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The present study evaluated the protective effect and the regulatory mechanism of taurine on growth inhibition and intestinal damage induced by glycinin in juvenile Rhynchocypris lagowskii Dybowski. The control diets had no glycinin and taurine, the glycinin diets contained only 80 g/kg glycinin, and the glycinin + taurine diets contained 80 g/kg glycinin+10 g/kg taurine. Juvenile Rhynchocypris lagowskii Dybowski (4.65 ± 0.03 g/tail) were respectively fed with these 3 diets for 8 weeks. The results showed that glycinin significantly decreased the final body weight, weight gain rate, specific growth rate, protein efficiency rate, feed efficiency rate and feeding rate of fish compared with the control group (P < 0.05). While taurine supplementation improved the growth performance and feed efficiency, but final body weight, weight gain rate, specific growth rate of the glycinin + taurine group were still significantly lower than the control group (P < 0.05). Compared with the glycinin group, taurine supplementation significantly increased whole-body and muscle crude protein content, and hepatopancreas and intestinal protease activities (P < 0.05). Distal intestinal villous dysplasia and mucosal damage, and increased intestinal mucosal permeability were observed in the glycinin group, while taurine supplementation alleviated these adverse effects. Usefully, taurine supplementation could also partially restore the impaired immune function and antioxidant capacity of fish fed glycinin diets. Compared with the glycinin group, taurine supplementation down-regulated pro-inflammatory cytokines TNF‐α and IL-1β mRNA levels, and up-regulated anti-inflammatory cytokines IL-10 and TGF-β mRNA levels. Furthermore, taurine partially reversed the reduction of antioxidant genes Nrf 2、 HO-1 , CAT and GPx mRNA levels in distal intestine induced by glycinin. Concluded, 80 g/kg glycinin led to intestinal damage, digestive dysfunction and increased intestinal mucosal permeability in juvenile Rhynchocypris lagowskii Dybowski, and these adverse effects were ultimately manifested in growth inhibition. But taurine supplementation could partially mitigate the negative effects induced by glycinin. • Taurine supplement could alleviate the growth inhibition induced by glycinin in Rhynchocypris lagowskii Dybowski. • Taurine can effectively enhance serum immunity and alleviate intestinal inflammation caused by high-dose glycinin. • Taurine can alleviate high-dose glycinin-induced oxidative stress in fish through the Nrf2 - Keap1 signaling pathway. • When the Rhynchocypris lagowskii Dybowski diet contains 80 g/kg glycinin, it is recommended to supplement 10 g/kg taurine. [ABSTRACT FROM AUTHOR]

The direct methanol fuel cell (DMFC) is an efficient and non-polluting green energy conversion device. However, the electrocatalysts for the anodic methanol oxidation reaction (MOR) in DMFC are often precious metal catalysts, which suffer from high cost, poor stability, and easy deactivation. In this work, two isostructural metal-organic frameworks (MOFs) [M 3 (μ 3 -OH)(TATB)(Nic) 2 (H 2 O) 2 (DMA)] (M = Co, Ni) were successfully synthesized under solvothermal conditions. Both frameworks possess a unique trinuclear cluster [M 3 (μ 3 -OH)(COO) 5 ] secondary building unit (SBU) and a rare binodal (3,7)-connected network. Due to the high density of metal sites and prominent pore system within CTGU-36-Ni, it can serve as an effective molecular electrocatalyst for MOR, while CTGU-36-Co is an inert material. Further experimental results showed that the introduction of conductive substances could lead to a significant increase in the MOR area activity of CTGU-36-Ni. This work not only provides a non-noble metal molecular MOR electrocatalyst but also opens a new vision for the design and application of crystalline materials in various energy conversion processes. Two isostructural metal-organic frameworks (MOFs) with atypical trinuclear cluster have been constructed successfully, which exhibit good electrocatalytic properties toward methanol oxidation reaction as molecular electrocatalysts or after the addition of conductive carbon mediums. [Display omitted] • Two isostructural MOFs with atypical trinuclear cluster have been constructed. • CTGU-36-Ni and its composites exhibit remarkable electrocatalytic activity for MOR. • This work provides a molecular MOR catalyst and a new vision for the application of MOFs. [ABSTRACT FROM AUTHOR]

The epithelial-mesenchymal transition (EMT) is a process of cell transformation under certain physiological and pathological states in which epithelial cells are transformed into mesenchymal cells with fibroblast-like properties, which confers upon them the increased invasion and migration capabilities of cancer cells. Previous studies have demonstrated that SRY-related high-mobility-group box 4 (Sox4) protein coordinates EMT-related pathways and EMT-related transcription factors, thereby regulating the EMT process. The focus of this review is to evaluate recent advances regarding the role of Sox4 protein in the cancer EMT. First, we provide an overview of the general background of Sox4 (structure and function) and the EMT in cancer. Next, we introduce the interactions between Sox4 protein and various factors during cancer EMT. Finally, we suggest directions for future investigations. In general, the information compiled in this paper should serve as a comprehensive repository of information on the subject matter and contribute to the design of other research and future efforts to develop therapeutic strategies that target the Sox4 protein. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Bakuchiol (BAK), [(1E,3S)-3-ethenyl-3,7-dimethyl-1,6-octadien-1-yl]phenol is a prenylated phenolic monoterpene extracted from the fruit of Psoralea corylifolia L., which belongs to the Leguminosae plant family. Previous research has shown that BAK exerts a variety of pharmacological effects, including antioxidant, antibacterial, anti-inflammatory, antiaging and estrogen-like effects. In addition, recent studies have indicated that BAK exerts protective effects in the heart, liver, skin and other organs. BAK treatment protects the heart against ischemia-reperfusion injury through modulating cardioprotective pathways. BAK also inhibits liver fibrosis via promoting myofibroblast apoptosis and relieves the hepatotoxicity of multiple toxicants by suppressing oxidative stress and inflammatory changes. BAK inhibits the proliferation of various cancer cells, including stomach, breast and skin cancer cells, thereby exerting anticancer effects. Further, BAK effectively slows skin aging by preserving skin collagen. BAK treatment can protect against bone loss and delay osteoporosis by exerting estrogen-like effects. In addition, BAK remarkably reduces blood glucose and triglycerides and might be a potential pharmacological agent that can be used to protect against pancreatic beta-cell damage and diabetes progression. In this review, the pharmacological mechanisms and protective effects of BAK in human diseases are discussed, with a focus on the protective effects of BAK in the heart, liver and other important organs. [ABSTRACT FROM AUTHOR]

Highlights • A new method (PPIs-WDSVM) for prediction protein–protein interactions. • The protein sequence features are extracted by fusing the PseAAC, AC and EBGW methods. • 2-D wavelet denoising can effectively remove the redundant information in the protein sequences. • We compared the effect of the five different classifiers on the results. • The proposed method increases the prediction performance over several methods. Abstract Research on protein–protein interactions (PPIs) not only helps to reveal the nature of life activities but also plays a driving role in understanding the mechanisms of disease activity and the development of effective drugs. The rapid development of machine learning provides new opportunities and challenges for understanding the mechanism of PPIs. It plays an important role in the field of proteomics research. In recent years, an increasing number of computational methods for predicting PPIs have been developed. This paper proposes a new method for predicting PPIs based on multi-information fusion. First, the pseudo-amino acid composition (PseAAC), auto-covariance (AC) and encoding based on grouped weight (EBGW) methods are used to extract the features of protein sequences, and the extracted three groups of feature vectors were fused. Secondly, the fused feature vectors are denoised by two-dimensional (2-D) wavelet denoising. Finally, the denoised feature vectors are input to the support vector machine (SVM) classifier to predict the PPIs. The ACC of PPIs of Helicobacter pylori (H. pylori) and Saccharomyces cerevisiae (S. cerevisiae) datasets were 95.97% and 95.55% by 5-fold cross-validation test and compared with other prediction methods. The experimental results show that the proposed multi-information fusion prediction method can effectively improve the prediction performance of PPIs. The source code and all datasets are available at https://github.com/QUST-AIBBDRC/PPIs-WDSVM/. [ABSTRACT FROM AUTHOR]

Phototherapy is an emerging non-pharmacological treatment for depression, circadian rhythm disruptions, and neurodegeneration, as well as pain conditions including migraine and fibromyalgia. However, the mechanism of phototherapy-induced antinociception is not well understood. Here, using fiber photometry recordings of population-level neural activity combined with chemogenetics, we found that phototherapy elicits antinociception via regulation of the ventral lateral geniculate body (vLGN) located in the visual system. Specifically, both green and red lights caused an increase of c-fos in vLGN, with red light increased more. In vLGN, green light causes a large increase in glutamatergic neurons, whereas red light causes a large increase in GABAergic neurons. Green light preconditioning increases the sensitivity of glutamatergic neurons to noxious stimuli in vLGN of PSL mice. Green light produces antinociception by activating glutamatergic neurons in vLGN, and red light promotes nociception by activating GABAergic neurons in vLGN. Together, these results demonstrate that different colors of light exert different pain modulation effects by regulating glutamatergic and GABAergic subpopulations in the vLGN. This may provide potential new therapeutic strategies and new therapeutic targets for the precise clinical treatment of neuropathic pain. • Green light activates glutamatergic neurons in vLGN. • Red light activates GABAergic neurons in vLGN. • Activation of glutaminergic neurons in vLGN mimics the analgesic effects of green light. • Glutamatergic neurons in vLGN may be a new therapeutic target of neuropathic pain. [ABSTRACT FROM AUTHOR]

Serelaxin, a recombinant form of human relaxin-2, is currently regarded as a novel drug for treatment of acute heart failure. However, whether therapeutic effects of serelaxin are achieved by inhibiting cardiac fibrosis remains unclear. In this study, we investigate effects of serelaxin on inhibiting cardiac fibrosis. Cardiac fibroblasts (CFs) were isolated from the hearts of adult rats. Effects of serelaxin on differentiation of CFs towards myofibroblasts (MFs) and their fibrotic behaviors after induction with TGF-β1 were examined. Synthesis and degradation of collagens, secretion of IL-10, and expression of ALK-5 and p-Smad2/3 of TGF-β1-induced cells were assessed after treatment with serelaxin. Serelaxin inhibited differentiation of TGF-β1-induced CFs towards MFs, and reduced proliferation and migration of the induced cells. Moreover, serelaxin down-regulated expression of collagen I/III and TIMP-2, and up-regulated expression of MMP-2 and MMP-9 in the cells. After treatment with serelaxin, activity of MMP-2 and MMP-9 and secretion of IL-10 increased, expression of ALK-5 and the level of Smad2/3 phosphorylation was reduced significantly. These results suggest that serelaxin can inhibit differentiation of TGF-β1-induced CFs towards MFs, reduce production of collagens by suppressing ALK-5/Smad2/3 signaling pathway, and enhance extracellular matrix degradation by increasing MMP-2/TIMP-2 ratio and IL-10 secretion. Serelaxin may be a potential therapeutic drug for inhibiting cardiac fibrosis. [ABSTRACT FROM AUTHOR]

For the first time, sodium caprylate has been investigated to direct the crystal growth of 3D Ag-MOF, [Ag 2 (ddcba)(4,4′-bipy) 2 ] ( 1 ), constructing from 3,5-(di(2′,5′-dicarboxylphenyl)benozoic acid and 4,4′-bipy. The single crystal diffraction analyses shows that complex 1 possess 3D neutral framework with a three-connected ThSi 2 (10 3 -b) topology. Compound 1 exhibits predominant catalytic activity towards the degradation of o- Nitrophenol (ONP), m- Nitrophenol (MNP) and p- Nitrophenol (PNP) in aqueous solution. The kinetics of such catalytic degradation reactions was also studied. [ABSTRACT FROM AUTHOR]

Sarcolipin (SLN), an important membrane protein expressed in the sarcoplasmic reticulum (SR), regulates muscle contractions in cardiac and skeletal muscle. The phosphorylation at amino acid Thr5 of the SLN protein modulates the amount of Ca 2+ that passes through the SR. Using molecular dynamics simulation, we evaluated the phosphorylation at Thr5 of pentameric SLN (phospho-SLN) channel’s energy barrier and pore characteristics by calculating the potential of mean force (PMF) along the channel pore and determining the diffusion coefficient. The results indicate that pentameric phospho-SLN promotes penetration of monovalent and divalent ions through the channel. The analysis of PMF, pore radius and diffusion coefficient indicates that Leu21 is the hydrophobic gate of the pentameric SLN channel. In the channel, water molecules near the Leu21 pore demonstrated a clear hydrated-dehydrated transition; however, the mutation of Leu21 to an Alanine (L21A) destroyed the hydrated-dehydrated transitions. These water-dynamic behaviors and PMF confirm that Leu21 is the key residue that regulates the ion permeability of the pentameric SLN channel. These results provide the structural-basis insights and molecular-dynamic information that are needed to understand the regulatory mechanisms of ion permeability in the pentameric SLN channel. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) affects millions of people worldwide. Although the etiology of this disease is uncertain, accumulating evidence indicates a key role for the activated mucosal immune system. In the present study, we examined the effects of the natural compound fraxinellone on dextran sulfate sodium (DSS)-induced colitis in mice, an animal model that mimics IBD. Treatment with fraxinellone significantly reduced weight loss and diarrhea in mice and alleviated the macroscopic and microscopic signs of the disease. In addition, the activities of myeloperoxidase and alkaline phosphatase were markedly suppressed, while the levels of glutathione were increased in colitis tissues following fraxinellone treatment. This compound also decreased the colonic levels of interleukin (IL)-1β, IL-6, IL-18 and tumor necrosis factor (TNF)-α in a concentration-dependent manner. These effects of fraxinellone in mice with experimental colitis were attributed to its inhibition of CD11b + macrophage infiltration. The mRNA levels of macrophage-related molecules in the colon, including intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2), were also markedly inhibited following fraxinellone treatment. The results from in vitro assays showed that fraxinellone significantly reduced lipopolysaccharide (LPS)-induced production of nitric oxide (NO), IL-1β and IL-18 as well as the activity of iNOS in both THP-1 cells and mouse primary peritoneal macrophages. The mechanisms responsible for these effects were attributed to the inhibitory role of fraxinellone in NF-κB signaling and NLRP3 inflammasome activation. Overall, our results support fraxinellone as a novel drug candidate in the treatment of colonic inflammation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Excessive release of inflammatory mediators and oxidative stress play important roles in the increased vascular permeability and systemic edema during the early stage of severe burn. This study investigates the effect of 200 mEq/L Na+ hypertonic saline (HS) on systemic inflammatory response and oxidative stress in severely burned rats. Materials and methods: Sprague-Dawley rats were divided into three groups: sham group, burn plus lactated Ringer's group, and burn plus HS group. Lung edema was assessed in terms of wet-weight-to-dry-weight ratio. Tumor necrosis factor α and interleukin 6 concentrations in serum were examined by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells were isolated and the expression of p38 mitogen-activated protein kinase was determined by Western blot analysis. The lung and intestinal concentrations of malondialdehyde, an indicator of oxidative stress, were also measured. Results: Resuscitation with 200 mEq/L Na+ HS significantly decreased the lung wet-weight-to-dry-weight ratio and abolished hyponatremia induced by burn injury. HS treatment also prevented the increases of myeloperoxidase activity and malondialdehyde content in the lung and intestine of severely burned rats. However, there were no significant differences, either in serum tumor necrosis factor α and interleukin 6 concentrations or with respect to the p38 mitogen-activated protein kinase expression in peripheral blood mononuclear cells, between the burn plus lactated Ringer's group and burn plus HS group (P > 0.05). Conclusions: Initial resuscitation with 200 mEq/L Na+ HS after severe burn injury decreases pulmonary edema, prevents hyponatremia, and attenuates oxidative stress, but is not capable of inhibiting the systemic inflammatory response. [Copyright &y& Elsevier]

Abstract: In the present study, we aimed to investigate the immunosuppressive activity of vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, on T lymphocytes both in vitro and in vivo, and further explored its potential molecular mechanism. Resveratrol had a wide spectrum of healthy beneficial effects with multiple targets. Interestingly, its tetramer, vaticaffinol, exerted more intensive immunosuppressive activity than resveratrol. Vaticaffinol significantly inhibited T cells proliferation activated by concanavalin A (Con A) or anti-CD3 plus anti-CD28 in a dose- and time-dependent manner. It also induced Con A-activated T cells undergoing apoptosis through mitochondrial pathway. Moreover, this compound prevented cells from entering S phase and G2/M phase during T cells activation. In addition, vaticaffinol inhibited ERK and AKT signaling pathways in Con A-activated T cells. Furthermore, vaticaffinol significantly ameliorated ear swelling in a mouse model of picryl chloride-induced ear contact dermatitis in vivo. In most of the aforementioned experiments, however, resveratrol had only slight effects on the inhibition of T lymphocytes compared with vaticaffinol. Taken together, our findings suggest that vaticaffinol exerts more preferable immunosuppressive activity than its precursor resveratrol both in vitro and in vivo by affecting multiple targets against activated T cells. [Copyright &y& Elsevier]

Abstract: Water-soluble and highly stable dispersions of copper nanoparticles were obtained using a biomolecule-assisted synthetic method. Dopamine was utilized as both reducing and capping agent in aqueous medium. The successful formation of DA-stabilized copper particles was demonstrated by ultraviolet–visible spectroscopy (UV–Vis), transmission electron microscopy (TEM), Zeta potential measurement, and Fourier transform infrared spectroscopy (FT-IR). The mechanism of dopamine on the effective reduction and excellent stability of copper nanoparticles was also discussed. This facile biomolecule-assisted technique may provide a useful tool to synthesize other nanoparticles that have potential application in biotechnology. [Copyright &y& Elsevier]

Abstract: In this study, we report the effect of endothelial progenitor cells (EPCs) on the biological behavior of osteoclast precursors in vitro by establishing an indirect co-culture system of mice EPCs and RAW 264.7 monocyte cells. Results show that the survival, migration, and differentiation of osteoclast precursors were greatly enhanced when co-cultured with EPCs. These phenotypic changes coincide with the upregulation of multiple genes affected cell behavior, including phospho-VEGFR-2, CXCR4, phospho-Smad2/3, phospho-Akt, phospho-ERK1, and phospho-p38 MAPK. The results collectively suggest that EPCs could modulate the survival, migration, and differentiation potential of osteoclast precursors, thus providing new insights in understanding of correlation between angiogenesis and bone homeostasis. [Copyright &y& Elsevier]

Abstract: In the present paper, we aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. Cerebroside D significantly reduced the weight loss, mortality rate and alleviated the macroscopic and microscopic appearances of colitis induced by dexran sulfate sodium. This compound also decreased the levels of TNF-α, IFN-γ and IL-1β in intestinal tissue of mice with experimental colitis in a concentration-dependent manner, accompanied with markedly increased serum level of IL-10. Cerebroside D inhibited proliferation and induced apoptosis of T cells activated by concanavalin A or anti-CD3 plus anti-CD28 antibodies. The compound did not show an effect on naive lymphocytes but prevented cells from entering S phase and G2/M phase during T cells activation. Moreover, the treatment of cerebroside D led to apoptosis of activated T cells with the cleavage of caspase 3, 9, 12 and PARP. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation. [Copyright &y& Elsevier]

Abstract: In this paper, the meshless local Petrov–Galerkin (MLPG) method is extended to solve the incompressible fluid flow problems. The streamline upwind Petrov–Galerkin (SUPG) method is applied to overcome oscillations in convection-dominated problems, and the pressure-stabilizing Petrov–Galerkin (PSPG) method is applied to satisfy the so-called Babuška–Brezzi condition. The same stabilization parameter τ(τ SUPG = τ PSPG ) is used in the present method. The circle domain of support, linear basis, and fourth-order spline weight function are applied to compute the shape function, and Bubnov–Galerkin method is applied to discretize the PDEs. The lid-driven cavity flow, backward facing step flow and natural convection in the square cavity are applied to validate the accuracy and feasibility of the present method. The results show that the stability of the present method is very good and convergent solutions can be obtained at high Reynolds number. The results of the present method are in good agreement with the classical results. It also seems that the present method (which is a truly meshless) is very promising in dealing with the convection- dominated problems. [ABSTRACT FROM AUTHOR]

[Display omitted] A critical challenge in the enzymatic conversion of acylglycerols is the limited exposure of the enzyme dissolved in the aqueous solution to the hydrophobic substrate in the oil phase. Positioning the enzyme in a microenvironment with balanced hydrophobicity and hydrophilicity in Pickering emulsion will facilitate the acylglycerol-catalyzing reactions at the interface between the oil and liquid phases. In this work, to overcome the challenge of biphasic catalysis, we report a method to immobilize enzymes in polyethylene glycol (PEG)-based hydrogel microparticles (HMPs) at the interface between the oil and water phases in Pickering emulsion to promote the enzymatic conversion of acylglycerols. 3 wt% of HMPs can stabilize the oil-in-water Pickering emulsion for at least 14 days and increase the viscosity of emulsions. Lipase-HMP conjugates showed significantly higher hydrolytic activity in Pickering emulsion; HMP-immobilized lipase SMG1 showed an activity about three times that of free lipase SMG1. Co-immobilization of a lipase and a fatty acid photodecarboxylase from Chlorella variabilis (CvFAP) in Pickering emulsion enables light-driven cascade conversion of triacylglycerols to hydrocarbons, transforming waste oil to renewable biofuels in a green and sustainable approach. HMPs stabilize the Pickering emulsion and promote interfacial biocatalysis in converting acylglycerols to renewable biofuels. [ABSTRACT FROM AUTHOR]

A colorimetric sensor based on gold nanoparticles (AuNPs) and single-stranded DNA (ssDNA) is a simple and rapid method for detecting foodborne pathogens. However, the colorimetric method employed in previous studies involved short ssDNA (<100 nucleotides), including the aptamer and PCR products, resulting in the high detection limit of this technique. In this study, a colorimetric sensor was developed based on long ssDNA of asymmetric PCR (aPCR) and non-functionalized AuNPs for detecting Salmonella Typhimurium (S. Typhimurium). In the presence of S. Typhimurium, the long ssDNA (547 nt) amplified by aPCR-protected AuNPs from NaCl-induced aggregation, while the solution retained a red color. After optimizing parameters, the limit of detection (LOD) of the colorimetric sensor was 2.56 CFU/mL with high specificity. Recovery studies showed its feasibility for detecting S. Typhimurium (102 CFU/mL, 104 CFU/mL, and 106 CFU/mL) in spiked lettuce samples. This colorimetric sensor provides new opportunities for the highly sensitive detection of bacteria in real food samples. [Display omitted] • Colorimetric method based on long ssDNA and non-functionalized gold nanoparticles. • Long ssDNA could be obtained by aPCR-protected AuNPs from NaCl-induced aggregation. • The limit of detection was 2.56 CFU/mL. • Recovery rate of S. Typhimurium in s piked lettuce ranged from 91.84% to 110.2%. [ABSTRACT FROM AUTHOR]

Abstract: Synthetic oligonucleotides had been employed in DNA repair and promised great potentials in gene therapy. To test the ability of single-stranded oligonucleotide (SSO)-mediated gene repair within a chromosomal site in human cells, a HeLa cell line stably integrated with mutant enhanced green fluorescence protein gene (mEGFP) in the genome was established. Transfection with specific SSOs successfully repaired the mEGFP gene and resulted in the expression of functional fluorescence proteins, which could be detected by fluorescence microscopy and FACS assay. Western blot showed that EGFP was only present in the cells transfected with correction SSOs rather than the control SSOs. Furthermore, DNA sequencing confirmed that phenotype change resulted from the designated nucleotide correction at the target site. Using this reporter system, we determined the optimal structure of SSO by investigating the effect of length, modifications, and polarities of SSOs as well as the positions of the mismatch-forming nucleotide on the efficiency of SSO-mediated gene repair. Interestingly, we found that SSOs with mismatch-forming nucleotide positioned at different positions have varying potencies that homology at the 5′-end of SSOs was more crucial for the SSO’s activity. These results provided guidance for designing effective SSOs as tools for treating monogenic inherited diseases. [Copyright &y& Elsevier]

Direct methanol fuel cells (DMFCs) can permit the utilization of noble-metal-free electrocatalysts, which certainly reduces the cost and accelerates their practical implementation. With the exploration of efficient and economical methanol oxidation reaction (MOR) catalysts, Ni-based nanostructures have been recognized as the most promising MOR catalysts in alkaline media. Herein, we construct a novel heterojunction MOR electrocatalyst composed of Ni-based metal-organic framework (Ni-MOF) and NiFe-based layered double hydroxides (LDHs) through a coordination-induced self-assembly strategy. Owing to the synergic effect between Ni and Fe sites, coupled with the effect of hetero-interface, the resultant Ni-MOF/NiFe-LDH composite exhibits remarkable MOR activity in 0.1 M KOH electrolyte with the oxidation current density (32.66 mA cm−2) is 2.65 and 2.44 times higher than that of the primitive NiFe-LDH and Ni-MOF. The excellent stability of the Ni-MOF/NiFe-LDH electrocatalyst has also been confirmed by long-term chronoamperometry (CA) analysis. Our work paves a facile controllable way for fabricating MOF/LDH heterostructure targets on MOR and underlines its potential to boost energy conversion efficiency through the manipulation of synergic components. A novel Ni-MOF/NiFe-LDH heterojunction MOR electrocatalyst has been successfully constructed through a coordination-induced self-assembly strategy, which exhibits a collaborative enhancement in electrocatalytic properties toward alkaline MOR. [Display omitted] • A heterojunction composite has been constructed through a coordination-induced self-assembly strategy. • Ni-MOF/NiFe-LDH exhibits remarkable electrocatalytic activity toward alkaline MOR. • This work underlines the potential of MOF/LDH heterostructure in enhancing energy conversion efficiency. [ABSTRACT FROM AUTHOR]

Globally, there is a noticeable increasing trend in farmland abandonment, which directly affects farmers' livelihood and food security. The abandonment status, its determinants and impact vary by spatial and socioeconomic context. In order to study this important issue, we selected three different villages representing three ecological regions (Mountain, Hill, and Tarai) in the Koshi River Basin (KRB), and applied two methods: the Unmanned Aerial Vehicle (UAV) and a social survey. The UAV captured 3711 images and we carried out 162 households' survey with structured questionnaires. Pix4Dmapper and ArcGIS tools were used for combining and processing the images. On-screen digitalization and binary logistic regression (BLR) were applied to examine the status and determinants of farmland abandonment. The results show a higher proportion of farmland abandonment in the villages located in the Hill and Mountain regions compared to those in the Tarai region. Almost 10.3% area of total land and 22.3% area of total farmland was abandoned in the Hill village. The Tarai village had the least farm abandonment (3.7%). Farmers perceived that climate change (less precipitation, increasing temperatures, and drought), shifting occupations, crops damaged by wildlife, migration, lack of irrigation, and a labor shortage are the leading determinants of farmland abandonment. These factors varied slightly across the different ecological regions. The BLR model was a good fit with Nagelkerke's R 2 = 0.776, with a correct model prediction (87.7%) and p = 0.032. The results from the regression model suggest that an increase in temperature (p = 0.000), decrease in rainfall (p = 0.001), lack of machinery used for farm-work (p = 0.000), lack of irrigation (p = 0.000), and reduction of labor-force (p = 0.000) are the main contributing determinants of farmland abandonment. This synergy of high-resolution remote sensing and farmers' perception-based findings facilitates the improvement of land-use governmental policies to improve farmers' quality of life and build sustainable farmland management. Image 1 • Status and determinants of farmland abandonment vary by regions in the Koshi basin. • Biophysical attributes and farm characteristics were the important determinants. • Farmers' livelihood in Mountain and Hill regions is highly affected by this issue. • Improving policies is key to reduce farm abandonment and ensure food security. [ABSTRACT FROM AUTHOR]

In a lake basin, there is a mismatch between river and lake water quality targets and a method for setting specific water quality targets for these rivers is urgently needed. Using Dianchi Lake as an example, we proposed a lake basin water quality management system based on the river-lake water quality response relationship, coupled with a Soil and Water Assessment Tool (SWAT) basin hydrological model and Environmental Fluid Dynamics Code (EFDC) lake water quality hydrodynamic model. River water quality control requirements based on the river-lake water quality response were proposed, under the premise that the Dianchi Lake water quality reaches the required standard. Then, water quality control targets for rivers were determined, and corrected for influencing factors, such as current river water quality and composition of flow. Our systematic approach efficiently identified key lake basin pollution sources, and accurately located key points for water quality improvement and pollution control. Combined with a correction for clean water source and current water quality of each river, the proposed water quality targets were practical and operable. Meanwhile, the EFDC model was used to verify the entire process to ensure that river water quality targets could be set to achieve lake water quality targets. To ensure that Dianchi Lake water quality can reach Class IV standard, the Chemical oxygen demand (COD) concentration would need to be maintained under 30 mg/L,Waihai total nitrogen (TN) below 7 mg/L, total phosphorus (TP) below 0.2 mg/L, and ammonia nitrogen (NH 3 –N) below 2 mg/L. • There is a mismatch between river and lake water quality targets. • COD and TP concentration of the inflow rivers needs to be strictly controlled. • The required concentration of TN and NH 3 –N in the rivers could be slightly lowered. [ABSTRACT FROM AUTHOR]

Psoralidin (PSO) is a natural phenolic coumarin that is extracted from the seeds of Psoralea corylifolia L. PSO possesses a variety of pharmacological activities, including anti-oxidative, antibacterial, anti-inflammatory, anti-depressive and estrogenic-like effects. Other studies have indicated that PSO plays a beneficial role in multiple disease, especially cancer and osteoporosis. In this review, we first outline the basic background of PSO. Then we introduced the molecular mechanisms and signaling pathways of PSO in multiple cancers to elucidate its anticancer potential via inducing oxidative stress and apoptosis, inhibiting proliferation, promoting autophagy-dependent cell death, and activating the estrogen receptors (ER)-signaling pathway. Finally, we recommend the direction of future investigations. In general, the information compiled in this paper should serve as a comprehensive repository of information to help design PSO in other research and future efforts. [ABSTRACT FROM AUTHOR]

ZnO as an eco-friendly material shows bright luminescence under UV illumination when it is tailored into nanoscale size, which makes it a promising luminescent nanomaterial. However, the poor stability of ZnO hinders its applications drastically. In this work, multi-ZnO-cores@uni-BaSO 4 -shell (mZnO@uBaSO 4 ) nanocomposite has been prepared through a non-equilibrium sorption process employing ZnO QDs as the “seeds” and BaSO 4 as the “valve”. The mZnO@uBaSO 4 nanocomposite shows improved photo-, thermal- and ambient-stability compare with bare ZnO QDs. The fluorescence efficiency of the mZnO@uBaSO 4 nanocomposite decreases little even after 60 h of UV irradiation compare with ZnO QDs. The mZnO@uBaSO 4 nanocomposite shows bright luminescence with little decrease even the ambient temperature up to 160 °C and the nanocomposite shows strong resistance to harsh environment. By coating the mZnO@uBaSO 4 nanocomposite and commercial phosphors onto UV-chip, light-emitting diode (LED) with correlated color temperature, Commission Internationale de L'Eclairage coordinate, color rendering index and luminous efficiency of 6109 K, (0.32, 0.33), 85 and 47.33 lm/W have been realized, and this will make a great step towards eco-friendly UV-pumped LEDs. [ABSTRACT FROM AUTHOR]

Direct methanol fuel cells (DMFCs) are considered one of the most promising energy conversion devices due to their environmentally friendly and high-energy density features. However, the sluggish anode kinetics of the methanol oxidation reaction (MOR) acts as a bottleneck in the DMFCs system. Herein, a series of MOF-based heterogeneous electrocatalysts (NiWO 4 /MOF-74- x, Ni 3 V 2 O 8 /MOF-74- x) is constructed via a coordination-driven self-assembly strategy to enhance the catalytic property of the MOR. The heterogeneous interface between MOF-74 and Ni compounds is built by the Ni–O coordination interaction, which provides fast charge transfer and mass diffusion efficiency. Therefore, the optimal catalyst NiWO 4 /MOF-74 (3) exhibits excellent MOR activity and operation durability with a peak current density of 28.58 ​mA·cm-2. This work is expected to inspire the design of more efficient MOF-based heterogeneous electrocatalysts for MOR and other energy conversion applications. A series of MOF-based heterogeneous electrocatalysts have been constructed successfully via a coordination-driven self-assembly strategy, which exhibits excellent MOR activity and operational durability in the alkaline medium. [Display omitted] • A series of MOF-based heterogeneous electrocatalysts have been constructed via a coordination-driven self-assembly strategy. • NiWO 4 /MOF-74 (3) composite exhibits good activity and operation durability for MOR. • This work provides a new vision for the design of heterogeneous MOR electrocatalysts. [ABSTRACT FROM AUTHOR]

[Display omitted] • EH 6 surfactant molecules can rapidly migrate to newly formed interfaces and adsorb intensively to achieve surface wettability reversal and regulate droplet impact behavior on hydrophobic leaves. • EH 6 surfactant adsorbs intensively at the contact line and achieves rapid wetting on the hydrophobic surface driven by Marangoni forces. • EH 6 as a tank-mix adjuvant significantly improves the physicochemical properties of spray dilutions and enhances the dose delivery efficiency to achieve efficient delivery of pesticides. • EH 6 as a tank-mix adjuvant increases pesticide deposition and adhesion, thereby reducing pesticide use and environmental risk. Droplet rebound from hydrophobic leaves is a major factor influencing pesticide utilization. The use of a surfactant is a major strategy to reduce droplet rebound, promoting pesticide deposition on hydrophobic agricultural plant leaves. However, most surfactants known to regulate droplet rebound are either anionic or cationic. In this study, ethoxylated propoxylated 2-ethyl-1-haxanol (EH 6) was identified as a nonionic surfactant that inhibits droplet rebound while promoting the complete spreading of the droplet on hydrophobic leaves. Compared with the widely reported nonionic surfactant Tween 20, EH 6 performs better at concentrations above 0.3%. This phenomenon can be attributed to the rapid migration of EH 6 from the bulk to the newly generated interface, significantly reducing the surface tension. We introduce a simple and effective strategy that can be used to enhance droplet deposition on hydrophobic plant surfaces, which may offer future economic and environmental benefits. [ABSTRACT FROM AUTHOR]

Hypoxia is arguably the first recognized cancer microenvironment hallmark and affects virtually all cellular populations present in tumors. During the past decades the complex adaptive cellular responses to oxygen deprivation have been largely elucidated, raising hope for new anti cancer agents. Despite undeniable preclinical progress, therapeutic targeting of tumor hypoxia is yet to transition from bench to bedside. This review focuses on new pharmacological agents that exploit tumor hypoxia or interfere with hypoxia signaling and discusses strategies to maximize their therapeutic impact. [ABSTRACT FROM AUTHOR]

Our recent multi-omics studies have revealed rich sources of novel bioactive proteins and polypeptides from marine organisms including cnidarians. In the present study, we initially conducted a transcriptomic analysis to review the composition profile of polypeptides from Zoanthus sociatus. Then, a newly discovered NPY-like polypeptide-ZoaNPY was selected for further in silico structural, binding and virtually pharmacological studies. To evaluate the pro-angiogenic effects of ZoaNPY, we employed an in vitro HUVECs model and an in vivo zebrafish model. Our results indicate that ZoaNPY, at 1–100 pmol, enhances cell survival, migration and tube formation in the endothelial cells. Besides, treatment with ZoaNPY could restore a chemically-induced vascular insufficiency in zebrafish embryos. Western blot results demonstrated the application of ZoaNPY could increase the phosphorylation of proteins related to angiogenesis signaling including PKC, PLC, FAK, Src, Akt, mTOR, MEK, and ERK1/2. Furthermore, through molecular docking and surface plasmon resonance (SPR) verification, ZoaNPY was shown to directly and physically interact with NPY Y2 receptor. In view of this, all evidence showed that the pro-angiogenic effects of ZoaNPY involve the activation of NPY Y2 receptor, thereby activating the Akt/mTOR, PLC/PKC, ERK/MEK and Src- FAK-dependent signaling pathways. Furthermore, in an excision wound model, the treatment with ZoaNPY was shown to accelerate the wound healing process in mice. Our findings provide new insights into the discovery and development of novel pro-angiogenic drugs derived from NPY-like polypeptides in the future. [Display omitted] [ABSTRACT FROM AUTHOR]

Co-BDC/Ti 3 C 2 T x hybrid nanosheets with rich bridging bonds and tight contact interface were in-situ fabricated via a simple two-step approach including solvothermal reaction and low-temperature annealing, which ensure the high overall conductivity and reactivity as well as stability, and hence bring improved electrochemical performance to HSC. [Display omitted] The design and synthesis of high-performance metal–organic frameworks (MOFs)-based electrodes are important for hybrid supercapacitors (HSC). Herein, enhanced interfacial interaction in Co-BDC/Ti 3 C 2 T x (denoted as CoTC) hybrid nanosheets is achieved through thermal treatment, giving remarkably improved capacity performance compared with CoTC. The low temperature annealing treatment enables modulation of the bridging bonds content of CoTC and thus regulates the interfacial coupling effect between Co-BDC and Ti 3 C 2 T x. Moreover, both the detailed XPS and XANES analysis reveal that the strong interfacial interactions between the two components promote a partial electron transfer from Ti 3 C 2 T x to Co-BDC through the Ti-O-Co interfacial bonds. Consequently, it endows the Co-BDC with enhanced conductivity as well as the higher valence of Ti species in Ti 3 C 2 T x , hence contributes a remarkable enhanced specific capacity. This work will provide a pathway to design advanced MOF/MXene materials for HSC. [ABSTRACT FROM AUTHOR]

Integrating metal-organic frameworks (MOFs) with transition hydroxides has the potential to enhance the inadequate electronic conductivity and address the slow diffusion of MOF materials in electrochemical applications. Herein, we synthesized a 2D Cu-MOF and successfully prepared a Cu-MOF@Co(OH) 2 heterostructure using a one-step hydrothermal method on a Co(OH) 2 /NF (nickel foam) substrate. The hybrid Cu-MOF@Co(OH) 2 material exhibits high electrochemical reactivity, resulting in enhanced pseudocapacitor performance, with a specific capacitance of 2039.8 mF cm−2 at a current density of 1.0 mA cm−2. In addition, an asymmetric two-electrode cell was constructed using Cu-MOF@Co(OH) 2 /NF and activated carbon (AC)/NF, exhibiting a specific capacitance of 444.5 mF cm−2 at a current density of 1.0 mA cm−2, and demonstrating decent cycling durability with 90.1 % retention after 2000 cycles. One 2D Cu-MOF with MOF-110 analogs has been obtained and crystallographically characterized. The Cu-MOF@Co(OH) 2 heterostructure acted as asymmetric supercapacitor electrode material, which delivered enhance pseudocapacitor performance. Besides, the asymmetric two-electrode Cu-MOF@Co(OH) 2 //AC devices possessed the good specific capacitance and cycling durability. [Display omitted] • One 2D Cu-MOF with MOF-110 analogs has been synthesized and crystallographically characterized. • The Cu-MOF@Co(OH) 2 hybrid material has been fabricated, characterized and showed enhanced pseudocapacitor performance. • The asymmetric two-electrode Cu-MOF@Co(OH) 2 //AC devices possessed the good specific capacitance and cycling durability. [ABSTRACT FROM AUTHOR]

DMF hydrolysis is not scaring, but further condensation of HDO over strong acid sites is the intrinsic cause for loss in PX selectivity and carbon balance. [Display omitted] • Acid strength exhibits a significant influence on PX selectivity. • DMF hydrolysis to HDO is not the intrinsic cause for decrease in PX selectivity. • Condensation of HDO over strong acid sites results in loss of PX selectivity. • The process starting with HDO and ethylene for PX production is investigated. • Reducing strong acid site amount helps to improve PX selectivity. Although a precise understanding of acid strength would be essential to elucidate the reaction mechanism and boost the catalytic activity, it is still severely deficient during p -xylene (PX) production from 2,5-dimethylfuran (DMF). Herein, a series of metal phosphate catalysts featuring varied acid strength are prepared and afford an ideal platform. A combination study including kinetic analysis, converting pathway investigation and isotopic labelling experiments reveal the reversible reaction between DMF and 2,5-hexanedione (HDO) and the vital role of strong acid sites during the further conversion of HDO. DMF hydrolysis to HDO is not the intrinsic cause for decrease in PX selectivity, but further condensation of HDO over the strong acid sites is to blame. It destroys the equilibrium state of the reversible reaction and leads to loss in PX selectivity and carbon balance. Besides, the process starting with HDO and ethylene for PX production and strategies to improve PX selectivity have also been proposed. This work provides a much deeper insight into the crucial role of acid strength, which would be constructive for rational design of new catalysts and the corresponding mechanistic understanding. [ABSTRACT FROM AUTHOR]

Abstract: Targeted gene repair mediated by single-stranded DNA oligonucleotides (SSOs) is a promising method to correct the mutant gene precisely in prokaryotic and eukaryotic systems. We used a HeLa cell line, which was stably integrated with mutant enhanced green fluorescence protein gene (mEGFP) in the genome, to test the efficiency of SSO-mediated gene repair. We found that the mEGFP gene was successfully repaired by specific SSOs, but the efficiency was only ∼0.1%. Then we synthesized a series of nonspecific oligonucleotides, which were single-stranded DNA with different lengths and no significant similarity with the SSOs. We found the efficiency of SSO-mediated gene repair was increased by 6-fold in nonspecific oligonucleotides-treated cells. And this improvement in repair frequency correlated with the doses of the nonspecific oligonucleotides, instead of the lengths. Our evidence suggested that this increased repair efficiency was achieved by the transient alterations of the cellular proteome. We also found the obvious strand bias that antisense SSOs were much more effective than sense SSOs in the repair experiments with nonspecific oligonucleotides. These results provide a fresh clue into the mechanism of SSO-mediated targeted gene repair in mammalian cells. [Copyright &y& Elsevier]

Abstract: In this study, we report the role of integrin α5 in promoting melanoma metastasis. The α5 expression was remarkably elevated in highly metastatic B16F10 melanoma cells compared to lowly metastatic B16F1 cells, whereas no significant changes were detected in those of integrin α4, αv, and β1 subunits. Neutralization of α5 with anti-α5 antibody significantly suppressed the potential of B16F10 cells for pulmonary metastasis in mice and inhibited cell adhesion or spreading to fibronectin in vitro. Furthermore, loss of the interaction between α5 and fibronectin diminished cell survival and induced apoptosis in B16F10 cells. Above results provide clear evidence that integrin α5 is positively correlated with melanoma metastasis and might be an anti-melanoma target. [Copyright &y& Elsevier]

Relapse of pulmonary tuberculosis (PTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis . Severe immunodeficiency or immune disorders may be the main reason for TB recurrence. This study aimed to quantify serum inflammatory cytokine and soluble adhesion molecule levels in Re-treated smear-positive PTB patients before and after re-anti-TB drug therapy. Serum samples were collected from 30 healthy controls and 215 Treated active PTB patients at baseline and 2, 4, and 6 months post-re-treatment. Levels of 18 serum cytokines and soluble adhesion molecules were measured by a high-throughput Cytometric Bead Array. At baseline, IL-1, IL-2, IL-12P70, and soluble CD62E levels were significantly higher in PTB patients than those in the healthy controls (p < 0.05); IL-4, IL-5, IL-7, IL-8, IL-10, IL-17, IL-21, soluble CD54, MIG, and TGF-β levels in PTB patients were significantly lower than those in the healthy controls (p < 0.05), of which TGF-β, IL-7, IL-8, IL-10, soluble CD54, and MIG were most notably (p < 0.0005). After re-treatment, IFN-γ, IL-2, IL-7, and soluble CD54 levels and IL-2/IL-10 and IFN-γ/IL-10 ratios showed an upward trend during the re-treatment period. They were more sensitive than other cytokines and adhesion molecules and could be effective as serum indicators for re-treatment response. The immune response was imbalance in treated smear-positive PTB patients: Th1 response was elevated, but Th2 and Th17 responses were reduced. Systematic and comprehensive understanding of the cytokine and soluble adhesion molecule profiles provides a theoretical basis for immuno-diagnosis, immunotherapy, and immuno-monitoring of Re-treated PTB patients. [ABSTRACT FROM AUTHOR]

Aquatic macrophytes and algae are the most important sources of autochthonous dissolved organic matter (DOM), and their transformation and reuse significantly affect aquatic ecosystem health. In this study, Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was used to identify the molecular features between submerged macrophyte-derived DOM (SMDOM) and algae-derived DOM (ADOM). The photochemical heterogeneity between SMDOM and ADOM by UV 254 -irradiation and their molecular mechanism were also discussed. The results showed that the molecular abundance of SMDOM was dominated by lignin/CRAM-like structures, tannins, and concentrated aromatic structures (sum of 91.79%), while that of ADOM was dominated by lipids, proteins, and unsaturated hydrocarbons (sum of 60.30%). UV 254 -radiation resulted in a net reduction of tyrosine-like, tryptophan-like and terrestrial humic-like, and conversely a net production of marine humic-like. The light decay rate constants obtained by the multiple exponential function model fitting revealed that both tyrosine-like and tryptophan-like components of SMDOM could be rapidly and directly photodegraded, while the photodegradation of tryptophan-like in ADOM depended on the production of photosensitizers. The photo-refractory fractions of both SMDOM and ADOM were as follows: humic-like > tyrosine-like > tryptophan-like. Our results provide new insights into the fate of autochthonous DOM in aquatic ecosystems where "grass-algae" coexist or evolve. • Significant differences at the molecular level between SMDOM and ADOM. • SMDOM is more photolabile than ADOM. • The rapid photodegradation of SMDOM is attributed to abundant tannins. • Photodegradation of tryptophan-like in ADOM depends on photosensitizer production. [ABSTRACT FROM AUTHOR]

Postoperative pain is a common form of acute pain that, if not managed effectively, can become chronic pain. Evidence has shown that glia, especially microglia, mediate neuroinflammation, which plays a vital role in pain sensitization. Moreover, toll-like receptor 4 (TLR4), the tumor necrosis factor receptor (TNF-R), the interleukin-1 receptor (IL-1R), and the interleukin-6 receptor (IL-6R) have been considered key components in central pain sensitization and neuroinflammation. Therefore, we hypothesized that activation of the body’s endogenous “immune brakes” will inhibit these receptors and achieve inflammation tolerance as well as relieve postoperative pain. After searching for potential candidates to serve as this immune brake, we identified and focused on the suppressor of cytokine signaling 3 (SOCS3) gene. To regulate SOCS3 expression, we used paeoniflorin to induce heat shock protein 70 (HSP70)/TLR4 signaling. We found that paeoniflorin significantly induced SOCS3 expression both in vitro and in vivo and promoted the efflux of HSP70 from the cytoplasm to the extracellular environment. Furthermore, paeoniflorin markedly attenuated incision-induced mechanical allodynia, and this effect was abolished by small interfering RNAs targeting SOCS3. These findings demonstrated an effective and safe strategy to alleviate postoperative pain. [ABSTRACT FROM AUTHOR]

Dredged sediments derived from eutrophicated lakes poses hardness of sludge disposal and ecological risks. The proper pretreatment and utilization of dredged sediments presented a challenge. In this study, Dianchi Lake sediments were dredged, thermally treated and utilized as particle capping material in batch experiments. The effects of calcination on phosphorus speciation and sediment-water interface environment as well as P immobility mechanism were predominantly explored. The microstructures and chemical compositions of calcined sediments were investigated, indicating the porosity and mineralization components were greatly enhanced. The fractional analysis of phosphorus revealed that the calcination process reduced the percentage of unsteady phosphorus, transforming into stable inert phosphorus fractions (Al–P, Ca–P and Res-P), respectively, thereby minimized its mobility and eutrophication risk. Interestingly, calcination temperatures of 700 °C and 800 °C resulted in smaller releasing potentials and equilibrium phosphorus concentrations, despite having lower adsorption capacities than 550 °C. Furthermore, the results of redox potential monitoring showed that the thermally treated Dianchi Lake sediments could enhance the redox potential and dissolved oxygen in the surface sediment, indicating the amelioration of interfacial environment. The practical monitoring experiments confirmed the capping depressed the DTP to 0.031 mg L−1. The investigation of this study provided explicit evidence of Ca coupled P and aerobic Fe bound P strengthened the immobilization effects, and the development of sediment calcination demonstrates a promising strategy for alleviating the burden of endogenous pollution and improving aerobic environment, which are of great significance for lake ecological remediation. [Display omitted] • The composition and morphology of thermally treated sediments were characterized. • Phosphorus releasing potential was reduced at higher calcination temperatures. • The mobile phosphorus contents were dramatically decreased by thermal treatment. • SRP in overlying water can be effectively reduced by the increased Ca–P complexes. [ABSTRACT FROM AUTHOR]

Oxidative stress plays a significant role in the development of hepatic insulin resistance, but the underlying molecular mechanisms remain poorly understood. In this study, we discovered that C-terminal-binding protein 2 (CtBP2) level was decreased in insulin resistance. Taking into account the relationship between CtBP family protein (ANGUSTIFOLIA) and reactive oxygen species (ROS) accumulation, we conjectured CtBP2 was involved in insulin resistance through ROS induced stress. In order to verify this hypothesis, we over-expressed CtBP2 in palmitate (PA) treated HepG2 cells. Here, we found that over-expression of CtBP2 ameliorated insulin sensitivity by increasing phosphorylation of glycogen synthase kinase 3β (GSK3β) and protein kinase B (AKT). These data suggest that CtBP2 plays a critical role in the development of insulin resistance. Moreover, CtBP2 reversed the effects of PA on ROS level, lipid accumulation, hepatic glucose uptake and gluconeogenesis. We also found that over-expression of CtBP2 could suppress PA induced c-jun NH2 terminal kinase (JNK) activation. Furthermore, JNK inhibitor SP600125 was shown to promote the effect of CtBP2 on insulin signaling. Thus, we demonstrated that CtBP2 ameliorated PA-induced insulin resistance via ROS-dependent JNK pathway. [ABSTRACT FROM AUTHOR]

The limited cardiomyocyte proliferation is insufficient for repair of the myocardium. Therefore, activating cardiomyocyte proliferation might be a reasonable option for myocardial regeneration. Here, we investigated effect of retinoic acid (RA) on inducing adult cardiomyocyte proliferation and assessed efficacy of self-assembling peptide (SAP)-released RA in activating regeneration of the infarcted myocardium. Effect of RA on inducing cardiomyocyte proliferation was examined with the isolated cardiomyocytes. Expression of the cell cycle-associated genes and paracrine factors in the infarcted myocardium was examined at one week after treatment with SAP-carried RA. Cardiomyocyte proliferation, myocardial regeneration and improvement of cardiac function were assessed at four weeks after treatment. In the adult rat myocardium, expression of RA synthetase gene Raldh2 and RA concentration were decreased significantly. After treatment with RA, the proliferated cardiomyocytes were increased. The formulated SAP could sustainedly release RA. After treatment with SAP-carried RA, expression of the pro-proliferative genes in cell cycle and paracrine factors in the infarcted myocardium were up-regulated. Myocardial regeneration was enhanced, and cardiac function was improved significantly. These results demonstrate that RA can induce adult cardiomyocytes to proliferate effectively. The sustained release of RA with SAP is a promise strategy to enhance repair of the infarcted myocardium. [Display omitted] • Synthesis of retinoic acid in adult myocardium is decreased. • Retinoic acid can induce proliferation of adult cardiomyocytes. • Sustained release of retinoic acid is effective for repair of the infarcted myocardium. [ABSTRACT FROM AUTHOR]

Oxidative stress is an important pathogenesis of insulin resistance (IR) and Type 2 diabetes mellitus (T2DM). Studies have shown that knockdown of PTEN-induced putative kinase 1 (PINK1) causes oxidative stress and mitophagy. In db/db mice, PINK1 protein level is down-regulated. However, little is known regarding the mechanism by which PINK1 modulates IR in response to reactive oxygen species (ROS) induced stress. In our study, PINK1 expression decreased during palmitate (PA) induced IR in HepG2 cells and the hepatic tissues of high fat diet (HFD) fed mice. Additionally, free fatty acids (FFAs) could increase ROS and suppress insulin signaling pathway, which was indicated by reduced phosphorylation of protein kinase B (AKT) and glycogen synthase kinase 3β (GSK-3β). In addition, insulin induced glucose uptake decreased and the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), two key gluconeogenic enzymes, was up-regulated after PA treatment. Intriguingly, PINK1 overexpression could lead to opposite results. Moreover, PA induced hepatic IR through C-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways, which were rescued by PINK1 overexpression. In summary, our results demonstrate that PINK1 promoted hepatic IR via JNK and ERK pathway in PA treated HepG2 cells, implying a novel molecular target for the therapy of diabetes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Three unique ent -clerodane diterpenoid dimers were isolated from Callicarpa arborea. • The absolute configuration of 1 was deduced by single-crystal X-ray diffraction. • The absolute configuration of 2 and 3 was confirmed by NMR calculations with DP4 + analysis and ECD calculations. • The compound 2 and 3 showed potent cytotoxicity against MCF-7 and HCT-116 cell lines. Callicarpnoids A–C (1 – 3), three new ent -clerodane diterpenoid dimers formed via a [4 + 2] hetero Diels-Alder cycloaddition, appeared as a third example of this type of dimers, were isolated from the stems of Callicarpa arborea Roxb.. Their structures were elucidated by comprehensive spectroscopic analysis, and the absolute configurations were confirmed by single-crystal X-ray diffraction and electronic circular dichroism (ECD) calculations, as well as DP4 + analysis. Cytotoxicity test in two cell lines indicated that compounds 2 and 3 had significant cytotoxic effect against breast cancer cell (MCF-7) and colorectal cancer cell (HCT-116) with IC 50 ranging from 5.2 to 7.2 μ M, comparable to those of the positive control. Furthermore, the western blot analysis revealed that the protein expression levels of Bax were increased following compounds 2 and 3 treatment, whereas the expression levels of caspase 8, caspase 3, caspase 9 and Bcl 2 were decreased in a dose-dependent manner, indicating that compounds 2 and 3 may induce apoptosis via both intrinsic and extrinsic pathways in MCF-7 and HCT-116 cells. [ABSTRACT FROM AUTHOR]

Cell-free DNA (cfDNA), as a non-invasive approach, has been introduced in a wide range of applications, including cancer diagnosis/ monitoring, prenatal testing, and transplantation monitoring. Yet, studies of cfDNA fragmentomics in physiological conditions are lacking. In this study, we aim to explore the correlation of fragmentation patterns of cfDNA with blood biochemical and hematological parameters in healthy individuals. We addressed the impact of physiological variables and abnormal blood biochemical and hematological parameters on cfDNA fragment size distribution. We also figured and validated that hematological inflammation markers, including leukocyte, lymphocyte, neutrophil, and platelet distribution width as well as aspartate transaminase levels were significantly correlated with the genome-wide cfDNA fragmentation pattern. Our findings suggest that cfDNA fragmentation profiles were associated with physiological parameters related to cardiovascular risk factors, inflammatory response and hepatocyte injury, which may provide insights for further research on the potential role of cfDNA fragmentation in diagnosis and monitor of several disease. • Blood triglyceride and glucose level correlated with short cfDNA fragment ratio. • cfDNA fragmentation correlated with inflammation-related hematological parameters. • AST was significantly correlated with cfDNA fragmentation patterns. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii ( T . gondii ) is an important pathogen which can causes serious public health problems. Since the current therapeutic drugs for toxoplasmosis present serious host toxicity, research on effective and new substances of relatively low toxicity is urgently needed. This study was carried out to evaluate the anti-parasitic effect of oxymatrine (OM) and matrine (ME) against T . gondii in vitro and in vivo . In our study, the anti- T . gondii activities of ME and OM were evaluated in vitro using cell counting kit-8 assay, morphological observation and trypan blue exclusion assay. In vivo , mice were sacrificed four days post-infection and ascites were drawn out to determine the extent of tachyzoite proliferation. Viscera indexes and liver biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione (GSH) and malondialdehyde (MDA), were examined to evaluate the toxicity of compounds to mice. As a result, OM and ME showed anti- T . gondii activity but low selectivity toxicity to HeLa cells. Both compounds also significantly decreased the number of tachyzoites in peritoneal cavity and recovered the levels of ALT, AST, GSH and MDA in liver. Moreover, the mice treated with OM or ME achieved better results in viscera index and survival rate than that of spiramycin. These results suggest that OM and ME are likely the sources of new drugs for toxoplasmosis, and further studies will be necessary to compare the efficacy of drug combination, as well as identify its action of mechanism. [ABSTRACT FROM AUTHOR]

Three new coordination polymers, namely, {[Ni(H 2 L)(bix)(H 2 O) 2 ]·2h 2 O} n (1), {[Ni(HL)(Hdpa)(H 2 O) 2 ]·H 2 O} n (2), {[Ni(L) 0.5 (bpp)(H 2 O)]·H 2 O} n (3) (H 4 L=terphenyl-2,2′,4,4′-tetracarboxylic acid; bix=1,4-bis(imidazol-1-ylmethyl)benzene; dpa =4,4′-dipyridylamine; bpp=1,3-bis(4-pyridyl)propane), based on rigid H 4 L ligand and different N-donor co-ligands, have been synthesized under hydrothermal conditions. Compound 1 features a 3D 4-connected 6 6 -dia- type framework with H 4 L ligand adopts a μ 2 -bridging mode with two symmetry-related carboxylate groups in μ 1 - η 1 : η 0 monodentate mode. Compound 2 displays a 1D [Ni(HL)(Hdpa)] n ribbon chains motif, in which the H 4 L ligand adopts a μ 2 -bridging mode with two carboxylate groups in μ 1 - η 1 : η 1 and μ 1 - η 1 : η 0 monodentate modes, while 3 possesses a (4,4)-connected 3D frameworks with bbf topology, with H 4 L ligand displays a μ 4 -bridging coordination mode. The H 4 L ligand displays not only different deprotonated forms but also diverse coordination modes and conformations. The structural diversities among 1 – 3 have been carefully discussed, and the roles of N-donor co-ligands in the self-assembly of coordination polymers have been well documented. [ABSTRACT FROM AUTHOR]

The utilization of porous metal-organic frameworks (MOFs) as catalyst support has attracted intensive attentions in heterogeneous catalysis. However, the study of structure-activity relationship in this confined catalysis system is still scarce. Herein, three isostructural Co(II)-MOFs {Co 2 L(bpy)} n (CTGU-11), {Co 2 L(bpe)} n (CTGU-12) and {Co 2 L(bib)} n (CTGU-13) were synthesized by using 4,4′,4″,4‴-(1,3,6,8-Pyrenetetrayl)tetrabenzoic acid (H 4 L) as an organic ligand, and introducing three N-donor ligands (bpy ​= ​4,4′-dipyridyl, bpe ​= ​1,2-di(4-pyridyl)ethylene, bib ​= ​1,4-bis(1-imidazoly)benzene) with different length. Among these Co(II)-MOFs, each L4− anion bridges four typical paddle wheel secondary building units (SBUs) to form a two dimensional (2D) sheet, which further expanded to the three-fold interpenetrated structure with the aid of different pillared ligands. Inspired by the eligible structure/surface feature of these frameworks, a series of Co-MOF-supported heterogeneous catalysts (NM@Co-MOFs, NM = Ag, Ru, Pd and Au) have been fabricated successfully via solution infiltration, for the reduction of 4-nitrophenol (4NP). Impressively, 2-Ru@Co-MOFs exhibit remarkable activity in comparison to other NM@Co-MOFs composites with the apparent rate constant reach 50.72 ​s-1 ​g-1, 26.14 ​s-1 ​g-1, and 22.79 ​s-1 ​g-1, respectively. Furthermore, the possible catalytic mechanism of 2-Ru@Co-MOFs has also been discussed based on the analysis of reaction kinetics. Three isostructural Co(II)-MOFs were synthesized by using a conjugated tetrabenzoic acid(H 4 L) as an organic ligand, and introducing three N-donor ligands with different length. Among these Co(II)-MOFs, each L4− anion bridges four typical paddle wheel secondary building units (SBUs) to form a two dimensional (2D) sheet, which further expanded to the three-fold interpenetrated structure with the aid of different pillared ligands. Inspired by the eligible structure/surface feature of these frameworks, a series of Co-MOF-supported heterogeneous catalysts (NM@Co-MOFs, NM = Ag, Ru, Pd and Au) have been fabricated successfully via solution infiltration, for the reduction of 4-nitrophenol. [Display omitted] • Three novel isostructural 3D Co(II)-MOFs have been prepared. • The integration metal nanoparticles into MOFs shows positive effect on reduction of 4-NP. • The electronic effects between noble metal and MOFs accelerate catalytic process. [ABSTRACT FROM AUTHOR]

Abstract: Long-term excessive fluoride intake is known to be toxic and can damage a variety of organs and tissues in the human body. However, the molecular mechanisms underlying fluoride-induced male reproductive toxicity are not well understood. In this study, we used a rat model to simulate the situations of human exposure and aimed to evaluate the roles of endoplasmic reticulum (ER) stress and inflammatory response in fluoride-induced testicular injury. Sprague–Dawley rats were administered with sodium fluoride (NaF) at 25, 50 and 100mg/L via drinking water from pre-pregnancy to gestation, birth and finally to post-puberty. And then the testes of male offspring were studied at 8weeks of age. Our results demonstrated that fluoride treatment increased MDA accumulation, decreased SOD activity, and enhanced germ cell apoptosis. In addition, fluoride elevated mRNA and protein levels of glucose-regulated protein 78 (GRP78), inositol requiring ER-to-nucleus signal kinase 1 (IRE1), and C/EBP homologous protein (CHOP), indicating activation of ER stress signaling. Furthermore, fluoride also induced testicular inflammation, as manifested by gene up-regulation of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in a nuclear factor-κB (NF-κB)-dependent manner. These were associated with marked histopathological lesions including injury of spermatogonia, decrease of spermatocytes and absence of elongated spermatids, as well as severe ultrastructural abnormalities in testes. Taken together, our results provide compelling evidence that ER stress and inflammation would be novel and significant mechanisms responsible for fluoride-induced disturbance of spermatogenesis and germ cell loss in addition to oxidative stress. [Copyright &y& Elsevier]

Four new isostructural coordination polymers, [M 2 (μ 2 -H 2 O)(DTBC) 2 ] (CTGU- 26(M), M ​= ​Zn, Cd, Co and Ni] have been prepared with a new butterfly-typed nitroheterocyclic 4,6-di- 1H-1,2,4-triazol-1-yi-1,3-benzenedicarboxylic acid(H 2 DTBC) ligand and metal salts under hydrothermal condition. CTGU-26(Zn) features an unusual 2-nodal (4, 8)-connected scu topological network generated by [Zn 2 (μ 2 -H 2 O)(COO) 4 ] units and DTBC2− anion linkers. Luminescent properties measurements indicate that both CTGU-26(Zn) and CTGU-26(Cd) show intense fluorescence-emission compared with free H 2 DTBC ligand in solid state. Moreover, the electrocatalytic activities of CTGU-26(Co) and CTGU-26(Ni) towards methanol oxidation reaction (MOR) of two compounds were also investigated. Remarkably, by combining each MOF with the conductive 2,3,6,7,10,11-hexahydroxytriphenylene(HHTP) additive, a composite material, HHTP/CTGU-26(Ni)–I was confirmed to have an excellent performance for MOR with a high mass specific peak current of 25.55 ​mA ​cm−2. Four new isostructural coordination polymers, [M 2 (μ 2 -H 2 O)(DTBC) 2 ] (CTGU-26(M), M ​= ​Zn, Cd, Co and Ni] have been prepared with one new butterfly-typed nitroheterocyclic carboxylate ligand was prepared and characterized. And the luminescent properties and methanol oxidation reaction were also discussed. [Display omitted] • Four new isostructural coordination polymers have been prepared with a new butterfly-typed nitroheterocyclic carboxylic acid. • They feature an unusual 2-nodal (4,8)-connected scu topological network generated by binuclear units and DTBC2− anion linkers. • The luminescent properties and the electrocatalytic MOR activities of four complexes has been studied and discussed. [ABSTRACT FROM AUTHOR]

Abstract: In the present paper, we examined the effects of a natural cyclopeptide RA-V on human breast cancer cells and the underlying mechanisms. RA-V significantly inhibited the growth of human breast cancer MCF-7, MDA-MB-231 cells and murine breast cancer 4T1 cells. In addition, RA-V triggered mitochondrial apoptotic pathway which was indicated by the loss of mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase cascade. Further study showed that RA-V dramatically inhibited phosphorylation of AKT and 3-phosphoinositide dependent protein kinase 1 (PDK1) in MCF-7 cells. Moreover, RA-V disrupted the interaction between PDK1 and AKT in MCF-7 cells. Furthermore, RA-V-induced apoptosis could be enhanced by phosphatidylinositol 3-kinase inhibitor or attenuated by over-expression of AKT in all the three kinds of breast cancer cells. Taken together, this study shows that RA-V, which can induce mitochondria-mediated apoptosis, exerts strong anti-tumor activity against human breast cancer. The underlying anti-cancer mechanism of RA-V is related to the blockage of the interaction between PDK1 and AKT. [Copyright &y& Elsevier]

Abstract: The ideal gene-therapy vector for treating genetic disorders should deliver intact therapeutic genes and their essential regulatory elements into the specific “safe genomic site” and realize long-term, self-regulatory expression. For β-thalassemia gene therapy, viral vectors have been broadly used, but the accompanying insertional mutation and immunogenicity remain problematic. Hence, we aimed to develop new non-viral vectors that are efficient and safe in treating diseases. As previous studies have demonstrated that physiological expression of β-globin genes requires both a 5′ locus control region and 3′ specific elements, we constructed a new human chromosome-derived targeting vector to transfer the intact β-globin gene cluster into K562 cells. The whole β-globin gene cluster was precisely integrated into the target site and expressed in a self-regulatory pattern. The results proved that the human chromosome-derived vector was specifically targeted to the human genome and this could provide a novel platform for further gene therapy research. [Copyright &y& Elsevier]