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Increased sympathetic nerve excitability has been reported to aggravate a variety of chronic pain conditions, and an increase in the number of sympathetic nerve fibers in the dorsal root ganglion (DRG) has been found in neuropathic pain (NP) models. However, the mechanism of the neurotransmitter norepinephrine (NE) released by sympathetic nerve fiber endings on the excitability of DRG neurons is still controversial, and the adrenergic receptor subtypes involved in this biological process are also controversial. In our study, we have two objectives: (1) To determine the effect of the neurotransmitter NE on the excitability of different neurons in DRG; (2) To determine which adrenergic receptors are involved in the excitability of DRG neurons by NE released by sprouting sympathetic fibers. In this experiment, a unique field potential recording method of spinal cord dorsal horn was innovatively adopted, which can be used for electrophysiological study in vivo. The results showed that： Forty days after SNI, patch clamp and field potential recording methods confirmed that NE enhanced the excitability of ipsilateral DRG large neurons, and then our in vivo electrophysiological results showed that the α 2 receptor blocker Yohimbine could block the excitatory effect of NE on A-fiber and the inhibitory effect on C-fiber, while the α 2A -adrenergic receptor agonist guanfacine (100 μM) had the same biological effect as NE. Finally, we concluded that NE from sympathetic fiber endings is involved in the regulation of pain signaling by acting on α 2A -adrenergic receptors in DRG. • After nerve injury, sympathetic nerve fibers sprouted in DRG mainly surrounded large diameter neurons. • The number of sympathetic nerve buds in DRG 14 days after SNI was small, and the cell excitability did not change after norepinephrine (NE) administration. • Our electrophysiological study demonstrated that NE is involved in the regulation of neuralgia through α2A adrenergic receptors in large diameter neurons. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H 2 S) is an important gaseous signal molecule which participates in various abiotic stress responses. However, the underlying mechanism of H 2 S associated salt tolerance remains elusive. In this study, sodium hydrosulfide (NaHS, donor of H 2 S) was used to investigate the protective role of H 2 S against salt stress at the biochemical and proteomic levels. Antioxidant activity and differentially expressed proteins (DEPs) of rice seedlings treated by NaCl or/and exogenous H 2 S were investigated by the methods of biochemical approaches and comparative proteomic analysis. The protein-protein interaction (PPI) analysis was used for understanding the interaction networks of stress responsive proteins. In addition, relative mRNA levels of eight selected identified DEPs were analyzed by quantitative real-time PCR. The result showed that H 2 S alleviated oxidative damage caused by salt stress in rice seedling. The activities of some antioxidant enzymes and glutathione metabolism were mediated by H 2 S under salt stress. Proteomics analyses demonstrated that NaHS regulated antioxidant related proteins abundances and affected related enzyme activities under salt stress. Proteins related to light reaction system (PsbQ domain protein, plastocyanin oxidoreductase iron-sulfur protein), Calvin cycle (phosphoglycerate kinase, sedoheptulose-1,7-bisphosphatase precursor, ribulose-1,5-bisphosphate carboxylase/oxygenase) and chlorophyll biosynthesis (glutamate-1-semialdehyde 2,1-aminomutase, coproporphyrinogen III oxidase) are important for NaHS against salt stress. ATP synthesis related proteins, malate dehydrogenase and 2, 3-bisphosphoglycerate-independent phosphoglycerate mutase were up-regulated by NaHS under salt stress. Protein metabolism related proteins and cell structure related proteins were recovered or up-regulated by NaHS under salt stress. The PPI analysis further unraveled a complicated regulation network among above biological processes to enhance the tolerance of rice seedling to salt stress under H 2 S treatment. Overall, our results demonstrated that H 2 S takes protective roles in salt tolerance by mitigating oxidative stress, recovering photosynthetic capacity, improving primary and energy metabolism, strengthening protein metabolism and consolidating cell structure in rice seedlings. • Exogenous H 2 S alleviates the growth inhibition and oxidative damage caused by NaCl in rice seedlings. • Exogenous H 2 S increases the abundance of antioxidant enzymes under salt stress. • Exogenous H 2 S enhances the abundance of proteins related to photosynthesis under salt stress. • Exogenous H 2 S accumulates proteins related to glycolysis, TCA and ATP synthesis under salt stress. • Exogenous H 2 S accumulates proteins related to protein metabolism and cell structure under salt stress. [ABSTRACT FROM AUTHOR]

Metabolic and autoimmune disorders have long represented challenging health problems because of their growing prevalence in companion animals. The gut microbiome, made up of trillions of microorganisms, is implicated in multiple physiological and pathological processes. Similar to human beings, the complicated microbiome harbored in the gut of canines and felines emerges as a key factor determining a wide range of normal and disease conditions. Evidence accumulated from recent findings on canine and feline research uncovered that the gut microbiome is actively involved in host metabolism and immunity. Notably, the composition, abundance, activity, and metabolites of the gut microbiome are all elements that shape clinical outcomes concerning metabolism and immune function. This review highlights the implications of the gut microbiome for metabolic disorders (obesity, diabetes, and hepatic lipidosis) and autoimmune diseases (inflammatory bowel disease, osteoarthritis, asthma, and myasthenia gravis) in canine and feline animals, providing novel strategies and therapeutic targets for the prevention and treatment of pet diseases. • The gut microbiome plays a pivotal role in the pathogenesis and progression of metabolic and autoimmune disorders. • The association between the gut microbiome and metabolic disorders has been observed in dogs and cats. • Evidence has established a connection between dysbiosis in the gut of dogs and cats and autoimmune disorders. • Elucidating the role of the gut microbiome in metabolic and autoimmune disorders will provide novel therapeutic targets. [ABSTRACT FROM AUTHOR]

As a natural aldehyde organic compound, cinnamaldehyde (CA) is one of the main components of cinnamon essential oil with multiple bioactivities. In this study, we investigated the protective effects of CA on zearalenone (ZEA)-induced apoptosis, barrier dysfunction and mucin reduction, as well as underlying mechanisms in LS174T cells. In the present study, cells pre-treated with or without CA for 24 h were left untreated or subjected to ZEA for indicated time points Our results showed that 10 μM CA significantly prevented ZEA-induced cell viability decline, reversed ZEA-induced increase of the LDH level, cell cycle disruption and apoptosis in LS174T cells. Periodic acid-schiff (PAS) staining analysis showed that CA significantly alleviated the reduction of mucin secretion in LS174T cells caused by ZEA exposure. Western blot analysis showed that CA significantly reversed ZEA-induced reduction of the expression of mucin 2 (MUC2) and tight junction (TJ) proteins (claudin-1, claudin-3, ZO-1 and ZO-2) in LS174T cells. Notably, CA can significantly reduce the upregulation of the main effector of MAPK and NF-κB signaling pathways in LS174T cells. Further study showed that CA protects cells against ZEA-induced cellular damage through JNK/NF-κB signaling pathway in LS174T cells. Supplementation with CA might be an potential strategy to alleviate the damaging effect of ZEA on epithelial cells. • We found that ZEA exposure led to decreased cell viability, impaired barrier function, and reduced secretion of mucin, and increased apoptosis, which were effectively alleviated by CA in LS174T cells. • We proved for the first time that the protective effect of CA on ZEA-induced damage of LS174T cells is mediated by JNK/NF-κB signaling pathway. • Supplementation with CA might be a potential therapeutic option for IBD-related barrier dysfunction. [ABSTRACT FROM AUTHOR]

Adoptive T cell-based immunotherapies can mediate complete and durable regressions in patients with advanced cancer, but current response rates remain inadequate. Maneuvers to improve the fitness and antitumor efficacy of transferred T cells have been under extensive exploration in the field. Small non-coding microRNAs have emerged as critical modulators of immune system homeostasis and T cell immunity. Here, we summarize recent advances in our understanding of the role of microRNAs in regulating T cell activation, differentiation, and function. We also discuss how microRNA therapeutics could be employed to fine-tune T cell receptor signaling and enhance T cell persistence and effector functions, paving the way for the next generation of adoptive immunotherapies. [ABSTRACT FROM AUTHOR]

In 1911, Dubouis determined all positive integers that are represented by a sum of k positive squares for any k ≥ 4 . In this article, we generalize Dubouis' result to the binary case. We determine all binary forms that are represented by a sum of k nonzero squares for any k ≥ 5 . [ABSTRACT FROM AUTHOR]

When used as an N-terminal fusion expression partner, the Escherichia coli stress-responsive protein, CysQ dramatically increased the cytoplasmic solubility of various aggregation-prone heterologous proteins: Pseudomonas putida cutinase (CUT), human granulocyte colony-stimulating factor (hG-CSF), human ferritin light chain (hFTN-L), arginine deiminase (ADI), human interleukin-2 (IL2), human activation induced cytidine deaminase (AID), and deletion mutant of human glutamate decarboxylase (GAD448-585). As compared with well-known fusion tags such as glutathione-S-transferase (GST) and maltose-binding protein (MBP), the performance of CysQ as solubility enhancer was evidently better than GST and was similar to or better than MBP for the seven heterologous proteins above. This is likely due to the intrinsic ability of CysQ to form its native conformation, probably promoting the binding of molecular chaperones during the folding of CysQ-fusion protein. When used as a substrate, p-nitrophenyl butyrate (PNB) was successfully hydrolyzed to p-nitrophenol by CysQ-CUT fusion mutant. Even after CysQ was removed, the solubility of hFTN-L and hG-CSF, the secondary structure of hG-CSF, and self-assembly activity of hFTN-L were successfully maintained. Conclusively, it seems that CysQ is a highly effective solubility enhancer and fusion expression partner for the production of a variety of bio-active recombinant proteins. [ABSTRACT FROM AUTHOR]

Angiogenesis is an important biological process in tissue development and repair. Fucoidan has previously been shown to potentiate in vitro tube formation in the presence of basic fibroblast growth factor (FGF-2). However, the underlying molecular mechanism remains largely unknown. This study was designed to investigate the action of fucoidan in angiogenesis in human umbilical vein endothelial cells (HUVECs) and to explore fucoidan-signalling pathways. First, we evaluated the effect of fucoidan on cell proliferation. Matrigel-based tube formation and wound healing assays were performed to investigate angiogenesis. Matrix metalloproteinase-2 (MMP-2) mRNA expression and activity levels were analysed by reverse transcription polymerase chain reaction (RT-PCR) and zymography, respectively. Additionally, phosphorylation of mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) was detected by Western blot. The results indicate that fucoidan treatment significantly increased cell proliferation in the presence of FGF-2. Moreover, compared to the effect of FGF-2 alone, fucoidan and FGF-2 had a greater effect on tube formation and cell migration, and this effect was found to be synergistic. Furthermore, fucoidan enhanced the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, and AKT. MMP-2 activation was also significantly increased. Specific inhibitors of p38 (SB203580) and JNK (SP600125) inhibited tube formation and wound healing, while an ERK inhibitor (PD98059) did not. MMP-2 activation and AKT phosphorylation were also attenuated and associated with the suppression of p38 and JNK phosphorylation, but not with that of ERK. These results indicate that fucoidan, in the presence of FGF-2, induces angiogenesis through AKT/MMP-2 signalling by activating p38 and JNK. These findings provide basic molecular information on the effect of fucoidan on angiogenesis in the presence of FGF-2. [ABSTRACT FROM AUTHOR]

Abstract: Hippo-Yap signaling has been implicated in organ size determination via its regulation of cell proliferation, growth and apoptosis (Pan, 2007). The vertebrate lens comprises only two major cell types, lens progenitors and differentiated fiber cells, thereby providing a relatively simple system for studying size-controlling mechanisms. In order to investigate the role of Hippo-Yap signaling in lens size regulation, we conditionally ablated Yap in the developing mouse lens. Lens progenitor-specific deletion of Yap led to near obliteration of the lens primarily due to hypocellularity in the lens epithelium (LE) and accompanying lens fiber (LF) defects. A significantly reduced LE progenitor pool resulted mainly from failed self-renewal and increased apoptosis. Additionally, Yap-deficient lens progenitor cells precociously exited the cell cycle and expressed the LF marker, β-Crystallin. The mutant progenitor cells also exhibited multiple cellular and subcellular alterations including cell and nuclear shape change, organellar polarity disruption, and disorganized apical polarity complex and junction proteins such as Crumbs, Pals1, Par3 and ZO-1. Yap-deficient LF cells failed to anchor to the overlying LE layer, impairing their normal elongation and packaging. Furthermore, our localization study results suggest that, in the developing LE, Yap participates in the cell context-dependent transition from the proliferative to differentiation-competent state by integrating cell density information. Taken together, our results shed new light on Yap's indispensable and novel organizing role in mammalian organ size control by coordinating multiple events including cell proliferation, differentiation, and polarity. [Copyright &y& Elsevier]

Abstract: Liver cancer development follows a multistep process that includes epigenetic changes beginning at the initiation stage, changes that have been studied for their potential diagnostic value. Here, we examined long-term, cancer-associated epigenetic changes during carcinogenesis using a mouse model of liver cancer. WW45-haploinsufficient (WW45 +/−) mice developed liver cancer after 12months due to dysregulation of the Hippo pathway and consequent Yap overexpression. There was no pathological sign of neoplastic regions in the livers of 10-month-old WW45 +/− mice but whole-gene expression patterns statistically proved the resemblance between 10-month-old livers and hepatomas from WW45 +/− mice. We found epigenetic features in the livers of 10-month-old WW45 +/− mice which were already distinctive from the wild-type counterparts prior to tumorigenesises. H19 ICR showed loss-of-imprinting in two steps and allelic histone marker signature during tumorigenesis showed similarity with ES cells. Progressive cancer pathognomonic global hypomethylation was a characteristic post-10-month feature and was well reflected in retrotransposons. Heterochromatic histone modifications also decreased in retrotransposons after 10months in the liver of WW45 +/− mice. This study showed potential epigenetic features for cancer prognostic use and supported the epigenetic progenitor model of cancer. [ABSTRACT FROM AUTHOR]

Abstract: Novel calcium-alginate (Ca-alginate) capsules with aqueous core and thermo-responsive membrane are successfully prepared by introducing a co-extrusion minifluidic approach, and the thermo-responsive gating characteristics of Ca-alginate capsule membranes embedded with poly(N-isopropylacrylamide) (PNIPAM) microspheres are investigated systematically. The experimental results show that the prepared Ca-alginate capsules are highly monodisperse, and the average diameter and membrane thickness of Ca-alginate capsules are about 2.96mm and 0.11mm respectively. The Ca-alginate capsule membranes exhibit desired thermo-responsive gating property. With increasing the content of PNIPAM microspheres embedded in the Ca-alginate capsule membranes, the thermo-responsive gating coefficient of the capsule membranes increases simply. When solute molecules diffuse through the capsule membrane, the thermo-responsive gating coefficient is significantly affected by the molecular weight of solute molecules. [ABSTRACT FROM AUTHOR]

Abstract: This study evaluated the anti-asthmatic activities of four diterpene acids isolated from Aralia cordata root that are proposed to be the active ingredients in its traditional use as a treatment for inflammation, overheating, pain and spasm in Korea. The diterpene acids were identified as kaurenoic acid, 7-oxo-sandaracopimaric acid, 17-hydroxy-ent-kaur-15-en-19-oic acid, and hederagenin, by comparing their phytochemical and spectroscopic data with previous reports. The effects of diterpene acids on asthma were evaluated by determining the specific airway resistance (sRaw) during the immediate asthmatic response (IAR) and the late-phase asthmatic response (LAR) in guinea pigs with IgE-mediated asthma. Recruitment of leukocytes and the presence of chemical mediators in bronchoalveolar lavage fluid (BALF) were determined, and histopathological surveys performed. The four diterpene acids dosed at 25∼100mg/kg had dose-dependently anti-asthmatic effects: 7-oxo-sandaracopimaric acid>17-hydroxy-ent-kaur-15-en-19-oic acid>kaurenoic acid>hederagenin. 7-oxo-sandaracopimaric acid (25mg/kg) significantly (p <0.05) inhibited sRaw by 59.5% in IAR and LAR, and also dose-dependently inhibited recruitment of eosinophils and neutrophils into lung and release of chemical mediators, histamine, and the activity of phospholipase A2 and eosinophil peroxidase in BALF. 7-Oxo-sandaracopimaric acid had the highest activity among the diterpene acids. But its effect was lower than cromolyn sodium, salbutamol, or dexamethasone in both the IAR and the LAR. These results suggested that C7-oxo radical of 7-oxo-sandaracopimaric acid was more active than the C7-hydroxy and hydrogen of the other compounds, and showed diterpene acids have anti-asthmatic effects, supporting the traditional application of this herb in treating IgE-mediated asthma. [Copyright &y& Elsevier]

Abstract: Rap small GTPases regulate excitatory synaptic strength and morphological plasticity of dendritic spines. Changes in spine structure are mediated by the F-actin cytoskeleton, but the link between Rap activity and actin dynamics is unclear. Here, we report a novel interaction between SPAR, a postsynaptic inhibitor of Rap, and α-actinin, a family of actin-cross-linking proteins. SPAR and α-actinin engage in bidirectional structural plasticity of dendritic spines: SPAR promotes spine head enlargement, whereas increased α-actinin2 expression favors dendritic spine elongation and thinning. Surprisingly, SPAR and α-actinin2 can function in an additive rather than antagonistic fashion at the same dendritic spine, generating combination spine/filopodia hybrids. These data identify a molecular pathway bridging the actin cytoskeleton and Rap at synapses, and suggest that formation of spines and filopodia are not necessarily opposing forms of structural plasticity. [Copyright &y& Elsevier]

Abstract: We investigated the hypolipidemic effect of resveratrol focused on the mRNA expression and hepatic HMG-CoA reductase (HMGR) activity in hamsters fed a high-fat diet. Male Syrian Golden hamsters were fed a high-fat diet containing 0.025% fenofibrate or 0.025% resveratrol for 8 weeks. The concentrations of serum total cholesterol and triglyceride were significantly lower in the resveratrol-fed group than in the control group. The resveratrol contained diet significantly decreased Apo B, Lp(a), and cholesterol–ester–transport protein (CETP) concentrations, but increased Apo A-I levels and the Apo A-I/Apo B ratio. The contents of cholesterol and triglyceride in hepatic tissue were significantly lower in the resveratrol group than in the control group. Real-time PCR analysis revealed that HMGR mRNA expression was significantly lower in the resveratrol group than in the control group. These results indicate that dietary resveratrol reduces serum cholesterol by down-regulating hepatic HMGR mRNA expression in hamsters fed a high-fat diet. [Copyright &y& Elsevier]

Peptides pore-forming in cell membrane have been identified from a wide range of animals. A putative pore-forming peptide deduced from a cDNA clone of Clonorchis sinensis (clonorin) was predicted to consist of four amphipathic α-helices. Clonorin contained six invariably conserved cysteine residues, identified to form three disulfide bonds. These predicted structural features are highly homologous with pore-forming peptides, the amoebapores. Recombinant clonorin showed hemolytic activity toward rabbit erythrocytes. The hemolytic activity of C. sinensis extract increased dose-dependently and was inhibited by anti-clonorin immune sera. The clonorin was expressed developmentally in juvenile and adult flukes and localized in the intestinal epithelium of adult flukes. It is proposed that, through lysing host cellular components, clonorin could enhance proteolytic digestion in the intestine of C. sinensis. [Copyright &y& Elsevier]

In this study, a new electrochemical method was used to simultaneously efficient removal of Mn2+ and NH 4 +-N in wastewater with Cu plate as cathode. The effects of various reaction parameters on the concentrations of Mn2+, NH 4 +-N and by-products (NO 3 −-N and NO 2 −-N, free chlorine and residual chlorine), as well as the removal mechanism were investigated. The results showed that the removal efficiencies of Mn2+ and NH 4 +-N were 99.1% and 92.9%, and the concentrations of NO 3 −-N, NO 2 −-N, free chlorine and residue chlorine were 0.73 mg/L, 0.15 mg/L, 0.13 mg/L and 0.63 mg/L reacting for 3 h at room temperature, respectively, when the current density was 10 mA/cm2, the mass ratio of ClO− and Cl− was 1:1, the initial pH was 9. The concentrations of Mn2+, NH 4 +-N and by-products in wastewater met the integrated wastewater discharge standard (GB8978-1996). In addition, spherical manganese oxide was deposited on the anode plate, and spherical manganese oxide collapsed over electrolysis time. Manganese was mainly removed in the form of MnO, Mn(OH) 2 and MnO 2. NH 4 +-N was mainly oxidized to N 2. Economic evalution revealed that the treatment cost was 2.93 $/m3. Image 1 • The removal efficiencies of Mn2+ and NH 4 +-N were 99.1% and 92.9%, respectively. • The concentrations of by-products were less than the standard (GB8978-1996). • Manganese was mainly removed as manganese oxides. • NH 4 +-N was mainly oxidized to N 2. [ABSTRACT FROM AUTHOR]

Medical named entity recognition (NER) in Chinese electronic medical records (CEMRs) has drawn much research attention, and plays a vital prerequisite role for extracting high-value medical information. In 2018, China Health Information Processing Conference (CHIP2018) organized a medical NER academic competition aiming to extract three types of malignant tumor entity from CEMRs. Since the three types of entity are highly domain-specific and interdependency, extraction of them cannot be achieved with a single neural network model. Based on comprehensive study of the three types of entity and the entity interdependencies, we propose a collaborative cooperation of multiple neural network models based approach, which consists of two BiLSTM-CRF models and a CNN model. In order to tackle the problem that target scene dataset is small and entity distributions are sparse, we introduce non-target scene datasets and propose sentence-level neural network model transfer learning. Based on 30,000 real-world CEMRs, we pre-train medical domain-specific Chinese character embeddings with word2vec, GloVe and ELMo, and apply them to our approach respectively to validate effects of pre-trained language models in Chinese medical NER. Also, as control experiments, we apply Gated Recurrent Unit to our approach. Finally, our approach achieves an overall F1-score of 87.60%, which is the state-of-the-art performance to the best of our knowledge. In addition, our approach has won the champion of the medical NER academic competition organized by 2019 China Conference on Knowledge Graph and Semantic Computing, which proves the outstanding generalization ability of our approach. [ABSTRACT FROM AUTHOR]

The establishment of cell lines with a high protein production is the most crucial objective in the field of biopharmaceuticals. To this end, efforts have been made to increase transgene expression through promoter improvement, but the efficiency or stability of protein production was insufficient for use in commercial production. Here, we developed a novel strategy to increase the efficiency and stability of protein production by hybridizing a promoter that exhibits higher expression levels at the transient level with a promoter that exhibits higher stability at the stable level. Expression levels of transgenes by each promoter were measured at transient and stable levels for five single promoters: Rous sarcoma virus (RSV), cytomegalovirus (CMV), human phosphoglycerate kinase (hPGK), simian virus 40 (SV40), and zebrafish ubiquitin B (Ubb). The hPGK promoter enabled high-yield transgene expression at transient levels and the SV40 promoter enabled sustained expression at stable levels. Therefore, hPGK and SV40 promoters were selected as candidates for establishing hybrid promoters and two hybrid promoters were constructed; one hybrid promoter in which the SV40 promoter is added before the hPGK promoter (a.k.a. SKYI) and the other hybrid promoter in which the SV40 promoter is added after the hPGK promoter (a.k.a. SKYII). Of the two hybrid promoters, the hybrid promoter SKYII promoted high-yield transgene expression at both transient and stable levels compared to single hPGK and SV40. Together, our findings open new doors in the field of biopharmaceuticals by presenting a novel promoter platform that can be used for high-yield and sustained protein production. • hPGK promoter enables higher expression at transient levels and SV40 promoter enables sustained expression at stable levels. • hPGK and SV40 promoters are selected as candidates for establishing hybrid promoters. • The novel hybrid promoter enables sustained protein production with high yields. [ABSTRACT FROM AUTHOR]

Abstract: Dendritic spine morphology is thought to play important roles in synaptic development and plasticity, and morphological derangements in spines are correlated with several neurological disorders. Here, we identified an interaction between Spine-Associated RapGAP (SPAR), a postsynaptic protein that reorganizes actin cytoskeleton and drives dendritic spine head growth, and PDLIM5/Enigma Homolog (ENH), a PDZ-LIM (postsynaptic density-95/Discs large/zona occludens 1-Lin11/Isl-1/Mec3) family member. PDLIM5 has been implicated in susceptibility to bipolar disorder, major depression, and schizophrenia, but its function in neurological disease is poorly understood. We show that PDLIM5 is present in the postsynaptic density, where it promotes decreased dendritic spine head size and longer, filopodia-like morphology. Conversely, RNA interference against PDLIM5 or loss of PDLIM5 interaction with SPAR caused increased spine head diameter. Furthermore, PKC activation promoted delivery of PDLIM5 into dendritic spines and increased its spine colocalization with SPAR. These data reveal new postsynaptic functions for PDLIM5 in shrinkage of dendritic spines that may be relevant to its association with psychiatric illness. [Copyright &y& Elsevier]

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergency of various lineages through mutations and recombination. In the Delta lineage, we identified recombination events in the ORF1a gene, which divided the Delta sublineages into three different genotypes (Delta R1-R3). The regional distributions of Delta R1 and Delta R2 were not correlated, indicating that recombination occurred early in the Delta outbreak. The impact of the ORF1a gene on SARS-CoV-2 transmission remains unclear; however, our findings suggest that recombination may have contributed to the evolution and global spread of the Delta lineage. • We found three recombinant groups in Delta VOC have distinct ORF1a gene. • The recombination occurred in the early stage of the Delta outbreak. • Two major recombinant were detected globally without regional correlation. [ABSTRACT FROM AUTHOR]

• An endophytic fungus, Colletotrichum sp. JS-0361 was isolated from Morus alba. • Colletotrichalactones A-Ca with a 5/6/10-fused ring were isolated from the strain. • The structures were completely established by spectral and chemical methods. • They had unstable aldehydes which are easily converted into acetals in solvents. • Compounds 1 and 3a displayed cytotoxic activities against MCF7 cells. Three unusual polyketides with a 5/6/10-fused ring system, named colletotrichalactones A-Ca (1 - 3a), were isolated from cultures of the endophytic fungus, Colletotrichum sp. JS-0361, which was isolated from a leaf of Morus alba. Their structures, including their absolute stereochemistries, were completely established using extensive spectroscopic methods together with a chemical reaction utilizing competing enantioselective acylation coupled with LC/MS. Compounds possessing this ring skeleton were previously reported in three studies. Our rigorous chemical investigation revealed the complete configuration of this skeleton, which agreed with the results for glabramycin B with this ring skeleton established by computational chemistry and enantioselective synthesis in previous reports. 1 and 2 had unstable aldehyde groups that were easily converted to acetal groups in the presence of solvents. Meanwhile, compound 3a , with terminal acetal functionality, was deduced to be an artefact originating from compound 3 with a terminal aldehyde group. Compounds 1 and 3a displayed moderate-to-potent cytotoxic activities against MCF7 cells with IC 50 s of 35.06 and 25.20 µM, respectively. [ABSTRACT FROM AUTHOR]

In vivo approaches to inducing an effective immune response focus on targeted antigen (Ag) delivery to dendritic cells (DCs). In this study, we developed a new method of targeting plasmid DNA and/or the antigen (Ag)–antibody (Ab) complex to DCs via the DC receptor DEC-205, also known as cluster of differentiation CD205. We cloned and expressed a recombinant protein composed of mouse DEC-205-specific single-chain fragment variable region (mDEC-205-scFv), the streptococcal protein G (SPG) IgG-binding domain and cationic peptide (CP), which named mDEC205-scFv-SPG-CP (msSC). In vitro, the recombinant protein msSC can specifically bind to DCs through the section of mDEC-205-scFv, and bound the Ag–Ab complex via SPG as well as plasmid DNA through electrostatic bonding with CP in vitro. In addition, msSC functioned in a manner similar to anti-DEC-205 monoclonal Ab and bound to mouse bone marrow-derived DCs. It was demonstrated in vivo that msSC can target plasmid DNA to DCs, resulting in efficient uptake and expression. Moreover, msSC can form a complex with pGL3-CMV and transport it to draining lymph nodes when injected in vivo. These results indicate that msSC can be used as a carrier protein for vaccine delivery to DCs via formation of plasmid DNA-Ag–Ab ternary complexes. [ABSTRACT FROM AUTHOR]

Highlights: [•] Imprinted genes represent differential allelic expression patterns in hPSCs. [•] Some imprinted genes are conserved in the allelic expression during differentiation. [•] Allelic expression of imprinted genes can be changed in a cell type-specific manner. [•] Imprinted genes are vulnerable in hPSCs during in vitro differentiation. [ABSTRACT FROM AUTHOR]

Abstract: Monodisperse microspheres composed of thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) core and biocompatible porous ethyl cellulose (EC) shell embedded with PNIPAM gates have been successfully prepared by microfluidic emulsification, solvent evaporation and free radical polymerization. Attributing to the coating of EC shell, the mechanical strength and biocompatibility of the core–shell microsphere are much better than those of the PNIPAM core itself. Fourier transform infrared (FT-IR) spectrometer and scanning electron microscopy (SEM) are employed to examine chemical compositions and microstructures of prepared microparticles. By the cooperative action of EC shell with PNIPAM gates and PNIPAM core, the proposed core–shell microspheres exhibit satisfactory thermo-responsive controlled release behaviors of model drug molecules rhodamine B (Rd B) and VB12. At temperatures above the volume phase transition temperature (VPTT) of PNIPAM, the release rate of solute molecules is much faster than that at temperatures below the VPTT. The controlled factor of the prepared core–shell microspheres for VB12 release reaches to as high as 11.7. The proposed microspheres are highly attractive for controlled drug delivery. [Copyright &y& Elsevier]

Abstract: Sustained elevations of glucose and free fatty acid concentration have deleterious effects on pancreatic beta cell function. One of the hallmarks of such glucolipotoxicity is a reduction in insulin gene expression, resulting from decreased insulin promoter activity. Sterol regulatory element binding protein-1c (SREBP-1c), a lipogenic transcription factor, is related to the development of beta cell dysfunction caused by elevated concentrations of glucose and free fatty acid. Small heterodimer partner (SHP) interacting leucine zipper protein (SMILE), also known as Zhangfei, is a novel protein which interacts with SHP that mediates glucotoxicity in INS-1 rat insulinoma cells. Treatment of INS-1 cells with high concentrations of glucose and palmitate increased SREBP-1c and SMILE expression, and decreased insulin gene expression. Adenovirus-mediated overexpression of SREBP-1c in INS-1 cells induced SMILE expression. Moreover, adenovirus-mediated overexpression of SMILE (Ad-SMILE) in INS-1 cells impaired glucose-stimulated insulin secretion as well as insulin gene expression. Ad-SMILE overexpression also inhibited the expression of beta-cell enriched transcription factors including pancreatic duodenal homeobox factor-1, beta cell E box transactivator 2 and RIPE3b1/MafA, in INS-1 cells. Finally, in COS-1 cells, expression of SMILE inhibited the insulin promoter activity induced by these same beta-cell enriched transcription factors. These results collectively suggest that SMILE plays an important role in the development of beta cell dysfunction induced by glucolipotoxicity. [Copyright &y& Elsevier]

Abstract: The pathophysiological relevance of S-nitrosoglutathione (GSNO)-induced endothelial cell injury remains unclear. The main objective of this study was to elucidate the molecular mechanisms of GSNO-induced oxidative stress in endothelial cells. Morphological evaluation through DAPI staining and propidium iodide (PI) flow cytometry was used to detect apoptosis. In cultured EA.hy926 endothelial cells, exposure to GSNO led to a time- and dose-dependent apoptotic cascade. When intracellular reactive oxygen species (ROS) production was measured in GSNO-treated cells with the fluorescent probes 5-(and-6)-carboxy-2′,7′-dichlorofluorescein diacetate, we observed elevated ROS levels and a concomitant loss in mitochondrial membrane potential, indicating that GSNO-induced death signaling is mediated through a ROS-mitochondrial pathway. Importantly, we found that peroxynitrite formation and Omi/HtrA2 release from mitochondria were involved in this phenomenon, whereas changes of death-receptor dependent signaling were not detected in the same context. The inhibition of NADPH oxidase activation and Omi/HtrA2 by a pharmacological approach provided significant protection against caspase-3 activation and GSNO-induced cell death, confirming that GSNO triggers the death cascade in endothelial cells in a mitochondria-dependent manner. Taken together, our results indicate that ROS overproduction and loss of mitochondrial Omi/HtrA2 play a pivotal role in reactive nitrogen species-induced cell death, and the modulation of these pathways can be of significant therapeutic benefit. [Copyright &y& Elsevier]