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The Ili River Valley, located in the northwest of China, serves as a vital repository for fish genetic resources. Its extensive water network and diverse climate have given rise to a unique fish composition and endemic species. In this study, we collected the cytochrome c oxidase subunit I (COI) sequences from 660 fish specimens in the Ili River Valley. The effectiveness of DNA barcoding in identifying fish species in the area was assessed by examining genetic distances, constructing phylogenetic trees, and performing ABGD (Automatic Barcode Gap Discovery) analyses, among other methods. In total, 20 species were identified, including one unidentified species (Silurus sp.). Except for Silurus asotus and Hypophthalmichthys molitrix (only one sample), the maximum intraspecific genetic distance among the remaining species was smaller than the minimum interspecific distance, which proves that the species exhibit obvious barcode gaps. In the Neighbor‐Joining trees, 20 species formed separate monophyletic branches. According to ABGD analysis, 660 sequences were categorized into 19 Operational Taxonomic Units, with Silurus sp. and S. asotus grouped into a single OTU. The Silurus in this study exhibits shared haplotypes and significant genetic divergence, suggesting the potential presence of cryptic species. Furthermore, the nucleotide diversity across all species fell below the threshold level, indicating that the local fish population is gradually declining. In conclusion, this study has demonstrated the effectiveness of DNA barcoding in identifying fish species in the Ili River Valley, providing valuable data to support the conservation of local fish resources. [ABSTRACT FROM AUTHOR]

The relationship among polycystic ovary syndrome (PCOS), endometrial cancer (EC), and glycometabolism remains unclear. We explored shared genes between PCOS and EC, using bioinformatics to unveil their pathogenic connection and influence on EC prognosis. Gene Expression Omnibus datasets GSE226146 (PCOS) and GSE196033 (EC) were used. A protein–protein interaction (PPI) network was constructed to identify the central genes. Candidate markers were screened using dataset GSE54250. Differences in marker expression were confirmed in mouse PCOS and human EC tissues using RT‐PCR and immunohistochemistry. The effect of PGD on EC proliferation and migration was explored using Ki‐67 and Transwell assays. PGD's impact on the glycometabolic pathway within carbon metabolism was assessed by quantifying glucose content and lactic acid production. R software identified 31 common genes in GSE226146 and GSE196033. Gene Ontology functional classification revealed enrichment in the "purine nucleoside triphosphate metabolism process," with key Kyoto Encyclopedia of Genes and Genomes pathways related to "carbon metabolism." The PPI network identified 15 hub genes. HK2, NDUFS8, PHGDH, PGD, and SMAD3 were confirmed as candidate markers. The RT‐PCR analysis validated distinct HK2 and PGD expression patterns in mouse PCOS ovarian tissue and human EC tissue, as well as in normal and EC cells. Transfection experiments with Ishikawa cells further confirmed PGD's influence on cell proliferation and migration. Suppression of PGD expression impeded glycometabolism within the carbon metabolism of EC cells, suggesting PGD as a significant PCOS risk factor impacting EC proliferation and migration through modulation of single carbon metabolism. These findings highlight PGD's pivotal role in EC onset and prognosis. [ABSTRACT FROM AUTHOR]

Sucrose is a commonly utilized nutritive sweetener in food and beverages due to its abundance in nature and low production costs. However, excessive intake of sucrose increases the risk of metabolic disorders, including diabetes and obesity. Therefore, there is a growing demand for the development of nonnutritive sweeteners with almost no calories. d‐Allulose is an ultra‐low‐calorie, rare six‐carbon monosaccharide with high sweetness, making it an ideal alternative to sucrose. In this study, we developed a cell factory for d‐allulose production from sucrose using Escherichia coli JM109 (DE3) as a chassis host. The genes cscA, cscB, cscK, alsE, and a6PP were co‐expressed for the construction of the synthesis pathway. Then, the introduction of ptsG‐F and knockout of ptsG, fruA, ptsI, and ptsH to reprogram sugar transport pathways resulted in an improvement in substrate utilization. Next, the carbon fluxes of the Embden‐Meyerhof‐Parnas and the pentose phosphate pathways were regulated by the inactivation of pfkA and zwf, achieving an increase in d‐allulose titer and yield of 154.2% and 161.1%, respectively. Finally, scaled‐up fermentation was performed in a 5 L fermenter. The titer of d‐allulose reached 11.15 g/L, with a yield of 0.208 g/g on sucrose. [ABSTRACT FROM AUTHOR]

The rice stem borer (RSB), Chilo suppressalis, a notorious rice pest in China, has evolved a high resistance level to commonly used insecticides. Tetraniliprole, a new anthranilic diamide insecticide, effectively controls multiple pests, including RSB. However, the potential resistance risk of RSB to tetraniliprole is still unknown. In this study, the tetraniliprole‐selection (Tet‐R) strain was obtained through 10 continuous generations of selection with tetraniliprole 30% lethal concentration (LC30). The realized heritability (h2) of the Tet‐R strain was 0.387, indicating that resistance of RSB to tetraniliprole developed rapidly under the continuous selection of tetraniliprole. The Tet‐R strain had a high fitness cost (relative fitness = 0.53). We established the susceptibility baseline of RSB to tetraniliprole (lethal concentration at LC50 = 0.727 mg/L) and investigated the resistance level of 6 field populations to tetraniliprole. All tested strains that had resistance to chlorantraniliprole exhibited moderate‐ to high‐level resistance to tetraniliprole (resistance ratio = 27.7−806.8). Detection of ryanodine receptor (RyR) mutations showed that the Y4667C, Y4667D, I4758M, and Y4891F mutations were present in tested RSB field populations. RyR mutations were responsible for the cross‐resistance between tetraniliprole and chlorantraniliprole. Further, the clustered regularly interspaced palindromic repeats (CRISPR) / CRISPR‐associated protein 9‐mediated genome‐modified flies were used to study the contribution of RyR mutations to tetraniliprole resistance. The order of contribution of a single RyR mutation to tetraniliprole resistance was Y4667D > G4915E > Y4667C ≈ I4758M > Y4891F. In addition, the I4758M and Y4667C double mutations conferred higher tetraniliprole resistance than single Y4667C mutations. These results can guide resistance management practices for diamides in RSB and other arthropods. [ABSTRACT FROM AUTHOR]

This paper, in the context of agency problem, examines the impacts of multiple large shareholders on firm innovation. A dataset of non‐financial listed firms in China was established from 2007 to 2019. Innovation is divided into innovative quantity and innovative quality. The results demonstrate that multiple large shareholders can trigger innovative quantity and improve innovative quality. Multiple large shareholders restrict excessive earnings management and optimize pay gap by top manager to support innovation. It also finds that multiple large shareholders have a positive impact on firm's innovation through reducing share pledge and tunneling action of controlling shareholders. Moreover, it is also confirmed that better information environment and legal framework contribute to the positive effect of multiple large shareholders in corporate governance, along with firm innovation superior. [ABSTRACT FROM AUTHOR]

This study comprehensively assessed the effect of enhanced recovery after surgery (ERAS) on wound infection and postoperative complications in patients undergoing liver surgery. The PubMed, EMBASE, MEDLINE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang electronic databases were searched to collect published studies on the use of ERAS in liver surgery until December 2022. Literature selection was performed independently by two investigators according to the inclusion and exclusion criteria, and quality evaluation and data extraction were performed. RevMan 5.4 software was used in this study. Compared with the control group, the ERAS group showed a significantly lower incidence of postoperative wound infection (odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.41–0.84, P =.004) and overall postoperative complication rate (OR: 0.43, 95% CI: 0.33–0.57, P <.001) and significantly shorter postoperative hospital stay (mean difference: −2.30, 95% CI: −2.92 to −1.68, P <.001). Therefore, ERAS was safe and feasible when applied to liver resection, reducing the incidence of wound infection and total postoperative complications, and shortening the length of hospital stay. However, further studies are required to investigate the impact of ERAS protocols on clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Although various studies have examined availability, access barriers and patient experiences of rural health services for the ageing population, no synthesis of this literature exists in Australia. Objective: The objective of this study was to examine the current literature surrounding rural service provision and to evaluate the barriers to access for older individuals and to recognise gaps in the literature. Design: A systematic scoping review of peer‐reviewed literature from three online databases (PUBMED, SCOPUS and Web of Science). Findings: Thirty‐two papers were included in analysis. The most prominent types of health service discussed were residential aged care (n = 12) and community health care (n = 10). More studies explored the perspectives of health personnel than the service end users. Qualitative synthesis revealed three themes associated with health service and rural ageing: access to services, health workforce experiences and end user experiences. Discussion: Access to health services for the elderly population is a complex issue. Promoting positive experiences for both health providers and patients is critical to assisting in healthy ageing for people living in rural and remote areas. This requires intervention on a social and institutional level. Key research gaps in the literature include the effectiveness of an integrated approach to institutional interventions, utilisation of preventative measures such as screening programs for cancer and greater identification of the health needs and perceptions among culturally diverse elderly residents. These studies are critical to promote appropriate and patient‐centred care for elderly populations in rural and remote areas. Conclusion: The review highlights the need to address availability, retention and service innovations across health services to improve access to care and health outcomes of rural elderly residents. [ABSTRACT FROM AUTHOR]

Carcinoma cells possess high proliferative and invasive potentials and exhibit a resilience against stresses, metabolic disorder, and therapeutic efforts. These properties are mainly acquired by genetic alterations including driver gene mutations. However, the detailed molecular mechanisms have not been fully elucidated. Here, we provide a novel mechanism connecting oncogenic signaling and the tumorigenic properties by a transforming growth factor‐β1‐stimulated clone 22 (TSC‐22) family protein, THG‐1 (also called as TSC22D4). THG‐1 is localized at the basal layer of normal squamous epithelium and overexpressed in squamous cell carcinomas (SCCs). THG‐1 knockdown suppressed SCC cell proliferation, invasiveness, and xenograft tumor formation. In contrast, THG‐1 overexpression promoted the EGF‐induced proliferation and stratified epithelium formation. Furthermore, THG‐1 is phosphorylated by the receptor tyrosine kinase (RTK)‐RAS‐ERK pathway, which promoted the oncogene‐mediated tumorigenesis. Moreover, THG‐1 involves in the alternative splicing of CD44 variants, a regulator of invasiveness, stemness, and oxidative stress resistance under the RTK pathway. These findings highlight the pivotal roles of THG‐1 as a novel effector of SCC tumorigenesis, and the detection of THG‐1 phosphorylation by our established specific antibody could contribute to cancer diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Surgery‐induced renal ischemia and reperfusion (I/R) injury and nephrotoxic drugs like cisplatin can cause acute kidney injury (AKI), for which there is no effective therapy. Lipid accumulation is evident following AKI in renal tubules although the mechanisms and pathological effects are unclear. Here, we report that Ehmt2‐encoded histone methyltransferase G9a is upregulated in patients and mouse kidneys after AKI. Renal tubular specific knockout of G9a (Ehmt2Ksp) or pharmacological inhibition of G9a alleviates lipid accumulation associated with AKI. Mechanistically, G9a suppresses transcription of the lipolytic enzyme Ces1; moreover, G9a and farnesoid X receptor (FXR) competitively bind to the same promoter regions of Ces1. Ces1 is consistently observed to be downregulated in the kidney of AKI patients. Pharmacological inhibition of Ces1 increases lipid accumulation, exacerbates renal I/R‐injury and eliminates the beneficial effects on AKI observed in Ehmt2Ksp mice. Furthermore, lipid‐lowering atorvastatin and an FXR agonist alleviate AKI by activating Ces1 and reducing renal lipid accumulation. Together, our results reveal a G9a/FXR‐Ces1 axis that affects the AKI outcome via regulating renal lipid accumulation. Synopsis: The histone methyltransferase G9a promotes acute kidney injury (AKI) by increasing lipid accumulation via suppressing the lipolytic enzyme Ces1. Inhibition of G9a, activation of Ces1, or lipid‐lowering agents may be considered for AKI therapy. G9a affects renal lipid accumulation by negatively regulating Ces1 in a methyltransferase‐dependent manner.G9a inhibition or Ces1 activation alleviates AKI.Lipid‐lowering drugs like atorvastatin reduce renal lipid accumulation and alleviate AKI. [ABSTRACT FROM AUTHOR]

Limited by the electrostatic interaction, the oxidation reaction of cations at the anode and the reduction reaction of anions at the cathode in the electrocatalytic system nearly cannot be achieved. This study proposes a novel strategy to overcome electrostatic interaction via strong complexation, realizing the electrocatalytic reduction of cyanide (CN−) at the cathode and then converting the generated reduction products into nitrogen (N2) at the anode. Theoretical calculations and experimental results confirm that the polarization of the transition metal oxide cathodes under the electric field causes the strong chemisorption between CN− and cathode, inducing the preferential enrichment of CN− to the cathode. CN− is hydrogenated by atomic hydrogen at the cathode to methylamine/ammonia, which are further oxidized into N2 by free chlorine derived from the anode. This paper provides a new idea for realizing the unconventional and unrealizable reactions in the electrocatalytic system. [ABSTRACT FROM AUTHOR]

Limited by the electrostatic interaction, the oxidation reaction of cations at the anode and the reduction reaction of anions at the cathode in the electrocatalytic system nearly cannot be achieved. This study proposes a novel strategy to overcome electrostatic interaction via strong complexation, realizing the electrocatalytic reduction of cyanide (CN−) at the cathode and then converting the generated reduction products into nitrogen (N2) at the anode. Theoretical calculations and experimental results confirm that the polarization of the transition metal oxide cathodes under the electric field causes the strong chemisorption between CN− and cathode, inducing the preferential enrichment of CN− to the cathode. CN− is hydrogenated by atomic hydrogen at the cathode to methylamine/ammonia, which are further oxidized into N2 by free chlorine derived from the anode. This paper provides a new idea for realizing the unconventional and unrealizable reactions in the electrocatalytic system. [ABSTRACT FROM AUTHOR]

Laryngeal squamous cell carcinoma (LSCC), although one of the most common head and neck cancers, has a static or slightly decreased survival rate because of difficulties in early diagnosis, lack of effective molecular targeting therapy, and severe dysfunction after radical surgical treatments. Therefore, a novel therapeutic target is crucial to increase treatment efficacy and survival rates in these patients. Glycoprotein NMB (GPNMB), whose role in LSCC remains elusive, is a type 1 transmembrane protein involved in malignant progression of various cancers, and its high expression is thought to be a poor prognostic factor. In this study, we showed that GPNMB expression levels in LSCC samples are significantly higher than those in normal tissues, and GPNMB expression is observed mostly in growth‐arrested cancer cells. Furthermore, knockdown of GPNMB reduces monolayer cellular proliferation, cellular migration, and tumorigenic growth, while GPNMB protein displays an inverse relationship with Ki‐67 levels. Therefore, we conclude that GPNMB may be an attractive target for future LSCC therapy. [ABSTRACT FROM AUTHOR]

The 25.23% of newborns ( I n i = 81) carried one P/LP mutations, and 7.17% and 0.93% of newborns ( I n i = 23 and I n i = 3) carried two or three P/LP mutations, respectively. In addition, WGS identified two infants carrying compound heterozygous P/LP variants in I GJB2 i (Figure 3) and four children carrying pathogenic mutations in I MT-RNR1 (c1095T > i I C) i , suggesting an increased risk of late-onset deafness or drug-induced hearing loss, respectively. We investigated whether screening by whole genome sequencing (WGS) in unselected newborns provides more information of potentially curable or treatable medical conditions than routine newborn screening (NBS). Of the 136 P/LP mutations, 42.65% corresponded to genetic disorders, 6.62% were associated with PIDs and 50.74% were related to metabolic disorders, including organic acid conditions (14.71%), amino acid disorders (14.71%), fatty acid oxidation disorders (7.35%) and endocrine disorders (13.97%). [Extracted from the article]

Linker histone H1.2 (H1.2), encoded by HIST1H1C (H1C), is a major H1 variant in somatic cells. Among five histone H1 somatic variants, upregulated H1.2 was found in human hepatocellular carcinoma (HCC) samples and in a diethylnitrosamine (DEN)‐induced HCC mouse model. In vitro, H1.2 overexpression accelerated proliferation of HCC cell lines, whereas H1.2 knockdown (KD) had the opposite effect. In vivo, H1.2 insufficiency or deficiency (H1c KD or H1c KO) alleviated inflammatory response and HCC development in DEN‐treated mice. Mechanistically, H1.2 regulated the activation of signal transducer and activator of transcription 3 (STAT3), which in turn positively regulated H1.2 expression by binding to its promoter. Moreover, upregulation of the H1.2/STAT3 axis was observed in human HCC samples, and was confirmed in mouse models of methionine‐choline‐deficient diet induced nonalcoholic steatohepatitis or lipopolysaccharide induced acute inflammatory liver injury. Disrupting this feed‐forward loop by KD of STAT3 or treatment with STAT3 inhibitors rescued H1.2 overexpression‐induced proliferation. Moreover, STAT3 inhibitor treatment‐ameliorated H1.2 overexpression promoted xenograft tumor growth. Therefore, H1.2 plays a novel role in inflammatory response by regulating STAT3 activation in HCC, thus, blockade of the H1.2/STAT3 loop is a potential strategy against HCC. [ABSTRACT FROM AUTHOR]

In the production of chloroprene rubber, acetylene dimerization over the Nieuwland catalyst is an important step. The addition of Mg2+ to the Nieuwland catalyst improves the acetylene conversion and the selectivity toward vinyl acetylene. In this study, active component crystal structure, the role of Mg2+ in the Nieuwland catalyst, the reason for the catalyst deactivation, and the reaction mechanism were analyzed by different characterization techniques. The results indicate that the main reason for the Nieuwland catalyst deactivation is the loss of Cu2+. The addition of Mg2+ will increase the exposure of active sites, reduce the residence time of acetylene in the catalyst, and inhibit the reduction of Cu2+, thereby improving the catalytic performance and stability of the catalyst. [ABSTRACT FROM AUTHOR]

Xylitol is a salutary sugar substitute that has been widely used in the food, pharmaceutical, and chemical industries. Co‐fermentation of xylose and glucose by metabolically engineered cell factories is a promising alternative to chemical hydrogenation of xylose for commercial production of xylitol. Here, we engineered a mutant of SecY protein‐translocation channel (SecY [ΔP]) in xylitol‐producing Escherichia coli JM109 (DE3) as a passageway for xylose uptake. It was found that SecY (ΔP) channel could rapidly transport xylose without being interfered by XylB‐catalyzed synthesis of xylitol‐phosphate, which is impossible for native XylFGH and XylE transporters. More importantly, with the coaction of SecY (ΔP) channel and carbon catabolite repression (CCR), the flux of xylose to the pentose phosphate (PP) pathway and the xylitol synthesis pathway in E. coli could be automatically controlled in response to glucose, thereby ensuring that the mutant cells were able to fully utilize sugars with high xylitol yields. The E. coli cell factory developed in this study has been proven to be applicable to a broad range of xylose‐glucose mixtures, which is conducive to simplifying the mixed‐sugar fermentation process for efficient and economical production of xylitol. [ABSTRACT FROM AUTHOR]

Significant achievements have been made in breeding programs for the heavy‐panicle‐type (HPT) rice (Oryza sativa) in Southwest China. The HPT varieties now exhibit excellent lodging resistance, allowing them to overcome the greater pressures caused by heavy panicles. However, the genetic mechanism of this lodging resistance remains elusive. Here, we isolated a major quantitative trait locus, Panicle Neck Diameter 1 (PND1), and identified the causal gene as GRAIN NUMBER 1A/CYTOKININ OXIDASE 2 (Gn1A/OsCKX2). The null gn1a allele from rice line R498 (gn1aR498) improved lodging resistance through increasing the culm diameter and promoting crown root development. Loss‐of‐function of Gn1a/OsCKX2 led to cytokinin accumulation in the crown root tip and accelerated the development of adventitious roots. Gene pyramiding between the null gn1aR498 allele with two gain‐of‐function alleles, STRONG CULM 2 (SCM2) and SCM3, further improved lodging resistance. Moreover, Gn1a/OsCKX2 had minimal influence on overall rice quality. Our research thus highlights the distinct genetic components of lodging resistance of HPT varieties and provides a strategy for tailor‐made crop improvement of both yield and lodging resistance in rice. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer among women. Glycoprotein non–metastatic melanoma protein B (GPNMB), a type I transmembrane protein that is highly expressed in many cancers, including breast cancer, has been shown to be a prognostic factor. We previously reported that GPNMB overexpression confers tumorigenic potential, as evidenced by invasive tumor growth in vivo, sphere formation, and cellular migration and invasion to non–tumorigenic mammary epithelial cells. In this study, we focused on the serine (S) residue in the intracellular domain of GPNMB (S530 in human isoform b and S546 in mouse), which is predicted to be a phosphorylation site. To investigate the roles of this serine residue, we made an antibody specific for S530‐phosphorylated human GPNMB and a point mutant in which S530 is replaced by an alanine (A) residue, GPNMB(SA). Established GPNMB(SA) overexpressing cells showed a significant reduction in sphere formation in vitro and tumor growth in vivo as a result of decreased stemness‐related gene expression compared to that in GPNMB(WT)‐expressing cells. In addition, GPNMB(SA) impaired GPNMB‐mediated cellular migration. Furthermore, we found that tyrosine kinase receptor signaling triggered by epidermal growth factor or fibroblast growth factor 2 induces the serine phosphorylation of GPNMB through activation of downstream oncoproteins RAS and RAF. [ABSTRACT FROM AUTHOR]

Pictures have been used for a wide range of marketing purposes, but few studies have focused on the specific uses of abstract versus concrete images in marketing field. This study explores the impact of image type on consumer attitudes based on the conception of imagery elaboration. We find that the interaction between product category and image type has a significant effect on consumer attitudes. Specifically, for hedonic product, abstract image is more likely to motivate consumers to form a positive attitude than concrete image, whereas for utilitarian product, concrete image is more effective. We also show the mediating role of imagery elaboration. The interaction of product category and image type has a significant effect on imagery elaboration: in the case of hedonic product, product with abstract image was found to be better for evoking imagery elaboration, whereas in the case of utilitarian product, adding a concrete image to the product was more successful at generating imagery elaboration. Furthermore, imagery elaboration has a significant effect on consumer attitudes. This study offers specific suggestions that companies can incorporate into product design and marketing. [ABSTRACT FROM AUTHOR]

Pathological TDP‐43 aggregation is characteristic of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD‐TDP); however, how TDP‐43 aggregation and function are regulated remain poorly understood. Here, we show that O‐GlcNAc transferase OGT‐mediated O‐GlcNAcylation of TDP‐43 suppresses ALS‐associated proteinopathies and promotes TDP‐43's splicing function. Biochemical and cell‐based assays indicate that OGT's catalytic activity suppresses TDP‐43 aggregation and hyperphosphorylation, whereas abolishment of TDP‐43 O‐GlcNAcylation impairs its RNA splicing activity. We further show that TDP‐43 mutations in the O‐GlcNAcylation sites improve locomotion defects of larvae and adult flies and extend adult life spans, following TDP‐43 overexpression in Drosophila motor neurons. We finally demonstrate that O‐GlcNAcylation of TDP‐43 promotes proper splicing of many mRNAs, including STMN2, which is required for normal axonal outgrowth and regeneration. Our findings suggest that O‐GlcNAcylation might be a target for the treatment of TDP‐43‐linked pathogenesis. SYNOPSIS: O‐GlcNAcylation of TDP‐43 suppresses TDP‐43 proteinophathies and promotes TDP‐43's mRNA splicing activity, with potential implications for ALS/FTLD pathogenesis. TDP‐43 can be O‐GlcNAcylated by the enzyme OGT in vitro and in vivo, and O‐GlcNAcylation of TDP‐43 suppresses protein aggregation and hyperphosphorylation.TDP‐43 O‐GlcNAcylation affects the locomotion and longevity of Drosophila.O‐GlcNAcylation of TDP‐43 prevents aberrant splicing of key neuron genes, such as STMN2, Dnajc5, and Sort1. [ABSTRACT FROM AUTHOR]

Three‐dimensional (3D) culturing mimics the heterogeneous cellular conditions of the in vivo tumor microenvironment compared to 2D monolayer‐cultured cells and 3D cultures of established cancer cell lines (sphere culture) or patient‐derived cancer cells (organoid culture) are frequently used for cancer research or drug screening and evaluation. To establish more cost and time‐efficient 3D culture methods for cancer cell lines, we supplemented sphere culture medium with polyvinyl alcohol (PVA) and found that 3D sphere cultures of breast and pancreatic cancer cell lines were significantly increased. Mechanistically, we found that PVA prevented cell death and promoted cellular proliferation while maintaining levels of stemness‐related gene expression. Furthermore, we showed that polyvinyl formal resin (PVF) 3D scaffolds made by cross‐linked PVA can function in serum‐free, long‐term 3D cultures to support maintenance of sphere‐ or tumor‐like cell masses for diverse cancer cell types. Taken together, we demonstrate the effectiveness of PVA and PVF in human cancer cell line culture protocols. [ABSTRACT FROM AUTHOR]

The uncertainties in tire cornering stiffness can degrade the path following the performance of autonomous vehicles, especially in low adhesive conditions, to deal with this problem, a novel multi‐model adaptive predictive control is proposed in this study. Firstly, a model predictive path following controller is designed based on a combined model of vehicle dynamics and road‐related kinematics relationship. Then, to deal with the model uncertainties, the multiple model adaptive theory is introduced, and the recursive least adaptive law is proposed with its convergence proved by Lyapunov theory. Finally, the multiple‐model adaptive law is combined with the proposed model predictive control by a convex polytope of tire cornering stiffness. In this way, the proposed algorithm can be adaptive to the uncertainties of tire cornering stiffness. Simulation results show the effectiveness and robustness of the proposed method to the uncertainties of the tire cornering stiffness resulting in an excellent performance in any road condition without introducing conservativeness. [ABSTRACT FROM AUTHOR]

This study proposes an effective trajectory planning algorithm based on the quartic Bézier curve and dangerous potential field for automatic vehicles. To generate collision‐free trajectories, potential field functions are introduced to evaluate the collision risk of path candidates. However, many studies on artificial potential field approaches primarily focus on static and straight roads, and attach less importance to more complex driving scenarios, such as curving roads. In this study, a novel method based on the Frenet coordinate system is proposed to address such limitations. Moreover, to balance the driving comfortability and the driving safety of the path candidate, the path‐planning problem is converted to an optimisation problem, and sequential quadratic programming algorithm is employed to tackle this task. Another merit of this algorithm is the curvature of the generated path is continuous even at the joints of adjacent sub‐trajectories by utilising several specific properties of the Bézier curve. Furthermore, to execute the generated trajectory, a framework of velocity generation is proposed while vehicle dynamic constraints are considered. Some typical traffic scenarios, including lane‐changing, lane‐keeping, and collision avoidance have been designed to verify the performance of the proposed algorithm, and simulations demonstrate the validity of this method. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor α (TNFα)‐ and interleukin 1β (IL‐1β)‐induced nuclear factor‐κB (NF‐κB) activation play key roles in inflammation, immunity, and cancer development. Here, we identified one of the deubiquitinating enzymes (DUBs), ubiquitin‐specific protease 15 (USP15), as a positive regulator in both TNFα‐ and IL‐1β‐induced NF‐κB activation. Overexpression of USP15 potentiated TNFα‐ or IL‐1β‐triggered NF‐κB activation and downstream gene transcription, whereas knockdown of USP15 had opposite effects. Mechanistically, upon TNFα stimulation, USP15 showed an enhanced interaction with transforming growth factor‐β activated kinase‐1 (TAK1)‐TAK1 binding protein (TAB) complex to inhibit the proteolysis of TAB2/3 by different pathways. Apart from deubiquitination dependently inducing cleavage of lysine 48‐linked TAB2 ubiquitination, USP15 also DUB independently inhibited lysosome‐associated TAB2 degradation, thus enhanced TAB2 stabilization. For TAB3, USP15 inhibited NBR1‐mediated selective autophagic TAB3 degradation independent of its deubiquitinating activity. Together, our results reveal a novel USP15‐mediated mechanism through which efficient NF‐κB activation is achieved by differentially maintaining the TAB2/3 stability. [ABSTRACT FROM AUTHOR]

Summary: Burst traffic is a common traffic pattern in modern IP networks, and it may lead to the unfairness problem and seriously degrade the performance of switches and routers. From the perspective of switching mechanism, the majority of commercial switches adopt the on‐chip shared‐memory switching architecture, and high‐speed packet buffer with efficient queue management is required to deal with the unfairness and congestion problem. In this paper, the performance of a shared‐private buffer management scheme is analyzed in detail. In the proposed scheme, the total memory space is split into shared area and private area. Each output port has a private memory area that cannot be used by other ports. The shared area is completely shared among all output ports. A theoretical queuing model of the proposed scheme is formulated, and closed‐form formulas for multiple performance parameters are derived. Through the numerical studies, we demonstrate that a nearly optimal buffer partition policy can be obtained by setting an equally small amount of private area for each queue. This work is validated by simulations as well as hardware experiments. Software simulations show that the proposed scheme performs better than existing methods, and packet dropping caused by burst traffic can be significantly reduced. Besides, a prototype of the buffer management module is implemented and evaluated in field programmable gate array platform. The evaluation shows that the proposed scheme can ensure the efficiency and fairness while keeping a high throughput in real workload. [ABSTRACT FROM AUTHOR]

Triblemma Ching is a genus proposed by Ching Ren‐Chang in 1978, and it is composed of two species, Triblemma lancea (Thunb.) Ching and Triblemma zeylanica (Hook.) Ching. There has been much debate on the systematic position of Triblemma, and this genus has always been included in Diplazium. Here, we have described new features of tracheary elements, epidermis, spore, scale, and rachis of Triblemma revealed using light and scanning electron microscopy and proposed that Triblemma is closely related to Athyriopsis, which conflicts with the traditional viewpoint. [ABSTRACT FROM AUTHOR]

The transcription factor p53 is known as the guardian of the genome for its powerful anti-tumour capacity. However, mutations of p53 that undermine their protein structure, resulting in loss of tumour suppressor function and gain of oncogenic function, have been implicated in more than half of human cancers. The crucial role of mutant forms of p53 in cancer makes it an attractive therapeutic target. A large number of candidates, including low MW compounds, peptides, and nucleic acids, have been identified or designed to rescue p53 mutants and reactivate their anti-tumour capacity through a variety of mechanisms. In this review, we summarize the progress made in the reactivation of mutant forms of p53, focusing on the pharmacological mechanisms of the reactivators of p53 mutants. [ABSTRACT FROM AUTHOR]

Key points: Diabetic kidney disease (DKD) is a major complication of diabetes. We found that UTX (ubiquitously transcribed tetratricopeptide repeat on chromosome X, also known as KDM6A), a histone demethylase, was upregulated in the renal mesangial and tubular cells of diabetic mice and DKD patients.In cultured renal mesangial and tubular cells, UTX overexpression promoted palmitic acid‐induced elevation of inflammation and DNA damage, whereas UTX knockdown or GSK‐J4 treatment showed the opposite effects.We found that UTX demethylase activity‐dependently regulated the transcription of inflammatory genes and apoptosis; moreover, UTX bound with p53 and p53‐dependently exacerbated DNA damage.Administration of GSK‐J4, an H3K27 demethylase inhibitor, ameliorated the diabetes‐induced renal abnormalities in db/db mice, an animal model of type 2 diabetes.These results revealed the possible mechanisms underlying the regulation of histone methylation in DKD and suggest UTX as a potential therapeutic target for DKD. Diabetic kidney disease (DKD) is a microvascular complication of diabetes and the leading cause of end‐stage kidney disease worldwide without effective therapy available. UTX (ubiquitously transcribed tetratricopeptide repeat on chromosome X, also known as KDM6A), a histone demethylase that removes the di‐ and tri‐methyl groups from histone H3K27, plays important biological roles in gene activation, cell fate control and life span regulation in Caenorhabditis elegans. In the present study, we report upregulated UTX in the kidneys of diabetic mice and DKD patients. Administration of GSK‐J4, an H3K27 demethylase inhibitor, ameliorated the diabetes‐induced renal dysfunction, abnormal morphology, inflammation, apoptosis and DNA damage in db/db mice, comprising an animal model of type 2 diabetes. In cultured renal mesanglial and tubular cells, UTX overexpression promoted palmitic acid induced elevation of inflammation and DNA damage, whereas UTX knockdown or GSK‐J4 treatment showed the opposite effects. Mechanistically, we found that UTX demethylase activity‐dependently regulated the transcription of inflammatory genes; moreover, UTX bound with p53 and p53‐dependently exacerbated DNA damage. Collectively, our results suggest UTX as a potential therapeutic target for DKD. Key points: Diabetic kidney disease (DKD) is a major complication of diabetes. We found that UTX (ubiquitously transcribed tetratricopeptide repeat on chromosome X, also known as KDM6A), a histone demethylase, was upregulated in the renal mesangial and tubular cells of diabetic mice and DKD patients.In cultured renal mesangial and tubular cells, UTX overexpression promoted palmitic acid‐induced elevation of inflammation and DNA damage, whereas UTX knockdown or GSK‐J4 treatment showed the opposite effects.We found that UTX demethylase activity‐dependently regulated the transcription of inflammatory genes and apoptosis; moreover, UTX bound with p53 and p53‐dependently exacerbated DNA damage.Administration of GSK‐J4, an H3K27 demethylase inhibitor, ameliorated the diabetes‐induced renal abnormalities in db/db mice, an animal model of type 2 diabetes.These results revealed the possible mechanisms underlying the regulation of histone methylation in DKD and suggest UTX as a potential therapeutic target for DKD. [ABSTRACT FROM AUTHOR]

miR‐372/373, a cluster of stem cell‐specific microRNAs transactivated by the Wnt pathway, has been reported to be dysregulated in various cancers, particularly colorectal cancer (CRC); however, the unique role of these microRNAs in cancer remains to be discovered. In the present study, we characterized the upregulation in expression of miR‐372/373 in CRC tissues from The Cancer Genome Atlas data, and then showed that overexpression of miR‐372/373 enhanced the stemness of CRC cells by enriching the CD26/CD24‐positive cell population and promoting self‐renewal, chemotherapy resistance and the invasive potential of CRC cells. To clarify the mechanism underlying microRNA‐induced stemness, we profiled 45 cell signaling pathways in CRC cells overexpressing miR‐372/373 and found that stemness‐related pathways, such as Nanog and Hedgehog, were upregulated. Instead, differentiation‐related pathways, such as NFκB, MAPK/Erk and VDR, were markedly repressed by miR‐372/373. Numerous new targets of miR‐372/373 were identified, including SPOP, VDR and SETD7, all of which are factors important for cell differentiation. Furthermore, in contrast to the increase in miR‐372/373 expression in CRC tissues, the expression levels of SPOP and VDR mRNA were significantly downregulated in these tissues, indicative of the poor differentiation status of CRC. Taken together, our findings suggest that miR‐372/373 enhance CRC cell stemness by repressing the expression of differentiation genes. These results provide new insights for understanding the function and mechanisms of stem cell‐specific microRNAs in the development of metastasis and drug resistance in CRC. The miR‐372/373 cluster can induce cancer stem cell phenotypes in colorectal cancer. Over‐expression of miR‐372/373 repress developmental pathways, including NFκB, and enhance key stemness‐related pathways, such as Nanog. A series of differentiation‐related genes, including SPOP, VDR and SETD7, were identified as targets of miR‐372/373, which were shown to be responsible for the transition from cancer cell to cancer stem‐cell phenotype. [ABSTRACT FROM AUTHOR]

Kinesin family member 20B (KIF20B, also known as MPHOSPH1) is a kinesin protein that plays a critical role in cytokinesis. Previously, we and others have demonstrated the oncogenic role of KIF20B in several cancers; however, the exact mechanisms underlying its tumorigenic effects remain unclear. Herein, we showed overexpression of KIF20B in human hepatocellular carcinoma (HCC) and reported a negative correlation between KIF20B level and prognosis of patients. Mechanistically, reducing KIF20B blockades mitotic exit of HCC cells at telophase in a spindle assembly checkpoint independent way. Importantly, reducing KIF20B acts synergistically with three microtubule‐associated agents (MTA) to p53‐ or p14ARF‐dependently suppress p53‐wt or p53‐null HCC cells. In addition to taxol, reducing KIF20B also enhanced the toxicity of two chemotherapeutic drugs, hydroxycamptothecin and mitomycin C. In conclusion, we found a novel mechanism in that blocking cytokinesis by KIF20B inhibition increases the efficacy of MTA; our results thus suggested a dual‐mitotic suppression approach against HCC by combining MTA with KIF20B inhibition, which simultaneously blocks mitosis at both metaphase and telophase. We found a novel mechanism in that blocking cytokinesis by MPHOSPH1 inhibition increases the efficacy of MTA. Based on this finding, we proposed and validated an effective dual‐mitotic suppression strategy against HCC by combining antimitotic drugs with cytokinesis inhibition, which blocks mitosis at both metaphase and telophase. Moreover, our work raised the possibility that proteins essential for cytokinesis may be considered as potential targets for cancer therapy, especially against SAC‐insensitive cancers. [ABSTRACT FROM AUTHOR]

Biological soil crusts are ecologically important communities in areas where vascular plant coverage is low, and their presence is often vital in prevention of soil erosion. Despite recurrent threats to biological soil crusts across different environments, their recovery after disturbance has been little studied. We therefore established experiments across a latitudinal gradient in Europe, from Öland, Sweden in the north, to Gössenheim, Germany and Hochtor, Austria, to Almeria, Spain in the south, spanning over 20° latitude and 2,300min altitude, and including natural and semi-natural sites. At each site 10 (1 ࡬1m) paired plots were constructed where the biological soil crusts were either completely removed, or left intact. Over a 2-year period (2012-2014) the plots were regularly sampled to assess functional group recovery (cyanobacteria, algae, lichens, bryophytes, vascular plants), soil stability, and chlorophyll, carbon, and nutrient contents. Cyanobacterial assemblages were examined by denaturing gradient gel electrophoresis, a technique used to detect DNA in environmental samples. The results indicated that recovery was site dependent, suggesting that physical and climatic parameters play a major role in biological soil crust recovery. This conclusion is supported by the results of the soil properties, which were found to differ between sites, although they did not show meaningful recovery over the study period. Although 2 years was insufficient for pronounced biological soil crust recovery, this study documents changes over the initial recovery period, suggests management practices for future projects, and recommends proxies for measuring recovery over time. [ABSTRACT FROM AUTHOR]

Many promising supercapacitor electrode materials have high resistivity and require conductive additives to function effectively. However, the detailed role of the additive is not understood. Here, this question is resolved by applying a quantitative model for resistance-limited supercapacitor electrodes to Co(OH)2-nanosheet/carbon nanotube composites. Without nanotubes, theory predicts and experiments show that while the low-rate capacitance increases linearly with electrode thickness, the high rate capacitance decreases with thickness due to slow charging. Experiments supported by theory show that nanotube addition has two effects. First, the nanotube network effectively distributes charge, increasing the intrinsic electrode performance to the limit associated with its accessible surface area. Second, at high-rate, the increased electrode conductivity shifts the rate-limiting resistance from electrode to electrolyte, thus removing the thickness-dependent capacitance falloff. Furthermore, the analysis quantifies the out-of-plane conductivity of the nanotube network, identifies the cross-over from resistance-limited to diffusion-limited behavior, and allows full electrode modeling, facilitating rational design. [ABSTRACT FROM AUTHOR]

Objective: Thalamic volume is a candidate magnetic resonance imaging (MRI)-based marker associated with neurodegeneration to hasten development of neuroprotective treatments. Our objective is to describe the longitudinal evolution of thalamic atrophy in MS and normal aging, and to estimate sample sizes for study design.Methods: Six hundred one subjects (2,632 MRI scans) were analyzed. Five hundred twenty subjects with relapse-onset MS (clinically isolated syndrome, n = 90; relapsing-remitting MS, n = 392; secondary progressive MS, n = 38) underwent annual standardized 3T MRI scans for an average of 4.1 years, including a 1mm3 3-dimensional T1-weighted sequence (3DT1; 2,485 MRI scans). Eighty-one healthy controls (HC) were scanned longitudinally on the same scanner using the same protocol (147 MRI scans). 3DT1s were processed using FreeSurfer's longitudinal pipeline after lesion inpainting. Rates of normalized thalamic volume loss in MS and HC were compared in linear mixed effects models. Simulation-based sample size calculations were performed incorporating the rate of atrophy in HC.Results: Thalamic volume declined significantly faster in MS subjects compared to HC, with an estimated decline of -0.71% per year (95% confidence interval [CI] = -0.77% to -0.64%) in MS subjects and -0.28% per year (95% CI = -0.58% to 0.02%) in HC (p for difference = 0.007). The rate of decline was consistent throughout the MS disease duration and across MS clinical subtypes. Eighty or 100 subjects per arm (α = 0.1 or 0.05, respectively) would be needed to detect the maximal effect size with 80% power in a 24-month study.Interpretation: Thalamic atrophy occurs early and consistently throughout MS. Preliminary sample size calculations appear feasible, adding to its appeal as an MRI marker associated with neurodegeneration. Ann Neurol 2018;83:223-234. [ABSTRACT FROM AUTHOR]

c‐MYC stimulates cell proliferation through the suppression of cyclin‐dependent kinase (CDK) inhibitors including P15 (CDKN2B) and P21 (CDKN1A). It also activates E‐box‐mediated transcription of various target genes including telomerase reverse transcriptase (TERT) that is involved in cellular immortality and tumorigenesis. Transforming growth factor‐beta 1 (TGF‐β1)‐stimulated clone 22 (TSC‐22/TSC22D1) encodes a highly conserved leucine zipper protein that is induced by various stimuli, including TGF‐β. TSC‐22 inhibits cell growth in mammalian cells and in Xenopus embryos. However, underlying mechanisms of growth inhibition by TSC‐22 remain unclear. Here, we show that TSC‐22 physically interacts with c‐MYC to inhibit the recruitment of c‐MYC on the P15 (CDKN2B) and P21 (CDKN1A) promoters, effectively inhibiting c‐MYC‐mediated suppression of P15 (CDKN2B) and also P21 (CDKN1A) promoter activities. In contrast, TSC‐22 enhances c‐MYC‐mediated activation of the TERT promoter. Additionally, the expression of TSC‐22 in embryonic stem cells inhibits cell growth without affecting its pluripotency‐related gene expression. These results indicate that TSC‐22 differentially regulates c‐MYC‐mediated transcriptional activity to regulate cell proliferation. [ABSTRACT FROM AUTHOR]

In this study, a crosspoint‐queued (CQ) switch that features a buffer size larger than one and employs the work‐conserving random scheduling algorithm under uniform Bernoulli i.i.d. traffic is investigated through both theoretical analysis and simulation. The effect of the crosspoint buffer state on switch performance is modelled and quantified. A novel method for calculating the throughput and delay of a CQ switch with a given switch size, input load, and buffer size is proposed. Compared with existing models, the proposed calculation model offers a simpler and more accurate result, and can serve as a theoretical guide in designing high‐speed switch fabrics. [ABSTRACT FROM AUTHOR]

Objectives This study aims to reduce cesarean section rate and increase rate of vaginal delivery. Methods By using Lean Six Sigma (LSS) methodology, the cesarean section rate was investigated and analyzed through a 5-phase roadmap consisting of Define, Measure, Analyze, Improve, and Control. The principal causes of cesarean section were identified, improvement measures were implemented, and the rate of cesarean section before and after intervention was compared. Results After patients with a valid medical reason for cesarean were excluded, the main causes of cesarean section were maternal request, labor pain, parturient women assessment, and labor observation. A series of measures was implemented, including an improved parturient women assessment system, strengthened pregnancy nutrition guidance, implementation of painless labor techniques, enhanced midwifery team building, and promotion of childbirth-assist skills. Ten months after introduction of the improvement measures, the cesarean section rate decreased from 41.83% to 32.00%, and the Six Sigma score (ie, Z value) increased from 1.706 to 1.967 ( P < .001). Conclusion LSS is an effective way to reduce the rate of cesarean section. [ABSTRACT FROM AUTHOR]

The purpose of the Big Data to Knowledge initiative is to develop methods for discovering new knowledge from large amounts of data. However, if the resulting knowledge is so large that it resists comprehension, referred to here as Big Knowledge (BK), how can it be used properly and creatively? We call this secondary challenge, Big Knowledge to Use. Without a high-level mental representation of the kinds of knowledge in a BK knowledgebase, effective or innovative use of the knowledge may be limited. We describe summarization and visualization techniques that capture the big picture of a BK knowledgebase, possibly created from Big Data. In this research, we distinguish between assertion BK and rule-based BK (rule BK) and demonstrate the usefulness of summarization and visualization techniques of assertion BK for clinical phenotyping. As an example, we illustrate how a summary of many intracranial bleeding concepts can improve phenotyping, compared to the traditional approach. We also demonstrate the usefulness of summarization and visualization techniques of rule BK for drug-drug interaction discovery. [ABSTRACT FROM AUTHOR]

An analytical model has been developed in the present paper based on a square root transformation of white Gaussian noise. The mathematical expectation and variance of the new asymmetric distribution generated by white Gaussian noise after a square root transformation are analytically deduced from the preceding four terms of the Taylor expansion. The model was first evaluated against numerical experiments and a good agreement was obtained. The model was then used to predict time series of wind speeds and highway traffic flows. The simulation results from the new model indicate that the prediction accuracy could be improved by 0.1-1% by removing the mean errors. Further improvement could be obtained for non-stationary time series, which had large trends. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Automatic detection of early rottenness caused by P enicillium is still a challenge due to the high similarity between the rotten region and sound tissue, and the large variations in surface background color of apples. A hyperspectral reflectance imaging system and a systematic approach were developed to detect the early rottenness caused by P enicillium on Fuji apples. The principal component analysis of the hyperspectral reflectance images in the full region (400-1,000 nm) of spectra was used to develop hyperspectral image analytical algorithm and select the efficient wavelengths. Independent component analysis ( ICA) based on the selected efficient wavelengths (810 and 970 nm, respectively) and simple thresholding methods were used to segment and classify the rottenness from the sound tissue. Finally, ICA-based image processing and classification algorithm was developed based on the images at 810 and 970 nm to realize the fast inspection of early rottenness. The detection result with 97% overall accuracy indicated that the proposed system and algorithm were efficient and suitable for the detection of the early rottenness caused by P enicillium on Fuji apples. This study was the first attempt to use hyperspectral imaging system to detect the early rottenness caused by P enicillium on Fuji apples and would lay a foundation for the development of multispectral imaging system for fast inspection of rottenness. The limitation of our research is the limited inspection view of the samples. Future work will be focused on simultaneous whole surface inspection using multispectral imaging system. Practical Applications The algorithm and results in our paper can provide a foundational basis to develop a real-time inspection system to detect rottenness on apples in the postharvest processing line, or develop a monitoring system to monitor the quality changes in storage shelf. [ABSTRACT FROM AUTHOR]

micro RNAs (mi RNAs) are important nonprotein-coding genes that are involved in almost all biological processes, including cell differentiation and fate determination, developmental regulation, and immune responses. Investigations have shown that some mi RNAs can highly affect plant agricultural traits, including virus resistance, nematode resistance, drought and salinity tolerance, heavy metal detoxification, biomass yield, grain yield, fruit development and flower development. Therefore, these mi RNAs are considered a newly identified gene resource for the genetic improvement of crops. In this review, we will summarize the recent findings of the rice mi RNA-directed regulatory network, which controls agronomic traits such as yield, quality and stress tolerance, and explore the outlook for the uses of these mi RNA-associated traits in rice biotechnology. [ABSTRACT FROM AUTHOR]

Background An increasing number of studies have revealed that micro RNA (mi RNA) contributes to the pathogenesis of autoimmune diseases. The objective of this study is to investigate the miR-146a and miR-155 levels in peripheral mononuclear blood cells from patients with primary Sjögren's syndrome ( pSS) who were not receiving medications and to examine the correlations between these mi RNA levels and the clinical features of the disease. Method Using real-time polymerase chain reaction analysis of mi RNAs, the miR-146a and miR-155 expression levels were assessed in peripheral mononuclear blood cells from 27 patients with pSS and 22 healthy controls, and the relationships between these mi RNA levels and the visual analog scale ( VAS) scores for dry mouth, dry eyes, and parotid gland swelling were investigated. Results Compared with the healthy controls, the miR-146a expression level was significantly increased in the patients with pSS ( P = 0.0182) and was positively correlated with the VAS scores for parotid swelling ( r = 0.4475, P = 0.0192) and dry eyes ( r = 0.4051, P = 0.0361). Although the miR-155 expression level was significantly decreased in the patients with pSS ( P = 0.0131), the miR-155 expression positively correlated with the VAS score for dry eyes ( r = 0.4894, P = 0.0096). Conclusion Our results demonstrated miR-146a overexpression and miR-155 underexpression in the peripheral mononuclear blood cells of the patients with pSS. Furthermore, the expression levels of these miRNAs correlated with the patients' clinical features. Our data suggest that miR-146a and miR-155 might play important roles in the pathogenesis of pSS and that their expression levels may be useful for diagnosing pSS and for predicting disease activity and therapeutic responses. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to investigate the potential role of Toll-like receptor 9-dependent p38 MAPK signaling pathway in the pathogenesis of primary Sjögren's syndrome (p SS) in NOD/ Ltj mouse, aiming to identify an ideal target therapy model for human p SS. Methods NOD/ Ltj mice were chosen as a model of p SS. The Toll-like receptor 9 and p-p38 MAPK double-positive peripheral blood mononuclear cells ( PBMCs) of 4-, 5-, 8-, 10-, and 15-week-old NOD/ Ltj mouse were analyzed by flow cytometry. The expressions of Toll-like receptor 9 and p-p38 MAPK in the submandibular gland ( SMG) were also examined by immunohistochemistry. The change of stimulated salivary flow rate was dynamically measured, and the histopathology of SMG was evaluated by hematoxylin and eosin stain. Results The stimulated salivary flow rate in NOD/ Ltj was reduced to 50-60% of the flow rate of control mice since the fifth week onwards. The Toll-like receptor 9 and p-p38 MAPK double-positive PBMCs in both groups increased gradually from 5 weeks, peaked at 8 weeks and then gradually decreased at 10 weeks, yet the percentage of Toll-like receptor 9 and p-p38 MAPK double-positive PBMCs in 5-, 8-, and 10-week-old NOD/ Ltj mouse was significantly increased compared with those in control subjects. After the 10th week onwards, there were no significant differences in the Toll-like receptor 9 and p-p38 MAPK double-positive PBMCs between NOD/ Ltj mice and controls. Immunohistochemical staining showed that Toll-like receptor 9 was positive in the acinar epithelium cells and infiltrating lymphocytes in NOD/ Ltj mice. p-p38 MAPK was detected in infiltrating lymphocytes and few ductal or acinar epithelium cells adjacent to infiltrating lymphocytes in NOD/ Ltj mice. Conclusions From the fifth week till the tenth week, Toll-like receptor 9 and p-p38 MAPK double-positive PBMCs were significantly increased in NOD/ Ltj mice, accompanied with reduced stimulated salivary flow rate and Toll-like receptor 9 or p-p38 MAPK positive infiltrating lymphocytes observed in the SMG of NOD/ Ltj mouse. Our results indicated that activation of Toll-like receptor 9-depended p38 MAPK signal pathway in PBMCs was an early event in p SS which made NOD/ Ltj as an ideal therapy model to test the treatment effects of p38 MAPK or Toll-like receptor 9 inhibitors on p SS. [ABSTRACT FROM AUTHOR]

Key points Diabetic nephropathy (DN) is a major complication of diabetes, key features of which include glomerular mesangial expansion, hypertrophy, renal inflammation and accumulation of extracellular matrix proteins in the kidney., Histone acetylation plays an important role in the regulation of inflammation in DN., We found that apelin-13, the most active member of the adipokine apelin group, decreased glomerular filtration rate, proteinuria, glomerular hypertrophy and mesangial expansion, down-regulated histone acetylation and suppressed renal inflammation in Akita mouse, a spontaneous DN mouse model., In mesangial cell lines, apelin-13 treatment not only inhibited high glucose-induced histone hyperacetylation and inflammation factors, but also up-regulated histone deacetylase 1., These results revealed the possible mechanisms underlying the regulation of histone acetylation in DN and provide novel approaches to explore the beneficial effects of apelin-13 on DN., Abstract Diabetic nephropathy is the primary cause of end-stage renal disease. Increasing numbers of patients are suffering from this disease and therefore novel medications and therapeutic approaches are urgently needed. Here, we investigated whether apelin-13, the most active member of the adipokine apelin group, could effectively suppress the development of nephropathy in Akita mouse, a spontaneous type 1 diabetic model. Apelin-13 treatment decreased diabetes-induced glomerular filtration rate, proteinuria, glomerular hypertrophy, mesangial expansion and renal inflammation. The inflammatory factors, activation of NF-κB, histone acetylation and the enzymes involved in histone acetylation were further examined in diabetic kidneys and high glucose- or sodium butyrate-treated mesangial cells in the presence or absence of apelin-13. Apelin-13 treatment inhibited diabetes-, high glucose- and NaB-induced elevation of inflammatory factors, and histone hyperacetylation by upregulation of histone deacetylase 1. Furthermore, overexpression of apelin in mesangial cells induced histone deacetylation under high glucose condition. Thus, apelin-13 may be a novel therapeutic candidate for treatment of diabetic nephropathy via regulation of histone acetylation. [ABSTRACT FROM AUTHOR]

Schottky junctions made from a titanium dioxide nanotube (TiO2NT) array in contact with a monolayer graphene (MLG) film are fabricated and utilized for UV light detection. The TiO2NT array is synthesized by the anodization and the MLG through a simple chemical vapor deposition process. Photoconductive analysis shows that the fabricated Schottky junction photodetector (PD) is sensitive to UV light illumination with good stability and reproducibility. The corresponding responsivity ( R), photoconductive gain ( G), and detectivity ( D*) are calculated to be 15 A W−1, 51, and 1.5 × 1012 cm Hz1/2 W−1, respectively. It is observed that the fabricated PD exhibits spectral sensitivity and a simple power-law dependence on light intensity. Moreover, the height of the Schottky junction diode is derived to be 0.59 V by using a low temperature I-V measurement. Finally, the working mechanism of the TiO2NT array/MLG film Schottky junction PD is elucidated. [ABSTRACT FROM AUTHOR]