Nonalcoholic steatohepatitis (NASH) is a progressive disease that is often accompanied by metabolic syndrome and poses a high risk of severe liver damage. However, no effective pharmacological ...treatment is currently available for NASH. Here we report that CASP8 and FADD-like apoptosis regulator (CFLAR) is a key suppressor of steatohepatitis and its metabolic disorders. We provide mechanistic evidence that CFLAR directly targets the kinase MAP3K5 (also known as ASK1) and interrupts its N-terminus-mediated dimerization, thereby blocking signaling involving ASK1 and the kinase MAPK8 (also known as JNK1). Furthermore, we identified a small peptide segment in CFLAR that effectively attenuates the progression of steatohepatitis and metabolic disorders in both mice and monkeys by disrupting the N-terminus-mediated dimerization of ASK1 when the peptide is expressed from an injected adenovirus-associated virus 8-based vector. Taken together, these findings establish CFLAR as a key suppressor of steatohepatitis and indicate that the development of CFLAR-peptide-mimicking drugs and the screening of small-molecular inhibitors that specifically block ASK1 dimerization are new and feasible approaches for NASH treatment.
In early January 2012, the Longjiang River was subjected to a serious cadmium (Cd) pollution accident, which led to negatively environmental and social impacts. A series of measures of emergency ...treatment were subsequently taken to reduce water Cd level. However, little information was available about the change of Cd level in environmental matrices and long-term effect of this pollution accident to aquatic ecosystem. Thus, this study investigated the distribution of Cd in water and sediment of this river for two years since pollution accident, as well as assessed its ecological risk to aquatic ecosystem of Longjiang River. The results showed that it was efficient for taking emergency treatment measures to decrease water Cd concentration to below the threshold value of national drinking water quality standard of China. There was high risk (HQ > 1) to aquatic ecosystem in some of reaches between February and July 2012, but low or no risk (HQ < 1) between December 2012 to December 2013. Cd concentration in sediment in polluted reaches increased after pollution accident and emergency treatments in 2012, but decreased in 2013. During flood period, the sediment containing high concentration of Cd in Longjiang River was migrated to downstream Liujiang River. Cd content in sediment was reduced to background level after two years of the pollution accident occurrence. The study provides basic information about Cd levels in different media after pollution accident, which is helpful in evaluating the effectiveness of emergency treatments and the variation of ecological risk, as well as in conducting water management and conservation.
•Ecological risks (ERs) of cadmium-contaminated water and sediment were assessed.•ER decreased in water, but increased in sediment after emergent treatments.•Recovery for water occurred approximately one month later, but two years for sediment.•ER in sediment after accident decreased during flood period.
A universal strategy for efficient, mild, and purification‐free synthesis and in situ screening of functional polymer‐peptide nanomaterials is described. More than 1000 polymer–peptide conjugates ...(PPCs) with various chemical structures, compositions, and therapeutic efficacy are created. According to this strategy, the structure–function relationship of the PPCs is revealed, and the antitumor efficacies of the top performing PPCs are evaluated in vivo.
This study examines the role of farmers' risk attitudes toward fertilizer use in cotton production in China. Contradicting previous studies, this paper theoretically shows that the relationship ...between farmers' risk aversion and fertilizer use is not always monotonic. Field survey data were collected to test this relationship using the Cobb–Douglas production function. Results suggest that when the elasticity of fertilizer use and the probability of achieving the desired effects from fertilizer use are high, risk-averse farmers apply more fertilizer than risk-taking farmers. Conversely, when the elasticity of fertilizer use and the probability of achieving the desired effects are low, risk-taking farmers apply more fertilizer than risk-neutral or risk-averse farmers.
Systematic interrogation of single-nucleotide variants (SNVs) is one of the most promising approaches to delineate the cellular heterogeneity and phylogenetic relationships at the single-cell level. ...While SNV detection from abundant single-cell RNA sequencing (scRNA-seq) data is applicable and cost-effective in identifying expressed variants, inferring sub-clones, and deciphering genotype-phenotype linkages, there is a lack of computational methods specifically developed for SNV calling in scRNA-seq. Although variant callers for bulk RNA-seq have been sporadically used in scRNA-seq, the performances of different tools have not been assessed.
Here, we perform a systematic comparison of seven tools including SAMtools, the GATK pipeline, CTAT, FreeBayes, MuTect2, Strelka2, and VarScan2, using both simulation and scRNA-seq datasets, and identify multiple elements influencing their performance. While the specificities are generally high, with sensitivities exceeding 90% for most tools when calling homozygous SNVs in high-confident coding regions with sufficient read depths, such sensitivities dramatically decrease when calling SNVs with low read depths, low variant allele frequencies, or in specific genomic contexts. SAMtools shows the highest sensitivity in most cases especially with low supporting reads, despite the relatively low specificity in introns or high-identity regions. Strelka2 shows consistently good performance when sufficient supporting reads are provided, while FreeBayes shows good performance in the cases of high variant allele frequencies.
We recommend SAMtools, Strelka2, FreeBayes, or CTAT, depending on the specific conditions of usage. Our study provides the first benchmarking to evaluate the performances of different SNV detection tools for scRNA-seq data.
Global tea consumption has risen significantly alongside rapid expansion of international trade in recent years. However, few studies have systematically examined the relationship among the major tea ...markets worldwide. Using weekly data from 2012–2019, this study empirically analyzed the price series of the world's major black tea auction markets. The estimation results showed that these markets are connected, even though heterogeneities vary. This finding holds not only for regional markets but also for international markets. The findings offer important implications for tea-producing countries with millions of smallholder farmers.
Microbes are an important part of the vineyard ecosystem, which significantly influence the quality of grapes. Previously, we identified a bud mutant variety (named 'Fengzao') from 'Kyoho' grapes. ...The variation of microbial communities in grape and its bud mutant variety has not been studied yet. So, in this study, with the samples of both 'Fengzao' and 'Kyoho', we conducted high-throughput microbiome sequencing and investigated their microbial communities in different tissues. Obvious differences were observed in the microbial communities between 'Fengzao' and 'Kyoho'. The fruit and the stem are the tissues with relatively higher abundance of microbes, while the leaves contained less microbes. The fruit and the stem of 'Kyoho' and the stem of 'Fengzao' had relatively higher species diversity based on the alpha diversity analysis. Proteobacteria, Enterobacteriaceae and Rhodobacteraceae had significantly high abundance in 'Fengzao'. Firmicutes and Pseudomonas were highly abundant in the stems of 'Kyoho', and family of Spirochaetaceae, Anaplasmataceae, Chlorobiaceae, and Sphingomonadaceae, and genera of Spirochaeta, Sphingomonas, Chlorobaculum and Wolbachia were abundant in the fruits of 'Kyoho'. These identified microbes are main components of the microbial communities, and could be important regulators of grapevine growth and development. This study revealed the differences in the microbial compositions between 'Kyoho' and its bud mutant, and these identified microbes will be significant resources for the future researches on the quality regulation and disease control of grapevines.
Thousands of tons of neonicotinoids are widely used around the world as broad-spectrum systemic insecticides and veterinary drugs. Researchers originally thought that neonicotinoids exhibited low ...mammalian toxicity. However, following their widespread use, it became increasingly evident that neonicotinoids could have various toxic effects on vertebrates and invertebrates. The primary focus of this review is to summarize the research progress associated with oxidative stress as a plausible mechanism for neonicotinoid-induced toxicity as well as neonicotinoid metabolism. This review summarizes the research conducted over the past decade into the production of reactive oxygen species, reactive nitrogen species, and oxidative stress as aresult of neonicotinoid treatments, along with their correlation with the toxicity and metabolism of neonicotinoids. The metabolism of neonicotinoids and protection of various compounds against neonicotinoid-induced toxicity based on their antioxidative effects is also discussed. This review sheds new light on the critical roles of oxidative stress in neonicotinoid-induced toxicity to nontarget species.
Chronic pain easily leads to concomitant mood disorders, and the excitability of anterior cingulate cortex (ACC) pyramidal neurons (PNs) is involved in chronic pain-related anxiety. However, the ...mechanism by which PNs regulate pain-related anxiety is still unknown. The GABAergic system plays an important role in modulating neuronal activity. In this paper, we aimed to study how the GABAergic system participates in regulating the excitability of ACC PNs, consequently affecting chronic inflammatory pain-related anxiety. A rat model of CFA-induced chronic inflammatory pain displayed anxiety-like behaviors, increased the excitability of ACC PNs, and reduced inhibitory presynaptic transmission; however, the number of GAD65/67 was not altered. Interestingly, intra-ACC injection of the GABA
R agonist muscimol relieved anxiety-like behaviors but had no effect on chronic inflammatory pain. Intra-ACC injection of the GABA
R antagonist picrotoxin induced anxiety-like behaviors but had no effect on pain in normal rats. Notably, chemogenetic activation of GABAergic neurons in the ACC alleviated chronic inflammatory pain and pain-induced anxiety-like behaviors, enhanced inhibitory presynaptic transmission, and reduced the excitability of ACC PNs. Chemogenetic inhibition of GABAergic neurons in the ACC led to pain-induced anxiety-like behaviors, reduced inhibitory presynaptic transmission, and enhanced the excitability of ACC PNs but had no effect on pain in normal rats. We demonstrate that the GABAergic system mediates a reduction in inhibitory presynaptic transmission in the ACC, which leads to enhanced excitability of pyramidal neurons in the ACC and is associated with chronic inflammatory pain-related anxiety.
Plant roots significantly affect soil erosion, while few works have pursued why root-penetrated soil obtained higher soil erosion resistance as compared with plain soil. For the purpose to ...investigate the relative contribution of root physical enlacing (root net-link and root-soil bond functions) and root biochemistrical exudates to soil erosion resistance. This study selected Purple alfalfa root- and designed root-penetrated Loess soil as study object, and subjected to flow scouring. The results showed that roots could significantly ameliorate soil properties, especially for soil enzymes. Root physical enlacing is the main reason, accounting for 77.7–82.0% of the root total effect in strengthening soil erosion resistance. And of this total, the relative contribution ratio of net-link and soil-root bond functions to soil erosion resistance was 0.71:0.29, averagely. Root surface area density could effectively reflect root physical enlacing effect. This kind of study may provide theoretical explanations for
the root reinforcement in the flow-induced erosion regions.
•Root physical enlacing contributes 77.7–82.0% of root effect to erosion resistance.•Contributing ratio of net-link:soil-root bond to erosion resistance is 0.71:0.29.•Root surface area density could effectively reflect root physical enlacing effect.
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