon cycling, and improves the amount of lithium-ion storage; moreover, the high loading content of the silver component in the composite improves the electrical conductivity of the electrode. The structural integrity of the composite was maintained upon long-term charge/discharge cycling, indicating its significant stability

Natural Product-Inspired Targeted Protein Degraders: Advances and Perspectives

Targeted protein degradation (TPD), a promising therapeutic strategy in drug discovery, has great potential to regulate the endogenous degradation of undruggable targets with small molecules. As vital resources that provide diverse structural templates for drug discovery, natural products (NPs) are a rising and robust arsenal for the development of therapeutic TPD. The first proof-of-concept study of proteolysis-targeting chimeras (PROTACs) was a natural polyketide ovalicin-derived degrader; since then, NPs have shown great potential to promote TPD technology. The use of NP-inspired targeted protein degraders has been confirmed to be a promising strategy to treat many human conditions, including cancer, inflammation, and nonalcoholic fatty liver disease. Nevertheless, the development of NP-inspired degraders is challenging, and the field is currently in its infancy. In this review, we summarize the bioactivities and mechanisms of NP-inspired degraders and discuss the associated challenges and future opportunities in this field

Bioavailability and Antioxidant Activity of Rambutan (<i>Nephelium lappaceum</i>) Peel Polyphenols during <i>in Vitro</i> Simulated Gastrointestinal Digestion, Caco‑2 Monolayer Cell Model Application, and Colonic Fermentation

The bioavailability of rambutan peel polyphenols (RPPs) was studied via in vitro simulated digestion, a Caco-2 monolayer cell model, and colonic fermentation. Total phenolic content of RPPs decreased with the progress of the simulated digestion. A total of 38 phenolic compounds were identified during the digestion and colonic fermentation, of which 12 new metabolites were found during colonic fermentation. The possible biotransformation pathways were inferred. Geraniin was transformed into corilagin, ellagic acid, and gallic acid during the digestion and colonic fermentation. Ellagic acid could be further transformed into urolithin under the action of intestinal microbiota. The transformation of ellagitannins could be beneficial to transport on Caco-2 monolayer cell. The antioxidant capacity of RPPs increased with the progress of gastrointestinal digestion. Furthermore, RPPs could increase the yield of short-chain fatty acids, decrease the pH value, promote the growth of beneficial bacteria, and inhibit the growth of pathogenic Escherichia coli/Shigella during colonic fermentation

Data_Sheet_1_Screening for CCNF Mutations in a Chinese Amyotrophic Lateral Sclerosis Cohort.PDF

<p>Previous research has identified CCNF mutations in familial (FALS) and sporadic amyotrophic lateral sclerosis (SALS), as well as in frontotemporal dementia (FTD). The aim of our study was to measure the frequency of CCNF mutations in a Chinese population. In total, 78 FALS patients, 581 SALS patients and 584 controls were included. We found 19 missense mutations, nine synonymous mutations and two intron variants. According to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines for the interpretation of sequence variants, eight variants were judged to be pathogenic or likely pathogenic variants. The frequency of such variants was 2.56% in FALS and 1.03% in SALS. In conclusion, CCNF mutations are common in FALS and SALS patients of Chinese origin, and further study is still needed.</p

Controlled Ambipolar Doping and Gate Voltage Dependent Carrier Diffusion Length in Lead Sulfide Nanowires

We report a simple, controlled doping method for achieving n-type, intrinsic, and p-type lead sulfide (PbS) nanowires (NWs) grown by chemical vapor deposition without introducing any impurities. A wide range of carrier concentrations is realized by adjusting the ratio between the Pb and S precursors. The field effect electron mobility of n-type PbS NWs is up to 660 cm²/(V s) at room temperature, in agreement with a long minority carrier diffusion length measured by scanning photocurrent microscopy (SPCM). Interestingly, we have observed a strong dependence of minority carrier diffusion length on gate voltage, which can be understood by considering a carrier concentration dependent recombination lifetime. The demonstrated ambipolar doping of high quality PbS NWs opens up exciting avenues for their applications in photodetectors and photovoltaics

Association of Plasma Transforming Growth Factor-β1 Levels and the Risk of Atrial Fibrillation: A Meta-Analysis

<div><p>Introduction</p><p>Numerous studies have demonstrated that plasma transforming growth factor-β1 (TGF-β1) may be involved in the pathogenesis of atrial fibrillation (AF), but some discrepancy remained. We performed a meta-analysis to evaluate the association between the plasma level of TGF-β1 and the risk of AF.</p><p>Methods</p><p>Published clinical studies evaluating the association between the plasma level of TGF-β1 and the risk of AF were retrieved from PubMed and EMBASE databases. Two reviewers independently evaluated the quality of the included studies and extracted study data. Subgroup analysis and sensitivity analysis were performed to evaluate for heterogeneity between studies.</p><p>Results</p><p>Of the 395 studies identified initially, 13 studies were included into our analysis, with a total of 3354 patients. Higher plasma level of TGF-β1 was associated with increased risk of AF when evaluated as both a continuous variable (SMD 0.67; 95%CI 0.29–1.05) and a categorical variable (OR 1.01, 95% CI 1.01–1.02).</p><p>Conclusions</p><p>This meta-analysis suggests an association between elevated plasma TGF-β1 and new onset AF. Additional studies with larger sample sizes are needed to further investigate the relationship between plasma TGF-β1 and the occurrence of AF.</p></div

Patients characteristics of included studies.

<p>Patients characteristics of included studies.</p

Discovery of a Novel Ketohexokinase Inhibitor with Improved Drug Distribution in Target Tissue for the Treatment of Fructose Metabolic Disease

Excessive fructose absorption and its subsequent metabolisms are implicated in nonalcoholic fatty liver disease, obesity, and insulin resistance in humans. Ketohexokinase (KHK) is a primary enzyme involved in fructose metabolism via the conversion of fructose to fructose-1-phosphate. KHK inhibition might be a potential approach for the treatment of metabolic disorders. Herein, a series of novel KHK inhibitors were designed, synthesized, and evaluated. Among them, compound 14 exhibited more potent activity than PF-06835919 based on the rat KHK inhibition assay in vivo, and higher drug distribution concentration in the liver. Its good absorption, distribution, metabolism, and excretion and pharmacokinetic properties make it a promising clinical candidate