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Cinnamaldehyde is a natural antimicrobial food preservative. Previous studies have suggested that cinnamaldehyde interacts with the cell membrane, but the molecular targets of cinnamaldehyde action on foodborne pathogens are still unclear. In this study, the structural changes of Staphylococcus aureus and Escherichia coli cells were observed after cinnamaldehyde treatment. Then, quantitative real-time polymerase chain reaction (PCR) and parallel reaction monitoring were used for determining the effects of cinnamaldehyde treatment of these bacteria on the expression of genes and proteins associated with glycerophospholipid biosynthesis. Changes in fatty acids (raw materials for the biosynthesis of glycerophospholipids) and glycerophospholipids in S. aureus and E. coli after cinnamaldehyde treatment were analyzed to confirm the results of gene and protein expression experiments. Cinnamaldehyde regulated the glycerophospholipid biosynthesis pathways of these foodborne pathogens, mainly targeting phosphatidylglycerol and phosphatidylethanolamine, which resulted in the disruption of cell membrane integrity.

Evidence suggests that complex interactions between the immune system and brain have important etiological and therapeutic implications in schizophrenia. However, the detailed cellular and molecular basis of immune dysfunction in schizophrenia remains poorly characterized. To better understand the immune changes and molecular pathways, we systemically compared the cytokine responses of peripheral blood mononuclear cells (PBMCs) derived from patients with schizophrenia and controls against bacterial, fungal, and purified microbial ligands, and identified aberrant cytokine response patterns to various pathogens, as well as reduced cytokine production after stimulation with muramyl dipeptide (MDP) in schizophrenia. Subsequently, we performed single-cell RNA sequencing on unstimulated and stimulated PBMCs from patients and controls and revealed widespread suppression of antiviral and inflammatory programs as well as impaired chemokine/cytokine-receptor interaction networks in various immune cell subpopulations of schizophrenic patients after MDP stimulation. Moreover, serum MDP levels were elevated in these patients and correlated with the course of the disease, suggesting increased bacterial translocation along with disease progression. In vitro assays revealed that MDP pretreatment altered the functional response of normal PBMCs to its re-stimulation, which partially recapitulated the impaired immune function in schizophrenia. In conclusion, we delineated the molecular and cellular landscape of impaired immune function in schizophrenia, and proposed a mutual interplay between innate immune impairment, reduced pathogen clearance, increased MDP translocation along schizophrenia development, and blunted innate immune response. These findings provide new insights into the pathogenic mechanisms that drive systemic immune activation, neuroinflammation, and brain abnormalities in schizophrenia.

A method of ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) combined with modified QuEChERS purification technology was developed for the simultaneous determination of 25 veterinary medicine residues including four classes (sulfonamides, quinolones, chloramphenicols and amantidines) in chicken and egg. The samples were hydrolyzed by dilute hydrochloric acid, extracted by acetonitrile. Sodium chloride was added into the extracting solution to salt out. The acetonitrile was took out and degreased by n-hexanecyclohexane solution (1∶1,V/V) after stratification of acetonitrile and aqueous phase and concentrated to dry. The residues were dissolved with 0.2% formic acid ethyl acetate to remove the sodium chloride by filtrating and the filtrate was concentrated to dry again, then the sample was purified with a mixture of 30 mg of C18 and 60 mg PSA after adding 0.2% formic acid methanol. The target compounds were separated by ZORBAX C18 chromatography column (50 mm×2.1 mm×1.8 μm), the mass spectrometer data were acquired under multiple reaction monitoring (MRM) of positive and negative modes at the same time, and the residues were quantitated by isotope internal standard method. The results showed that the linear of 25 veterinary medicines is good in the range of 0.2~250 μg/L. The linear correlation coefficients are more than 0.99, and the detection limits are in the range of 0.1~0.9 μg/kg. The limits of quantification are 0.3~3.0 μg/kg. The average recoveries at three spiked levels (about 1, 5 and 20 folds of quantitative limits) are 79.5%~119% with the relative standard deviations of 0.9%~9.2%. The method is rapid,simple, accurate, sensitive and cheap, which is suitable for simultaneous determination of multiple vererinary medicine residues in eggs and chicken.

Porous materials for C2 H2 /CO2 separation mostly suffer from high regeneration energy, poor stability, or high cost that largely dampen their industrial implementation. A desired adsorbent should have an optimal balance between excellent separation performance, high stability, and low cost. We herein report a stable, low-cost, and easily scaled-up aluminum MOF (CAU-10-H) for highly efficient C2 H2 /CO2 separation. The suitable pore confinement in CAU-10-H can not only provide multipoint binding interactions with C2 H2 but also enable the dense packing of C2 H2 inside the pores. This material exhibits one of the highest C2 H2 storage densities of 392 g L-1 and highly selective adsorption of C2 H2 over CO2 at ambient conditions, achieved by a low C2 H2 adsorption enthalpy (27 kJ mol-1 ). Breakthrough experiments confirm its exceptional separation performance for C2 H2 /CO2 mixtures, affording both large C2 H2 uptake of 3.3 mmol g-1 and high separation factor of 3.4. CAU-10-H achieves the benchmark balance between separation performance, stability, and cost for C2 H2 /CO2 separation.

Spontaneous senile osteoporosis severely threatens the health of the senior population which has emerged as a severe issue for society. A SAMP6 mouse model was utilized to estimate the impact of intragastrically administered Astragalus Membranaceus (AR) on spontaneous senile osteoporosis. Bone mineral density (BMD) and bone microstructure were measured using Micro-CT; contents of calcium and phosphorus were determined with the colorimetric method; and gene and protein expressions of fibroblast growth factor 23 (FGF23), Klotho, Vitamin D receptor (VDR), CYP27B1 and CYP24A1 were detected using qPCR, Western blot and ELISA assays, respectively. The findings indicated that AR could improve the femoral BMD and bone microstructure, elevate the contents of calcium and phosphorus, and increase the expression of Klotho, VDR, and CYP27B1 whereas decreasing the expression of FGF23 and CYP24A1 in SAMP6 mice in a dose independent manner. The present study has demonstrated that AR can promote osteogenesis and alleviate osteoporosis. It is also expected to provide a new insight for the treatment of spontaneous senile osteoporosis and to serve as a research basis for AR application., Graphical Abstract

Contamination of soils by nickel (Ni) has become a serious environmental problem throughout the world, and this substance wields dangerous effects on the ecosystem and food chain. A pot experiment was conducted to examine the effect of rice straw (RS), rice straw biochar (BI), and calcite (CC) at 1% and 2% application rates in a Ni-contaminated soil. The objective was to potentially stabilize Ni and reduce its bioavailability to spinach (Spinacia Oleracea L.). Spinach plants were grown in a Ni-contaminated Ultisol (commonly known as a red clay soil). Plant growth parameter results indicated that a BI 2% application rate significantly increased the root and shoots dry biomass increased by 1.7- and 6.3-fold, respectively, while essential nutrients were enhanced in the spinach plant compared to those in the untreated soil (CK). Moreover, adding amendments significantly decreased CaCl2 extractable Ni by 62.5% 94.1%, and 87.2%, while the toxicity characteristics leaching procedure (TCLP) fell by 26.7%, 47.8%, and 41.7% when using RS, BI, and CC, respectively, at 2% compared to CK. The Ni concentrations in the spinach roots declined by 51.6%, 73.3%, and 68.9%, and in the shoots reduced by 54.1%, 76.7%, and 70.8% for RS, BI, and CC, at a 2% application rate, respectively. Bio-concentration factor (BCF) and translocation factor (TF) dropped significantly by as much as 72.7% and 20%, respectively, for BI 2% application rate. Results of the present study clearly indicated that biochar potential soil amendments for Ni stabilization, thereby reducing its bioavailability in the Ni-contaminated soil. This process enhanced the safety of food to be consumed and mitigated security risks.

In view of the current situation of high cost and low catalytic efficiency of the commercial Pd-based catalysts, adding transition metals (Ni, Co, etc.) to form the Pd-M bimetallic catalyst not only reduces the consumption of Pd but also greatly improves the catalytic activity and stability, which has attracted increasing attention. In this work, the three-dimensional network Pd-Ni bimetallic catalysts were prepared successfully by a liquid-phase in situ reduction method with the hydroxylated γ-Al2O3 as the support. Through investigating the effects of the precursor salt amount, reducing agent concentration, stabilizer concentration, and reducing stirring time on the synthesis of the Pd-Ni nanocatalyst, the three-dimensional network Pd-Ni bimetallic nanostructures with four different atomic ratios were prepared under an optimal condition. The obtained wire-like Pd-Ni catalysts have a uniform diameter size of about 5 nm and length up to several microns. After closely combining with the hydroxylated γ-Al2O3, the supported Pd-Ni/γ-Al2O3 catalysts exhibit nearly 100% conversion rate and selectivity for the hydrogenation of nitrobenzene to aniline at low temperature and normal pressure. The stability testing of the supported Pd-Ni/γ-Al2O3 catalysts shows that the conversion rate still remained above 99% after 10 cycles. There is no doubt that the supported catalysts show significant catalytic efficiency and recyclability, which provides important theoretical basis and technical support for the preparation of low-cost, highly efficient catalysts for the hydrogenation of nitrobenzene to aniline.

The effect of mulberry leaf powder and components on preventing obesity and regulating lipid metabolism were investigated in the present study. The mechanism of action was explored by examining the gut microbiota and lipid metabolism-related signaling pathways. As evidenced by the nutritional obesity rats model experiments, the middle concentration mulberry leaf powder (MLP) group (0.8 g/kg·d) significantly reduced Lee's index (25.1, compared with model control group [MC] 25.7) and had the strongest lipid metabolism regulation effect. Furthermore, the suppression effects of different mulberry leaf components on nutritional obesity were compared and the mulberry leaf phenolics and fiber mixture (Mulberry leaf mixture [MLM]) group (0.6 g/kg·d) was found to have the strongest efficacy (body weight [BW] reduced 12.4%). Real time PCR (RT-qPCR) and western blot analyses demonstrated that MLP (0.8 g/kg·d) and its components inhibited adipocyte differentiation and triglyceride synthesis through the PPAR-γ- C/EBP-α signaling pathway, resulting in lipid metabolism regulation. Gut microbiota analysis indicated that MLM (0.6 g/kg·d) prevented the reduction in intestinal flora diversity (reach 491 species) caused by high-energy feed, and reduced the Firmicutes/Bacteroidetes ratio (to 7.99%) and the obesity associated flora, Lachnospiraceae (to 19.1%), whereas it improved the content of the beneficial flora, Lactobacilli, Lactobacillus_johnsonii (reach 11.77%). MLM improved the bioaccessibility and bioavailability of the two functional components (phenolics and fiber) and maximized the anti-obesity effect through the gut microbiota-host metabolism pathway. PRACTICAL APPLICATION: The anti-obesity and lipid metabolism regulation effect of mulberry leaf components were evaluated in this study. The fiber and phenolics of this plant have the potential for development of weight-loss functional foods.

Based on Krstulovic-Dabic model, this paper modifies the center particle hydration model according to the features of copper tailings, and then simulates the hydration process of cement-based composite binding system mixed with copper tailings. The hydration exothermic features were analyzed under different dosages, and different temperatures. Then, the simulated parameter values of the hydration process were compared with those measured in experiments. The results show that: the mixing of copper tailings powder can reduce the hydration heat release and slow down hydration rate of the composite binding material, and improve the thermal performance of the concrete; the prepared copper tailings powder is active enough to replace fly ash and ground-granulated blast furnace slag (GGBS) as cement admixtures; When the dosage surpasses 40%, the copper tailings can be applied to mass concrete projects.

Failure of pancreatic and duodenal homeobox factor 1 (PDX1) to localise in the nucleus of islet beta cells under high-fat diet (HFD) conditions may be an early functional defect that contributes to beta cell failure in type 2 diabetes; however, the mechanism of PDX1 intracellular mislocalisation is unclear. Stress granules (SGs) are membrane-less cytoplasmic structures formed under stress that impair nucleocytoplasmic transport by sequestering nucleocytoplasmic transport factors and components of the nuclear pore complex. In this study, we investigated the stimulators that trigger SG formation in islet beta cells and the effects of SGs on PDX1 localisation and beta cell function. The effect of palmitic acid (PA) on nucleocytoplasmic transport was investigated by using two reporters, S-tdTomato and S-GFP. SG assembly in rat insulinoma cell line INS1 cells, human islets under PA stress, and the pancreas of diet-induced obese mice was analysed using immunofluorescence and immunoblotting. SG protein components were identified through mass spectrometry. SG formation was blocked by specific inhibitors or genetic deletion of essential SG proteins, and then PDX1 localisation and beta cell function were investigated in vitro and in vivo. We showed that saturated fatty acids (SFAs) are endogenous stressors that disrupted nucleocytoplasmic transport and stimulated SG formation in pancreatic beta cells. Using mass spectrometry approaches, we revealed that several nucleocytoplasmic transport factors and PDX1 were localised to SGs after SFA treatment, which inhibited glucose-induced insulin secretion. Furthermore, we found that SFAs induced SG formation in a phosphoinositide 3-kinase (PI3K)/eukaryotic translation initiation factor 2α (EIF2α) dependent manner. Disruption of SG assembly by PI3K/EIF2α inhibitors or genetic deletion of T cell restricted intracellular antigen 1 (TIA1) in pancreatic beta cells effectively suppressed PA-induced PDX1 mislocalisation and ameliorated HFD-mediated beta cell dysfunction. Our findings suggest a link between SG formation and beta cell dysfunction in the presence of SFAs. Preventing SG formation may be a potential therapeutic strategy for treating obesity and type 2 diabetes.

Separation of acetylene (C2H2) from ethylene (C2H4) and carbon dioxide (CO2) is of great importance in the petrochemical industry but remains a daunting challenge due to their very similar sizes and physical properties. Although a number of porous materials have been developed as promising adsorbents for either C2H2/C2H4 or C2H2/CO2 separation, few materials exhibit simultaneously high selectivities for both gas mixtures. Herein, we report the use of a four-connected N-donor organic linker to construct a novel water-stable SIFSIX-type material, [Cu(TPB)SiF6]n (termed ZJU-280, TPB = 1,2,4,5-tetra(pyridin-4-yl)benzene). This material features suitable rhombic pores and functional surfaces to interact optimally with C2H2 molecules, affording high C2H2 capture capacity and simultaneously high C2H2/CO2 (18.1) and C2H2/C2H4 (44.5) selectivities under ambient conditions. Theoretical calculations indicate that the suitable rhombic pores and functional sites can provide a multipoint binding environment to not only preferentially interact with C2H2 but also enable the dense packing of C2H2 molecules within the framework. Actual breakthrough experiments demonstrate that ZJU-280a can efficiently separate C2H2 from C2H2/CO2 (50/50, v/v) and C2H2/C2H4 (1/99 and 50/50) mixtures, respectively.

The mechanism and site-selectivity for Fe-catalyzed azaindoline formation from 1,2,3,4-tetrazole were examined computationally. The H-atom abstraction/radical rebound stepwise mechanism is proposed. The aliphatic H-atom abstraction (HAA) vs. electrophilic aromatic substitution (EAS) steps are responsible for the sp3vs. sp2 C–H amination site-selectivity and a larger steric congestion disfavors sp2 EAS, thus resulting in Fe-catalyzed site-selectivity toward sp3 C–H amination.

Hyphantria cunea (Drury) is a destructive invasive pest species in China that uses type II sex pheromone components. To date, however, the binding mechanisms of its sex pheromone components to their respective pheromone-binding proteins (HcunPBPs 1/2/3) have not been explored. In the current study, all three HcunPBPs were expressed in the antennae of both sexes. The prokaryotic expression and ligand binding assays were employed to study the binding of the moth's four sex pheromone components, including two aldehydes and two epoxides, and 24 plant volatiles to the HcunPBPs. Our results showed that the abilities of these HcunPBPs to bind to the aldehydes were significantly different from binding to the epoxides. These three HcunPBPs also selectively bind to some of the plant volatiles tested. Our molecular docking results indicated that some crucial hydrophobic residues might play a role in the binding of HcunPBPs to their sex pheromone components. Three HcunPBPs have different selectivities for pheromone components with both major and minor structural differences. Our study provides a fundamental insight into the olfactory mechanism of moths at the molecular level, especially for moth species that use various type II pheromone components.

Reduction oxidation (REDOX) reaction is crucial in life activities, and its dynamic balance is regulated by ROS. Reactive oxygen species (ROS) is associated with a variety of metabolic diseases involving in multiple cellular signalling in pathologic and physiological signal transduction. ROS are the by-products of numerous enzymatic reactions in various cell compartments, including the cytoplasm, cell membrane, endoplasmic reticulum (ER), mitochondria, and peroxisome. ROS signalling is not only involved in normal physiological processes but also causes metabolic dysfunction and maladaptive responses to inflammatory signals, which depends on the cell type or tissue environment. Excess oxidants are able to alter the normal structure and function of DNA, lipids, and proteins, leading to mutations or oxidative damage. Therefore, excessive oxidative stress is usually regarded as the cause of various pathological conditions, such as cancer, neurodegeneration, cardiovascular diseases (CVDs), diabetes, and kidney diseases. Currently, it has been possible to detect diabetes and other cardiac diseases by detecting derivatives accompanied by oxidative stress in vivo as biomarkers, but there is no effective method to treat these diseases. In consequence, it is essential for us to seek new therapy targeting these diseases through understanding the role of ROS signalling in regulating metabolic activity, inflammatory activation, and cardiac diseases related to metabolic dysfunction. In this review, we summarize the current literature on REDOX and its role in the regulation of cardiac metabolism and inflammation, focusing on ROS, local REDOX signalling pathways, and other mechanisms.

PIWI-interacting RNAs (piRNAs) are abundantly expressed during cardiac hypertrophy. However, their functions and molecular mechanisms remain unknown. Here, we identified a cardiac-hypertrophy-associated piRNA (CHAPIR) that promotes pathological hypertrophy and cardiac remodelling by targeting METTL3-mediated N6-methyladenosine (m6A) methylation of Parp10 mRNA transcripts. CHAPIR deletion markedly attenuates cardiac hypertrophy and restores heart function, while administration of a CHAPIR mimic enhances the pathological hypertrophic response in pressure-overloaded mice. Mechanistically, CHAPIR-PIWIL4 complexes directly interact with METTL3 and block the m6A methylation of Parp10 mRNA transcripts, which upregulates PARP10 expression. The CHAPIR-dependent increase in PARP10 promotes the mono-ADP-ribosylation of GSK3β and inhibits its kinase activity, which results in the accumulation of nuclear NFATC4 and the progression of pathological hypertrophy. Hence, our findings reveal that a piRNA-mediated RNA epigenetic mechanism is involved in the regulation of cardiac hypertrophy and that the CHAPIR-METTL3-PARP10-NFATC4 signalling axis could be therapeutically targeted for treating pathological hypertrophy and maladaptive cardiac remodelling.

Introduction: Loratadine (LOR) (Fig. 1), an active H1 receptor antagonist, is often used in the treatment of allergic disorders such as seasonal allergies and skin rash [1]. LOR was clinically approved for symptomatic relief of nasal and non-nasal symptoms of allergic rhinitis in children ≥2years. Materials and Methods: An adapted method of liquid chromatography-mass spectrometry (LC/MS/MS) was developed and validated to measure the concentrations of loratadine (LOR) and its active metabolite descarboethoxyloratadine (DCL) from pediatric plasma. After being mixed with the internal standard (IS, propranolol) and precipitated with methanol, samples were centrifuged and 20 μL of the supernatants were injected into the HPLC system. Separation was carried out on a reversed-phase C18 gradient column using a mobile phase consisting of water (containing 0.1 % formic acid) and acetonitrile. The flow rate was 0.5 mL/min and the running time was 5.0 min for each sample. Results and Conclusion: Quantitation of LOR, DCL and IS was performed using MRM mode and the transitions were: 383.1 → 337.1 for LOR, 311.1 → 259.0 for DCL and 260.2 → 116.0 for propranolol, respectively. The method was validated according to FDA guidelines, precisions and accuracies met the requirements in all cases. Calibration curves were 0.2–50.0 ng/mL for both LOR and DCL. This method was then applied for a pilot study examining the pharmacokinetics and therapeutic drug monitoring of LOR in children.

The biological nitrogen fixation in planted and nonplanted paddy soils was quantified using a chamber-based 15N2-labeling technique, and the active diazotrophs of soil were assessed by 15N2-DNA-stable isotope probing (SIP). In addition, the nanometer scale secondary ion mass spectrometry (NanoSIMS) was applied to analysis the 15N-enrichment of soil DNA in SIP fractions. 15N2-labeling experiment showed that BNF was 11.33 ± 1.90 kg N ha−1 in the rice-planted soil and 3.55 ± 1.18 kg N ha−1 in the nonplanted soil after 28-day labeling. The biologically fixed 15N was mainly (> 95%) recovered in the surface layer (0–0.5 cm) in the rice-planted soil. High throughput sequencing of nifH genes extracted from surface soil showed that the presence of rice affected the community composition of diazotrophs. The relative abundance of Nostocales and Stigonematales was significantly higher in rice-planted soil than in nonplanted soil (P < 0.05). After CsCl gradient ultracentrifugation, NanoSIMS images clearly showed that 15N was incorporated into soil DNA in the 15N2-labeling SIP gradient fractions. Analyses of nifH genes in 15N-enriched SIP gradient fractions suggested that Nostocales and Stigonematales were the major contributors to BNF in the rice-soil system. Taken together, these results have highlighted the contributions of cyanobacteria to the BNF in paddy fields and improved our understanding of the close relationship between rice plants and cyanobacteria.

Choline acetyltransferase (ChAT) synthesizes the neurotransmitter acetylcholine (Ach). Exogenous supplementation with ChAT can functionally compensate for decreased Ach levels and ameliorate memory and cognitive deficits. In this paper, the treatment efficacy of recombinant ChAT (peptide transduction domain (PTD)-ChAT) and donepezil were compared in aged dementia mice, and their mechanisms were explored by performing the gene function annotation and enrichment analysis of differentially expressed genes. The Morris water maze test showed that the swimming times of PTD-ChAT-treated (4 mg/kg) and donepezil-treated (0.5 mg/kg) mice with mild and moderate dementia were significantly shortened (P 0.01 vs aged dementia mice), and no significant changes were observed between the PTD-ChAT- and donepezil-treated groups. In contrast, the swimming times of PTD-ChAT-treated mice with severe dementia were noticeably shorter than those of donepezil-treated mice with severe dementia (P 0.01), indicating that the treatment efficacy of PTD-ChAT is superior to that of donepezil. The effect of PTD-ChAT was further confirmed in transgenic dementia mice (C57BL/6J-TgN (APP/PS1) ZLFILAS). Gene function annotation and enrichment analysis showed that PTD-ChAT improved cognitive deficits through Ach and was implicated in neuroprotection, synaptic plasticity, neuronal survival, and cerebrovascular remodeling through ACh and vascular endothelial growth factor (VEGF) pathway activation. Donepezil was significantly correlated with the immune inflammatory response and the insulin and IGF-1 signaling pathways. Therefore, although PTD-ChAT and donepezil were both effective in the treatment of aged dementia mice, their mechanisms were significantly different. Our research indicated that PTD-ChAT has potential promise for research on new drugs for AD treatment.

Na+/H+ antiporter (NHX1) was reported to be induced by NaCl in plants and NaCl can alleviate the toxic effect in plants caused by cadmium (Cd). However, it is unknown whether the NHX1 gene is involved in Cd adaptation in plants. This study aimed to explore the relationship between Cd resistance and NHX1 in plants. SseNHX1 gene obtained by shuffling using SsNHX1 from Suaeda salsa and SeNHX1 from Salicornia europaea as sequence templates in our previous work, conferred higher salt tolerance to yeast than SsNHX1 and SeNHX1. The overexpression of SsNHX1, SeNHX1, or SseNHX1 genes in tobacco was performed to explore the relationship between Cd resistance and NHX1 gene expression in plants. The NHX1 inhibitor amiloride was also used to assess the relationship between Cd resistance and NHX1 in plants. Under Cd stress treatment, transgenic tobacco exhibited better growth status, increased chlorophyll content, improved photosynthesis capacity and enhanced content of Na+ and K+ compared to wildtype plants. Moreover, transgenic tobacco showed less ROS accumulation, reduced MDA production, and decreased Cd2+ accumulation compared to WT plants. More importantly, transgenic tobaccos overexpressing SseNHX1 gene showed a greater resistance to Cd stress and less Cd accumulation than the transgenic tobaccos overexpressing SsNHX1 or SeNHX1 genes. Cd resistance and Cd accumulation in transgenic tobacco plants was closely correlated with the expression of NHX1 gene.

A partial life cycle test was performed with silkworms (Bombyx mori) exposed to different levels of halogenated organic pollutants (HOPs). The aims were to investigate the fate of HOPs during metamorphosis and the adverse effects of HOP exposures on silkworm development. Contaminant exposures resulted in decreased body weights, increased development times, and reductions of fecundity in silkworms. Assimilation efficiencies of HOPs decreased with an increasing octanol-water partition coefficient (log KOW). From the larvae to the pupae stage, bioamplification factors (BAmFs) exhibited concentration-dependent results, in which there was a positive correlation with the log KOW at the high concentrations but no correlation at the low concentrations. From the pupae to the moth stage, BAmFs were linearly negatively correlated with the log KOW for males, but a parabolic correlation with the log KOW was more suitable for females. Regarding reproductive activities, female moths selectively transferred low log KOW HOPs to eggs by the oviposition except for highly halogenated lipophilic pollutants. However, BAmFs of male moths during mating showed no correlation with the log KOW, although highly halogenated lipophilic pollutants had the highest BAmF values. The sex-specific bioamplification processes and special behaviors of highly halogenated lipophilic pollutants deserve further research.

Salicylic acid (SA) plays vital roles in the stress response of plants. However, the relationship between SA signaling and plant tolerance to nZnO stress has not been reported. The effects of different sizes and concentrations of nZnO on tobacco plants grown in MS medium or soil were evaluated. The effects of exogenous and endogenous SA on the morphological and biochemical parameters of tobacco plants by exogenous application of SA and overexpression of LcSABP2 gene were also investigated in this study. The endogenous SA content and the expression of salicylic acid-binding protein 2 (SABP2) gene increased in tobacco individuals with nZnO treatment. Exogenously applied SA increased the germination rate of tobacco seeds, and enhanced the root length and chlorophyll content of tobacco seedlings. Overexpression of LcSABP2 gene in transgenic tobacco significantly increased SA content in plants with nZnO treatment. Compared to the wild type plants, transgenic tobacco with nZnO treatment showed higher chlorophyll content, net photosynthetic rate, related gene expression, activities of SOD, POD and CAT, and less contents of H2O2, O2− and MDA, which suggested that LcSABP2 might play important regulatory roles in plant resistance to nZnO toxicity by elevating the level of endogenous SA, promoting the action of photosynthetic system, and enhancing the activities of antioxidant enzymes. This study illustrated that exogenous and endogenous SA might all be involved in alleviating the toxicity of nZnO on plants.

Background: The detection of glutamic acid decarboxylase 65 (GAD65) autoantibodies is essential for the prediction and diag nosis of latent autoimmune diabetes in adults (LADA). The aim of the current study was to compare a newly developed electro chemiluminescence (ECL)-GAD65 antibody assay with the established radiobinding assay, and to explore whether the new assay could be used to define LADA more precisely. Methods: Serum samples were harvested from 141 patients with LADA, 95 with type 1 diabetes mellitus, and 99 with type 2 dia betes mellitus, and tested for GAD65 autoantibodies using both the radiobinding assay and ECL assay. A glutamic acid decarbox ylase antibodies (GADA) competition assay was also performed to assess antibody affinity. Furthermore, the clinical features of these patients were compared. Results: Eighty-eight out of 141 serum samples (62.4%) from LADA patients were GAD65 antibody-positive by ECL assay. Com pared with ECL-GAD65 antibody-negative patients, ECL-GAD65 antibody-positive patients were leaner (P

Mulberry possesses many biological characteristics, such as reduce blood sugar and antioxidant properties, but whether mulberry galacto-oligosaccharide (MGO) can impact the characteristics of the gut microbiota is not yet clear. The objective of this work was to investigate the protective effects of MGO in type 2 diabetic (T2D) mice. The analysis of typical diabetic symptoms and serum status showed that oral MGO alleviated hyperglycemia, insulin resistance and oxidative stress in diabetic mice. These changes were caused by up-regulating the expression of key proteins in the PI3K/Akt pathway, involved in the control of liver glycolysis and gluconeogenesis, and liver glucose metabolism having a positive hypoglycemic effect. Additionally, the gut microbiota indicated that MGO treatment could positively modulate the microbiome composition to decrease the blood glucose in diabetic mice by promoting the growth of Prevotellaceae and Lactobacillus, whereas decreasing the abundance of Lachnospiraceae.

Background: Luteinized unruptured follicular follicle syndrome (LUFS) is a special type of ovulatory dysfunction and a common cause of infertility. It is estimated that its prevalence is 13% ~ 73% in endometriosis patients. Increasing evidences prove that LUFS is one of the reasons for endometriosis-related infertility. Any alteration in FF components and GCs in endometriosis may influence the developing oocyte and ovulation. This study aimed to explore the effect of local elevated progesterone in follicular fluid (FF) on ovulation in endometriosis patients.Methods: A Prospective study with matched pairs design was conducted at a reproductive medicine center between July 2017 and January 2018 in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection treatment (ICSI), while granulosa tumor-like cell line KGN (Bena culture collection, China) was used as in vitro cell model. Alterations in follicular and peritoneal fluid (PF) components identified with metabolomics analyses; Differentially expressed genes in GCs identified with transcriptome analysis; Polymerase chain reaction (PCR), western blot, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence were used to determine the expression of progesterone, NF-кB related genes, HPGD and COX-2; NF-кB binding identified with chromatin immunoprecipitation (ChIP).Results: Patients with endometriosis exhibited a significantly higher basal serum progesterone level, higher serum level of progesterone on trigger day and higher progesterone expression level in FF and PF. GCs from endometriosis patients revealed decreased expression of HPGD, COX-2 and suppressed NF-кB signaling, as manifested by decreased expressions of IL1R1 and IRAK3. Similarly, progesterone treatment in vitro down-regulated HPGD and COX2 expression and suppressed NF-кB signaling in KGN cells in a dose dependent manner, as manifested by decreased expressions of IL1R1, IRAK3, reduced pIкBα/IкBα ratio and nucleus translocation of p65. TNF-α, by contrast, increased expression of IL1R1, IRAK3, pIкBα, p65 and HPGD in KGN cells. Furthermore, one potential p65 binding site was identified in the promoter region of HPGD by chromatin immunoprecipitation.Conclusion: Endometriosis showed repression of NF-кB pathways and down-regulation of HPGD and COX2, which play important roles in the process of ovulation by participating in the metabolism of prostaglandin E2 (PGE2), in granulosa cells (GCs) due to elevated progesterone in FF.

We report the growth of direct bandgap single-crystalline Ge1−xSnx thin films on unheated substrates by a modified magnetron sputtering system. The Ge1−xSnx thin films were deposited on Si, Ge, and GaAs substrates at room temperature. They were characterized by X-ray diffraction and X-ray photoelectron spectroscopy that revealed the existence of Ge1−xSnx (004) peak and Ge-Sn bonds. Transmission and photoluminescence (PL) measurements confirm the direct bandgap dominated transition, and the bandgap values obtained are in agreement with the results calculated by 8-band k.p method. This article provides a simple and cost-effect way for fabrication direct bandgap GeSn films.

Modification on nucleic acid plays a pivotal role in controlling gene expression. Various kinds of modifications greatly increase the information-encoding capacity of DNA and RNA by introducing extra chemical group to existing bases instead of altering the genetic sequences. As a marker on DNA or RNA, nucleic acid modification can be recognized by specific proteins, leading to versatile regulation of gene expression. However, modified and regular bases are often indistinguishable by most conventional molecular methods, impeding detailed functional studies that require the information of genomic location. Recently, new technologies are emerging to resolve the positions of varied modifications on both DNA and RNA. Intriguingly, by integrating regional targeting tools and effector proteins, researchers begin to actively control the modification status of desired gene in vivo. In this review, we summarize the characteristics of DNA and RNA modifications, the available mapping and editing tools, and the potential application as well as deficiency of these technologies in basic and translational researches.

A defect-free, robust and selective barrier is essential for manufacturing membranes with targeted high permeability and selectivity. Here we report a new route to engineering a separation composite membrane by confining both channels in nanoscale metal organic frameworks (MOFs) and charges in a polyelectrolyte in the inner space of a porous support via a counter-diffusion method. A simple thermal annealing treatment of the interface between the MOF, polymer and support favorably reduced voids inside this nano-confinement environment. As this composite membrane combines both the support and barrier as one, it minimizes mass transfer resistance of water molecules. In a separation test, it readily achieved the state-of-the-art permeance. This simple chemical approach to upgrade membrane structures will offer wide opportunities in separation devices.

A series of novel dehydroabietic acid derivatives containing pyrimidine moieties were designed and synthesized to explore more efficacious and less toxic antitumor agents according to the principle of combination and hybridization. The cytotoxicity against human liver cancer (HepG2) cells, human breast cancer (MCF-7) cells, human colon cancer (HCT-116) cells, human lung cancer (A549) cells, and human normal liver cells (LO2) was estimated by MTT assay in vitro. Cytotoxic activity screening revealed that most of the compounds showed moderate to high levels of cytotoxicity against these four cancer cell lines and that some displayed more potent inhibitory activities compared with 5-FU. In particular, compound 3b exhibited promising cytotoxicity with IC50 values ranging from 7.00 to 11.93 μM against all the tested cell lines and displayed weak cytotoxicity towards normal cells. Besides, cell cycle analysis indicated that compound 3b mainly arrested MCF-7 cells at the S stage and induced cell apoptosis.

Aggregation-induced emission (AIE) properties have been widely investigated not only because they thoroughly circumvent the notorious aggregation-caused quenching effect encountered in conventional fluorophores but also due to their promising applications in organic light-emitting diodes, fluorescent sensors and bioimaging. In this work, we reported a study of the molecular packing and luminescence properties of AIE active positional isomers (m-BPCDM and p-BPCDM) with carbazole and dicyanovinyl groups. The compound m-BPCDM based on meta-substitution showed more evident AIE processes than the compound p-BPCDM based on para-substitution, which can be attributed to the strong π–π stacking effect brought by the spatial structure of p-BPCDM. Moreover, the two positional isomers also exhibited distinct mechanochromic luminescence properties.

Triclosan (TCS) is a chlorophenol which is highly bacteriostatic and used in a wide array of consumer products. TCS is now one of the most commonly detected organic pollutants in the sewage sludges. The sludge utilization for fertilizers on agricultural land would pose the risk of causing adverse effects on plant growth and yield by TCS. However, the toxicity of TCS toward plants is comparatively less understood. In this study, we assessed the effects of TCS on tobacco plants which were grown in MS medium or soils containing various concentrations of TCS. Our results indicated that TCS at the concentration of 2 mg/L could strongly inhibit the tobacco seed germination. TCS could suppress tobacco plant growth in soil with different concentrations (10, 20, and 50 mg/kg) of TCS through the downregulation of chlorophyll contents, restricting photosynthesis and increasing generation of reactive oxygen species (ROS). Salicylic acid (SA) plays important roles in the stress response of plants. The role of exogenous SA application in protecting tobacco plants from TCS stress was also investigated in this study. SA application could significantly increase net photosynthesis, enhance antioxidant enzyme activity, and thereby enhancing tobacco plant tolerance to TCS. Moreover, the activation of MPK3 and MPK6 induced by TCS was downregulated in plants with the treatment of SA. It was thus referred that mitogen-activated protein kinases (MAPKs) might play a key role in the signal transduction of TCS stress, and this process might be regulated by SA signaling. Overall, our results demonstrated that TCS had negative impacts on tobacco plants and SA played a protective role on tobacco plants against TCS stress.

Heptazine units with highly rich nitrogen sites were employed to fabricate a new porous organic polymer (POP-HE) via direct coupling of 2,5,8-trichloro-s-heptazine and 4,4′,4″,4‴-(ethene-1,1,2,2-tetrayl)tetraaniline with the mild base N, N′-diisopropylethylamine (DIPEA) in tetrahydrofuran (THF) solution. POP-HE displays good CO2 uptake capacity (50.6 cm3 g−1, 10 wt%, 1 bar/273 K) and highly selectively adsorptive separation of CO2 over CH4 under ambient conditions. Impressively, at 273 K, the predicted IAST selectivity of POP-HE is 47.0-13.4 for the natural gas mixture (CO2/CH4 = 5:95) at pressures varying from 0 to 1 atm. Meanwhile, the result of calculated band gap value based on Tauc plot motivated us to investigate its photocatalytic activity. POP-HE was applied as heterogeneous photocatalyst for visible light-induced selective oxidation of benzyl alcohol to benzaldehyde, and exhibited great conversion of 33.6% under irradiation of white LED light, which is much higher than that of g-C3N4. Moreover, POP-HE can be recycled up to three times without significant decrease in catalytic activity.

In this study, the core–shell method was used to prepare water polyurethane (WPU). First, two different prepolymers were synthesized; one contained a hydrophilic group (prepolymer A), whereas the other one had none (prepolymer B). Then, the two prepolymers were mixed at a certain ratio and emulsified to obtain a WPU emulsion. The effect of hydrophilic group content in prepolymer A on the emulsion properties was investigated and compared with the WPU properties prepared via one-pot method. Transmission electron microscopy analysis showed that latex particles with core–shell structures were formed. Results showed that the WPU particle size distribution was narrow. As the content of hydrophilic groups in prepolymer A increased, the emulsion solid content decreased, and the viscosity increased, which was inconducive for the preparation of a WPU with high solid content and low viscosity. When the prepolymer A/prepolymer B mass ratio was 1.2:1, and the hydrophilic group content in prepolymer A was 3%, a WPU with good stability with the solid content of 55.3% and the viscosity of 187.4 mPa s was prepared via core–shell method.

A direct nickel-catalyzed, high atom- and step-economical reaction of cyanohydrins with aldehydes or ketones via an unprecedented “cyano-borrowing reaction” has been developed., A direct nickel-catalyzed, high atom- and step-economical reaction of cyanohydrins with aldehydes or ketones via an unprecedented “cyano-borrowing reaction” has been developed. Cleavage of the C–CN bond of cyanohydrins followed by aldol condensation and conjugate addition of cyanide to α,β-unsaturated ketones proceeded to deliver a range of racemic β-cyano ketones with good to high yields. The practical procedure with the use of a commercial and less-toxic CN source bodes well for wide application of this protocol.

During plant polysaccharide extraction, polyphenols are usually oxidatively polymerized to produce quinone pigments adsorbed the macromolecular such as protein and polysaccharides. Whether these derived pigments affect the properties of polysaccharides remains unknown. In this study, green tea polysaccharide conjugates (gTPC) were prepared from low-grade green tea by means of combined-enzyme extraction followed by decoloring with anion-exchange column chromatography to obtain the corresponding fraction (gTPC-D). gTPC comprised two components, with molecular weights of 1.71 × 107 Da and 2.56 × 105 Da in mass proportions of 0.09% and 99.91%, respectively. gTPC-D consisted of one component of molecular weight 2.32 × 105 Da. gTPC UV–vis spectrum presented a shoulder-shaped peak, with an inflection point at 257 nm in the 240–300 nm range, whereas the spectrum of gTPC-D displayed a very weak wave-like curve in the 255–300 nm region associated with quinone pigments rather than their covalently bound protein. Quinone pigments increased the zeta potential of gTPC and reduced its water-holding capacity at high relative humidity (RH) (above 80%). gTPC-D had a significant dose-dependent inhibitory effect on HepG2 cells (p

Background Sanguisorba officinalis, a popular Chinese herb, called DiYu, has been shown to inhibit the growth of many human cancer cell lines, including colorectal cancer cells. The aims of this study were to discover the active compound and molecular mechanism of S. officinalis against Wnt/β-catenin signaling pathway and develop Wnt inhibitors from natural products as anti-colorectal cancer agents. Methods 1,4,6-Tri-O-galloyl-β-d-glucopyranose (TGG) was obtained by the preparative HPLC. The effect of DiYu on proliferation of NIH3T3 and HT29 was detected by MTT assay. Luciferase reporter assay was applied to investigate the activity of Wnt/β-catenin signaling in NIH3T3. The expression levels of mRNA and protein were detected by RT-PCR and western blot. Immunofluorescence assay was used to measure the level of β-catenin in cytoplasm and nucleus. Transcriptomic profiling study was performed to investigate the molecular mechanism of DiYu on the Wnt/β-catenin signaling pathway. Results TGG significantly inhibited the Wnt/β-catenin signaling pathway, down-regulated the expression of β-catenin and Wnt target genes (Dkk1, c-Myc, FGF20, NKD1, Survivin), up-regulated the levels of cleaved caspase3, cleaved PARP and ratio of Bax/Bcl-2, which may explain the apoptosis of HT29. Conclusions Our study enhanced the discovery of the materials and elucidation of mechanisms that account for the anti-Wnt activity of natural inhibitor (DiYu) and identified the potential of TGG to be developed as anti-colorectal cancer drugs.

Four isostructural dinuclear lanthanide complexes based on 4-azotriazolyl-3-hydroxy-2-naphthoic acid (H3ATNA) and 3-hydroxy-2-naphthoic acid (H2NA) ligands, {[Ln2(HATNA)2(HNA)2(H2O)4]·6DMF} (Ln = Dy (1), Tb (2), Sm (3), Eu (4); DMF = N, N-dimethylformamide) have been prepared and characterized by X-ray diffraction crystallography, dc/ac magnetic characterization, and fluorescent spectrometry. The crystallographic data reveal dinuclear lanthanide cores of complexes 1-4, bridged by phenoxo and μ1,3 carboxyl groups. Each nine-coordinated Ln(III) ion is located in a slightly distorted monocapped square antiprism. The ligand of H3ATNA displays a unique antenna effect in complex 4. Complexes 1-3 display only two ligand-centered fluorescent emissive peaks around 450 and 600 nm, and complex 4 shows four characteristic Eu(III)-centered emission bands at 593, 618, 653, and 698 nm under excitation at 348 nm. Complex 1 exhibits single-molecule magnet behavior that is rationalized through ab initio calculations.

Efficient non-noble metal catalysts for oxygen reduction reaction (ORR) have been highly attractive for the fabrication of cost-effective fuel cells. Metal–organic frameworks (MOFs) derived heteroa...

MicroRNAs (miRNAs) have been implicated in β cells dysfunction. Previous studies indicated that miR-127 was specifically abundant in β cells and one of its target genes, Kif3b, promoted cell proliferation. However, the impact of the miR-127-Kif3b axis on β cells remains unknown. In this study, we revealed that miR-127 level was declined both in islets from the mice with a high-fat diet and in MIN6 cells with elevated glucose treatment. The elevated level of miR-127 attenuated β cell proliferation by repressing Kif3b expression without affecting apoptosis and cell cycle, and it dampened insulin secretion. Moreover, β cell-derived miR-127 could also affect the islet endothelial cell-line, MS1, in vitro via the transfer of extracellular vesicles (EVs). Treating MS1 cells with the EVs secreted by MIN6 cells exhibited a higher ability in cell migration and tube formation. However, this effect was abolished by the miR-127 inhibitor co-cultured with EVs-treated MS1 cells. Thus, we define that miR-127 is a crucial regulator of insulin secretion and cell proliferation in pancreatic β cells as well as a potential functional regulation factor in islet endothelial cells.

Schiff base metal complexes are effective homogeneous catalysts used in oxidation reactions in organic synthesis. However, application of these catalysts in aqueous solution is limited by their effectiveness and stability. In this study, a novel graphene based Schiff base copper complex (Cu(salen)) was developed to effectively activate persulfate (PS) for the removal of organic pollutants in aqueous solution. Aminated reduced graphene oxide (ArGO) was used as a carrier of the heterogeneous catalyst, DArGO-Cu, which was synthesized by the condensation reaction of 3, 5-dibromosalicylaldehyde with ArGO followed by the complexing reaction with copper acetate monohydrate. The surface structure and morphology as well as elemental composition of DArGO-Cu were characterized by SEM, TEM, XPS, FTIR, Raman and elemental analysis. The catalytic performance of DArGO-Cu to activate PS was evaluated with the degradation of triclosan (TCS) in water at room temperature. The mechanism for DArGO-Cu to activate PS was the generation of SO4 − which was immediately converted to OH to degrade TCS. The role of graphene played in catalysis was not only as a carrier for Cu(salen) but also to build hydrophobic microdomains for the stabilization of the catalytic active sites in the reaction.

In the present study, mulberry oligosaccharides were produced from mulberry polysaccharide by physical ultrasonic hydrolysis, chemical acid hydrolysis and enzymatic hydrolysis. The impact of the oligosaccharides on the growth four probiotic bacteria—Lactobacillus plantarum, Leuconostoc mesenteroides, Lactobacillus casei and Lactobacillus rhamnosuswas examined. The oligosaccharides produced from β-mannanase hydrolysis had the greatest effect on the growth of L. rhamnosus (252% of the number of cells compared with medium without the hydrolyzate). The enzymatically-prepared mulberry oligosaccharides (EMPS) were superior to the untreated mulberry polysaccharide and commercially available prebiotics (isomaltooligosaccharides and galactooligosaccharides). L. rhamnosus was cultured with EMPS and then subjected to tolerance tests with artificial gastrointestinal fluids. Bacteria remained viable. Subsequently, simulated-digested L. rhamnosus cultured with EMPS was used in in vitro fermentation with human gut microbiota from fecal inoculum. After 48 h of the incubation, in the experimental group (with pretreated L. rhamnosus), the ratio of Bacteroidetes to Firmicutes was 0.848, compared with 0.659 in the control group (saline instead of L. rhamnosus), suggesting that L. rhamnosus and constituents in EMPS were capable of regulating the growth of intestinal microorganisms. Our results inform the potential for the development of mulberry oligosaccharides as a prebiotics or synbiotics.

Unveiling the molecular features in the heart is essential for the study of heart diseases. Non-cardiomyocytes (nonCMs) play critical roles in providing structural and mechanical support to the working myocardium. There is an increasing amount of single-cell RNA-sequencing (scRNA-seq) data characterizing the transcriptomic profiles of nonCM cells. However, no tool allows researchers to easily access the information. Thus, in this study, we develop an open-access web portal, ExpressHeart, to visualize scRNA-seq data of nonCMs from five laboratories encompassing three species. ExpressHeart enables comprehensive visualization of major cell types and subtypes in each study, visualizes gene expression in each cell type/subtype in various ways, and facilitates identifying cell-type-specific and species-specific marker genes. ExpressHeart also provides an interface to directly combine information across datasets, for example, generating lists of high confidence DEGs by taking the intersection across different datasets. Moreover, ExpressHeart performs comparisons across datasets. We show that some homolog genes (e.g., Mmp14 in mice and mmp14b in zebrafish) are expressed in different cell types between mice and zebrafish, suggesting different functions across species. We expect ExpressHeart to serve as a valuable portal for investigators, shedding light on the roles of genes on heart development in nonCM cells.

The present study aimed to investigate the effects of TGF-β1, tissue inhibitor of metalloproteinase (TIMP)-1 small interfering (si)RNA and TIMP-2 siRNA on hepatic fibrosis in rats and explore the T helper (Th)1/Th2 balance. Moreover, IFN-γ, IL-4 and IL-13 are the main cytokines associated with Th1/Th2 responses and have significant influence on the progression of hepatic fibrosis. The expression levels of IFN-γ, IL-4 and IL-13 in rats with hepatic fibrosis that were treated with siRNAs against the aforementioned molecules were measured using various techniques including immunohistochemical staining, western blotting and reverse transcription-quantitative PCR. The principal outcomes revealed the downregulation of IFN-γ and the upregulation of IL-4 and IL-13 in the model group compared with the normal group. Moreover, the expression of IFN-γ was significantly increased, while IL-4 and IL-13 demonstrated no significant difference in the TGF-β1 siRNA treatment group compared with the model group. The TIMP-1 and TIMP-2 siRNA treatment groups exhibited significantly increased expression levels of IFN-γ, but lower expression levels of IL-4 and IL-13 compared with the model group. These results indicated that TIMP-1 and TIMP-2 were improved antifibrotic targets compared with TGF-β1.