N-Acetylcysteine ameliorates lipopolysaccharide-induced organ damage in conscious rats

Lipopolysaccharide is strongly associated with septic shock, leading to multiple organ failure. It can activate monocytes and macrophages to release proinflammatory mediators such as tumor necrosis factor- (TNF-), interleukin-1 (IL-1), and nitric oxide (NO). The present experiments were designed to induce endotoxin shock by an intravenous injection ofKlebsiella pneumoniae lipopolysaccharide (LPS, 10 mg/kg) in conscious rats. Arterial pressure and heart rate (HR) were continuously monitored for 48 h after LPS administration. N-Acetyl-cysteine was used to study its effects on organ damage. Biochemical substances were measured to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-, IL-1, methyl guanidine (MG), and nitrites/nitrates. LPS caused significant increases in blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-, IL-1, MG levels, and HR, as well as a decrease in mean arterial pressure and an elevation of nitrites/nitrates. N-Acetylcysteine suppressed the release of TNF-, IL-1, and MG, but enhanced NO production. These actions ameliorate LPS-induced organ damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound in sepsis prevention and treatment.     

Arabidopsis ADC1 functions as an N~δ-acetylornithine decarboxylase

Polyamines are small aliphatic amines found in almost all organisms, ranging from bacteria to plants and animals. In most plants, putrescine, the metabolic precursor for longer polyamines, such as spermidine and spermine, is produced from arginine, with either agmatine or ornithine as intermediates. Here we show that Arabidopsis thaliana(Arabidopsis) arginine decarboxylase 1(ADC1), one of the two known arginine decarboxylases in Arabidopsis, not only synthesizes agmatine from arginine, but also converts N~δ-acetylornithine to N-acetylputrescine. Phylogenetic analyses indicate that duplication and neofunctionalization of ADC1 and NATA1, the enzymes that synthesize N~δ-acetylornithine in Arabidopsis, co-occur in a small number of related species in the Brassicaceae. Unlike ADC2, which is localized in the chloroplasts, ADC1 is in the endoplasmic reticulum together with NATA1, an indication that these two enzymes have access to the same substrate pool. Together, these results are consistent with a model whereby NATA1 and ADC1 together provide a pathway for the synthesis of N-acetylputrescine in Arabidopsis.     

Charge Transfer Modulated Activity of Carbon‐Based Electrocatalysts

Electrocatalysis is the most important electrode reactions for many energy storage and conversion devices, which are considered a key part of the resolution of the energy crisis. Toward this end, design of efficient electrocatalysts is of critical significance. While extensive research has been extended to develop excellent electrocatalysts, the fundamental understanding of the relationship between the electronic and structural properties of electrocatalysts and the catalytic activity must remain a priority. In this review, the activity modulation of electrocatalysts by charge transfer effects, including intramolecular and intermolecular charge transfer, is systematically introduced. With suitable charge transfer modification, such as heteroatom doping, defect engineering, molecule functionalization, and heterojunctions, the electrocatalytic activity of carbon‐based electrocatalysts can be significantly boosted. The manipulation of the electronic structure of carbon‐based materials by charge transfer may serve as a fundamental mechanism for performance enhancement. After establishing an understanding of the relationship between catalytic activity and charge transfer, the opportunities and challenges for the design of electrocatalyst with charge transfer effects are discussed.     

Exosome biogenesis,secretion and function of exosomal miRNAs in skeletal muscle myogenesis

Exosomes are membrane‐bound extracellular vesicles that are produced in the endosomal compartment of most mammalian cell types and then released. Exosomes are effective carriers for the intercellular material transfer of material that can influence a series of physiological and pathological processes in recipient cells. Among loaded cargoes, non‐coding RNAs (ncRNAs) vary for the exosome‐producing cell and its homeostatic state, and characterization of the biogenesis and secretion of exosomal ncRNAs and the functions of these ncRNAs in skeletal muscle myogenesis remain preliminary. In this review, we will describe what is currently known of exosome biogenesis, release and uptake of exosomal ncRNAs, as well as the varied functions of exosomal miRNAs in skeletal muscle myogenesis.     

气候变化下生物交互作用对树线生态过程的影响

树线交错带是具有强烈生物交互作用的高寒生态过渡带,生物互作与树线生态过程密切相关。本研究系统综述了气候变化下植物间、动植物间和微生物与植物间互作因子对树线生态过程的影响。植物间互利或竞争作用的强度调控变暖背景下树线生态过程的变化,目前尚缺少树轮生态学证据,且亟待检验高阶互作的适用性;动物采食活动、微生物与植物间互作可通过影响土壤状况、改变树木生长和更新等生态过程动态,增强或削弱树线与气候间耦合关系。迄今为止,地下与地上过程联系如何影响气候变暖下的树线动态尚不明晰,而营养级间互作可能调制树线生态过程对气候响应。青藏高原等高寒区具有开展此类研究的优势与潜力。     

β-1,6葡聚糖酶前体编码基因Ss4p对甘蔗黑穗病菌分泌蛋白组的影响

甘蔗(Saccharum spp.)是世界也是中国主要的糖料作物.由甘蔗黑穗病菌(Sporisorium scitamineum)引起的甘蔗黑穗病是中国甘蔗生产上最主要的病害,每年造成重大损失.分泌蛋白在真菌侵染寄主植物与获取营养及病理过程起重要作用.本实验室在分析甘蔗黑穗病菌基因组与转录组数据时,发现1个与真菌细胞壁降解有关的β-1,6葡聚糖酶前体的基因Ssa4p.为了揭示Ssa4p对甘蔗黑穗病菌致病性和分泌蛋白组的影响,本研究利用CRISPR/Cas9和T-DNA双元载体所构建的甘蔗黑穗菌基因敲除系统,成功获得了Ssa4p基因的失活突变株.ΔSsa4p突变株(Δ35-Ssa4p)与野生型菌株JG36的配合能力降低且致病性减弱.用iTRAQ方法对Δ35-Ssa4p和野生型菌株的分泌蛋白组进行比较分析,共鉴定到蛋白质1430个,其中上调差异表达蛋白质685个,下调差异表达蛋白质745个.GO功能富集分析及KEGG分析表明,差异蛋白主要定位于无膜细胞器和核糖体,其功能包括参与核糖体、氨基糖和核苷酸糖代谢等生物学过程.本研究发现β-1,6葡聚糖前体影响植物病原真菌的分泌蛋白,加深了对真菌致病性调控机制的认识.     

Microwell bioreactor system for cell-based high throughput proliferation and cytotoxicity assays

Cell-based high throughput proliferation and cytotoxicity assays are increasingly used in drug screening and bioprocess development. However, online monitoring of cell proliferation, pH, and dissolved oxygen (DO) has been a challenge in 3D cell-based assays. In this work, a 40-microwell bioreactor (40-MBR) system was developed from a 384-well plate for real-time, noninvasive monitoring of pH, DO, and cell proliferation in 3D microenvironments. Chinese hamster ovary (CHO) and MCF-07 breast cancer cells cultured in 40-MBR confirmed that the 40-MBR was capable of simultaneously monitoring DO and cell proliferation based on culture fluorescence and pH by measuring the absorbance of phenol red. Cytotoxicity studies of sodium butyrate on CHO cells demonstrated that 40-MBR with dynamic background fluorescence correction gave more reliable and highly reproducible growth kinetic data compared to conventional multiwells with static background correction. Furthermore, the dosage effects of two new anticancer drug candidates, 5,7-dihydroxy-2-(4-hydroxyphenyl)-8-[(E)-2-phenylethenyl]-3,4-dihydro-2H-1-benzopyran-4-one (DH-8P-DB) and 5,7-dihydroxy-2-(4-hydroxyphenyl)-6-[(E)-2-phenylethenyl]-3,4-dihydro-2H-1-benzopyran-4-one (DH-6P-DB), on HT-29 colon cancer cells were assessed using the 40-MBR, and the results indicated that DH-6P-DB would be a more potent drug in treating colon cancer than DH-8P-DB. These studies demonstrated that 40-MBR could serve as a high throughput platform for screening potential cancer drugs in early-stage drug discovery.     

Cell-based high-throughput proliferation and cytotoxicity assays for screening traditional Chinese herbal medicines

A simple, reliable, high-throughput screening method was developed and used to assess the pharmaceutical effects of extracts of traditional Chinese herbal medicines (TCHMs). This method is based on 3-dimensional (3-D) cultures of mouse embryonic stem (mES) and human colon cancer and breast cancer cells expressing enhanced green fluorescent protein (EGFP) in polyethylene terephthalate (PET) fibrous scaffolds on modified 384-well plates with online monitoring of culture fluorescence for dynamic responses of cells to drugs present in culture media. Cell responses to deoxycholic acid and the extracts of 3 TCHMs (Ganoderma lucidum spores, Ginkgo biloba, and Epimedium brevicornum) at various concentrations were investigated for their effects on proliferation and cytotoxicity. The screening results, i.e., the growth responses of cancer cells to those drugs, were consistent with what have been reported in the literature, confirming the reliability of the new screening approach. Different from previous screening methods for both TCHMs and western medicines that used animal models or 2-D cell-based assays with single cell lines, this 3-D cell-based screening method employs both cancer and normal cells and thereby provides a way for quick, direct evaluation of the anticancer effects of TCHMs. This method also offers assessment on the side effects of TCHMs.     

Does Serum 25-Hydroxyvitamin D Influence Muscle Development during Puberty in Girls? - A 7-Year Longitudinal Study

Vitamin D is well known for its regulatory role in calcium and phosphate homeostasis, but its role in muscle mass and strength during growth remains inconclusive. We explored the association of serum 25-hydroxyvitamin D (25(OH)D) with muscle development in girls from 11 to 18-years old. Whole body lean tissue mass (LM_WB), appendicular lean mass (aLM), muscle cross-sectional area at the lower leg (mCSA), maximal voluntary contraction of elbow flexors (MVC_elbow) and knee extensors (MVC_knee) were assessed in 217 girls aged 10–13 years (at baseline), 215 in 2-year and 226 in 7.5-year follow-up. Serum concentration of 25(OH)D and intact parathyroid hormone (PTH) were analyzed retrospectively and girls were categorized according to their 25(OH)D levels (consistently insufficient 25(OH)D G_LL <50 nmol/l and consistently sufficient G_HH >50 nmol/l from baseline to 7-year follow-up). We found that 25(OH)D level declined until menarche (p<0.05) while LM_WB, aLM, mCSA, MVC_elbow and MVC_knee continued to increase (p<0.001 for all) post menarche. At pre-menarche, the G_LL (n = 34) had higher LM_WB and aLM than the G_HH (n = 21, p<0.05), while post-menarche the G_HH (n = 15) had a greater catch-up gain in LM_WB (p = 0.004), aLM (p = 0.001) and mCSA (p = 0.027) compared to the G_LL (n = 65) over the first 2-year period. At the age of 18, no differences in muscle mass/strength between the low (n = 151) and high (n = 77) levels of 25(OH)D groups were found. This finding was independent of vitamin D receptor genotype and other confounders. In conclusion, our results showed that levels of 25(OH)D have no significant negative influence on the development of muscle mass and strength during pubertal growth both with longitudinal and cross-sectional comparison. On the contrary, our results suggest that the temporary negative association between 25(OH)D and muscle mass arises as a consequence of fast growth prior to menarche, and this negative association is diminished through catch-up growth after menarche.