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Previous studies have raised concerns that kidney disease is often closely related to low serum Se levels in patients and that hyposelenemia may increase the vulnerability of patients to complications. However, few studies examining renal injury caused by Se deficiency have been conducted. To determine the effects of a selenium-deficient diet on renal function, a mouse model was fed a selenium-deficient diet (0.02 mg Se/kg) for 20 weeks. Meanwhile, mice in the control group (selenium-adequate) were fed a standard diet (0.18 mg Se/kg). The cellular models were established by lentiviral Trnau1ap-shRNA vectors transfected into mouse podocyte (MPC5) and mouse renal tubular epithelial (TCMK1) cell lines. Significant increases in serum creatinine levels and urinary protein/creatinine ratios were accompanied by increased MDA content in the Se-deficient group compared to the control group. The morphological observations of tissues showed widespread inflammation and ultrastructural changes in the Se-deficient group, such as swollen mitochondria and extensive podocyte fusion and renal tubular microvilli shedding. In addition, the expression of COXIV and cytochrome c was significantly downregulated in the Se-deficient group. Importantly, the mRNA levels of silent mating type information regulation 2 homolog 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and the protein levels of SIRT1 were increased in the Se-deficient group compared with the normal control group. Our data indicate that Se deficiency induces renal injury in mice. The elevated oxidative stress caused by Se deficiency may result in mitochondrial damage, which might affect renal function. Moreover, the SIRT1/PGC1α axis likely plays an important role in the compensatory mechanism of mitochondrial dysfunction.

An amino curing agent containing silicon/titanium flame-retardant elements (STCA) based on (3-aminopropyl)triethoxysilane (APTES) and tetrabutyl titanate was successfully prepared. The thermal decomposition and flame-retardant properties of a STCA-cured trifunctional epoxy resin, which was facilely synthesized by 1,1,1-tris(4-hydroxyphenyl)ethane and epichlorohydrin via a two-step method, were compared with those of another amino curing agent containing silicon (SCA) based on APTES and methyltrimethoxysilane. The structures of STCA and SCA were characterized by Fourier transform infrared (FT-IR), 29Si NMR, and Raman spectroscopies. The STCA-cured thermoset not only had good thermal stability with an initial decomposition temperature of 344.8 °C and a char yield of 52.7% at 800 °C but also exhibited the overall improvement of flame-retardant properties. V-0 rating was achieved using the UL-94 test, and the value of limiting oxygen index reached 33.8%. From the thermogravimetry-infrared test, the yield of pyrolysis products of the STCA-cured thermoset was significantly decreased, indicating the lower toxicity in contrast to the SCA-cured thermoset. Flame-retardant performances were also investigated using the cone calorimetry test, and the flame retardancy mechanism was studied using scanning electron microscopy, FT-IR, and energy-dispersive spectrometry. The results indicate that the introduction of silicon/titanium to the system reveals the synergistic effects to promote the formation of an intumescent, sufficient, and compact char layer during combustion, which could effectively prevent heat, oxygen, and flame from penetrating into the interior structure, and lead to the retardance of further combustion.

(‐)‐Epigallocatechin gallate (EGCG), a catechin found in green tea, has been demonstrated to exhibit activity against grass carp reovirus (GCRV). In the current study, we found that EGCG is partially transformed in vivo into (‐)‐epicatechin gallate (ECG), which differs from EGCG only by the absence of a hydroxyl group, and exhibits similar pharmacokinetic behaviour to that of EGCG. ECG is also a major catechin in green tea, but little information on its antiviral activity is available. Therefore, we assessed whether ECG affects GCRV in vitro. We incubated grass carp (Ctenopharyngodon idellus) kidney (CIK) cells with ECG and GCRV‐JX01 at different concentrations, and typical cytopathogenic effect (CPE) values were observed for 5 and 10 µg/ml ECG. However, the CPE in 20 µg/ml ECG treatment group was low; no significant CPE was observed for 40 µg/ml ECG treatment; and a high ECG concentration (80 µg/ml) led to stress response in the CIK cells. Western blot results also revealed that ECG suppresses GCRV replication in CIK cells. Thus, the data indicate that ECG, as well as EGCG, exhibits potential as an antiviral agent for aquaculture.

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for rapid and accurate nucleic acid detection at the point of care. Here, we report an amplification-free nucleic acid immunoassay, implemented on a lateral flow strip, for the fluorescence detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in less than one hour. The assay uses DNA probes that are designed to bind to the conserved open reading frame 1ab (ORF1ab), envelope protein (E) and the nucleocapsid (N) regions of the SARS-CoV-2 genome, and a fluorescent-nanoparticle-labelled monoclonal antibody that binds to double-stranded DNA-RNA hybrids. In a multi-hospital randomized double-blind trial involving 734 samples (593 throat swabs and 141 sputum) provided by 670 individuals, the assay achieved sensitivities of 100% and specificities of 99% for both types of sample (ground truth was determined using quantitative PCR with reverse transcription). The inexpensive amplification-free detection of SARS-CoV-2 RNA should facilitate the rapid diagnosis of COVID-19 at the point of care.

Polygonum cuspidatum, an important medicinal plant in China, is a rich source of resveratrol compounds, and its synthesis related resveratrol synthase (RS) gene is highly expressed in stems. The sequence of the resveratrol synthase was amplified with specific primers. Sequence comparison showed that it was highly homologous to the STSs. The RS gene of Polygonum cuspidatum encodes 389 amino acids and has a theoretical molecular weight of 42.4 kDa, which is called PcRS1. To reveal the molecular basis of the synthesized resveratrol activity of PcRS1, we expressed the recombinant protein of full-length PcRS1 in Escherichia coli, and soluble protein products were produced. The collected products were purified by Ni-NTA chelation chromatography and appeared as a single band on SDS-PAGE. In order to obtain higher purity PcRS1, SEC was used to purify the protein and sharp single peak, and DLS detected that the aggregation state of protein molecules was homogeneous and stable. In order to verify the enzyme activity of the high-purity PcRS1, the reaction product was detected at 303 nm. By predicting the structural information of monomer PcRS1 and PcRS1 ligand complexes, we analyzed the ligand binding pocket and protein surface electrostatic potential of the complex, and compared it with the highly homologous STSs protein structures of the iso-ligand. New structural features of protein evolution are proposed. PcRS1 obtained a more complete configuration and the optimal orientation of the active site residues, thus improving its catalytic capacity in resveratrol synthesis.

Background As a lipid metabolic disorder, non-alcoholic fatty liver disease (NAFLD) is an important cause of cirrhosis and hepatocellular carcinoma, with no effective drug up to date. Previous studies have demonstrated increased methylation levels of key genes in NAFLD, suggesting that hydroxymethylation, a key step in demethylation, may be a possible strategy to reverse NAFLD. TET1 is well known as a key hydroxymethylase, however, its role and mechanism in NAFLD remains unclear. Methods In this study, we utilized TET1 knockout mice, fed with high-fat diet. Furthermore, by ChIP and hMeDIP. TET1 knockdown L02 and HepG2 cell lines. Results Their degree of liver steatosis was more severe than that of wild-type mice, suggesting that TET1 had a significant protective effect against NAFLD. We further found that PPARα, a key regulator of fatty acid oxidation, and its downstream key enzymes ACOX1 and CPT1A, as well as the fatty acid oxidation product β-HB were significantly decreased in TET1 knockout mice. While the key genes for fatty acid synthesis and uptake were not significantly changed, suggesting that TET1 inhibits NAFLD by promoting fatty acid oxidation via PPARα pathway. TET1 was confirmed to directly bind to the promoter of PPARα and elevate its hydroxymethylation level. Conclusions This study is the first to show that TET1 can activate PPARα, promote fatty acid oxidation and inhibit NAFLD progression by hydroxymethylation of PPARα promoter, which may be a new strategy to reverse NAFLD.

Kidney renal clear cell carcinoma (KIRC) is the most common and fatal subtype of renal cancer. Antagonistic associations between selenium and cancer have been reported in previous studies. Selenium compounds, as anti-cancer agents, have been reported and approved for clinical trials. The main active form of selenium in selenoproteins is selenocysteine (Sec). The process of Sec biosynthesis and incorporation into selenoproteins plays a significant role in biological processes, including anti-carcinogenesis. However, a comprehensive selenoprotein mRNA analysis in KIRC remains absent. In the present study, we examined all 25 selenoproteins and identified key selenoproteins, glutathione peroxidase 3 (GPX3) and type 1 iodothyronine deiodinase (DIO1), with the associated prognostic biomarker leucine-rich repeat containing 19 (LRRC19) in clear cell renal cell carcinoma cases from The Cancer Genome Atlas (TCGA) database. We performed validations for the key gene expression levels by two individual clear cell renal cell carcinoma cohorts, GSE781 and GSE6344, datasets from the Gene Expression Omnibus (GEO) database. Multivariate survival analysis demonstrated that low expression of LRRC19 was an independent risk factor for OS. Gene set enrichment analysis (GSEA) identified tyrosine metabolism, metabolic pathways, peroxisome, and fatty acid degradation as differentially enriched with the high LRRC19 expression in KIRC cases, which are involved in selenium therapy of clear cell renal cell carcinoma. In conclusion, low expression of LRRC19 was identified as an independent risk factor, which will advance our understanding concerning the selenium adjuvant therapy of clear cell renal cell carcinoma.

Emissive lanthanide ions are considered as luminescent species or optical probes for the analytes in ambient conditions or even cellular environment. But a variety of factors determine the stability of photo-luminescent signals due to the excitation sources, statistical errors or the selection of solvents. In this way, ratiometric assays effectively circumvent such problem and lead to more sensitive and reliable results. Herein, an organic-inorganic hybrid material has been developed with the europium complex as the core and the terbium species can be attached onto the surface of silica host. As for the evaluation of the internal structure, the terbium complex has been integrated into the hybrid network via weak forces and its sensitizing moiety will be easily attacked by Lewis acid-base interactions. In a different manner, the europium complex has been shielded from perturbation due to the protection of the outside silica shells. Such sharp difference in response to fluoride induces drastic signal changes and the conversion of binding process between fluoride and molecular receptors (boronic group) into readable optical outputs has afforded the lower detection limit for F− as 0.17 μM. In addition, the intracellular uptake and distribution of the hybrid material have been explored.

Receptor tyrosine kinase c-Met is an important antitumor drug target. Triazolotriazine analogues 2-10 were prepared efficiently and evaluated the enzymatic and cellular c-Met activities. Brief structure-activity relationships of triazolotriazine core and CF2-quinoline part were investigated, leading to the discovery of compound 8 with nanomolar enzymatic c-Met activity, and subnanomolar MKN45 and EBC-1 cellular potencies. The proposed binding model of 8 and c-Met unraveled that two canonical hydrogen bonds and a π-π stacking interaction formed between the inhibitor and the ATP binding site of c-Met kinase domain, which accounted for its potent c-Met activities.

There has been an increasing number of researches about microRNAs (miRNAs) in the progression of liver fibrosis from the point of their comprehensive functions in regulating the activation of hepatic stellate cells (HSCs). Among them, it has been reported that miR-212 is up-regulated in activated rat primary HSCs. However, its mechanism has not been determined yet. Here, we confirmed that the level of miR-212-3p was up-regulated in livers of carbon tetrachloride (CCl4)-treated mice compared with the normal control, which is a classical model of chronically damaged fibrotic liver. In vitro, we demonstrated that TGF-β, a master fibrogenic cytokine, could induce the level of miR-212. In turn, overexpression of miR-212 could induce the activation marker of HSC including α-smooth muscle actin (α-SMA) and collagens by activating TGF-β signaling pathway. Furthermore, SMAD7, a dominant suppressor of TGF-β pathway, was identified as a direct target of miR-212-3p. Our results indicate that miR-212-3p facilitates the activation of HSCs and TGF-β pathway by targeting SMAD7, highlighting that it can be served as a novel biomarker or therapeutic target for liver fibrosis.

In this study, two bio-based benzoxazines, PH-f and SA-f, were synthesized and used to prepare benzoxazine/chitosan (CS) composites of PH-f/CS and SA-f/CS and their corresponding curing products poly(PH-f)/CS and poly(SA-f)/CS. Differential scanning calorimeter (DSC) and Fourier-transform infrared spectroscopy (FTIR) spectra show that, compared with poly(PH-f)/CS, the formation of imine-linkages (C=N) between SA-f and CS accelerates the benzoxazine ring-opening reaction and lowers the curing temperature of SA-f/CS. Although poly(PH-f)/CS and poly(SA-f)/CS have lower thermal stability than corresponding pure polybenzoxazine, it is still high and their LOI values are >35, indicative of good flame retardancy. Due to the formation of C N bonds between SA-f and CS, the poly(SA-f)/CS composite has more regular surfaces and a more uniform pore distribution than poly(PH-f)/CS, with a specific area of 1.135 m2/g and porosity of 97.5%. The unique pore structure of the poly(SA-f)/CS composite gives it high adsorption capacity (reaching 95% for rhodamine B within 48 h), suggesting that it is a promising adsorption material.

In this work, the one- and two-photon absorption properties of two quadrupolar A–π–D–π–A dyes, featuring carbazole and triphenylamine as donors of varying strengths, are calculated using density functional theory. The characteristics of two-photon excitation are analysed by using the three-state model closest to the real physical process. By taking the intermediate state as a bridge, the charge transfer characteristics in the two-photon excitation process are studied in detail by using various visualisation methods. Comparing the intramolecular charge transfer (ICT) characteristics shows that increasing the ability of the push-pull electrons of the central substituents, thus increasing the intramolecular charge transfer, is a more efficient method to enhance the molecular σtp. Our study promotes a deeper understanding of the design of A–π–D–π–A molecules with large cross-sections in two-photon absorption.

Background Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases. However, the exact pathogenesis of NAFLD remains to be elucidated. Despite the association with tumors and cardiovascular diseases, the role of miR-222 in NAFLD remains unclear. The present study was to investigate the role of miR-222 in NAFLD. Methods Wild-type C57BL/6 mice were fed a high-fat diet for 12 weeks to induce NAFLD. Normal human liver cell line (L02) was cultured with free fatty acid (FFA)-containing medium to stimulate cell steatosis. The mRNA levels of miR-222 and acyl Coenzyme A xidase 1 (ACOX1) were detected by quantitative-PCR (Q-PCR). The prediction of ACOX1 as the target gene for miR-222 was conducted via TargetScan. The overexpression or inhibition of miR-222 was mediated by miR-222 mimics or antagomir, and intracellular triglyceride levels were measured using a triglyceride kit. Luciferase reporter assays verified ACOX1 as the target gene for miR-222. Results miR-222 was significantly elevated in both the in vivo and in vitro NAFLD models. Overexpression of miR-222 significantly increased triglyceride content in the L02 cells, while inhibition of miR-222 expression restricted the accumulation of triglyceride. Overexpression of miR-222 significantly inhibited ACOX1 expression. Transient transfection assays verified that ACOX1 3′-UTR luciferase reporter activity could be inhibited by miR-222 overexpression. Conclusions The present study suggested that miR-222 promotes the accumulation of triglycerides by inhibiting ACOX1.

In this work, we use the visualization method to study their intramolecular electric-magnetic interactions and reveal the physical mechanism of their electronic transition to explain the cause of the opposite ECD spectrum orientations. Azaphilone A and B are two chiral molecules, due to their differing chirality, the electronic circular dichroism (ECD) spectra of bromophilone A and B are very different at 431 nm. Based on the two-step transition process, the charge-transfer characteristics of the corresponding two-photon excited states of the two chiral molecules are analysed in detail by calculating the photoinduced charge transfer and electron-hole coherence in the two-photon absorption (TPA) process.

BACKGROUND Migraine is a chronic disease that interferes with life quality and work productivity. Valproate shows protective effects against migraine, yet the underlying mechanisms are unclear. This study aimed to evaluate the potential effect of valproate on migraine using a rat model of nitroglycerin-induced trigeminovascular activation, as well as to explore the underlying mechanism. MATERIAL AND METHODS Intraperitoneal injection of nitroglycerin was conducted to induce trigeminovascular activation in rats. To explore the protective effect of valproate, a low dose (100 mg/kg) or a high dose (200 mg/kg) of valproate was intraperitoneally injected into rats, and then the levels of 5-hydroxytryptamine and nitric oxide in the peripheral blood were examined. The mtDNA copy number and the protein levels of peroxisome proliferator-activated receptor-γ coactivator 1α, mitochondrial transcription factor A, and peroxisome proliferator-activated receptor-γ in the spinal trigeminal nucleus were detected to evaluate the biogenesis of mitochondria. The mitochondrial energy metabolism was determined by the mitochondrial membrane potential and the levels of adenosine triphosphate, cytochrome C oxidase, and reactive oxygen species. RESULTS Valproate attenuated nitroglycerin-induced trigeminovascular activation in rats, with reduced scratching behavior and restored 5-hydroxytryptamine and nitric oxide levels. Moreover, the mitochondrial energy metabolism and the biogenesis of mitochondria were preserved by valproate in nitroglycerin-treated rats. CONCLUSIONS The protective effect of valproate against migraine may be achieved through the modulation of mitochondrial biogenesis and function. Our study provides evidence for the potential use of valproate in the treatment of migraine.

Two new geranylated biphenyl esters, 2,3′,4,4′-tetrahydroxy-3-geranyl-5-carboxyethyl-biphenyl methyl ester (1), 2,3′,4,4′-tetrahydroxy-3-geranyl-5-carboxymethyl-biphenyl methyl ester (2), together with 4 known compounds were isolated from the methanol extract of the leaves of Artocarpus altilis. Their structures were established by spectroscopic means and by comparison with literature data. Compound 1 possessed moderate cytotoxicity toward MDA-MB-231 (a breast carcinoma cell line) with a half-maximal inhibitory concentration value of 30 µM and inhibited the growth of 8 bacteria, including gram-negative and gram-positive organisms, but was inactive against fungi.

For wheat straw, an ideal bio-refinery process is that all three major components of biomass could be efficiently utilized to make high value chemicals, MBSP could directly convert the hemicelluloses and lignin into xylo-oligosaccharides and lignosulfonate. However, these value-added compounds still present in spent liquor and thus should be isolated as an individual product. In present work, a simple and efficient ion exchange process was developed for separating xylo-oligosaccharides and lignosulfonate simultaneously from spent liquor. D354 resin was selected for its high adsorption capacity of magnesium lignosulfonate and remarkable selectivity. 93.09% of XOS and 98.03% of lignosulfonate were recovered from the treated spent liquor in a fixed bed column with D354 resin. Overall, 1 L of MBSP spent liquor could coproduce 9.5 g XOS and 74 g lignosulfonate. These results offer an opportunity for complete and effective utilization of biomass by a novel integrated process coupling of MBSP and ion-exchange process.

To get rid of the dependence on lactic acid neutralizer, a simple and economical approach for efficient in situ separation and production of l-lactic acid was established by Bacillus coagulans using weak basic anion-exchange resin. During ten tested resins, the 335 weak basic anion-exchange resins demonstrated the highest adsorption capacity and selectivity for lactic acid recovery. The adsorption study of the 335 resins for lactic acid confirmed that it is an efficient adsorbent under fermentation condition. Langmuir models gave a good fit to the equilibrium data at 50 °C and the maximum adsorption capacity for lactic acid by 335 resins was about 402 mg/g. Adsorption kinetic experiments showed that pseudo-second-order kinetics model gave a good fit to the adsorption rate. When it was used for in situ fermentation, the yield of l-lactic acid by B. coagulans CC17 was close to traditional fermentation and still maintained at about 82% even after reuse by ten times. These results indicated that in situ separation and production of l-lactic acid using the 335 resins were efficient and feasible. This process could greatly reduce the dosage of neutralizing agent and potentially be used in industry.

We present a dual-isothermal cascade strategy assisted by a lateral flow peptide nucleic acid biosensor for point-of-care detection of urinary microRNAs without a temperature protocol and complex instruments. The proposed assay is expected to be of great promise for bladder cancer diagnosis and point-of-care diagnostics.

This paper focuses on obtaining an asymptotic solution for coupled heat and mass transfer problem during the solidification of high water content materials. It is found that a complicated function involved in governing equations can be approached by Taylor polynomials unlimitedly, which leads to the simplification of governing equations. The unknown functions involved in governing equations can then be approximated by Chebyshev polynomials. The coefficients of Chebyshev polynomials are determined and an asymptotic solution is obtained. With the asymptotic solution, the dehydration and freezing fronts of materials are evaluated easily, and are consistent with numerical results obtained by using an explicit finite difference method.