Abstract Cyclic chiral lactide is the monomer chemical for polymerization of high molecular weight polylactic acid (PLA). The synthesis of cyclic l ‐lactide starts from poly‐condensation of l ‐lactic acid to a low molecular weight prepolymer and then depolymerized to cyclic l ‐lactide. Lignocellulose biomass is the most promising carbohydrate feedstock for lactic acid production, but the synthesis of cyclic l ‐lactide from l ‐lactic acid produced from lignocellulose has so far not been successful. The major barriers are the impurities of residual sugars and inhibitors in the crude cellulosic l ‐lactic acid product. Here we show a successful cyclic l ‐lactide synthesis from cellulosic l ‐lactic acid by lignocellulose biorefining with complete inhibitor removal and coordinated sugars assimilation. The removal of inhibitors from lignocellulose pretreatment was accomplished by biodetoxification using a unique fungus Amorphotheca resinae ZN1. The nonglucose sugars were completely and simultaneously assimilated at the same rate with glucose by the engineered l ‐lactic acid bacterium Pediococcus acidilactici . The l ‐lactic acid production from wheat straw was comparable to that from corn starch with high optical pure (99.6%), high l ‐lactic acid titer (129.4 g/L), minor residual total sugars (~2.2 g/L), and inhibitors free. The cyclic l ‐lactide was successfully synthesized from the regularly purified l ‐lactic acid and verified by detailed characterizations. This study paves the technical foundation of carbon‐neutral production of biodegradable PLA from lignocellulose biomass.
A series of lanthanide coordination polymers (LnCPs), namely [Ln(TZI) (H2O)5]n(1–5) [Ln = Nd (1), Eu (2), Gd (3), Tb (4) and Sm (5)], were synthesized through the self-assembly of 5-(1H-tetrazol-5-yl)isophthalic acid (H3TZI) ligand and lanthanide ions.
The SEPT9 gene methylation assay is the first FDA-approved blood assay for colorectal cancer (CRC) screening. Fecal immunochemical test (FIT), FIT-DNA test and CEA assay are also in vitro diagnostic (IVD) tests used in CRC screening. This meta-analysis aims to review the SEPT9 assay performance and compare it with other IVD CRC screening tests. By searching the Ovid MEDLINE, EMBASE, CBMdisc and CJFD database, 25 out of 180 studies were identified to report the SEPT9 assay performance. 2613 CRC cases and 6030 controls were included, and sensitivity and specificity were used to evaluate its performance at various algorithms. 1/3 algorithm exhibited the best sensitivity while 2/3 and 1/1 algorithm exhibited the best balance between sensitivity and specificity. The performance of the blood SEPT9 assay is superior to that of the serum protein markers and the FIT test in symptomatic population, while appeared to be less potent than FIT and FIT-DNA tests in asymptomatic population. In conclusion, 1/3 algorithm is recommended for CRC screening, and 2/3 or 1/1 algorithms are suitable for early detection for diagnostic purpose. The SEPT9 assay exhibited better performance in symptomatic population than in asymptomatic population.
Staphylococcus aureus poses a severe public health problem as one of the vital causative agents of healthcare- and community-acquired infections. There is a globally urgent need for new drugs with a novel mode of action (MoA) to combat S. aureus biofilms and persisters that tolerate antibiotic treatment. We demonstrate that a benzonaphthopyranone glycoside, chrysomycin A (ChryA), is a rapid bactericide that is highly active against S. aureus persisters, robustly eradicates biofilms in vitro, and shows a sustainable killing efficacy in vivo. ChryA was suggested to target multiple critical cellular processes. A wide range of genetic and biochemical approaches showed that ChryA directly binds to GlmU and DapD, involved in the biosynthetic pathways for the cell wall peptidoglycan and lysine precursors, respectively, and inhibits the acetyltransferase activities by competition with their mutual substrate acetyl-CoA. Our study provides an effective antimicrobial strategy combining multiple MoAs onto a single small molecule for treatments of S. aureus persistent infections.
Background Lysine acetylation is a crucial type of protein post-translational modification, which is involved in many important cellular processes and serious diseases. However, identification of protein acetylated sites through traditional experiment methods is time-consuming and laborious. Those methods are not suitable to identify a large number of acetylated sites quickly. Therefore, computational methods are still very valuable to accelerate lysine acetylated site finding. Result In this study, many biological characteristics of acetylated sites have been investigated, such as the amino acid sequence around the acetylated sites, the physicochemical property of the amino acids and the transition probability of adjacent amino acids. A logistic regression method was then utilized to integrate these information for generating a novel lysine acetylation prediction system named LAceP. When compared with existing methods, LAceP overwhelms most of state-of-the-art methods. Especially, LAceP has a more balanced prediction capability for positive and negative datasets. Conclusion LAceP can integrate different biological features to predict lysine acetylation with high accuracy. An online web server is freely available at http://www.scbit.org/iPTM/.
Abstract Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance ( P <2.69 × 10 −7 ), including three Asian-specific coding variants in known genes ( CETP p.Asp459Gly, PCSK9 p.Arg93Cys and LDLR p.Arg257Trp). Furthermore, missense variants at two novel loci— PNPLA3 p.Ile148Met and PKD1L3 p.Thr429Ser — also influence levels of triglycerides and low-density lipoprotein cholesterol, respectively. Another novel gene, TEAD2 , is found to be associated with high-density lipoprotein cholesterol through gene-based association analysis. Most of these newly identified coding variants show suggestive association ( P <0.05) with CAD. These findings demonstrate that exome-wide genotyping on samples of non-European ancestry can identify additional population-specific possible causal variants, shedding light on novel lipid biology and CAD.
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