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N6-methyladenosine (m(6)A) mRNA modification plays critical roles in various biological events and is involved in multiple complex diseases. However, the role of m(6)A modification in autophagy in nonalcoholic fatty liver disease (NAFLD) remains largely unknown. Here, we report that m(6)A modification was increased in livers of NAFLD mouse models and in free fatty acid (FFA)-treated hepatocytes, and the abnormal m(6)A modification was attributed to the upregulation of methyltransferase like 3 (METTL3) induced by lipotoxicity. Knockdown of METTL3 promoted hepatic autophagic flux and clearance of lipid droplets (LDs), while overexpression of METTL3 inhibited these processes. Mechanistically, METTL3 directly bound to Rubicon mRNA and mediated the m(6)A modification, while YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), as a partner of METTL3, interacted with the m(6)A-marked Rubicon mRNA and promoted its stability. Subsequently, RUBICON inhibited autophagosome-lysosome fusion and further blocked clearance of LDs. Taken together, our results showed a critical role of METTL3 and YTHDF1 in regulating lipid metabolism via the autophagy pathway and provided a novel insight into m(6)A mRNA methylation in NAFLD.

Pumpkin starch (PS) was extracted from Cucurbita maxima and utilized to prepare films in combination with cellulose nanocrystal (CNC) and cellulose nanofiber (CNF), using a solvent casting strategy. The PS was characterized to contain 26.6% of amylose, exhibiting a “B”-type crystalline structure and high stability against thermal degradation. PS/CNF films showed better thermal stability than PS/CNC films, whereas the CNC was more effective than CNF for enhancing the tensile strength (TS) of the films. The nanocomposite films containing 1% CNC showed the highest TS of 30.32 MPa. Fourier transform infrared spectra revealed stronger hydrogen bonding in the PS/CNC films, likely contributing to the observed high mechanical strength. CNC and CNF both decreased the transparency of PS films, by 5.2% and 13.1%, respectively. Overall, the properties of PS composite films can be effectively modified by incorporating CNC and CNF, as PS/CNC films with high mechanical strength and PS/CNF films with good thermal stability. Our results indicate that PS is a suitable material for CNC/CNF composite film fabrication. These films are expected to be especially useful in food packaging applications.

Maternal aging can impair the quality and decrease the developmental competence of ovulated oocytes. In this study, compromised germinal vesicle breakdown (GVBD) was found in aged mice oocytes. Furthermore, we observed increased reactive oxygen species (ROS) and mitochondrial Ca2+ levels, along with reduced mitochondrial temperature in aged oocytes. Maternal aging also changed the crotonylation level in oocytes. Forkhead box O3 (FoxO3a), a member of the forkhead protein family involved in the regulation of cell survival and life span reached a peak level in the metaphase II stage. Compared with a younger group, FoxO3a expression increased in aged oocytes. Intracellular localization of FoxO3a changed from the cytoplasm to chromatin in response to aging. The expression of the upstream regulator nicotinamide-phosphoribosyltransferase (Nampt) peaked in the GVBD stage. Moreover, Nampt expression was increased in aged oocytes, and more intense staining of Nampt was found in aged mice ovary. To further study the role of Nampt in mitochondrial function, specific agonist P7C3 and inhibitor FK866 were applied to aged oocytes, and FK866 significantly decreased adenosine triphosphate and mitochondrial membrane potential. In conclusion, mitochondrial dysfunction in aged oocytes was associated with elevated FoxO3a, and suppression of Nampt could further impair mitochondrial function.

Under physiological conditions, Bacillus fastidious uricase (BFU) activity shows negligible lagging phase before the exponential decrease; mutants are thus designed for long lagging phases before exponential activity decreases. On homodimer surface of BFU (4R8X.pdb), the last fragment ANSEYVAL at the C-terminus forms a loop whose Y319 is H-bonded by the buried D257 in the same monomer. Within 1.5 nm from the α-carboxyl group of the last leucine (L322), E30, K26, D257, R258, E311, K312 and E318 from the same monomer plus D126 and K127 from a monomer of the other homodimer generate an electrostatic interaction network. Within 1.5 nm from Y319, D307 and R310 in the same monomer interact with ionized residues around the inter-chain β-sheet in the same homodimer. Mutagenesis of Y319R is designed to strengthen the original interactions and concomitantly generate new electrostatic attractions between homodimers. Under physiological conditions, the mutant V144A/Y319R showed an approximately 4 week lagging phase before the exponential activity decrease, an apparent half-life of activity nearly three folds of mutant V144A, but comparable activity. The introduction of ionizable residues into the C-terminus contacting the other homodimer for additional and/or stronger electrostatic attractions between homodimers may be a universal approach to thermostable mutants of uricases.

Stable isotopic analysis is an important branch of analytical chemistry. Accurate determination of the stable isotopic compositions of substances is critical for tracing their sources and investigating their transformation processes. The new generation of mass spectrometry technology has greatly facilitated the development of high-precision stable isotopic analysis methods. In particular, multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) has emerged as a powerful tool for isotopic composition determination. However, isotopic analysis by MC-ICP-MS is highly sensitive to the sample matrix, which may compromise the precision and accuracy of the analysis. Therefore, it is particularly important to reduce the sample matrix effect using efficient sample purification techniques. This article summarizes the recent progress in sample purification and instrument hyphenation methods for MC-ICP-MS, and provides perspectives on the future application of MC-ICP-MS in different fields.

Fragrances are widely used in many aspects of our lives. They cannot only make people happy, but also treat many diseases. However, excessively fast evaporation rate is one of the main obstacles to the use of spices. In this study, mesoporous silica nanorods (MSNRs) and hollow mesoporous silica nanorods (HMSNRs) were prepared to encapsulate eugenol. These two nano-fragrances were named eugenol@MSNRs and eugenol@HMSNRs, respectively. The morphologies, size, interior structures and pore performances of MSNRs and HMSNRs. Besides, the performances of encapsulation and fragrance release of eugenol@MSNRs and eugenol@HMSNRs were compared and analyzed. The results showed that eugenol@HMSNRs encapsulated more fragrance and were faster to encapsulate compared with eugenol@MSNRs. Both the release rates of eugenol from eugenol@MSNRs and eugenol@HMSNRs were slow. But the eugenol was released from eugenol@MSNRs more slowly.

Silk has been widely used in the clothing industry due to their soft and smooth features, good biocompatibility, good heat dissipation, warmth and ultraviolet resistance. The application of fragrance to silk can significantly improve the performance of silk. However, there are two key scientific problems that need to be solved: slowing down the release rate of fragrances and increasing the scent lasting time of silk. In this study, cationic and temperature-sensitive liposomes were designed and prepared to encapsulate eugenol. These fragrance-loaded liposomes significantly slowed down the release rate of the fragrance and controlled the release rate of the fragrance in a thermo-sensitive manner. The liposomes adhered to the silk through electrostatic adsorption interaction. The positive charge on the fragrance-loaded liposomes neutralized much negative charge on silk and thereby increasing the adhesion efficiency.

The problem whether 1-hydroxylmethyl-3,5,7-trinitro-1,3,5,7-tetraazacyclooctane is the key active intermediate for the synthesis of 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX) from urotropine or 3,7-dinitro-1,3,5,7-tetraazabicyclo[3.3.1]nonane (DPT) remains to be illuminated for decades. In this paper, the hydrolysis and nitrolysis of the esterified intermediate 1-acetoxymethyl-3,5,7-trinitro-1,3,5,7-tetraazacyclooctane (PHX) were studied to solve the long-standing puzzle. The 1H NMR spectrum and 13C NMR spectrum of the 1-hydroxymethyl-3,5,7-trinitro-1,3,5,7-tetraazacyclooctane were detected by tracking the hydrolysis of PHX, which provide direct experimental evidences for its existence. Meanwhile, it was found that 1-nitroso-3,5,7-trinitro-1,3,5,7-tetraazacyclooctane (MNX) is a stable intermediate in the nitrolysis of PHX to generate HMX, and the presence of small amounts of water in the nitrolysis of PHX not only stimulate the redox reaction between nitric acid and formaldehyde but also promote the reaction by hydrolyzing PHX to corresponding N-hydroxymethyl derivative, which verify that 1-hydroxymethyl-3,5,7-trinitro-1,3,5,7-tetraazacyclooctane is the key active intermediate in the synthesis of HMX.

Herein, nickel-aluminum-layered double hydroxide (NiAl-LDH) films were prepared by the hydrothermal method. Based on the photoinduced reduction ability and degradation of LDHs on heavy metal ions and organic compounds, NiAl-LDH films displayed favorable simultaneous removal performance. Benefiting from the electron traps of heavy metals reduced from solution, the coexisting metal ions improved the photocatalytic activity of NiAl-LDH films on methyl orange. The higher the Fermi level of coexisting metal ion was, the higher the photocatalytic degradation rate of methyl orange obtained. Meanwhile, the removal rates of heavy metal ions (Ag+, Pb2+, and Cu2+) from wastewater were both enhanced and could reach 95%. NiAl-LDH films showed affinity toward Ag+. Furthermore, NiAl-LDH films are tightly coupled with the substrate, providing active sites and a simple method for the catalyst recovery. This study provides new insights into the simultaneous removal of heavy metal ions and organic pollutants using LDH films.

Cleavage of ether bonds is a crucial but challenging step for lignin valorization. To efficiently realize this transformation, the development of robust catalysts or catalytic systems is required. In this study, montmorillonite (MMT)-supported Ru (denoted as Ru/MMT) is fabricated as a dual-functional heterogeneous catalyst to cleave various types of ether bonds through transfer hydrogenolysis without using any additional acids or bases. The prepared Ru/MMT material is found to efficiently catalyze the cleavage of various lignin models and lignin-derived phenols; cyclohexanes (fuels) and cyclohexanols (key intermediates) are the main products. The synergistic effect between electron-enriched Ru and the acidic sites on MMT contributes to the excellent performance of Ru/MMT. Systematic studies reveal that the reaction proceeds through two possible reaction pathways, including the direct cleavage of ether bonds and the formation of intermediates with one hydrogenated benzene ring, for all examined types of ether bonds, namely, 4-O-5, α-O-4, and β-O-4.

Fermented porridge is usually made though the process of natural fermentation of grains with higher starch. Organic acids are the main flavor compounds in fermented porridge. However, the understanding of the correlation between the microbial communities and organic acids is limited in the fermentation process of traditional Chinese sour porridge (CSP). In this study, the dynamic of bacterial community and organic acids was investigated and the correlation between bacterial communities and organic acids was revealed during the fermentation process of CSP. The results showed that the richness and diversity of the bacterial communities at initial state (0h) were significantly higher than other period and the concentration of 9 organic acids (oxalic acid, tartaric acid, malic acid, lactic acid, acetic acid, citric acid, and succinic acid) increased with the fermentation process. Pediococcus and Lactobacillus were the dominative genus in the fermentation process of CSP and the fermentation process of CSP can be divided into three stages, with 0 h as the initial stage, 6–18 h as the second group and 24–36 h as the third based on PCA and cluster analysis. Moreover, 20 bacteria genus had significant correlation with (|ρ|>0.7) organic acids based on O2PLS analysis and The Lactobacillus and Acinetobacter were positively correlated with seven (succinic acid, tartaric acid, lactic acid, oxalic acid, acetic acid, malic acid and succinic acid) and four (tartaric acid, acetic acid, lactic acid, and α-ketoglutarate) organic acids respectively. Clostridium, Paenibacillus, Cupriavidus, Shinella, Streptococcus, Flavobacterium, Enterobacteriaceae, Cyanobacteria, Pseudomonas, Ralstonia, Microbacterium, Bradyrhizobiaceae, Escherichia-Shigella, Acidovorax, Leuconostoc, Alphaproteobacteria, Pediococcus, and Mitochondria were negatively correlated with organic acids in the fermentation process of CSP.

[Ca2+]i is essential for mammalian oocyte maturation and early embryonic development, as those processes are Ca2+ dependent. In the present study, we investigated the effect of [Ca2+]i on in vitro maturation and reprogramming of oocytes in a lower calcium model of oocyte at metaphase II (MII) stage, which was established by adding cell-permeant Ca2+ chelator BAPTA-AM to the maturation medium. Results showed that the extrusion of the first polar body (PB1) was delayed, and oocyte cytoplasmic maturation, including mitochondrial and endoplasmic reticulum distribution, was impaired in lower calcium model. The low-calcium-model oocytes presented a poor developmental phenotype of somatic cell nuclear transfer (SCNT) embryos at the beginning of activation of zygotic genome. At the same time, oxidative stress and apoptosis were observed in the low-calcium-model oocytes; subsequently, an RNA-seq analysis of the lower-calcium-model oocytes screened 24 genes responsible for the poor oocyte reprogramming, and six genes (ID1, SOX2, DPPA3, ASF1A, MSL3, and KDM6B) were identified by quantitative PCR. Analyzing the expression of these genes is helpful to elucidate the mechanisms of [Ca2+]i regulating oocyte reprogramming. The most significant difference gene in this enriched item was ID1. Our results showed that the low calcium might give rise to oxidative stress and apoptosis, resulting in impaired maturation of bovine oocytes and possibly affecting subsequent reprogramming ability through the reduction of ID1.

Protectin D1 (PD1), a DHA-derived lipid mediator, has recently been shown to possess anti-inflammatory and pro-resolving properties. To date, little is known about the effect of PD1 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The aim of the present study was to investigate the therapeutic effects of PD1 on LPS-induced ALI and its potential mechanisms of action. ALI was induced via an intraperitoneal injection of LPS, where PD1 (2 ng/mouse) was administered intravenously 30 min after LPS challenge. Mice were sacrificed 24 h after modeling. Lung histopathological changes were assessed using hematoxylin and eosin staining and myeloperoxidase (MPO) activity was tested using immunohistochemistry. Tumor necrosis-α and interleukin-6 levels in the bronchoalveolar lavage fluid (BALF) and serum were measured using ELISA. To detect neutrophil extracellular traps produced by infiltrated neutrophils in the lung tissue, immunofluorescence staining was performed using anti-MPO and anti-histone H3 antibodies. The results indicated that PD1 significantly attenuated histological damage and neutrophil infiltration in lung tissue, reduced the lung wet/dry weight ratio, protein concentration and proinflammatory cytokine levels in BALF and decreased proinflammatory cytokine levels in serum. Moreover, neutrophil citrullinated histone H3 (CitH3) expression was also reduced after PD1 administration. In conclusion, PD1 attenuated LPS-induced ALI in mice via inhibition of neutrophil extracellular trap formation in lung tissue. Therefore, PD1 administration may serve to be a new strategy for treating ALI.

Semiconducting single-walled carbon nanotubes (s-SWCNTs) with a diameter of around 1.0-1.5 nm, which present bandgaps comparable to silicon, are highly desired for electronic applications. Therefore, the preparation of s-SWCNTs of such diameters has been attracting great attention. The inner surface of SWCNTs has a suitable curvature and large contacting area, which is attractive in host-guest chemistry triggered by electron transfer. Here we reported a strategy of host-guest molecular interaction between SWCNTs and inner clusters with designed size, thus selectively separating s-SWCNTs of expected diameters. When polyoxometalate clusters of ∼1 nm in size were filled in the inner cavities of SWCNTs, s-SWCNTs with diameters concentrated at ∼1.3-1.4 nm were selectively extracted with the purity of ∼98% by a commercially available polyfluorene derivative. The field-effect transistors built from the sorted s-SWCNTs showed a typical behavior of semiconductors. The sorting mechanisms associated with size-dependent electron transfer from nanotubes to inner polyoxometalate were revealed by the spectroscopic and in situ electron microscopic evidence as well as the theoretical calculation. The polyoxometalates with designable size and redox property enable the flexible regulation of interaction between the nanotubes and the clusters, thus tuning the diameter of sorted s-SWCNTs. The present sorting strategy is simple and should be generally feasible in other SWCNT sorting techniques, bringing both great easiness in dispersant design and improved selectivity.

In order to understand better thermal safety of the nitrolysis solution from the nitration of hexamethylenetetramine, its decomposition behavior was studied. The nitrolysis solution prepared was analyzed using isoperibolic experiments, differential scanning calorimetry (DSC), differential thermal analysis-thermogravimetry, and fourier transform infrared spectroscopy. An accurate kinetic model was proposed to describe the decomposition in the nitrolysis solution by applying an ordinary differential equation fitting method to isothermal DSC data and non-isothermal DTA data. We found that the thermal decomposition in the mixed solution is attributed to pyrolysis of organic nitrates in acid solution. The process is coupled with rapid reaction rate, great heat release, and huge amounts of reddish-brown gas produced. The decomposition in the nitrolysis solution follows a 1.162th Prout-Tompkins equation with autocatalysis, with a differential kinetic mechanism function of f(α) = (1 − α)1.162·α0.4189. The thermal safety evaluation and safety parameters were finally studied based on four criteria and isoperibolic experiment data. The thermal safety margin is less than 164.57 K and the bursting point of pyrolysis is 338.43 K at 5 min of delay time. These results show that the nitrolysis solution is hazardous and the thermal sensitivity is higher than that of 2-ethylhexyl nitrate and hexogen.

Bisphenol S (BPS), a substitute of bisphenol A (BPA), is widely used for manufacturing different polymers. Due to its wide range of applications, BPS has been frequently detected in the foodstuffs, environment and human blood and excreta. In this study, we examined the effects of the perinatal exposure to BPS on obesity development using 1H NMR based on metabolomics strategy combined with gene expression analysis in male mouse offspring at a dosage of 100 ng/g bw/day. We found that perinatal exposure to BPS significantly increased the body weight, the weights of liver and epididymal white adipose tissue (epiWAT), serum alanine aminotransferase (ALT) activity, and the contents of triglyceride (TG) and cholesterol (T-Cho) in the liver. Histopathological analysis showed that lipids were accumulated significantly in liver tissues and epiWAT with BPS exposure. Furthermore, expressions of genes involved in the inflammatory pathways were significantly increased in liver tissues and epiWAT. Meanwhile, serum metabolomics study showed significant changes in the contents of metabolites associated with lipid and glucose metabolism. Correspondingly, the relative expression levels of genes involved in lipid and glucose metabolism were significantly changed in the liver tissue and epiWAT of male mouse offspring. In conclusion, these results showed that perinatal exposure to BPS may increase the risk of obesity by interfering with lipid and glucose metabolism in male mouse offspring. The potential health risks of BPS in the human required further detailed studies evaluating.

Pesticides are proposed as one of the many causes for the global decline in reptile population. To understand the potential impact of alpha-cypermethrin (ACP) in reptiles, in the current study, we used a tri-trophic food web (plants - herbivores - natural enemies of predators) to examine the reproductive toxicity and biomarker changes. Based on the Maximum Residue Limit (MRL) of ACP in several agricultural products, we designed three concentrations 0, 2 (MRL), and 20 mg/kg wet weight as three treatment groups for this research. Male and female lizards were fed ACP contaminated or uncontaminated diets for eight weeks during the breeding phase. The number of deaths was different among the three groups, and a dose-dependent trend was found. Decreases in food consumption of 26.6% and 28.1% were observed in the low- and high-dose group, respectively. Dietary exposure significantly induced a dose-dependent decrease in body mass index in lizards. Significant variations in glutathione-S-transferaseb activities, catalase activities, and malondialdehyde levels in gonads, suggest that lizards were under oxidative stress. In addition, ACP exposure altered sexual hormone levels in males, reduced reproductive output of females, and induced histopathological changes in testes. These negative effects highlight that ACP dietary exposure is a potential threat to lizards’ reproduction.

Numerous studies suggested that reptiles are sensitive to environmental pollution and the abundance of many species are in decline. Our research is aim to assess the toxic effects of pesticide in reptiles. And we also want to supply some data about nondestructive samples for environmental risk assessment in reptiles. Lizards were orally administered a single-dose of beta-cypermethrin (BCP) or myclobutanil (MC) at the concentration of 20 mg/kg body weight (bw). The results showed that pesticides could induce changes in enzymatic activities (SOD, CAT, LDH, AChE) and MDA levels in organs or tissues of lizards. BCP could cause more severe oxidative damage than that of MC. Salivary enzymes activities showed sensitivity changes to the toxicity of pesticides. We could use saliva to reflect whether the reptiles are toxic by pesticides. We also agree that buccal swabs could be used as a tool for saliva sampling.

The nitrolysis of 3,7-dinitro-1,3,5,7-tetraazabicyclo[3.3.1]nonane (DPT) to prepare 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX) in fuming HNO3 between −8 °C to −36 °C was tracked by 1H-NMR. It is found that DPT converted to 1-nitroso-3,5,7-trinitro-1,3,5,7-tetraazacyclooctane (MNX) immediately at the end of the feeding course; MNX was then gradually nitrolyzed to HMX. The latter reaction followed a pseudo-first order kinetics, and the selectivity of HMX was almost unaffected with the change in reaction temperature based on the kinetics study. The effects of water and N2O4 on this reaction were investigated and the results indicated that a small amount of water and N2O4 was beneficial to the generation of the intermediate product MNX. On the contrary, the presence of water and N2O4 hindered the conversion of MNX to HMX. Nitrosonium in the reaction system has two sources: one is from the nitrogen oxides such as N2O4 in fuming nitric acid; the other is from the redox reaction between nitric acid and formaldehyde, which was promoted by the H2O in fuming nitric acid. Based on the these results, the overall yield of the stepwise method for preparing HMX was up to 82.7% under the optimized reaction conditions.

The environmental contaminant, especially pesticides, threatened the amphibian population. In this assay, the enantioselective behavior of cyproconazole on Rana nigromaculata was studied. We found LC50 (lethal concentration causing 50% mortality) of 4-enantiomers was nearly twice as 3-enantiomers in 96 h acute toxicity test. Besides, the significant considerable variation of oxidative stress and LDH (lactic dehydrogenase) induced by the four enantiomers indicated that cyproconazole could enantioselectively affect enzymes in tadpoles. Bioaccumulation experiments showed the order of cyproconazole in the tadpoles was 4-enantiomers>3- enantiomers>2- enantiomers>1- enantiomers during the exposure for 28d. In tissue distribution test, cyproconazole was formed and accumulated in order of 4-enantiomers>2-enantiomers>3- enantiomers>1- enantiomers, except that in the gut. During the elimination experiment, cyproconazole was rapidly eliminated by 95% within the only 24 h. These results suggested that the influence of enantioselective behavior should consider when assessing ecological risk of chiral pesticides to amphibians.

We have reported that tumor-derived autophagosomes (DRibbles) were efficient carriers of tumor antigens and DRibbles antigens could be present by DRibbles-activated B cells to stimulate effect and naïve T cells in mice. However, the effect of DRibbles on human B cells remains unclear. Herein, we found that DRibbles can also efficiently induce proliferation and activation of human B cells and lead to the production of chemokines, cytokines and hematopoietic growth factors. We further demonstrated human B cells can effectively phagocytose DRibbles directly and cross-present DRibbles antigens to stimulate antigen-specific memory T cells. Furthermore, we found that membrane-bound high-mobility group B1 (HMGB1) on DRibbles was crucial for inducing human B cells activation. Therefore, these findings provide further evidence to promote the clinical application of B-DRibbles vaccines.

Simple Summary We sequenced the first third-generation transcriptome of chrysanthemum and analyzed the factors involved in the outgrowth of the second buds after decapitation. In addition to classic hormones (auxin, cytokinins, and strigolactone), jasmonates and sugars were also found to be involved in this process, which might be related to the initiation of dormant buds. Abstract Decapitation is common in horticulture for altering plant architecture. The decapitation of chrysanthemum plants breaks apical dominance and leads to more flowers on lateral branches, resulting in landscape flowers with good coverage. We performed both third- and second-generation transcriptome sequencing of the second buds of chrysanthemum. This third-generation transcriptome is the first sequenced third-generation transcriptome of chrysanthemum, revealing alternative splicing events, lncRNAs, and transcription factors. Aside from the classic hormones, the expression of jasmonate-related genes changed because of this process. Sugars also played an important role in this process, with upregulated expression of sucrose transport-related and TPS genes. We constructed a model of the initial growth of the second buds after decapitation. Auxin export and sugar influx activated the growth of these buds, while the JA-Ile caused by wounding inhibited the expression of CycD genes from 0 h to 6 h. After wound recovery, cytokinins accumulated in the second buds and might have induced ARR12 expression to upregulate CycD gene expression from 6 h to 48 h, together with sugars. Therefore, jasmonates, cytokinins, sugars, and auxin work together to determine the fate of the buds of plants with short internodes, such as chrysanthemum.

Background: Gastric intestinal metaplasia (IM) is an important precancerous lesion. Our previous study has shown that ectopic expression of HDAC6 promotes the activation of intestinal markers in bile acids (BA) induced gastric IM cells; however, the mechanism underlying how HDAC6-mediated epigenetic modifications regulate intestinal markers is not clear.Methods: RNA-sequencing (RNA-seq) was used to detect the molecular changes in GES-1 cells after HDAC6 overexpression. The potential binding sites of FOXP3 with the promoter region of HNF4α were verified by ChIP and luciferase reporter gene assays. The ChIP assay was also used to detect the histone deacetylation. The levels of mucin in gastric or intestinal mucosa were detected by AB-PAS staining. Transgenic mice were used to explore the pro-metaplastic function of DCA and HNF4α in vivo.Results: Deoxycholic acid (DCA) upregulated HDAC6 in gastric cells, which further inhibited the transcription of FOXP3. Then, FOXP3 transcriptionally inhibited HNF4α, which further inhibits the expression of downstream intestinal markers. These molecules have been shown to be clinically relevant, as FOXP3 levels were negatively correlated with HDAC6 and HNF4α in IM tissues. Transgenic mice experiments confirmed that HNF4α overexpression combined with DCA induced gastric mucosa to secrete intestinal mucus and caused an abnormal mucosal structure. Conclusions: Our findings suggest that HDAC6 reduces FOXP3 through epigenetic modification, thus forming HDAC6/FOXP3/HNF4α axis to promote gastric IM. Inhibition of HDAC6 may be a potential approach to prevent gastric IM in patients with bile reflux.

Plant growth can be influenced by the application of triazole pesticides as these regulate physiological processes such as plant hormonal levels and enzyme activity. Homology modeling and molecular docking studies suggested that inhibition of ADP-glucose pyrophosphorylase activity in two trans-stereoisomers treatments hinders starch accumulation during the grain filling stage. A field experiment investigated the effects of metconazole racemate, cis-1R,5S-stereostereoisomer, and cis-1S,5R-stereoisomer application at the flowering stage on wheat grain ripening and yield. The concentrations of racemate and both cis-stereoisomers were detected in wheat plant and grain samples. Compared with the racemate, both cis-stereoisomers were more persistent in the matrices. Treatment with cis-1R,5S-stereoisomer decreased grain weight and yield of wheat by delaying chlorophyll degradation, increasing the ethylene content, and decreasing the level of abscisic acid. The germination of harvested seeds was adversely affected by racemate treatment as a result of gibberellin and abscisic acid metabolism regulation and the transcription of signaling-related genes. Therefore, cis-1S,5R-stereoisomer was recommended to be used as metconazole pesticide at the flowering stage.

Aberrant expression of long non-coding RNA (lncRNA) H19 is tightly linked to multiple steps of tumorigenesis via the modulation of cell proliferation and apoptosis; however, the pathological significance and regulatory mechanisms of lncRNA H19 in macrophages remain obscure. To investigate whether lncRNA H19 modulates macrophage activation in rheumatoid arthritis (RA), lncRNA H19 levels in PMA-induced PBMC from patients with RA and healthy volunteers were assessed. In addition, the distribution of macrophage subsets, macrophage phenotypic characteristics, and pro-inflammatory gene expression were examined in lncRNA H19 smart silencer- or pcDNA 3.1- H19-transfected macrophages and AAV8-mediated H19 overexpression in a Freund' s complete adjuvant-induced arthritis mouse model. The level of lncRNA H19 was higher in RA patients than in healthy volunteers. Silencing of lncRNA H19 altered lipopolysaccharide plus interferon-induced M1 macrophage polarization and decreased IL-6, CD80, CCL8, and CXCL10 expression in macrophages of RA patients. LncRNA H19 overexpression markedly induced IL-6, CD80, HLA-DR, KDM6A, STAT1, IRF5, CCL8, CXCL9, CXCL10, and CXCL11 expression in macrophages and promoted macrophage migration. AAV8-mediated H19 overexpression aggravated arthritis in mice by promoting M1 macrophage polarization along with iNOS, IL-6, CCL8, CXCL9, CXCL10, CXCL11, MMP3, MMP13 and COX-2 expression in mononuclear cells isolated from the swollen ankle. GSK-J4, an inhibitor of KDM6A, suppressed the activity of lncRNA H19 in macrophages and ameliorated lncRNA H19-aggravated arthritis. In summary, the current study demonstrated that lncRNA H19 is upregulated in RA patients and arthritic mice. LncRNA H19 promotes M1 macrophage polarization and aggravates arthritis by upregulating KDM6A expression.

The residue of simazine herbicide in the environment is known as one of pollutant stress for lizards by crippling its fitness on direct toxic effects and indirect food shortage via the food chain effects. Both stressors were considered in our experiment in the simazine exposure and food availability to lizards (Eremias argus). The results revealed that starvation significantly reduced the lizard's energy reserve and native immune function, while the accumulation of simazine in the liver was significantly increased. Simazine caused oxidative stress in the liver of lizards, but oxidative damage only occurred in the starved lizards. Simazine also changed the energy reserves, native immune function and detoxification of well-fed lizards, while the starved lizards showed different sensitivity to simazine. Simazine or starvation treatment independently activated the lizard HPA axis, but co-treatment caused the HPA axis inhibition. Besides, according to the variations on amino acid neurotransmitters, corticosterone hormone and thermoregulatory behavior, we inferred that lizards in threatens take the appropriate strategy on energy investment and allocation through neural, endocrine and behavioral pathways to maximize benefits in dilemma. Energy allocation was necessary, while suppression on any physiological process comes at a cost that is detrimental to long-term individual fitness.

One-month continuous ozone (O3) measurement at a high-elevation and highly forested site discovered elevated O3 levels in the free troposphere (FT) over central China. O3 injuries to the old-growth...

Overweight or obese women seeking pregnancy is becoming increasingly common. Human maternal obesity gives rise to detrimental effects during reproduction. Emerging evidence has shown that these abnormities are likely attributed to oocyte quality. Oxidative stress induces poor oocyte conditions, but whether mitochondrial calcium homeostasis plays a key role in oocyte status remains unresolved. Here, we established a mitochondrial Ca2+ overload model in mouse oocytes. Knockdown gatekeepers of the mitochondrial Ca2+ uniporters Micu1 and Micu2 as well as the mitochondrial sodium calcium exchanger NCLX in oocytes both increased oocytes mitochondrial Ca2+ concentration. The overload of mitochondria Ca2+ in oocytes impaired mitochondrial function, leaded to oxidative stress, and changed protein kinase A (PKA) signaling associated gene expression as well as delayed meiotic resumption. Using this model, we aimed to determine the mechanism of delayed meiosis caused by mitochondrial Ca2+ overload, and whether oocyte-specific inhibition of mitochondrial Ca2+ influx could improve the reproductive abnormalities seen within obesity. Germinal vesicle breakdown stage (GVBD) and extrusion of first polar body (PB1) are two indicators of meiosis maturation. As expected, the percentage of oocytes that successfully progress to the germinal vesicle breakdown stage and extrude the first polar body during in vitro culture was increased significantly, and the expression of PKA signaling genes and mitochondrial function recovered after appropriate mitochondrial Ca2+ regulation. Additionally, some indicators of mitochondrial performance—such as adenosine triphosphate (ATP) and reactive oxygen species (ROS) levels and mitochondrial membrane potential—recovered to normal. These results suggest that the regulation of mitochondrial Ca2+ uptake in mouse oocytes has a significant role during oocyte maturation as well as PKA signaling and that proper mitochondrial Ca2+ reductions in obese oocytes can recover mitochondrial performance and improve obesity-associated oocyte quality.

Since the implementation of the "Air Pollution Prevention and Control Action Plan" (APPCAP) in 2013, the air quality in China has been greatly improved but still much exceeded the WHO guideline limit. Here we employed a novel approach, two-dimensional Si fingerprints, including stable Si isotopic composition (δ

The present study aimed to investigate the function of long non-coding RNA HEIH in gastric carcinoma (GC). Adjacent normal tissues and GC tissues were obtained from 72 patients. Real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to measure the expression of HEIH in cancer tissues and cells. Cell Counting Kit-8 and transwell assays were employed to evaluate cell proliferation, migration and invasion. An Annexin V-fluorescein-isothiocyanate (FITC)/propidium iodide (PI) Apoptosis Detection Kit was used to evaluate the apoptosis ratio. RT-qPCR was used to detect the expression level of miR-214-3p. The expression of HEIH in GC tissues was higher than in adjacent normal tissues. The expression of HEIH was upregulated in MKN-45, NCL-N87, KATO III cell lines compared within normal gastric epithelial cells. Knockdown of lncRNA HEIH significantly decreased the number of migrated and invaded cells. Additionally, downregulation of HEIH could increase GC cell apoptosis compared with the non-specific control (NC) group. We also proved that miR-214-3p was the direct target of lncRNA HEIH, and that overexpression of miR-214-3p could reverse the effects of HEIH. Silencing of HEIH could suppress Gastric Carcinoma cell proliferation, migration and invasion by inhibiting miR-214-3p. Thus, HEIH might represent a novel biomarker and therapeutic target.

Dihydroartemisinin (DHA) is an artemisinin derivative commonly used in malaria therapy, and a growing number of studies have focused on the potent anticancer activity of DHA. However, the reproductive toxicity of anticancer drugs is a major concern for young female cancer patients. Previous studies have suggested that DHA can cause embryonic damage and affect oocyte maturation. Here, we explored the side effects of DHA exposure on ovarian somatic cells. We exposed porcine granulosa cells to 5 μM and 40 μM DHA for 24 h or 48 h in vitro. DHA inhibited granulosa cell viability in a dose-dependent manner and, in the 48 h treatment group, DHA enhanced the apoptotic rate. We observed that the levels of intracellular calcium, mitochondrial calcium, and ATP concentration were elevated with DHA treatment. In granulosa cells exposed to DHA, the mRNA levels of endoplasmic reticulum stress-related genes GRP78 and ATF4 were increased. Furthermore, analysis of the unfolded protein response signaling pathway showed that the protein levels of P-PERK, P-eIF2α, and ATF4 were upregulated by DHA exposure. These results demonstrate that in granulosa cells, DHA exposure induces endoplasmic reticulum stress that then activates the PERK/eIF2α/ATF4 signaling pathway, thus providing insight into the mechanism underlying DHA-induced reproductive toxicity, and giving reference to DHA use in females.

The novel poly(m-phenylene isophthalamide) (PMIA) ultrafiltration membrane with enhanced anti-fouling performance was successfully designed using amphiphilic block copolymer Pluronic F127 via non-solvent induced phase separation (NIPS) technique combined with induced segregation. The influences of Pluronic F127 on PMIA membrane’s microstructure and properties were systematically conducted by employing a series of characterized methods. Meanwhile, the density functional theory (DFT) calculation was employed to study the intermolecular force among the bulk PMIA, Pluronic F127 additive, solvent, and inorganic agent. Results demonstrated that Pluronic F127, functioning as both a porogen and an induced-segregation additive, could effectively affect membrane structure and property. Specifically, the resultant membrane morphologies of the sublayer gradually altered from the finger-like pore to cavity-like shape, and the pore diameter and porosity displayed a stepwise upward trend via increasing the concentration of Pluronic F127, which further induced the loss of the membrane’s mechanical strength. The filtration experiments demonstrated that the water permeation was enhanced, along with the slightly reduced rejection to bovine serum albumin (BSA) with the increasing concentration of Pluronic F127. Furthermore, the fouling resistance and stability were improved remarkably, which benefited from the enhanced hydrophilicity caused by the migration of polyethylene glycol (PEO) segment of Pluronic F127 toward membrane surface and inner-pore wall. Additionally, DFT calculation confirmed the interaction energy among the dope components, which provided theoretical support on the dope design. In summary, the Pluronic F127/PMIA ultrafiltration membrane demonstrated great potential in the field of water purification and wastewater reclamation.

Autophagy is a protein degradation process by which intracellular materials are recycled for energy homeostasis. However, the metabolic status and energy source of autophagy-defective tumor cells are poorly understood. Here, our data show that amino acid uptake from the extracellular environment is increased in autophagy-deficient cells upon glutamine deprivation. This elevated amino acid uptake results from activating transcription factor 4 (ATF4)-dependent upregulation of AAT (amino acid transporter) gene expression. Furthermore, we identify SIRT6, a NAD+-dependent histone deacetylase, as a corepressor of ATF4 transcriptional activity. In autophagy-deficient cells, activated NRF2 enhances ATF4 transcriptional activity by disrupting the interaction between SIRT6 and ATF4. In this way, autophagy-deficient cells exhibit increased AAT expression and show increased amino acid uptake. Notably, inhibition of amino acid uptake reduces the viability of glutamine-deprived autophagy-deficient cells, but not significantly in wild-type cells, suggesting reliance of autophagy-deficient tumor cells on extracellular amino acid uptake.

The first amphibian skin secretion-derived Bowman-Birk type chymotrypsin inhibitor is described here from the Asian green frog, Hylarana erythraea, and was identified by use of molecular cloning and tandem mass spectrometric amino acid sequencing. It was named Hylarana erythraea chymotrypsin inhibitor (HECI) and in addition to inhibition of chymotrypsin (Ki = 3.92 ± 0.35 μM), the peptide also inhibited the 20 S proteasome (Ki = 8.55 ± 1.84 μM). Additionally, an analogue of HECI, named K9-HECI, in which Phe9 was substituted by Lys9 at the P1 position, was functional as a trypsin inhibitor. Both peptides exhibited anti-proliferation activity against the human cancer cell lines, H157, PC-3 and MCF-7, up to a concentration of 1 mM and possessed a low degree of cytotoxicity on normal cells, HMEC-1. However, HECI exhibited higher anti-proliferative potency against H157. The results indicate that HECI, inhibiting chymotryptic-like activity of proteasome, could provide new insights in treatment of lung cancer.

A novel energetic binder was prepared through the copolymerization between 3-difluoroaminomethyl-3-methyloxetane (DFAMO) and 3,3′-bis(azidomethyl)oxetane (BAMO). With the help of thermogravimetric analysis (TG) and differential scanning calorimetry (DSC), the thermal decomposition study of poly(DFAMO/BAMO) was conducted to understand its decomposition behavior and kinetics, and the possible mechanism, which are crucial parameters as an energetic binder. The results showed that the difluoroamino and azido groups mainly contributed to the weight loss during the themolysis of the polymer. The activation energy of the first and second pyrolysis shoulder are 115 ± 5 kJ mol−1 and 165 ± 5 kJ mol−1, respectively. Additionally, fourier transform infrared (FTIR) of pyrolysis residues suggested that the complete pyrolysis of the azido groups occurred after the pyrolysis of difluoroamino. And the main degradation products of the polymer were CH3+, NH3, H2O, HF, HCN, N2, NO, H2CO and CF4 by TG-FTIR-MS.

Rana amurensis is important in Chinese medicine as its skin secretions contain abundant bioactive peptides. Here, we have identified the antimicrobial peptide Amurin-2 and three highly-conserved variants, Amurin-2a, Amurin-2b and Amurin-2c through a combination of molecular cloning and MS/MS fragmentation sequencing. Synthetic replicates of these peptides demonstrate potent antimicrobial activity against S. aureus, whilst some have activity against C.albicans and even resistant bacterial MRSA. Furthermore, two Lys-analogues (K4-Amurin-2 and K11-Amurin-2) were designed to improve the bioactive function and the antimicrobial activity of K4-Amurin-2 against E.coli was enhanced distinctly. In addition, the two modified peptides also showed more potent activity against S. aureus, C. albicans and MRSA strains. Meanwhile, these peptides showed inhibitory effect on the cell viability of several cancer cells. As a result, these structural and functional studies of Amurin-2 variants and analogues could provide insights for future antimicrobial peptide design.

Mastoparan is a typical cationic and amphipathic tetradecapeptide found in wasp venom and exhibits potent biological activities. Yet, compared with other insect-derived peptides, such as melittin from the bee venom, this family have been underrated. Herein, we evaluated the biological activities of mastoparan-C (MP-C), which was identified from the venom of the European Hornet (Vespa crabro), and rationally designed two analogues (a skeleton-based cyclization by two cysteine residues and an N-terminal extension via tat-linked) for enhancing the stability of the biological activity and membrane permeability, respectively. Three peptides possessed broadly efficacious inhibiting capacities towards common pathogens, resistant strains, as well as microbial biofilm. Although, cyclized MP-C showed longer half-life time than the parent peptide, the lower potency of antimicrobial activity and higher degree of haemolysis were observed. The tat-linked MP-C exhibited more potent anticancer activity than the parent peptide, but it also loses the specificity. The study revealed that MP-C is good candidate for developing antimicrobial agents and the targeted-design could improve the stability and transmembrane delivery, but more investigation would be needed to adjust the side effects brought from the design.

Agricultural source pollution has been hypothesized as one of the main reasons for reptile declines over recent decades. In addition to their direct toxicity to reptiles, agrochemicals can also enter complex interactions with environmental factors, which alter the interspecific relationships within communities. The potentially resulting cascading effects affect our understanding of the links between contaminants and the extent of declines of reptile species. In the present study, plant-arthropod-lizard tritrophic microcosms were assessed to identify the ecological effect of the widely used herbicide simazine in simulated steppe ecosystems. Three dosages of simazine (0, 0.060, and 0.006 g a.i./m2) were applied to microcosms, and the responses of organisms at three trophic levels were examined after 30-day exposure. The results showed that simazine could inhibit the growth and ecological functions of primary producers, and caused a reduction in the content of primary and secondary metabolites. The number of arthropod populations decreased in the lower simazine application but increased in the higher simazine application, compared with the control. Simazine led to slow growth and poor physical conditions in lizards. The impact of simazine on the community could be attributed to the following three aspects: (1) a direct effect of simazine, (2) the driving force of food resources, and (3) behavioral dynamics. The physical conditions of lizards and of the arthropod population in the microcosms showed different responses to standard toxicological tests, and the forces of cascading causalities were identified as the main factors beyond the direct simazine toxicity. Therefore, the propagation and cascade across multitrophic levels should be considered in future assessments to avoid distorting conclusions.

The carbon aerogel (CA) uniformly doped neodymium oxide (Nd 2 O 3 ) nanoparticle was synthesized by an effective in-situ method via acid catalyzing and used as the cathode matrix for lithium-sulfur batteries. The doped materials with interconnected pore structure of CA and evenly dispersed Nd 2 O 3 offer crucial confinement role to anchor sulfur and suppress the loss of polysulfide ions for interrelate function of S/polysulfides by Nd 2 O 3 . The composited sulfur electrodes present high electrochemical performances and initial discharge capacities, especially, the Nd2-CA/S sample gains initial discharge capacity of 1327 mAh g − 1 at 0.2 C and remains at 1082 mAh g − 1 after 100 cycles. Meanwhile, it still remains capacity of about 907 mAh g − 1 at 0.5 C after 300 cycles. The enhanced electrochemical performances can be ascribed to the crosslink mesoporous CA materials and well distributed neodymium oxide. Furthermore, the metal additive also takes promoting effect on redox reactions of the Li/S batteries presenting higher discharge voltages.

A Sm2O3 decorated carbon aerogel (CA-Sm) was successfully synthesized through a sol-gel from resorcinol, phloroglucinol (P), formaldehyde and catalyst of oxalic acid and doping compound with Sm2O3 strategies. The small amount of active reactant phloroglucinol promotes synthesis of carbon aerogel (CA) and formation of uniform and porous carbon spheres. The CA-Sm composites present an interlinked porous structure and high specific surface area. The CA-Sm with sulfur loading (CA/S-Sm) from the composite via molten sulfur technique exhibits an enhanced performance with long-term cycling stability and high rate capacity. In particular, the cathode of CA/S-Sm-2 with Sm/C molar ratio of 2/400 achieved a high initial discharge capacity of 1347 and 976 mAh g−1 at 0.2C and 2C, respectively. And the cathode exhibited a nice long-term cycling stability with a high initial discharge capacity of 1175 mAh g−1 and maintained 861 mAh g−1 after 300 cycles at 0.5C. The excellent electrochemical performance of the battery is attributed to interrelated nanospheres, porous carbon structure, large specific surface area of Sm2O3-doped CA composites and improved electronic and ionic transport at the cathode.

ATG3 (autophagy-related 3) is an E2-like enzyme essential for autophagy; however, it is unknown whether it has an autophagy-independent function. Here, we report that ATG3 is a relatively stable protein in unstressed cells, but it is degraded in response to DNA-damaging agents such as etoposide or cisplatin. With mass spectrometry and a mutagenesis assay, phosphorylation of tyrosine 203 of ATG3 was identified to be a critical modification for its degradation, which was further confirmed by manipulating ATG3Y203E (phosphorylation mimic) or ATG3Y203F (phosphorylation-incompetent) in Atg3 knockout MEFs. In addition, by using a generated phospho-specific antibody we showed that phosphorylation of Y203 significantly increased upon etoposide treatment. With a specific inhibitor or siRNA, PTK2 (protein tyrosine kinase 2) was confirmed to catalyze the phosphorylation of ATG3 at Y203. Furthermore, a newly identified function of ATG3 was recognized to be associated with the promotion of DNA damage-induced mitotic catastrophe, in which ATG3 interferes with the function of BAG3, a crucial protein in the mitotic process, by binding. Finally, PTK2 inhibition-induced sustained levels of ATG3 were able to sensitize cancer cells to DNA-damaging agents. Our findings strengthen the notion that targeting PTK2 in combination with DNA-damaging agents is a novel strategy for cancer therapy.