Search

The increasing market demand for squalene requires novel biotechnological production platforms. Schizochytrium sp. is an industrial oleaginous host with high potential for squalene production due to its abundant native acetyl-CoA pool. We first found that iron starvation led to the accumulation of 1.5 g/L of squalene by Schizochytrium sp., which was 40-fold higher than in the control. Subsequent transcriptomic and lipidomic analyses showed that the high squalene titer is due to the diversion of precursors from lipid biosynthesis and increased triglycerides (TAG) content for squalene storage. Furthermore, we constructed the engineered acetyl-CoA C-acetyltransferase (ACAT)-overexpressing strain 18S::ACAT, which produced 2.79 g/L of squalene, representing an 86% increase over the original strain. Finally, a nitrogen-rich feeding strategy was developed to further increase the squalene titer of the engineered strain, which reached 10.78 g/L in fed-batch fermentation, a remarkable 161-fold increase over the control. To our best knowledge, this is the highest squalene yield in thraustochytrids reported to date. This article is protected by copyright. All rights reserved.

Changes in species interactions due to species loss are threatening ecological networks. To explore the responses of arthropod networks to global changes, we conducted a multifactorial field experiment in temperate grassland, in which nitrogen (N) deposition, drought and snowmelt timing were manipulated. We constructed modular networks for arthropod functional groups and assessed their complexity by connectance, interaction diversity and interaction strength. Specifically, the pattern of reduction of network complexity was different in N and drought conditions: (a) increased foliar N strengthened single pathway and weakened the net effect of other pathways in N treatment; (b) filtered plant species and changed micro-habitats in drought conditions. Whereas delayed snowmelt increased arthropod abundance only in early spring, but its interaction with N treatment or drought showed various impacts on functional groups. Therefore, it is suggested that the co-effect of multiple global change factors, occurring in different seasons, should be considered as a panorama.

Climate extremes pose enormous threats to natural ecosystems. Arbuscular mycorrhizal (AM) fungi are key plant symbionts that can affect plant community dynamics and ecosystem stability. However, knowledge about how AM fungal communities respond to climate extremes in natural ecosystems remains elusive. Based on a grassland extreme drought experiment in Inner Mongolia, we investigated the response of AM fungal communities to extreme drought in association with plant communities. The experiment simulated two types of extreme drought (chronic/intense) of once-in-20-year occurrence. AM fungal richness and community composition exhibited high sensitivity to extreme drought and were more sensitive to intense drought than chronic drought. This community sensitivity (i.e. decline in richness and shifts in community composition) of AM fungi can be jointly explained by soil moisture, plant richness, and aboveground productivity. Notably, the robustness of the plant-AM fungal community co-response increased with drought intensity. Our results indicate that AM fungal communities are sensitive to climate extremes, and we propose that the plant community mediates AM fungal community responses. Given the ubiquitous nature of AM associations, their climate sensitivity may have profound consequences on plant communities and ecosystem stability under climate change.

Extreme drought decreases aboveground net primary production (ANPP) in most grasslands, but the magnitude of ANPP reductions varies especially in C3 -dominated grasslands. Because the mechanisms underlying such differential ecosystem responses to drought are not well resolved, we experimentally imposed an extreme 4-yr drought (2015-2018) in two C3 grasslands that differed in aridity. These sites had similar annual precipitation and dominant grass species (Leymus chinensis) but different annual temperatures and thus water availability. Drought treatments differentially affected these two semiarid grasslands, with ANPP of the drier site reduced more than at the wetter site. Structural equation modeling revealed that community-weighted means for some traits modified relationships between soil moisture and ANPP, often due to intraspecific variation. Specifically, drought reduced community mean plant height at both sites, resulting in a reduction in ANPP beyond that attributable to reduced soil moisture alone. Higher community mean leaf carbon content enhanced the negative effects of drought on ANPP at the drier site, and ANPP-soil-moisture relationships were influenced by soil C:N ratio at the wetter site. Importantly, neither species richness nor functional dispersion were significantly correlated with ANPP at either site. Overall, as expected, soil moisture was a dominant, direct driver of ANPP response to drought, but differential sensitivity to drought in these two grasslands was also related to soil fertility and plant traits.

Lipotoxicity induced by saturated fatty acids (SFAs) plays a pathological role in the development of non‐alcoholic fatty liver disease (NAFLD); however, the exact mechanism(s) remain to be clearly elucidated. Toll‐like receptor (TLR) 4 plays a fundamental role in activating the innate immune system. Intriguingly, hepatocytes express TLR4 and machinery for TLR4 signalling pathway. That liver‐specific TLR4 knockout mice are protective against diet‐induced NAFLD suggests that hepatocyte TLR4 signalling pathway plays an important role in NAFLD pathogenesis. Herein, using cultured hepatocytes, we sought to directly examine the role of TLR4 signalling pathway in palmitate‐elicited hepatotoxicity and to elucidate underlying mechanism(s). Our data reveal that palmitate exposure up‐regulates TLR4 expression at both mRNA and protein levels in hepatocytes, which are associated with NF‐κB activation. The inhibition of TLR4 signalling pathway through both pharmacological and genetic approaches abolished palmitate‐induced cell death, suggesting that TLR4 signalling pathway activation contributes to palmitate‐induced hepatotoxicity. Mechanistic investigations demonstrate that inositol‐requiring enzyme 1α (IRE1α), one of three major signal transduction pathways activated during endoplasmic reticulum (ER) stress, is the downstream target of palmitate‐elicited TLR4 activation and mechanistically implicated in TLR4 activation‐triggered cell death in response to palmitate exposure. Collectively, our data identify that the TLR4‐IRE1α pathway activation contributes to palmitate‐elicited lipotoxicity in hepatocytes. Our findings suggest that targeting TLR4‐IRE1α pathway can be a potential therapeutic choice for the treatment of NAFLD as well as other metabolic disorders, with lipotoxicity being the principal pathomechanism.

Owing to their ability to rapidly proliferate in specific niches and their amenability to genetic manipulation, bacteria are frequently studied as potential diagnostic or therapeutic bioagents in a range of pathological contexts. A sustained oxygen supply within solid tumors is essential in order to achieve positive radiotherapy (RT) outcomes, as these intratumoral oxygen levels are necessary to facilitate RT-induced reactive oxygen species (ROS) generation. In this study, a genetically engineered variant of the tumor-targeting probiotic E. coli Nissle 1917 bacteria that secret catalase is utilized to alleviate intratumoral hypoxia and to thereby enhance tumor radiosensitivity. These engineered bacteria are able to facilitate robust O2 evolution and consequent ROS generation in response to X-ray irradiation both in vitro and in vivo, significantly inhibiting tumor growth. Overall, the study highlights a novel and practical approach to enhance the efficacy of tumor RT, underscoring the value of future research in the field of probiotic medicine.

The efficacy of combined vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibition in patients with advanced non-small-cell lung cancer (NSCLC) was well studied. However, few studies focused on the risk and adverse events (AEs) of combined targeted therapy. The aim of this meta-analysis was to evaluate the safety profile of combined targeted therapy against EFGR and VEGF in patients with advanced NSCLC. A comprehensive literature search in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ASCO Abstracts and ESMO Abstracts was conducted. Eligible studies were randomized clinical trials (RCTs) that compared safety profile of combined therapy inhibiting EFGR and VEGF pathways with control groups (placebo, single EGFR or VEGF inhibition therapy, chemotherapy or a combination of them) in patients with advanced NSCLC. The endpoints included treatment discontinuation, treatment-related deaths and AEs. The search identified 15 RCTs involving 6,919 patients. The outcomes showed that three of four pairwise comparisons detected more discontinuation due to AEs in combined targeted therapy, with odds ratio (OR) compared with the control groups ranged from 1.97 to 2.29. Treatment with combined inhibition therapy was associated with several all-grade and grade 3 or 4 AEs (e.g. rash, diarrhea and hypertension). Also, there was a significantly higher incidence of treatment-related deaths in combined inhibition using vandetanib versus single EGFR inhibition therapy (OR = 1.97, 95% CI 1.19-3.28). In conclusion, combined inhibition therapy against EGFR and VEGF in patients with advanced NSCLC was associated with increased toxicity. Increased AEs hinder patient compliance and reduce their quality of life, leading to dose reduction or discontinuation.

Despite the widespread use of silica nanoparticles (SiO2 NPs) in biological and medical fields, their adverse effects have not been clearly elucidated. In this study, spherical SiO2 NPs with a 50 nm diameter were used to study their interaction with HaCaT cells. SiO2 NPs were found to be readily internalized into HaCaT cells and localized in the cytoplasm, lysosomes and autophagosomes. Decreased cell viability and damaged cell membrane integrity showed the cytotoxicity of SiO2 NPs. Significant glutathione depletion and reactive oxygen species generation, which reduced the cellular antioxidant level, could be the major factor of cytotoxicity induced by SiO2 NPs. Copyright (c) 2013 John Wiley & Sons, Ltd.

The absorption spectra and refractive index of 2,4-dinitrotoluene (2,4-DNT) and 2,6-dinitrotoluene (2,6-DNT) were measured in the region of 0.3-2.0 THz by terahertz time-domain spectroscopy (THz-TDS) at room temperature. Gaussian 03 program was applied to predict geometric structure and vibrational frequencies of 2,6-DNT. Three absorption peaks at 1.09, 1.36 and 1.55 THz of 2,6-DNT were obtained and assigned to intermolecular interactions. Quantitative analysis with THz-TDS was undertaken for the mixture of 2,4-DNT and 2,6-DNT. The analytic weight ratio of 2,4-DNT to 2,6-DNT is consistent with the actual one with an analytic error of about 8%.

Acid-mediated intramolecular Friedel—Crafts reaction of MBH adducts (III) and (VI) is studied.

A multiphase model for the flow of dense, noncolloidal, settling slurries through horizontal pipelines, and an associated Galerkin-finite element numerical scheme to carry out computer simulations based on the model, were developed. The principal elements of the model are: equations for estimation of the velocity distributions for each component; and those for the concentration distributions. In the former, which are derived from the local volume-averaged, time-smoothed conservation of mass and momentum equations, the total stress is comprised of components to account for interparticle and particle-boundary as well as viscous and turbulent interactions. The governing equations for the concentration distributions are derived similarly from the convective diffusion equation, with the eddy diffusivity modified to account for the presence of the solid particles. Numerical simulations and detailed comparisons with experiment for the flow of gypsum, coal, crushed glass, sand and gravel, covering particle sizes from 38.3 μm to 13,000 μm, and pipe diameters from 4 cm to 49.5 cm, were carried out. The agreement between model prediction and experiment is excellent.