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Background Shoot branching is one of the important agronomic traits affecting yields and quality of tea plant (Camellia sinensis). Cytokinins (CTKs) play critical roles in regulating shoot branching. However, whether and how differently alternative splicing (AS) variant of CTKs-related genes can influence shoot branching of tea plant is still not fully elucidated. Results In this study, five AS variants of CTK biosynthetic gene adenylate isopentenyltransferase (CsA-IPT5) with different 3′ untranslated region (3ˊ UTR) and 5ˊ UTR from tea plant were cloned and investigated for their regulatory effects. Transient expression assays showed that there were significant negative correlations between CsA-IPT5 protein expression, mRNA expression of CsA-IPT5 AS variants and the number of ATTTA motifs, respectively. Shoot branching processes induced by exogenous 6-BA or pruning were studied, where CsA-IPT5 was demonstrated to regulate protein synthesis of CsA-IPT5, as well as the biosynthesis of trans-zeatin (tZ)- and isopentenyladenine (iP)-CTKs, through transcriptionally changing ratios of its five AS variants in these processes. Furthermore, the 3′ UTR AS variant 2 (3AS2) might act as the predominant AS transcript. Conclusions Together, our results indicate that 3AS2 of the CsA-IPT5 gene is potential in regulating shoot branching of tea plant and provides a gene resource for improving the plant-type of woody plants.

Molten salts are subjected to heating-cooling thermal shock cycle in the operation of concentrating solar power (CSP) plant. In this work, the quaternary nitrate-nitrite (QNN) mixed salt and Solar salt are comparatively studied under different thermal shock conditions. After 500 thermal shock test cycles, morphological and structural analysis of samples are carried out by wavelength dispersive x-ray fluorescence (WD-XRF), Fourier-transform infrared (FTIR), x-ray diffraction (XRD), scanning electron microscope (SEM) and energy dispersive spectrometer (EDS). Meanwhile, thermos-physical properties of samples are comparatively analyzed. The results show the average melting point and average initial crystal temperature of QNN mixed salt are maximum 135 °C, 82.6 °C lower than that of Solar salt, respectively. The decomposition temperature of QNN mixed salt is maximum 52.1 °C higher than that of Solar salt. The specific heat of QNN mixed salt increases with the increasing of thermal shock temperature. The specific heat and thermal conductivity of QNN mixed salt maximally increase 15.46% and 9.8% compared with its base salt, respectively. Meanwhile, the thermal conductivity and viscosity of QNN mixed salt are slight higher than that of Solar salt. The Solar salt viscosity decreases with the increasing of thermal shock temperature.

Depression is a serious neuropsychiatric disorder, which is characterized by sustaining mood disorders. Loganin, a major iridoid glycoside from Corni fructus, has a variety of pharmacological activities, including neuroprotective effect and hypnotic effect. However, little is known about the effects of loganin on stress-induced depression. To investigate the effects of loganin on behavioral despair of mice, and whether serotonin (5-HT) and/or noradrenaline (NE) are involved in this process. We tested the effectiveness of loganin using tail suspension test (TST). The possible mechanism was explored using reserpine-induced ptosis and hypothermia, and 5-HTP-induced head-twitch response in mice. The changes of 5-HT and NE in the prefrontal cortex, hippocampus, and striatum were measured through high-performance liquid chromatography (HPLC) analysis. Then, we identified the effects of depleting 5-HT and NE by PCPA (p-chlorophenylalanine) and DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) pretreatment, respectively. Loganin (12.5/50 mg/kg) induced antidepressant-like effects in mice submitted to TST. Loganin (12.5/50 mg/kg) ameliorated the reserpine-induced hypothermia and ptosis, as well as increased 5-HTP-induced head-twitch responses in mice. Loganin (50 mg/kg) significantly increased the levels of 5-HT in the prefrontal cortex, hippocampus, and striatum. Furthermore, only PCPA treatment could eliminate loganin-induced antidepressant-like effects in TST. Loganin exerts antidepressant-like effect in the TST depending on 5-HT levels in the central nervous system, which provide a potential agent for depression therapy.

In spite of the recent progress made in organic electrode materials, high-performance candidates are still lacking, especially when taking affordability into account. Herein, we report a novel polymeric lithium salt, namely dilithium salt of poly(2,5-dihydroxy-1,4-benzoquinone-3,6-methylene) (Li2PDBM), which can be easily synthesized by phenol-formaldehyde condensation, followed by lithiation in LiOH solution to eliminate the negative effect of phenol groups in PDBM. Benefiting from a high theoretical capacity (327 mA h g-1), structure stability, insolubility, and redox reversibility, Li2PDBM exhibits superior electrochemical performance as a cathode for rechargeable lithium batteries, including a high reversible capacity (256 mA h g-1), a high rate capability (79% @ 2000 mA g-1), and a high cycling stability (77% @ 2000th cycle). Besides the cost-effective electrode material synthesis approach, this work also provides an important mechanistic understanding of the structure-performance relationship of carbonyl-based electrode materials, especially those with -OH or -OM (M = Li, Na, and K) substituents.

p-Type electroactive polymers are promising cathodes for dual-ion batteries but cost-effective candidates are still lacking. In this study, the p-type polymer polyphenothiazine (PPTZ) is synthesized by a facile one-step oxidation polymerization from the low-cost phenothiazine (PTZ) monomer. As a cathode for rechargeable lithium batteries, PPTZ shows superior electrochemical performance to previously reported PTZ-based polymers with complicated structures and syntheses. For example, PPTZ has a high reversible capacity of 157 mAh g-1 within 2.5-4.3 V vs. Li+ /Li with an average discharge voltage of 3.5 V, and a high capacity retention of 77 % after 500 cycles. The highly reversible one-electron redox mechanism of PPTZ is also investigated in detail by electrochemical testing, ex situ FT-IR and X-ray photoelectron spectroscopy, and DFT calculations. PPTZ has the potential to serve as an attractive p-type cathode material for practical applications and the facile synthesis may be also extended to other polymer cathodes based on N-heteroaromatic units.

In this paper the failure reason of Q345R Welded Joint was studied through macroscopic observation, chemical properties, metallurgical analysis, scanning electron microscope (SEM) and EDS test method. The results showed that there were a large number of micro-cracks in the fracture surface. The reason of cracking is severe banded structure in base metal microstructure, which provided opportunity for hydrogen atoms to enter into the internal of steel when contact with wet hydrogen sulfide environment. The existence of tensile stress promotes the entry of hydrogen atoms and the propagation of cracks. The welding products of this procedure are not suitable for use under sour conditions.

Ultraviolet irradiation induces melanin accumulation, which can be reduced by the use of chemical whitening products. However, the associated safety concerns of such products have prompted the search for natural and harmless alternatives. This study aimed to identify a natural acidic formulation to reduce skin pigmentation. The metabolite propionic acid (CH3CH2COOH, PA) was the most abundant fatty acid in the filtrate from Pluronic F68 (PF68) fermentation of Cutibacterium acnes (C. acnes) and reduced the DOPA-positive melanocytes by significantly inhibiting cellular tyrosinase activity via binding to the free fatty acid receptor 2 (FFAR2). Moreover, 4 mM PA treatment did not alter melanocyte proliferation, indicating that it is an effective solution for hyperpigmentation, causing no cellular damage. The reduced DOPA-positive melanocytes and tyrosinase activity were also observed in mice ear skin tissue injected with a mixture of C. acnes and PF68, supporting that the inhibition of melanogenesis is likely to be mediated through fermentation metabolites from C. acnes fermentation using PF68 as a carbon source. Additionally, PA did not affect the growth of its parent bacteria C. acnes, hence is a potent fermentation metabolite that does not disrupt the balance of the skin microbiome.

A simple, rapid, and accurate method for determination of selenocystine (SeCys2), methyl selenocysteine (MeSeCys), selenourea (SeUr), selenite (Se(IV)), selenotmethionine (SeMet), and selenate (Se(VI)) in grain crops was developed, based on the coupling of ion-pair reversed-phase high-performance liquid chromatography (IP-RP-HPLC) and ultraviolet irradiation hydride generation atomic fluorescence spectrometry (UV-HG-AFS). The conditions of IP-RP-HPLC-UV-HG -AFS were studied. The conditions of the pretreatment sample, such as types and dosage of proteinases, were investigated. The detection limits (LODs) for six Se species were between 0.77 and 1.77 μg·L−1. Then, the proposed method has been successfully used to analyze selenium (Se) species in Se-enriched rice paddy (Oryza sativa L.), soybean (Glycine max (Linn.) Merr.), and sweet potato (Ipomoea batatas (L.) Lam.) with foliar application of sodium selenite solution. SeMet was the major Se spices in Se-enriched grain crops, ranged from 77–90% of the total Se contents. The capabilities of Se enrichment were relatively larger differences in three-grain corps as follows: soybean > rice paddy > sweet potato.

Biological nanopores are revolutionizing human health by the great myriad of detection and diagnostic skills. Their nano-confined area and ingenious shape are suitable to investigate a diverse range of molecules that were difficult to identify with the previous techniques. Additionally, high throughput and label-free detection of target analytes instigated the exploration of new bacterial channel proteins such as Fragaceatoxin C (FraC), Cytolysin A (ClyA), Ferric hydroxamate uptake component A (FhuA) and Curli specific gene G (CsgG) along with the former ones, like α-hemolysin (αHL), Mycobacterium smegmatis porin A (MspA), aerolysin, bacteriophage phi 29 and Outer membrane porin G (OmpG). Herein, we discuss some well-known biological nanopores but emphasize on MspA and compare the effects of site-directed mutagenesis on the detection ability of its mutants in view of the surface charge distribution, voltage threshold and pore–analyte interaction. We also discuss illustrious and latest advances in biological nanopores for past 2–3 years due to limited space. Last but not the least, we elucidate our perspective for selecting a biological nanopore and propose some future directions to design a customized nanopore that would be suitable for DNA sequencing and sensing of other nontrivial molecules in question.

Recent studies showed that exosomes obtained from adipose-derived stem cells (ADSCs) could improve the angiogenesis of fat grafts via overexpression of vascular endothelial growth factor (VEGF). Human antigen R (HuR) promotes the expression of VEGF in many cancers, but the effect of HuR in normal endothelial cells in the presence of ADSC-derived exosomes remains unclear. We aimed to investigate the effect of HuR on the expression of VEGF and angiogenesis of human umbilical vein endothelial cells (HUVECs) cultured with ADSCs-derived exosomes. The HuR-overexpressed HUVECs (HuR-HUVECs) were cocultured with ADSCs-derived exosomes. qRT-PCR and Western blotting were performed to examine the stability and expression of VEGF-A mRNA and protein. The proliferation, migration, and proangiogenic capacity of HuR-HUVECs were evaluated using cell counting kit-8 (CCK-8), scratch wound healing, and Matrigel tube formation assay. qRT-PCR showed that HuR-HUVECs had higher expression and slower attenuation of VEGF-A mRNA. Western blotting confirmed higher expression of VEGF-A in HuR-HUVECs. CCK-8, scratch wound healing, and Matrigel tube formation assay demonstrated an increased proangiogenic effect in HuR-HUVECs. HuR promotes angiogenesis of HUVECs cocultured with ADSCs-derived exosomes via stabilization and overexpression of VEGF in vitro. The HuR/VEGF pathway is an important regulatory mechanism of angiogenesis in endothelial cells.

As one of the most widely used materials, plastic polymer fragments can abrasively degrade into microplastic (MP) and smaller nanoplastic (NP) particles. The present study aimed to investigate the influence of particle size on neurodevelopmental toxicity induced by polystyrene nanoplastics (PS-NPs) in Caenorhabditis elegans and to explore the underlying potential mechanism. C. elegans were exposed to different concentrations of PS-NPs with various sizes (25, 50, and 100 nm) for 72 h. Our results showed that all of these PS-NPs could dose-dependently induce an increase in reactive oxygen species production and mitochondrial damage in C. elegans, resulting in inhibition of body length, head thrashes, body bending, and dopamine (DA) contents. A weaker neurotoxicity was found in 25 nm PS-NPs compared to 50 and 100 nm PS-NPs, which might be due to preferential cellular distribution and greater polymerization capability of the smaller particles. In addition, all these PS-NPs could induce lipofuscin accumulation and apoptosis independent of particle size, suggesting that oxidative damage and mitochondrial dysfunction may not be the only way responsible for NP-induced neurotoxic effects. Furthermore, the mutant test targeting two presenilin genes (sel-12 and hop-1) showed that sel-12 and hop-1 were involved in regulation of PS-NP-induced neurodevelopmental toxicity and mitochondrial damage. In conclusion, PS-NPs could induce neurodevelopmental toxicity dependent on particle sizes mediated by mitochondrial damage and DA reduction. Enhanced expression of presenilin plays a role in PS-NP-induced oxidative stress and neurodevelopmental toxicity.

Recent in vitro evidence shows that glycosaminoglycans (GAGs) and proteoglycans (PGs) in bone matrix may functionally be involved in the tissue-level toughness of bone. In this study, we showed the effect of biglycan (Bgn), a small leucine-rich proteoglycan enriched in extracellular matrix of bone and the associated GAG subtype, chondroitin sulfate (CS), on the toughness of bone in vivo, using wild-type (WT) and Bgn deficient mice. The amount of total GAGs and CS in the mineralized compartment of Bgn KO mouse bone matrix decreased significantly, associated with the reduction of the toughness of bone, in comparison with those of WT mice. However, such differences between WT and Bgn KO mice diminished once the bound water was removed from bone matrix. In addition, CS was identified as the major subtype in bone matrix. We then supplemented CS to both WT and Bgn KO mice to test whether supplemental GAGs could improve the tissue-level toughness of bone. After intradermal administration of CS, the toughness of WT bone was greatly improved, with the GAGs and bound water amount in the bone matrix increased, while such improvement was not observed in Bgn KO mice or with supplementation of dermatan sulfate (DS). Moreover, CS supplemented WT mice exhibited higher bone mineral density and reduced osteoclastogenesis. Interestingly, Bgn KO bone did not show such differences irrespective of the intradermal administration of CS. In summary, the results of this study suggest that Bgn and CS in bone matrix play a pivotal role in imparting the toughness to bone most likely via retaining bound water in bone matrix. Moreover, supplementation of CS improves the toughness of bone in mouse models.

Graphene has received many attentions from the scientist due to its outstanding properties since it was mechanically exfoliated. The rise of graphene has stimulated immense research on analogous two-dimensional (2D) materials, such as the hexagonal boron nitride (h-BN), monolayer transition metal dichalcogenides, black phosphorene, silicene, borophene and germanene. However, as a semimetal, gapless graphene has been limited in the application like semiconducting electronics. Previous theoretical calculations predict that a small bandgap will arise when the graphene is placed onto an h-BN substrate. Then graphene/h-BN (G/h-BN) lateral heterostructures have been fabricated by many research groups on metal substrates. Comparing vertical vdW layer assembling, the atomic G/h-BN system combining both the high carrier mobility and tunable bandgap can build in-plane integrated circuit directly. However, to reduce the interface scattering, a sharp atomic interface between graphene and h-BN is required. To date, some experiments have built high quality G/h-BN heterostructures with sharp atomic interfaces, while many others did not. The underlying growth mechanism is crucial to control the size and shapes of the G/h-BN heterostructures of high quality. In this review, we first review the growth mechanism of graphene, mainly focusing on the nucleating process, which plays a vital role to reduce the grain boundary in the overall growth. The nucleation behavior of graphene is influenced by the growth temperature, substrate, carbon source partial pressure and hydrogen partial pressure. We review the structure and energy evaluation of clusters in the graphene nucleation stage on the Ir(111) and Ni(111) surface. Moreover, the nucleation barrier and size can also be obtained by combing the first-principles calculations and classical nucleation theory. Secondly, we present an overview on experimental fabrication of G/h-BN heterojunctions. Up to now, lateral G/h-BN heterojunctions has been produced on some metal substrates such as Cu foil, Ru(0001), Rh(111), Ni(111), Ir(111) and Pt(111). There are several methods to construct G/h-BN heterojunctions in experiments which can be classified into two kinds: Batch chemical vapor deposition and two/multi-step growth. In the earlier period, the large area randomly hybridized h-BN and graphene are fabricated by this method through supplying C precursors and NH3-BH3 at the same time. Another routine is two/multi-step growth technique in which G/h-BN is deposited on a metal surface beforehand as seeds of the second step of growth. And afterwards, by alternating the type of source supply, in plane heterojunctions with the predeposited grains will be formed. The growth sequence is proved to be a crucial factor that determines the quality of heterostructures. For multistep growth, lithographically technology and etching process are introduced to get spatially controlled heterostructures. Then, we introduce recent studies on the growth mechanism of G/h-BN lateral heterostructure both by atomistic first-principles calculations and experimental observations. The heteroepitaxial growth of graphene along the predeposited h-BN domains is systematically investigated by classical nucleation theory. At the initial stage, C atoms tend to attach linearly along the B/N-edges rather than perpendicular to the edges which resemble the graphene growth on the metal surface. When the carbon concentration is low, the nucleation barriers of graphene at B/N-edges are lower compared to the case of a Cu terrace. Nevertheless, under high carbon concentration, the nucleation barriers and nucleation rates in the two cases become comparable. Therefore, the chemical potential of the carbon source should be controlled within a suitable range to produce high quality G/h-BN lateral heterostructures with sharply and continuously atomic interface. Finally, we give a prospect on this rising field.

Schisandra chinensis (Turcz.) Baill., Schisandraceae, is a common Chinese traditional medicine for the treatment of nervous system disorders and cardiovascular diseases. However, little is known about its efficacy in treating gastrointestinal diseases. In the present study, the protective effect of the ethanol extract of S. chinensis against ethanol-induced acute gastric lesions was investigated in mice. Furthermore, we developed a method based on high-performance liquid chromatography for the quantification of bioactive lignans with a dibenzocyclooctadiene skeleton. The ethanol extract of S. chinensis significantly decreased the ulcer index, sheltered mucosa from lesions, increased levels of superoxide dismutase, decreased malondialdehyde levels, and downregulated plasma levels of tumor necrosis factor-α and interleukin-1β. Our findings demonstrated the gastroprotective properties of the ethanol extract of S. chinensis.

Small molecular organic electrode materials (SMOEMs) enjoy favorable high capacity and low cost, but suffer from poor cycling stability and low Coulombic efficiency due to the unavoidable dissolution in aprotic electrolytes. Previous studies of the dissolution inhibition strategy mainly focused on the molecular designing or electrode engineering, but neglected the important or crucial influence of the electrolyte. Herein, a facial “high concentration electrolyte” strategy is employed to study two typical dianhydride molecules, namely 1,4,5,8-naphthalenetetracarboxylic dianhydride (NTCDA) and 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA), achieving dramatically improved cycling stability for both. Remarkably, in 3 ​M LiTFSI/DOL ​+ ​DME electrolyte (lithium bis(trifluoromethanesulphonyl)imide/1,3-dioxolane ​+ ​1,2-dimethoxyethane), PTCDA shows a high capacity retention of 87% (relative to the maximum capacity of 147 mAh g−1) after 1000 cycles at a current rate of 100 ​mA ​g−1, along with an exceptional average Coulombic efficiency of 99.99%, setting one of the best cycling performance records for SMOEMs. The comparative study of NTCDA and PTCDA in LiTFSI/DOL ​+ ​DME electrolytes with different concentrations (1, 2, 3, and 4 ​M) indicates that both intrinsic crystalline structure stability of the active material and appropriate electrolyte are key origins of good cycling stability. According to ex-situ characterization results, a “dissolution–redeposition” mechanism of SMOEMs is proposed to update researchers’ obscure understanding of the dissolution behavior. We believe this work provides not only confidence on the performance potential but also insightful mechanism understanding of SMOEMs, which are important for their further development towards practical application.

Objective The disruption of metabolic events and changes to nutrient and oxygen availability due to sustained inflammation in RA increases the demand of bioenergetic and biosynthetic processes within the damaged tissue. The current study aimed to understand the molecular mechanisms of SLC7A5 (amino acid transporter) in synoviocytes of RA patients. Methods Synovial tissues were obtained from OA and RA patients. Fibroblast-like synoviocytes (FLS) were isolated, and SLC7A5 expression was examined by using RT-qPCR, immunofluorescence, and Western blotting. RNAi and antibody blocking treatments were used to knockdown SLC7A5 expression or to block its transporter activities. mTOR activity assay and MMP expression levels were monitored in RA FLS under amino acid deprivation or nutrient-rich conditions. Results RA FLS displayed significantly upregulated expression of SLC7A5 compared to OA FLS. Cytokine IL-1β was found to play a crucial role in upregulating SLC7A5 expression via the NF-κB pathway. Intervening SLC7A5 expression with RNAi or blocking its function by monoclonal antibody ameliorated MMP3 and MMP13 protein expression. Conversely, upregulation of SLC7A5 or tryptophan supplementation enhanced mTOR-P70S6K signals which promoted the protein translation of MMP3 and MMP13 in RA FLS. Conclusion Activated NF-κB pathway upregulates SLC7A5, which enhances the mTOR-P70S6K activity and MMP3 and MMP13 expression in RA FLS.

Recent studies indicate that glucose metabolism is altered in rheumatoid arthritis. We hypothesize that Pkm2, as a key regulatory enzyme of glycolysis pathway, triggers the activation of macrophages (Mφ), which results in proinflammatory cytokine production during the arthritis progress. In this study, Pkm2 was found to be overexpressed in ED1-positive Mφ in spleens and synovial tissues from arthritic rats via immunofluorescence, Western blotting, and quantitative RT-PCR. To reveal the role of Pkm2, Dark Agouti rats were treated with either Pkm2 enzyme inhibitor shikonin or the RNA interference plasmids of Pkm2 and negative control plasmids, respectively, via i.p. injection. Pkm2 intervention could alleviate the severity of pristane-induced arthritis in aspects of the macroscopic arthritis score, perimeter changes of midpaw, and the synovitis and destruction of the bone and cartilage as well as reduce the ED1 and p-Stat1–positive cell population in rat synovial tissues. Silencing Pkm2 by RNA interference in classical activated rat and mouse Mφ resulted in less Tnf-α, Il-1β production via Stat1 signaling. Collectively, Pkm2 is highly expressed in ED1-positive Mφ of spleens and synovial tissues from arthritic rats and promotes Mφ activation via Stat1 signaling. Pkm2 might be a promising selective metabolic target molecule for rheumatoid arthritis treatment.

Background: The purpose of the current study was to explore whether Pinoresinol diglucoside (PD) could relieve osteoporosis through promoting osteogenic differentiation by activating phosphatidylinositol-3 kinase (PI3K)/AKT signaling pathway. Methods: Firstly, human bone marrow mesenchymal stem cells (hBMMSCs) and mouse embryo steoblast recursor cells (MC3T3-E1) were induced for osteogenic differentiation, and then the cells were subjected to 1 mol/l PD. Then, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot assay were used to detect the expression of osteogenic marker genes/proteins such as bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (Runx2), and Osterix. The activity of alkaline phosphatase (ALP) in cells was also detected. Cell viability was further detected by Cell Count Kit-8 (CCK-8), and cell apoptosis was detected by flow cytometer. Finally, the protein expression of p-AKT and AKT was detected by Western blot assay. Results: The results showed that osteogenic differentiation of hBMMSCs and MC3T3-E1 cells were successfully induced, evidenced by increased BMP2, Runx2, Osterix mRNA expression and ALP activity enhancement. The osteogenic differentiation of MC3T3-E1 cells and hBMMSCs was enhanced by PD administration. At the same time, PD promoted the viability of MC3T3-E1 cells and reduced the MC3T3-E1 cell apoptosis. In addition, PD increased the protein expression of p-AKT and the ratio of p-AKT/AKT in MC3T3-E1 cells, suggesting PI3K/AKT pathway activation. Conclusion: PD promoted osteogenic differentiation of hBMMSCs and MC3T3-E1 cells, and it could promoted osteoblast proliferation and inhibit apoptosis, thereby playing a protective role in osteoporosis.

The chromatin-remodelling complex SWI/SNF is highly conserved and has critical roles in various cellular processes, including transcription and DNA-damage repair1,2. It hydrolyses ATP to remodel chromatin structure by sliding and evicting histone octamers3–8, creating DNA regions that become accessible to other essential factors. However, our mechanistic understanding of the remodelling activity is hindered by the lack of a high-resolution structure of complexes from this family. Here we report the cryo-electron microscopy structure of Saccharomyces cerevisiae SWI/SNF bound to a nucleosome, at near-atomic resolution. In the structure, the actin-related protein (Arp) module is sandwiched between the ATPase and the rest of the complex, with the Snf2 helicase-SANT associated (HSA) domain connecting all modules. The body contains an assembly scaffold composed of conserved subunits Snf12 (also known as SMARCD or BAF60), Snf5 (also known as SMARCB1, BAF47 or INI1) and an asymmetric dimer of Swi3 (also known as SMARCC, BAF155 or BAF170). Another conserved subunit, Swi1 (also known as ARID1 or BAF250), resides in the core of SWI/SNF, acting as a molecular hub. We also observed interactions between Snf5 and the histones at the acidic patch, which could serve as an anchor during active DNA translocation. Our structure enables us to map and rationalize a subset of cancer-related mutations in the human SWI/SNF complex and to propose a model for how SWI/SNF recognizes and remodels the +1 nucleosome to generate nucleosome-depleted regions during gene activation9. The cryo-electron microscopy structure of the yeast SWI/SNF complex bound to a nucleosome substrate provides insights into the chromatin-remodelling function of this family of protein complexes and suggests mechanisms by which the mutated proteins may cause cancer.

This study aimed to investigate the involvement of long non-coding RNA (lncRNA) lung adenocarcinoma transcript 1 (LUADT1) LUADT1 in diabetic retinopathy (DR). We found LUADT1 may interact with miR-383 by RNA interaction prediction. QPCR analysis showed that lncRNA LUADT1 was downregulated, and miR-383 was upregulated in DR. However, correlation analysis revealed no significant correlation between them. In retinal pigment epithelial cells (RPEpiC, h1RPE7 from Sigma-Aldrich), overexpression of LUADT1 and miR-383 failed to affect the expression of each other. However, LUADT1 overexpression led to increased and miR-383 overexpression led to decreased expression level of peroxiredoxin 3 (PRX3). Cell apoptosis analysis showed that LUADT1 and PRX3 overexpression resulted in the decreased cell apoptosis. MiR-383 played an opposite role and reduced the effects of LUADT1 and PRX3 overexpression. Therefore, LUADT1 regulates PRX3 by serving as the endogenous sponge of miR-383 in DR to regulate cell apoptosis.

A fast and simple strategy for the detection of DNA based on a new type of electrochemical Zr(IV) signaling probe is reported. Briefly, this DNA biosensor was fabricated by covalently coupling the amino groups of peptide nucleic acid (PNA) probes with aldehyde groups on the surface of a glassy carbon electrode (GCE), for specifically capturing target DNA (tDNA). After this, Zr(IV) probes were attached to the phosphate groups of DNA directly with strong coordination interaction, and stoichiometrically labeled Zr(IV) probes can be detected via differential pulse voltammetry (DPV). Under optimized conditions, this strategy showed a good linear response from 0.01 nM to 100 nM tDNA, and the detection limit was 0.81 pM (R2 = 0.998). Moreover, this DNA biosensor is also successfully applied to the DNA detection in serum samples with satisfactory results and shows great potential in clinical analysis.

Oxidative decarboxylation/trifluoromethylselenolation of primary, secondary, and tertiary aliphatic carboxylic acids with the nucleophilic [Me4N][SeCF3] salt and an organic photocatalyst is describ...

The adverse effects of heavy metals, such as cadmium, zinc, and copper, occur due to the generation of reactive oxygen species (ROS). The use of Caenorhabditis elegans for the purposes of conservation and biomonitoring is of great interest. In the present study, ROS, malondialdehyde (MDA), and citric acid levels and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in a model organism were tested to study toxicity. C. elegans was exposed to three different concentrations of cadmium (CdCl2, 5, 10, 50 μM), zinc (ZnSO4, 10, 100, 500 μM), and copper (CuSO4, 10, 100, 500 μM) for 3 days. ROS levels increased by 1.3- to 2.1-fold with increasing metal concentrations. The MDA content increased by approximately 7-, 5-, 2-fold after exposure to high concentrations of cadmium, zinc, and copper, respectively. Furthermore, the citric acid content increased by approximately 3-fold in the cadmium (Cd, 5 μM), zinc (Zn, 10 μM), and copper (Cu, 100 μM) treatment groups compared to that in untreated C. elegans. Therefore, citric acid may play an important role in heavy metal detoxification. Excess citric acid also slightly increased the LC50 by 1.3- to 2.0-fold, basic movements by 1.0- to 1.5-fold, decreased the ROS content by 2.4- to 2.1-fold, the MDA content by 4- to 2-fold, the SOD activity by 9- to 3-fold, the GPx activity by 4.0- to 3.0-fold, and the mRNA expression levels of GPxs by 3.2- to 1.8-fold after metals treatment. And it is most significantly in the alleviation of citric acid to cadmium. This study not only provides information to further understand the effects of heavy metal exposure on ROS, MDA, GPx, SOD, and citric acid in worms but also indicates that supplemental citric acid can protect animals from heavy metal stress and has broad application prospects in decreasing oxidative damage caused by heavy metals.

To investigate the effect of atmospheric particulates on the chemistry and acidity of rainwater during the washout process in areas with highly acidic rainfall, rainwater and particulates (before, during and after rain) were sampled and analyzed from June 2008 to June 2009 in the Yangtze River Delta region, China. The volume-weighted mean pH of the rainwater was only 4.44 in Hangzhou, and the average concentrations of TSP (total-suspended particulates) and PM10 (particulates with aerodynamic equivalent diameters of less than 10 μm) during the study period were 191 μg/m3 and 155 μg/m3, respectively. The measured acid buffering capacities of PM10 and TSP were 1.31 ± 0.45 and 1.61 ± 0.84 ml/mg, on average, respectively, indicating that both had a certain acid buffering capacity. Rain appeared to have a pronounced scouring effect on particulates, except for F− and Cl− in PM10. Upon combining the correlation analysis between ions in particulates and rainwater with Enrichment Factor and Principal Component Analysis of the rainwater chemistry, the results suggested that the components of rainwater were mainly derived from washout processes acting on particulates from crustal dust and building industry sources (Ca2+), marine sources (Na+, K+ (in spring), Mg2+ and Cl−) and anthropogenic sources, especially secondary aerosols emitted from agricultural land, motor vehicles and industrial plants (NO3−, SO42-, and NH4+). The F− in rainwater was mainly contributed by gaseous pollutants, such as HF from cooling systems, coal burning and surrounding factories. Implications: The interaction between particulates and rain in areas with highly acidic rainfall include the following: rain appears to have a pronounced scouring effect on most components in the particulates; the components of the rainwater are mainly derived from washout processes acting on PM contributed by crustal dust, sea salt and secondary aerosol subcloud; and the acid buffering capacities of PM10 and TSP in Hangzhou are 1.31 ± 0.45 and 1.61 ± 0.84 ml/mg, respectively, and had a certain acid buffering capacity toward rainwater.

The quality of life and survival rates of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD–PAH) have been greatly improved by defect-repair surgery and personalized treatments. However, those who survive surgery may remain at risk of persistent PAH, the prognosis may be considerably worse than those unoperated. Dynamic monitoring of clinical measures during the perioperative period of shunt correction is therefore indispensable and of great value. In this study, we explored the plasma-metabolite profiling in 13 patients with CHD–PAH during the perioperative period of defect repair. Plasma was harvested at four time points: prior to cardiopulmonary bypass (CPB) after anesthesia (Pre), immediately after CPB (T0), 24 h (T24), and 48 h (T48) after defect repair. Untargeted metabolomics strategy based on UPLC Q-TOF MS was used to detect the metabolites. A total of 193 distinguishing metabolites were determined at different time points, enriched in pathways such as oxidation of branched-chain fatty acids. We found that 17 metabolite alterations were significantly correlated with the reduction in mean pulmonary arterial pressure (MPAP) at T48 versus Pre. Gradients in diastolic pulmonary arterial pressure (DPAP), bicarbonate in radial artery (aHCO(3)), bicarbonate in superior vena cava (svcHCO(3)), and the partial pressure of dissolved CO(2) gas in radial artery (aPCO(2)) were positively correlated with MPAP gradient. Notably, these clinical-measure gradients were correlated with alterations in shunt-correction-associated metabolites. In total, 12 out of 17 identified metabolites in response to defect repair were increased at both T24 and T48 (all P

WHAT IS KNOWN AND OBJECTIVES Dapagliflozin was the first oral treatment approved in type 1 diabetes mellitus (T1DM) patients, simultaneously improving body weight. However, the time course and dose effect of dapagliflozin on loss of weight in T1DM patients was still unknown. The present study aimed to investigate quantitative relationship between dapagliflozin and loss of weight in T1DM patients based on Model-based Meta-analysis. METHODS Five dapagliflozin dosage groups, two of them were 5 mg/day and three of them were 10 mg/day, 1612 T1DM patients were analysed with maximal effect (Emax ) model, and evaluation index was change rate of body weight from baseline value. RESULTS In these T1DM patients, dosages were not incorporated into model, indicating no significant dose-response relationship between 5 and 10 mg/day affecting loss of weight. Emax and the treatment duration to reach half of the maximal effects (ET50 ) of dapagliflozin influencing loss of weight in T1DM patients were -4.9% and 10.4 weeks, and the duration to achieve 25%, 50%, 75%, and 80% (plateau) of Emax were 3.5, 10.4, 31.2, and 41.6 weeks. WHAT IS NEW AND CONCLUSIONS It was the first time to explore quantitative relationship between dapagliflozin and loss of weight in T1DM patients. To achieve the plateau period in loss of weight, 5 mg/day dapagliflozin was required for at least 41.6 weeks.

Road dust enriched with heavy metals (HMs) is detrimental to ecosystems and human health in urban environments. In this study, it is to explore the concentrations, spatial distribution, contaminated levels, and source identification of six HMs (lead (Pb), zinc (Zn), copper (Cu), cobalt (Co), chromium (Cr), and nickel (Ni)) based on 130 road dusts in Xinyang urban area. The results indicated that the contents of Pb, Zn, Cu, and Co were higher than the background values in more than 99% of the samples, and their average concentrations were 15.2, 9.2, 8.6, and 6.3 times the background value, respectively. The spatial distribution of high-value areas for Pb, Zn, Cu, Cr, and Ni was more similar, which was associated with traffic density near major roads and population and settlement patterns. Co was relatively different from the five elements, which was distributed in the areas of residence, commerce, and industry. Furthermore, the investigated HMs were clearly polluted, with Pb, Zn, Cu, and Co indicating high levels of contamination, while Cr and Ni were moderately polluted. The comprehensive pollution of the six HMs was mostly moderate to heavy in this study. Moreover, three sources of HMs designated by correlation analysis (CA) and principal component analysis (PCA) were mixed traffic emissions and industrial waste for Cu and Cr; automotive emissions for Pb, Ni, and Zn; and mixed domestic waste and industrial activities for Co, with contributions of 42.3%, 46.4%, and 11.3% via the principal component analysis-multiple linear regression (PCA-MLR) model. The multi-factor index for pollution assessment combined with source identification is extremely effective and practical for providing reliable data support and a theoretical reference for pollution monitoring and governance.

The magnetic measurement is an effective tool to identify the source of pollutants and diagnose the urban pollution. In this study, 132 group samples (that topsoil and street dust were sampled at the same location is regarded as a group) were collected from Xinyang, central eastern China. In addition, the background samples (19 topsoils under woodland around the outskirts) were also sampled. Herein, the aim was to investigate and compare the magnetic characteristics of both topsoil and street dust, and further to discuss the source and environmental implications using magnetic and diffuse reflection spectrum methods. The following points are highlighted: (1) the primary magnetic carrier of both materials was magnetite and that of the background sample were magnetite and maghemite. Furthermore, the ferrimagnetic mineral concentration and magnetic domain follow the order: street dust > topsoil > background sample. (2) The source of both materials was mainly from anthropogenic activities (e.g. industrial and traffic vehicles). The difference between them was the contribution related to natural sources (e.g. parent materials), which was negligible in street dust, and played a secondary role in topsoil. (3) Both materials showed that areas with a higher intensity of anthropogenic activities had higher pollution level, whereas areas with a lower anthropogenic intensity had lower pollution level.

Jia Ke,1,* Meng-Ting Li,1,* Ya-Jing Huo,1 Yan-Qiong Cheng,2 Shu-Fen Guo,1 Yang Wu,1 Lei Zhang,3 Jianpeng Ma,4 Ai-Jun Liu,2 Yan Han1 1Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China; 3Department of Vascular Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Multiscale Research Institute of Complex Systems, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ai-Jun LiuDepartment of Pharmacology, School of Pharmacy, Second Military Medical University, 800 Xiangyin Road, Yangpu, Shanghai, 200433, People’s Republic of ChinaEmail mrliuaijun@163.comYan HanDepartment of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou, Shanghai, 200437, People’s Republic of ChinaTel +86 21 51322043Email hanyan.2006@aliyun.comPurpose: We aimed to investigate potential synergistic antiplatelet effects of Ginkgo biloba extract (GBE50) in combination with aspirin using in vitro models.Methods: Arachidonic acid (AA), platelet activating factor (PAF), adenosine 5ʹ-diphosphate (ADP) and collagen were used as inducers. The antiplatelet effects of GBE50, aspirin and 1:1 combination of GBE50 and aspirin were detected by microplate method using rabbit platelets. Synergy finder 2.0 was used to analyze the synergistic antiplatelet effect. The compounds in GBE50 were identified by UPLC-Q/TOF-MS analysis and the candidate compounds were screened by TCMSP database. The targets of candidate compounds and aspirin were obtained in TCMSP, CCGs, Swiss target prediction database and drugbank. Targets involving platelet aggregation were obtained from GenCLiP database. Compound-target network was constructed and GO and KEGG enrichment analyses were performed to identify the critical biological processes and signaling pathways. The levels of thromboxane B2 (TXB2), cyclic adenosine monophosphate (cAMP) and PAF receptor (PAFR) were detected by ELISA to determine the effects of GBE50, aspirin and their combination on these pathways.Results: GBE50 combined with aspirin inhibited platelet aggregation more effectively. The combination displayed synergistic antiplatelet effects in AA-induced platelet aggregation, and additive antiplatelet effects occurred in PAF, ADP and collagen induced platelet aggregation. Seven compounds were identified as candidate compounds in GBE50. Enrichment analyses revealed that GBE50 could interfere with platelet aggregation via cAMP pathway, AA metabolism and calcium signaling pathway, and aspirin could regulate platelet aggregation through AA metabolism and platelet activation. ELISA experiments showed that GBE50 combined with aspirin could increase cAMP levels in resting platelets, and decreased the levels of TXB2 and PAFR.Conclusion: Our study indicated that GBE50 combined with aspirin could enhance the antiplatelet effects. They exerted both synergistic and additive effects in restraining platelet aggregation. The study highlighted the potential application of GBE50 as a supplementary therapy to treat thrombosis-related diseases.Keywords: Ginkgo biloba, aspirin, antiplatelet, synergistic effect, Chinese herb, arachidonic acid

Background Efficient and stable delivery of neurotrophic factors (NTFs) is crucial to provide suitable microenvironment for peripheral nerve regeneration. Neurotrophin-3 (NT-3) is an important NTF during peripheral nerve regeneration which is scarce in the first few weeks of nerve defect. Exosomes are nanovesicles and have been served as promising candidate for biocarrier. In this work, NT-3 mRNA was encapsulated in adipose-derived stem cell (ADSC)-derived exosomes (ExoNT-3). These engineered exosomes were applied as NT-3 mRNA carrier and then were loaded in nerve guidance conduit (ExoNT-3-NGC) to bridge rat sciatic nerve defect. Method NT-3 mRNA was encapsulated in exosomes by forcedly expression of NT-3 mRNA in the donor ADSCs. ExoNT-3 were co-cultured with SCs in vitro; after 24 h of culture, the efficiency of NT-3 mRNA delivery was evaluated by qPCR, western blotting and ELISA. Then, ExoNT-3 were loaded in alginate hydrogel to construct the nerve guidance conduits (ExoNT-3-NGC). ExoNT-3-NGC were implanted in vivo to reconstruct 10 mm rat sciatic nerve defect. The expression of NT-3 was measured 2 weeks after the implantation operation. The sciatic nerve functional index (SFI) was examined at 2 and 8 weeks after the operation. Moreover, the therapeutic effect of ExoNT-3-NGC was also evaluated by morphology assay, immunofluorescence staining of regenerated nerves, function evaluation of gastrocnemius muscles after 8 weeks of implantation. Results The engineered exosomes could deliver NT-3 mRNA to the recipient cells efficiently and translated into functional protein. The constructed NGC could realize stable release of exosomes at least for 2 weeks. After NGC implantation in vivo, ExoNT-3-NGC group significantly promote nerve regeneration and improve the function recovery of gastrocnemius muscles compared with control exosomes (Exoempty-NGC) group. Conclusion In this work, NGC was constructed to allow exosome-mediated NT-3 mRNA delivery. After ExoNT-3-NGC implantation in vivo, the level of NT-3 could restore which enhance the nerve regeneration. Our study provide a potential approach to improve nerve regeneration.

TMEM120A, also named as TACAN, is a novel membrane protein highly conserved in vertebrates and was recently proposed to be a mechanosensitive channel involved in sensing mechanical pain. Here we present the single-particle cryogenic electron microscopy (cryo-EM) structure of human TMEM120A, which forms a tightly packed dimer with extensive interactions mediated by the N-terminal coiled coil domain (CCD), the C-terminal transmembrane domain (TMD), and the re-entrant loop between the two domains. The TMD of each TMEM120A subunit contains six transmembrane helices (TMs) and has no clear structural feature of a channel protein. Instead, the six TMs form an α-barrel with a deep pocket where a coenzyme A (CoA) molecule is bound. Intriguingly, some structural features of TMEM120A resemble those of elongase for very long-chain fatty acids (ELOVL) despite the low sequence homology between them, pointing to the possibility that TMEM120A may function as an enzyme for fatty acid metabolism, rather than a mechanosensitive channel.

Aim This study investigated the roles of bone morphogenetic protein-4 (BMP4) and ROS in diabetic endothelial dysfunction and explored whether Salvianolic acid B (Sal B) improved endothelial function by affecting BMP4-ROS in diabetic mice. Main methods db/db mice were orally administrated with Sal B (10 mg/kg/day) for one week while db/m + mice were injected with adenoviral vectors delivering BMP4 (3 × 108 pfu) and then received one week-Sal B treatment. ROS levels were assayed by DHE staining. Protein expression and phosphorylation were evaluated by Western blot. Aortic rings were suspended in myograph for force measurement. Flow-mediated dilatations in the second-order mesenteric arteries were determined by pressure myograph. Key findings We first revealed the existence of a BMP4-ROS cycle in db/db mice, which stimulated p38 MAPK/JNK/caspase 3 and thus participated in endothelial dysfunction. One week-treatment or 24 h-incubation with Sal B disrupted the cycle, suppressed p38 MAPK/JNK/caspase 3 cascade, and improved endothelium-dependent relaxations (EDRs) in db/db mouse aortas. Importantly, in vivo Sal B treatment also improved flow-mediated dilatation in db/db mouse second order mesenteric arteries. Furthermore, in vivo BMP4 overexpression induced oxidative stress, stimulated p38 MAPK/JNK/caspase 3, and impaired EDRs in db/m + mouse aortas, which were all reversed by Sal B. Significance The present study demonstrates that Sal B ameliorates endothelial dysfunction through breaking the BMP4-ROS cycle and subsequently inhibiting p38 MAPK/JNK/caspase 3 in diabetic mice and provides evidence for the additional new mechanism underlying the benefit of Sal B against diabetic vasculopathy.

TMEM120A, also named as TACAN, is a novel membrane protein highly conserved in vertebrates and was recently proposed to be a mechanosensitive channel involved in sensing mechanical pain. Here we present the single particle cryo-EM structure of human TMEM120A which forms a tightly packed dimer with extensive interactions mediate by the N-terminal coiled coil domain (CCD), the C-terminal transmembrane domain (TMD), and the re-entrant loop between the two domains. The TMD of each TMEM120A subunit contains six transmembrane helices (TMs) and has no clear structural feature of a channel protein. Instead, the six TMs form an α-barrel with a deep pocket where a coenzyme A (CoA) molecule is bound. Intriguingly, some structural features of TMEM120A resemble those of elongase for very long-chain fatty acid (ELOVL) despite low sequence homology between them, pointing to the possibility that TEME120A may function as an enzyme for fatty acid metabolism, rather than a mechanosensitive channel.

The anti-fouling copper-zinc-tin-selenide (CZTSe) nanocarambolas were synthesized and deposited on a hydrophilic filter membrane, as the full solar spectrum absorber and nanoporous vapor generator, for efficient and stable solar-driven interfacial water evaporation. The CZTSe nanocarambolas assembled membrane based self-floatable device with excellent light-to-heat conversion, abundant nanochannels, anti-fouling property, timely water supply and low heat loss achieved a remarkable solar evaporation rate of 1.528 kg/m2 h and a solar-to-vapor conversion efficiency up to 86.4% under one Sun, and stable solar desalination over 30 days without decay. This assembled membrane showed an excellent salt-rejection ability and a potential application of long-term efficient, stable and safe solar water purification of seawater and wastewater, and practical freshwater production under natural conditions.

Advances in pharmaceutical technology have promoted the development of colon-targeted delivery system for oral administration of bioactive peptides or proteins to enhance their bioavailability. In this study, a multi-unit nanofiber mat was fabricated by coaxial electrospinning and its feasibility as the colon-targeted delivery system for a bioactive peptide, salmon calcitonin (sCT), was investigated. Sodium alginate and sCT-loaded liposome coated with pectin served as the shell layer and core layer, respectively. An in vitro study demonstrated that the encapsulated sCT was released in a sustained and colon-targeted way. Analysis using different mathematical models showed that release followed a complex mechanism. In addition, greater amounts of sCT were released from the core-shell nanofiber mat into simulated colon fluid (SCF) than was released from a uniaxial nanofiber mat (65.2% vs. 47.8%). The use of a core-shell nanofiber mat further alleviated the burst release of sCT into simulated gastric and intestinal fluid (SGF and SIF), demonstrating the superiority of a multi-unit vehicle for colon-targeted delivery of sCT. Furthermore, 88% of the bioactivity of encapsulated sCT was retained. This multi-unit vehicle offers a better-designed vehicle for the colon-targeted sustained release of bioactive peptides or proteins and, thus, should improve oral bioavailability.