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Carbazole compounds are widely used in determining the direction of petroleum migration, but the effect of thermal maturity on carbazoles is still ambiguity. In this paper, using compaction pyrolysis simulation experiments, artificial mature samples with vitrinite reflectance (Ro) range from 0.38 to 3.0% were acquired. And the content and composition change characteristics of carbazole compounds were analyzed in coal source rocks. The experimental results showed that thermal maturity controls the generation of a large amount of carbazole compounds in coal rocks. Compared with the low mature stage, the content of carbazole compounds was about 10–100 times higher in the mature stage. With the increasing maturity, in the coal sample, the content of carbazole compounds showed a trend of first increasing and then decreasing. In derivatives of carbazole, the corresponding maturity for the maximum generation of ethylcarbazole (EC), dimethylcarbazole (DMCA), methylcarbazole (MCA), carbazole (CA) and benzocarbazole (BCA) performed the increasing sequence. With the increasing maturity, the relative abundance of 2-MCA, 1,7-DMCA and benzo[a]carbazole increased with the increasing maturity, while 4-MCA, 1,4-DMCA and benzo[c]carbazole gradually decreased. Benzocarbazole ratio [a]/[a] +[ c] varies only in a narrow range 0.36–0.61 in the entire maturity range, suggesting limited maturity dependence. The experimental conclusion provides more theoretical basis for future geochemical analysis using carbazole compounds. [ABSTRACT FROM AUTHOR]

BAZ2A, an epigenetic regulatory factor that affects ribosomal RNA transcription, has been shown to be highly expressed in several cancers and promotes tumor cell migration. This study explored the expression and mechanism of BAZ2A in tumorigenesis at the pan-cancer level. The Cancer Genome Atlas, Gene Expression Omnibus databases and TIMER2.0, cBioPortal and other tools were used to analyze the level of expression of BAZ2A in various tumor tissues and to examine the relationship between BAZ2A and survival, prognosis, mutation and immune invasion. In vitro experiments were performed to assess the function of BAZ2A in cancer cells. Using combined transcriptome and proteome analysis, we examined the possible mechanism of BAZ2A in tumors. BAZ2A exhibited high expression levels in multiple tumor tissues and displayed a significant association with cancer patient prognosis. The main type of BAZ2A genetic variation in cancer is gene mutation. Downregulation of BAZ2A inhibited proliferation, migration, and invasion and promoted apoptosis in LM6 liver cancer cell. The mechanism of BAZ2A in cancer development may involve lipid metabolism. These results help expand our understanding of BAZ2A in tumorigenesis and development and suggest BAZ2A may serve as a prognostic and diagnostic factor in several cancers. [ABSTRACT FROM AUTHOR]

BAZ2A, an epigenetic regulatory factor that affects ribosomal RNA transcription, has been shown to be highly expressed in several cancers and promotes tumor cell migration. This study explored the expression and mechanism of BAZ2A in tumorigenesis at the pan-cancer level. The Cancer Genome Atlas, Gene Expression Omnibus databases and TIMER2.0, cBioPortal and other tools were used to analyze the level of expression of BAZ2A in various tumor tissues and to examine the relationship between BAZ2A and survival, prognosis, mutation and immune invasion. In vitro experiments were performed to assess the function of BAZ2A in cancer cells. Using combined transcriptome and proteome analysis, we examined the possible mechanism of BAZ2A in tumors. BAZ2A exhibited high expression levels in multiple tumor tissues and displayed a significant association with cancer patient prognosis. The main type of BAZ2A genetic variation in cancer is gene mutation. Downregulation of BAZ2A inhibited proliferation, migration, and invasion and promoted apoptosis in LM6 liver cancer cell. The mechanism of BAZ2A in cancer development may involve lipid metabolism. These results help expand our understanding of BAZ2A in tumorigenesis and development and suggest BAZ2A may serve as a prognostic and diagnostic factor in several cancers. [ABSTRACT FROM AUTHOR]

Vital node discovery is a hotspot in network topology research. The key is using the Internet's routing characteristics to remove noisy paths and accurately describe the network topology. In this manuscript, a vital regional routing nodes discovery algorithm based on routing characteristics is proposed. We analyze the stability of multiple rounds of measurement results to overcome the single vantage point's path deviation. The unstable paths are eliminated from the regional network which is constructed through probing for target area, and the pruned topology is more in line with real routing rules. Finally, we weight the edge based on the actual network's routing characteristics and discover vital nodes in combination with the weighting degree. Unlike existing algorithms, the proposed algorithm reconstructs the network topology based on communication and transforms unweighted network connections into weighted connections. We can evaluate the node importance in a more realistic network structure. Experiments on the Internet measurement data (275 million probing results collected in 107 days) demonstrate that: the proposed algorithm outperforms four existing typical algorithms. Among 15 groups of comparison in 3 cities, our algorithm found more (or the same number) backbone nodes in 10 groups and found more (or the same number) national backbone nodes in 13 groups. [ABSTRACT FROM AUTHOR]

Angelman syndrome (AS) is a rare neurogenetic disorder caused by UBE3A deficiency and characterized by severe developmental delay, cognitive impairment, and motor dysfunction. In the present study, we performed RNA-seq on hippocampal samples from both wildtype (WT) and AS male mice, with or without contextual fear memory recall. There were 281 recall-associated differentially expressed genes (DEGs) in WT mice and 268 DEGs in AS mice, with 129 shared by the two genotypes. Gene ontology analysis showed that extracellular matrix and stimulation-induced response genes were prominently enriched in recall-associated DEGs in WT mice, while nuclear acid metabolism and tissue development genes were highly enriched in those from AS mice. Further analyses showed that the 129 shared DEGs belonged to nuclear acid metabolism and tissue development genes. Unique recall DEGs in WT mice were enriched in biological processes critical for synaptic plasticity and learning and memory, including the extracellular matrix network clustered around fibronectin 1 and collagens. In contrast, AS-specific DEGs were not enriched in any known pathways. These results suggest that memory recall in AS mice, while altering the transcriptome, fails to recruit memory-associated transcriptional programs, which could be responsible for the memory impairment in AS mice. [ABSTRACT FROM AUTHOR]

Vital node discovery is a hotspot in network topology research. The key is using the Internet's routing characteristics to remove noisy paths and accurately describe the network topology. In this manuscript, a vital regional routing nodes discovery algorithm based on routing characteristics is proposed. We analyze the stability of multiple rounds of measurement results to overcome the single vantage point's path deviation. The unstable paths are eliminated from the regional network which is constructed through probing for target area, and the pruned topology is more in line with real routing rules. Finally, we weight the edge based on the actual network's routing characteristics and discover vital nodes in combination with the weighting degree. Unlike existing algorithms, the proposed algorithm reconstructs the network topology based on communication and transforms unweighted network connections into weighted connections. We can evaluate the node importance in a more realistic network structure. Experiments on the Internet measurement data (275 million probing results collected in 107 days) demonstrate that: the proposed algorithm outperforms four existing typical algorithms. Among 15 groups of comparison in 3 cities, our algorithm found more (or the same number) backbone nodes in 10 groups and found more (or the same number) national backbone nodes in 13 groups. [ABSTRACT FROM AUTHOR]

Gallate material, a luminescent matrix with excellent performance is normally prepared by vapor deposition or solid phase sintering method at high temperature. However, it has not been solved to prepare gallate-based fluorescent materials with full-color luminescent properties at low temperature. In this paper, ZnGa2O4 undoped or doped with Cr or Mn nanoflowers composed of nanosheet-level structure were prepared by hydrothermal method at low temperature. Under ultraviolet light irradiation, ZnGa2O4, ZnGa2O4:Mn2+ and ZnGa2O4:Cr3+ display three primary colors of blue, green and red luminescence through self-excitation, Mn2+ and Cr3+ excitation respectively. The solid fluorescence yields of blue, green, and red colors are 32.3, 36.5, and 40.7%, respectively. It is highly expected to be applied to color display, biological imaging, white light devices. [ABSTRACT FROM AUTHOR]

In socially monogamous prairie voles (Microtus ochrogaster), parental behaviors not only occur in mothers and fathers, but also exist in some virgin males. In contrast, the other virgin males display aggressive behaviors towards conspecific pups. However, little is known about the molecular underpinnings of this behavioral dichotomy, such as gene expression changes and their regulatory mechanisms. To address this, we profiled the transcriptome and DNA methylome of hippocampal dentate gyrus of four prairie vole groups, namely attacker virgin males, parental virgin males, fathers, and mothers. While we found a concordant gene expression pattern between parental virgin males and fathers, the attacker virgin males have a more deviated transcriptome. Moreover, numerous DNA methylation changes were found in pair-wise comparisons among the four groups. We found some DNA methylation changes overlapping with transcription differences, across gene-bodies and promoter regions. Furthermore, the gene expression changes and methylome alterations are selectively enriched in certain biological pathways, such as Wnt signaling, which suggest a canonical transcription regulatory role of DNA methylation in paternal behavior. Therefore, our study presents an integrated view of prairie vole dentate gyrus transcriptome and epigenome that provides a DNA epigenetic based molecular insight of paternal behavior. [ABSTRACT FROM AUTHOR]

Research on router ownership inference is central to many Internet studies, such as network failure diagnosis, network boundary identification, network resilience assessment, and inter-domain congestion detection. The existing router ownership inference method bdrmapIT has relatively few constraints on routers at the end of traceroute paths, resulting in some inference errors. In this paper, a router ownership inference method based on the classification of intra- and inter-domain links is proposed. In this method, the differentiating Internet Protocol (IP) address vector distance feature, the autonomous system relationship feature of the IP link, and the fan-in and fan-out features are designed to support the discrimination of IP link types. The use of additional information derived from the link type enriches the basis for router ownership inference and improves the accuracy of the inference result. Experimental results show that the accuracy reaches 96.4% and 94.6% on the two verification sets, respectively, which is 3.2–11.2% better than the existing typical methods. [ABSTRACT FROM AUTHOR]

Atopic Dermatitis (AD) or eczema, a recurrent allergic inflammation of the skin, afflicts 10–20% of children and 5% adults of all racial and ethnic groups globally. We report a new topical treatment of AD by a Nuclear Transport Checkpoint Inhibitor (NTCI), which targets two nuclear transport shuttles, importin α5 and importin β1. In the preclinical model of AD, induced by the active vitamin D3 analog MC903 (calcipotriol), NTCI suppressed the expression of keratinocyte-derived cytokine, Thymic Stromal Lymphopoietin (TSLP), the key gene in AD development. Moreover, the genes encoding mediators of TH2 response, IL-4 and its receptor IL-4Rα were also silenced together with the genes encoding cytokines IL-1β, IL-6, IL-13, IL-23α, IL-33, IFN-γ, GM-CSF, VEGF A, the chemokines RANTES and IL-8, and intracellular signal transducers COX-2 and iNOS. Consequently, NTCI suppressed skin infiltration by inflammatory cells (eosinophils, macrophages, and CD4 + T lymphocytes), and reduced MC903-evoked proliferation of Ki-67-positive cells. Thus, we highlight the mechanism of action and the potential utility of topical NTCI for treatment of AD undergoing Phase 1/2 clinical trial (AMTX-100 CF, NCT04313400). [ABSTRACT FROM AUTHOR]

Most of the smallest flying insects use bristled wings. It was observed that during the second half of their upstroke, the left and right wings become parallel and close to each other at the back, and move upward at zero angle of attack. In this period, the wings may produce drag (negative vertical force) and side forces which tend to push two wings apart. Here we study the aerodynamic forces and flows of two simplified bristled wings experiencing such a motion, compared with the case of membrane wings (flat-plate wings), to see if there is any advantage in using the bristled wings. The method of computational fluid dynamics is used in the study. The results are as follows. In the motion of two bristled wings, the drag acting on each wing is 40% smaller than the case of a single bristled wing conducting the same motion, and only a very small side force is produced. But in the case of the flat-plate wings, although there is similar drag reduction, the side force on each wing is larger than that of the bristled wing by an order of magnitude (the underlying physical reason is discussed in the paper). Thus, if the smallest insects use membrane wings, their flight muscles need to overcome large side forces in order to maintain the intended motion for less negative lift, whereas using bristled wings do not have this problem. Therefore, the adoption of bristled wings can be beneficial during upward movement of the wings near the end of the upstroke, which may be one reason why most of the smallest insects adopt them. [ABSTRACT FROM AUTHOR]

Here, we report well–preserved skulls and postcranial specimens of genus Hippotherium from the Linxia Basin, Gansu, China. Based on morphological comparison, the species of Hippotherium in China, Hippotherium weihoense and Hippotherium chiai, should be ascribed to the same species, H. weihoense. We also reviewe other Old World hipparion species in the very early Late Miocene and figure out two evolutionary routes: the Hippotherium and Cormohipparion lineages. Analysis of locomotive ability indicates that H. weihoense likely lived in an open habitat, whereas other species of Hippotherium likely lived in closed habitats. This result shows a palaeoecological pattern in the early Late Miocene in Eurasia influenced by a series of geological events as aridification of mid–latitude Asia progressed, whereas Europe and North Africa remained relatively humid. As the genus originated from East Asia, hipparion horses divided rapidly into different groups with differing functional morphology to occupy diverse niches. [ABSTRACT FROM AUTHOR]

Thyroid hormone (TH) and thyroid hormone receptor (THR) regulate stem cell proliferation and differentiation during development, as well as during tissue renewal and repair in the adult. THR undergoes posttranslational modification by small ubiquitin-like modifier (SUMO). We generated the THRA (K283Q/K288R)−/− mouse model for in vivo studies and used human primary preadipocytes expressing the THRA sumoylation mutant (K283R/K288R) and isolated preadipocytes from mutant mice for in vitro studies. THRA mutant mice had reduced white adipose stores and reduced adipocyte cell diameter on a chow diet, compared to wild-type, and these differences were further enhanced after a high fat diet. Reduced preadipocyte proliferation in mutant mice, compared to wt, was shown after in vivo labeling of preadipocytes with EdU and in preadipocytes isolated from mice fat stores and studied in vitro. Mice with the desumoylated THRA had disruptions in cell cycle G1/S transition and this was associated with a reduction in the availability of cyclin D2 and cyclin-dependent kinase 2. The genes coding for cyclin D1, cyclin D2, cyclin-dependent kinase 2 and Culin3 are stimulated by cAMP Response Element Binding Protein (CREB) and contain CREB Response Elements (CREs) in their regulatory regions. We demonstrate, by Chromatin Immunoprecipitation (ChIP) assay, that in mice with the THRA K283Q/K288R mutant there was reduced CREB binding to the CRE. Mice with a THRA sumoylation mutant had reduced fat stores on chow and high fat diets and reduced adipocyte diameter. [ABSTRACT FROM AUTHOR]

In the paper, adaptive neural fuzzy (ANF) PID control is applied on the stability analysis of phase-shifted full-bridge (PSFB) zero-voltage switch (ZVS) circuit, which is used in battery chargers of electric vehicles. At first, the small-signal mathematical model of the circuit is constructed. Then, by fuzzing the parameters of PID, a closed-loop system of the small-signal mathematical model is established. Further, after training samples collected from the fuzzy PID system by adaptive neural algorithm, an ANF PID controller is utilized to build a closed-loop system. Finally, the characteristics of stability, overshoot and response speed of the mathematical model and circuit model systems are analyzed. According to the simulation results of PSFB ZVS circuit, the three control strategies have certain optimizations in overshoot and adjustment time. Among them, the optimization effect of PID control in closed-loop system is the weakest. From the results of small-signal model and circuit model, the ANF PID system has highest optimization. Experiments demonstrate that the ANF PID system gives satisfactory control performance and meets the expectation of optimization design. [ABSTRACT FROM AUTHOR]

The screening of non-small cell lung cancer (NSCLC) tumors for anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements is important because of the dramatically favorable therapy response to ALK inhibitor. However, the exact mechanism of poor survival in ALK fusion lung cancer patients without receiving targeted therapy is unclear. In this study, total of 521 tumor specimens from Chinese patients with lung cancer were screened for ALK fusion by immunohistochemistry (IHC) and confirmed by fluorescence in situ hybridization (FISH). As results, there were no cases of coexisting EGFR and ALK mutations identified. Fourteen cases (2.7%) harbored ALK fusion, including eight solid adenocarcinomas with signet ring cell features, four acinar adenocarcinomas with cribriform pattern containing mucin, one adenosquamous carcinoma and one micropapillary adenocarcinoma with mucin. Six (42.9%) of fourteen patients with ALK-positive lung cancer had stage IV disease, and five ALK-positive patients treated with platinum-based chemotherapy had poor outcome (all patients were dead and the mean survival time was 12 months), compared to 72 months for patients with ALK inhibitor therapy. Furthermore, Five ALK-positive cases were analyzed by whole exome sequencing (WES) and via direct transcript counting using a digital probe-base (NanoString) to explore the driver genes. Deregulation of PI3K/AKT signaling pathway in ALK-positive lung cancer was demonstrated by WES analysis, and significantly increased mRNA of ALK, ROS1, MET, SPP1 and PI3K signaling pathway was identified by NanoString assay. The concordance between NanoString, IHC and FISH methodologies for detecting ALK fusion was 100%. Significant overexpression of SPP1 protein in ALK-positive lung cancer was confirmed by IHC compared to paired adjacent normal tissues and ALK-negative cancers. Thus we concluded that SPP1 overexpression is associated with poor outcomes for patients with ALK fusion lung cancer without receiving targeted therapy and PI3K/AKT/SPP1 pathway may become the promising targets in patients with aggressive lung cancer. [ABSTRACT FROM AUTHOR]

Hyperlipidemia, the hallmark of Metabolic Syndrome that afflicts millions of people worldwide, exacerbates life-threatening infections. We present a new evidence for the mechanism of hyperlipidemic hypersensitivity to microbial inflammation caused by pathogen-derived inducer, LPS. We demonstrate that hyperlipidemic animals succumbed to a non-lethal dose of LPS whereas normolipidemic controls survived. Strikingly, survival of hyperlipidemic animals was restored when the nuclear import of stress-responsive transcription factors (SRTFs), Sterol Regulatory Element-Binding Proteins (SREBPs), and Carbohydrate-Responsive Element-Binding Proteins (ChREBPs) was impeded by targeting the nuclear transport checkpoint with cell-penetrating, biselective nuclear transport modifier (NTM) peptide. Furthermore, the burst of proinflammatory cytokines and chemokines, microvascular endothelial injury in the liver, lungs, heart, and kidneys, and trafficking of inflammatory cells were also suppressed. To dissect the role of nuclear transport signaling pathways we designed and developed importin-selective NTM peptides. Selective targeting of the importin α5, ferrying SRTFs and ChREBPs, protected 70–100% hyperlipidemic animals. Targeting importin β1, that transports SREBPs, was only effective after 3-week treatment that lowered blood triglycerides, cholesterol, glucose, and averted fatty liver. Thus, the mechanism of hyperlipidemic hypersensitivity to lethal microbial inflammation depends on metabolic and proinflammatory transcription factors mobilization, which can be counteracted by targeting the nuclear transport checkpoint. [ABSTRACT FROM AUTHOR]

Controversial results have been reported about the association of calcium, magnesium, and phosphorus and stroke risk, but none in China. To investigate the association between dietary calcium, magnesium, phosphorus, and stroke incidence in Chinese adults, we collected data from the China Health and Nutrition Survey (CHNS) from 2004 to 2011, including 6411 participants aged 45–79 years and free of stroke at baseline. Diet was assessed by interviews combining 3-d 24-h food recalls and household food inventory weighing at each survey round. The stroke incident was identified based on the validated self-report. Multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). For 32,024 person-years of follow-up, 179 stroke cases were documented. After adjustment for major lifestyle and dietary risk factors, calcium intake was positively associated with reduced stroke risk, and the HR of stroke comparing extreme quartiles was 0.53 (95% CI 0.29–0.96, Ptrend = 0.03). In further stratified analyses, significant heterogeneity across sex strata was found (Pinteraction = 0.03). Dietary calcium intake among men was more inversely related to stroke, with HRs being 0.33 (95% CI 0.15–0.76, Ptrend = 0.02), compared to 1.24 (95% CI 0.46–3.35, Ptrend = 0.89) among women. However, no significant association between stroke and magnesium or phosphorus was revealed. Our findings suggest that higher dietary calcium intake was associated with a lower risk of stroke in Chinese adults, particularly in men. [ABSTRACT FROM AUTHOR]

Human blood cells (HBCs) play essential roles in multiple biological processes but their roles in development of uterine polyps are unknown. Here we implemented a Mendelian randomization (MR) analysis to investigate the effects of 36 HBC traits on endometrial polyps (EPs) and cervical polyps (CPs). The random-effect inverse-variance weighted method was adopted as standard MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Genetic instruments of HBC traits was extracted from a large genome-wide association study of 173,480 individuals, while data for EPs and CPs were obtained from the UK Biobank. All samples were Europeans. Using genetic variants as instrumental variables, our study found that both eosinophil count (OR 0.85, 95% CI 0.79–0.93, P = 1.06 × 10−4) and eosinophil percentage of white cells (OR 0.84, 95% CI 0.77–0.91, P = 2.43 × 10−5) were associated with decreased risk of EPs. The results were robust in sensitivity analyses and no evidences of horizontal pleiotropy were observed. While we found no significant associations between HBC traits and CPs. Our findings suggested eosinophils might play important roles in the pathogenesis of EPs. Besides, out study provided novel insight into detecting uterine polyps biomarkers using genetic epidemiology approaches. [ABSTRACT FROM AUTHOR]

Thyroid hormone signaling plays an essential role in muscle development and function, in the maintenance of muscle mass, and in regeneration after injury, via activation of thyroid nuclear receptor alpha (THRA). A mouse model of resistance to thyroid hormone carrying a frame-shift mutation in the THRA gene (THRA-PV) is associated with accelerated skeletal muscle loss with aging and impaired regeneration after injury. The expression of nuclear orphan receptor chicken ovalbumin upstream promoter-factor II (COUP-TFII, or Nr2f2) persists during myogenic differentiation in THRA-PV myoblasts and skeletal muscle of aged THRA-PV mice and it is known to negatively regulate myogenesis. Here, we report that in murine myoblasts COUP-TFII interacts with THRA and modulates THRA binding to thyroid response elements (TREs). Silencing of COUP-TFII expression restores in vitro myogenic potential of THRA-PV myoblasts and shifts the mRNA expression profile closer to WT myoblasts. Moreover, COUP-TFII silencing reverses the transcriptomic profile of THRA-PV myoblasts and results in reactivation of pathways involved in muscle function and extracellular matrix remodeling/deposition. These findings indicate that the persistent COUP-TFII expression in THRA-PV mice is responsible for the abnormal muscle phenotype. In conclusion, COUP-TFII and THRA cooperate during post-natal myogenesis, and COUP-TFII is critical for the accelerated skeletal muscle loss with aging and impaired muscle regeneration after injury in THRA-PV mice. [ABSTRACT FROM AUTHOR]

The association between dietary fat intake during pregnancy and the risk of developing preeclampsia has been examined in many epidemiological studies, but the results remain inconsistent. The aim of this study was to clarify this association in pregnant Chinese women. After conducting 1:1 matching, 440 pairs consisting of pregnant women with preeclampsia and hospital-based, healthy pregnant women matched by gestational week (± 1 week) and age (± 3 years) were recruited. A 79-item semi-quantitative food frequency questionnaire administered during face-to-face interviews was used to estimate the participants' dietary intake of fatty acids. We found that the intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were inversely associated with the risk of developing preeclampsia. Compared with the lowest quartile intake, the multivariate-adjusted odds ratios (95% confidence interval) of the highest quartile intake were 0.42 (0.26–0.68, p-trend < 0.001) for EPA, 0.52 (0.3–0.83, p-trend = 0.005) for DHA, and 0.41 (0.19–0.88, p-trend = 0.007) for AA. However, we did not observe any significant associations between the intake of total fatty acids, saturated fatty acids, and mono-unsaturated fatty acids and the risk of developing preeclampsia. Our results showed that the dietary intake of long-chain polyunsaturated fatty acids (i.e., EPA, DHA, and AA) may protect pregnant Chinese women against the development of preeclampsia. [ABSTRACT FROM AUTHOR]

Teleost fishes display the largest array of sex-determining systems among animals, resulting in various reproductive strategies. Research on sex-related genes in teleosts will broaden our understanding of the process, and provide important insight into the plasticity of the sex determination process in vertebrates in general. Crimson seabream (Parargyrops edita Tanaka, 1916) is one of the most valuable and abundant fish resources throughout Asia. However, little genomic information on P. edita is available. In the present study, the transcriptomes of male and female P. edita were sequenced with RNA-seq technology. A total of 388,683,472 reads were generated from the libraries. After filtering and assembling, a total of 79,775 non redundant unigenes were obtained with an N50 of 2,921 bp. The unigenes were annotated with multiple public databases, including NT (53,556, 67.13%), NR (54,092, 67.81%), Swiss-Prot (45,265, 56.74%), KOG (41,274, 51.74%), KEGG (46,302, 58.04%), and GO (11,056, 13.86%) databases. Comparison of the unigenes of different sexes of P. edita revealed that 11,676 unigenes (9,335 in females, 2,341 in males) were differentially expressed between males and females. Of these, 5,463 were specifically expressed in females, and 1,134 were specifically expressed in males. In addition, the expression levels of ten unigenes were confirmed to validate the transcriptomic data by qRT-PCR. Moreover, 34,473 simple sequence repeats (SSRs) were identified in SSR-containing sequences, and 50 loci were randomly selected for primer development. Of these, 36 loci were successfully amplified, and 19 loci were polymorphic. Finally, our comparative analysis identified many sex-related genes (zps, amh, gsdf, sox4, cyp19a, etc.) and pathways (MAPK signaling pathway, p53 signaling pathway, etc.) of P. edita. This informative transcriptomic analysis provides valuable data to increase genomic resources of P. edita. The results will be useful for clarifying the molecular mechanism of sex determination and for future functional analyses of sex-associated genes. [ABSTRACT FROM AUTHOR]

We studied the magnetization evolution in three-dimensional chiral nanostructures, including nanotubes and circularly curved thin films, by micromagnetic simulations. We found that in a nanotube skyrmions can be formed by broken of the helical stripes on the left and right sides of the nanotube, and the formation of skyrmions doesn't correspond to any abrupt change of topological number. Skyrmions can exist in a large range of magnetic field, and the thinner nanotube has a larger field range for skyrmion existence. The configuration of a skyrmion in nanotubes is different from the one in thin film. From the outer to the inner circular layer, the size of the skyrmion becomes larger, and the deformation becomes more obvious. In circularly curved magnetic films with fixed arc length, there are three kinds of hysteresis processes are found. For the curved films with a large radius, the magnetization evolution behavior is similar to the case in two-dimensional thin films. For the curved films with a small radius, the skyrmions are created by broken of the helical stripes on the left and right sides of the curved film. For the curved film with a medium radius, no skyrmion is formed in the hysteresis process. [ABSTRACT FROM AUTHOR]

The ubiquitin ligase, Ube3a, plays important roles in brain development and functions, since its deficiency results in Angelman Syndrome (AS) while its over-expression increases the risk for autism. We previously showed that the lack of Ube3a-mediated ubiquitination of the Ca2+-activated small conductance potassium channel, SK2, contributes to impairment of synaptic plasticity and learning in AS mice. Synaptic SK2 levels are also regulated by protein kinase A (PKA), which phosphorylates SK2 in its C-terminal domain, facilitating its endocytosis. Here, we report that PKA activation restores theta burst stimulation (TBS)-induced long-term potentiation (LTP) in hippocampal slices from AS mice by enhancing SK2 internalization. While TBS-induced SK2 endocytosis is facilitated by PKA activation, SK2 recycling to synaptic membranes after TBS is inhibited by Ube3a. Molecular and cellular studies confirmed that phosphorylation of SK2 in the C-terminal domain increases its ubiquitination and endocytosis. Finally, PKA activation increases SK2 phosphorylation and ubiquitination in Ube3a-overexpressing mice. Our results indicate that, although both Ube3a-mediated ubiquitination and PKA-induced phosphorylation reduce synaptic SK2 levels, phosphorylation is mainly involved in TBS-induced endocytosis, while ubiquitination predominantly inhibits SK2 recycling. Understanding the complex interactions between PKA and Ube3a in the regulation of SK2 synaptic levels might provide new platforms for developing treatments for AS and various forms of autism. [ABSTRACT FROM AUTHOR]

To explore the efficacy and safety of fecal microbiota transplantation (FMT) as a treatment approach for ulcerative colitis (UC), a comprehensive systematic review and meta-analysis of randomized controlled trials was conducted. To collect and evaluate randomized controlled trials of high quality on FMT for UC, we searched a number of databases, including PubMed, Web of Science, Cochrane, Embase, and Medline, for studies published between the establishment of the databases and March 2023. We conducted a meta-analysis of the studies using Review Manager software (version 5.4.1) to determine the differences in rates of remission and adverse reactions between the FMT group and the control group, utilizing the risk ratio (RR) and 95% confidence interval (CI) to combine our findings. A total of 13 randomized controlled trials (RCTs) on the efficacy of FMT in patients with UC were included in the study, in which 580 patients participated, including 293 patients treated with FMT and 287 control subjects. Meta-analysis revealed that clinical remission was significantly better in the FMT group than in the control group [RR = 1.73; 95% CI = (1.41, 2.12); P < 0.00001]; endoscopic remission was significantly better in the FMT group than in the control group [RR = 1.74; 95% CI = (1.24, 2.44); P = 0.001]. Additionally, there were no significant differences in the incidence of adverse reactions between the two groups [RR = 1.00; 95% CI = (0.86, 1.15); P = 0.96]. Fecal microbiota transplantation has shown potential as a therapeutic intervention for inducing clinical remission in ulcerative colitis UC; nevertheless, the attainment of endoscopic remission and the maintenance of long-term remission continue to present challenges. Safety concerns persist throughout the treatment process, necessitating the implementation of measures to augment both safety and success rates. [ABSTRACT FROM AUTHOR]

Vitiligo is the most common depigmenting disorder to which both genetic and environmental factors contribute. The aim of the current work was to evaluate the relationship between polymorphisms of the gene nuclear receptor subfamily 1 Group H member 3 (NR1H3) and the risk of vitiligo and phototherapy effects in the Chinese Han population. Two independent samples were enrolled to form the discovery set (comprised of 1668 nonsegmental vitiligo [NSV] patients and 2542 controls) and the validation set (comprised of 745 NSV patients and 1492 controls). A total of 13 tag single nucleotide polymorphisms (SNPs) were genotyped in the samples from the discovery stage. SNPs that achieved nominal significance were validated in another independent sample set. The serum level of NR1H3 protein was assayed using enzyme-linked immunosorbent assay kits in the validation set. Genetic association analysis was carried out at allelic and genotypic levels. The therapeutic effects of significant SNPs were examined in the validation set. The SNP rs3758672 was significantly associated with NSV. The A allele was correlated with NSV risk and poorer therapeutic effects. The A allele was strongly correlated with the increased level of serum NR1H3 in both controls and patients. In summary, SNP rs3758672 in NR1H3 was significantly associated with both disease susceptibility and individualized therapeutic effects of NSV in study participants with Han Chinese ancestry. [ABSTRACT FROM AUTHOR]

Tertiary relict flora in East Asia can be divided into northern and southern regions. North China is a diversity hotspot because it can be the secondary contact zone of ancient lineages from the two regions. To test the extent of ancient lineages hybridization and distinguish between the putative species pair Acer pictum subsp. mono and Acer truncatum, we conducted genetic and ecological studies within a maple hybrid zone in North China. Our results suggest that the two lineages of Acer coexist in the hybrid zone and that adult and offspring populations show typical bimodal genetic patterns. Hybrid individuals are established at intermediate altitudes between the two parental lineages. Flowering phenology is divergent between lineages, whereas the complex sexual system of Acer may ensure pollination among lineages. Leaf and fruit morphologies are different between the northern and southern origin lineages, corresponding to A. pictum subsp. mono and A. truncatum, respectively. Reduced gene flow between lineages suggests that they should be considered as two species. However, large morphological variations within each species and the existence of hybrids offer low reliability of species identification based solely on morphological traits. Our study underscores North China as an overlooked diversity hotspot that requires further study in the future. [ABSTRACT FROM AUTHOR]

In 2016, China initiated the merge of the urban resident basic medical insurance scheme and new rural cooperative medical scheme into one unified health insurance scheme: the urban and rural resident basic medical insurance. This study investigates the impact of integrated insurance on the direct hospitalization cost of inpatients with catastrophic illnesses. An interrupted time series analysis was conducted based on a sample of 6174 inpatients with catastrophic illness from January 2014 to December 2018. The factors surveyed included per capita total inpatient expense, out-of-pocket expense, and reimbursement ratio. Univariate analysis indicated that after the implementation of the unified urban and rural medical insurance, the reimbursed expense increased from 9398 to 13,842 Yuan (P < 0.001), average reimbursement ratio increased from 0.57 to 0.59 (P < 0.05). Expenses on both western and traditional medicines increased, although the proportion of medicine expense decreased after the integration. Interrupted time series analysis showed that per capita total inpatient expense and per capita out-of-pocket expense increased but showed a gradually decreasing trend after the integration. After the integration of urban and rural medical insurance, the average reimbursement ratio increased slightly, which had limited effect on the alleviation of patients' financial burden. Furthermore, the integration effect on inpatient expense is offset by increased out-of-pocket medical expense due to suspected supplier-induced demand. [ABSTRACT FROM AUTHOR]

Weight loss through behavioral modification is central to treating non-alcoholic fatty liver disease (NAFLD). To achieve this, patients need to accurately self-perceive their health behaviors. We aimed to identify predictors of concordance between self-perception and objective measures of body weight, physical activity (PA) and dietary behaviors. We used data from the Harris County NAFLD Cohort, an ongoing prospective study in a regional safety-net healthcare system. Patients completed self-administered baseline questionnaires on demographics, diet, PA, and self-perceptions. We assessed concordance between actual and self-perceived body weight and energy-balance behaviors. Multivariable logistic regression identified predictors of concordance. Patients (n = 458; average age 46.5 years) were 90% Hispanic and 76% female. PA and fruit/vegetable intake guidelines were met among 37% and 9%, respectively. Most (89%) overweight/obese patients accurately perceived themselves as such. However, 41% of insufficiently-active and 34% of patients not meeting fruit/vegetable intake guidelines inaccurately self-perceived their behaviors as "just right". Women were 3 times more likely to accurately self-perceive weight status (adjusted odds ratio [AOR] 3.24; 95% CI 1.68–6.25) but 51% less likely to accurately self-perceive PA levels than men (AOR 0.49; 95% CI 0.29–0.81). Lower acculturation was associated with higher odds of accurate PA self-perception. Patients with prediabetes or diabetes vs normoglycemia were more likely to accurately self-perceive their fruit/vegetable intake. Most NAFLD patients accurately self-perceived their body weight. A third or more of those not meeting fruit/vegetable intake or PA guidelines had inaccurate perceptions about their behaviors. Our findings highlight key areas to target in NAFLD-specific behavioral modification programs. [ABSTRACT FROM AUTHOR]

Small cell lung cancer (SCLC) is heterogenous in phenotype and microenvironment. Dynamic phenotypic reprogramming, leading to heterogeneity, is prevalent in SCLC, while the mechanisms remain incompletely understood. Cancer-associated fibroblasts (CAFs) possess comprehensive roles in cancer progression, while their function in phenotypic reprogramming of SCLC remain elusive. Here, we obtained transcriptome data of SCLC tissues from publicly available databases, subsequently estimated abundance of CAFs. We found CAF-abundant SCLC exhibited non-neuroendocrine (Non-NE) characteristics. Supporting this, the positive correlation of expression level of α-SMA, the CAF marker, and expression level of REST, protein typically expressed in Non-NE type SCLC, was identified in SCLC tissue arrays. Moreover, we revealed that fibroblasts inhibited NE markers expression and cell proliferation of SCLC cells in the co-culture system comprising lung fibroblasts and SCLC cells, indicating a phenotypic reprogramming from NE to Non-NE. During this process, fibroblast-derived IL-6 activated the JAK2/STAT3 signaling, upregulated c-MYC expression, and subsequently activated the NOTCH pathway, driving phenotypic reprogramming. Moreover, CAF-enriched SCLC exhibited increased immune cell infiltration, elevated expression of immune activation-related signatures, and checkpoint molecules. Our data also highlighted the chemoresistance induced by fibroblasts in SCLC cells, which was effectively reversed by JAK inhibitor. In conclusion, fibroblasts induced phenotypic reprogramming of SCLC cells from NE to Non-NE, likely contributes to inflamed immune microenvironment and chemoresistance. These findings provide novel insights into the clinical implications of CAFs in SCLC. [ABSTRACT FROM AUTHOR]

To evaluate the association of uric acid (UA) with adverse outcomes and its potential mediator in patients with left ventricular diastolic dysfunction (LVDD) and pulmonary hypertension (PH). We retrospectively analyzed 234 patients with LVDD and PH. The baseline characteristics of patients with low UA (≤ 330 µmol/L) group were compared with high UA (> 330 µmol/L) group. Adverse outcomes included all-cause mortality, cardiac death and heart failure (HF) hospitalization. Their association with UA and the mediator were evaluated using Cox regression and mediation analysis. The mediation proportion was further quantified by the R mediation package. During a mean follow-up of 50 ± 18 months, there were 27 all-cause deaths, 18 cardiovascular deaths and 41 incidents of HF hospitalization. Multivariable Cox regression analysis showed UA was an independent risk factor of adverse outcomes in LVDD and PH patients, even after adjusting for age, sex, body mass index, medical histories, systolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, eGFR, BNP and medications. The hazard ratios (HRs) for UA (per 10 µmol/L increase) were as below: for all-cause mortality, HR 1.143, 95% CI 1.069–1.221, P < 0.001; for cardiac death, HR 1.168, 95% CI 1.064–1.282, P = 0.001; for HF hospitalization, HR 1.093, 95% CI 1.035–1.155, P = 0.001. Neutrophil-to-lymphocyte ratio (NLR) played a partial mediation role in the association, and the mediation proportion for NLR on the UA-adverse outcomes were 21%, 19% and 17%, respectively. In patients of LVDD with PH, higher UA level was independently correlated with adverse outcomes. Furthermore, NLR partially mediated the effect of UA on the risk of all-cause mortality, cardiac death and HF hospitalization. [ABSTRACT FROM AUTHOR]

The preoperative diagnosis of thyroid nodules now routinely includes BRAFV600E genetic testing in most provincial and municipal hospitals in China. This study identified the most suitable patients of thyroid nodule for BRAFV600E genetic testing. We retrospectively collected data of patients from the Hospital Information System that had undergone fine needle aspiration biopsy (FNAB) from May 2019 to December 2021. Data of FNAB, BRAFV600E genetic testing, and post-surgical pathological diagnosis were collected. A total of 12,392 patients were included in this study. Among them, 7,010 patients underwent solely FNAB, while 5,382 patients had both FNAB and BRAFV600E genetic testing. In the FNAB group, 2,065 thyroid nodules were surgically removed, with a 93.12% malignancy rate. In the FNAB + BRAF group, 2,005 nodules were dissected, and the malignancy rate was 98.20%. However, it was evident that in the subgroups, the combination of FNAB and BRAFV600E genetic testing only benefited Bethesda III (p < 0.001) and V (p = 0.001) nodules. Overall, the combination of FNAB with BRAFV600E genetic testing significantly improved the malignancy rate of surgical thyroid nodes at our hospital when compared to FNAB alone. The subgroup analysis showed that BRAFV600E genetic testing only benefited Bethesda III and V nodules. These findings provide a clinical reference for rationally selecting the most suitable population for BRAFV600E genetic testing. [ABSTRACT FROM AUTHOR]

Previous studies have shown that polydatin (Poly) confer cardioprotective effects. However, its underlying mechanisms remain elusive. This study showed that Poly (10 µM) treatment reversed the high glucose (HG)-induced decrease in acetylcholine-elicited vasodilation in aortas. Poly also improved the acetylcholine-induced vasodilation of aortic vessels isolated from diabetic rats. Meanwhile, Poly ameliorated the morphological damage of the thoracic aorta and improved the viability of HUVECs under HG conditions. Furthermore, analysis of the vasoprotective effect of Poly under HG conditions by transmission electron microscopy, Western blotting, and qPCR revealed that Poly improved endothelial pyroptosis through the NLRP3/Caspase/1-IL-1β pathway, enhanced dynamin-related protein 1-mediated mitochondrial fission, and increased the mitochondrial membrane potential under HG conditions. In conclusion, Poly restored acetylcholine-induced vasodilation impaired by HG incubation, which was associated with reduced oxidation, inflammation, and pyroptosis, the recovery of the mitochondrial membrane potential and maintenance of mitochondrial dynamic homeostasis of endothelial cells in the aortas. [ABSTRACT FROM AUTHOR]

The preoperative diagnosis of thyroid nodules now routinely includes BRAFV600E genetic testing in most provincial and municipal hospitals in China. This study identified the most suitable patients of thyroid nodule for BRAFV600E genetic testing. We retrospectively collected data of patients from the Hospital Information System that had undergone fine needle aspiration biopsy (FNAB) from May 2019 to December 2021. Data of FNAB, BRAFV600E genetic testing, and post-surgical pathological diagnosis were collected. A total of 12,392 patients were included in this study. Among them, 7,010 patients underwent solely FNAB, while 5,382 patients had both FNAB and BRAFV600E genetic testing. In the FNAB group, 2,065 thyroid nodules were surgically removed, with a 93.12% malignancy rate. In the FNAB + BRAF group, 2,005 nodules were dissected, and the malignancy rate was 98.20%. However, it was evident that in the subgroups, the combination of FNAB and BRAFV600E genetic testing only benefited Bethesda III (p < 0.001) and V (p = 0.001) nodules. Overall, the combination of FNAB with BRAFV600E genetic testing significantly improved the malignancy rate of surgical thyroid nodes at our hospital when compared to FNAB alone. The subgroup analysis showed that BRAFV600E genetic testing only benefited Bethesda III and V nodules. These findings provide a clinical reference for rationally selecting the most suitable population for BRAFV600E genetic testing. [ABSTRACT FROM AUTHOR]

Previous studies have shown that polydatin (Poly) confer cardioprotective effects. However, its underlying mechanisms remain elusive. This study showed that Poly (10 µM) treatment reversed the high glucose (HG)-induced decrease in acetylcholine-elicited vasodilation in aortas. Poly also improved the acetylcholine-induced vasodilation of aortic vessels isolated from diabetic rats. Meanwhile, Poly ameliorated the morphological damage of the thoracic aorta and improved the viability of HUVECs under HG conditions. Furthermore, analysis of the vasoprotective effect of Poly under HG conditions by transmission electron microscopy, Western blotting, and qPCR revealed that Poly improved endothelial pyroptosis through the NLRP3/Caspase/1-IL-1β pathway, enhanced dynamin-related protein 1-mediated mitochondrial fission, and increased the mitochondrial membrane potential under HG conditions. In conclusion, Poly restored acetylcholine-induced vasodilation impaired by HG incubation, which was associated with reduced oxidation, inflammation, and pyroptosis, the recovery of the mitochondrial membrane potential and maintenance of mitochondrial dynamic homeostasis of endothelial cells in the aortas. [ABSTRACT FROM AUTHOR]

With the discovery of magnetoreceptor mechanisms in animals, it materialized the novel applications of controlling cell and animal behaviors using magnetic fields. T cells have shown to be sensitive to magnetic fields. Here, we reported that exposure to moderate SMFs (static magnetic fields) led to increased granule and cytokine secretion as well as ATP production and mitochondrial respiration from CD8+ T cells. These effects were inhibited by knocking down the Uqcrb and Ndufs6 genes of mitochondrial respiratory chain, whose transcriptions were regulated by candidate magnetoreceptor genes Isca1 and Cry1/Cry2. SMF exposure also promoted CD8+ T cell granule and cytokine secretion and repressed tumor growth in vivo. SMFs enhanced CD8+ T cell cytotoxicity, and the adoptive transfer into tumor-bearing mice resulted in enhanced antitumor effects. Collectively, our study suggests that moderate SMFs enhance CD8+ T cell cytotoxicity by promoting mitochondrial respiration and promoted the antitumor function of CD8+ T cells. [ABSTRACT FROM AUTHOR]

Whether nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of mortality remains controversial. The present study aimed to clarify this issue. A systematic search of PubMed and Embase was conducted through October 2018. Studies providing risk estimates of NAFLD and mortality were included. A random-effects model was employed to calculate summary risk estimates. Subgroup analyses were performed to identify potential effect modifiers. Fourteen studies, involving 498501 subjects and 24234 deaths, were included. Patients with NAFLD were found to be at an elevated risk of all-cause mortality compared with those without [hazard ratio (HR) = 1.34; 95% confidence interval (CI) 1.17–1.54)]. The significantly positive association between NAFLD and all-cause mortality could not be modified by age, sex, follow-up duration, and adjustment for body mass index, diabetes, smoking or hypertension (all Pinteraction > 0.05), and remained in sensitivity analyses. No significant associations of NAFLD with CVD (HR = 1.13; 95% CI 0.92–1.38) and cancer (HR = 1.05; 95% CI 0.89–1.25) mortality were found. In conclusion, NAFLD is a predictor of increased all-cause mortality but not CVD and cancer mortality. These findings have important implications for decision making in public health and clinical practice, and highlight the urgency of developing effective treatments for NAFLD. [ABSTRACT FROM AUTHOR]

Multiple lines of evidence have shown that systemic lupus erythematosus (SLE) is attributable to both genetic and environmental factors. The product of GRB2 is a key factor in the activation of B cells and has been reported to be significantly associated with SLE in European populations. In the study, we aimed to investigate the relationship between GRB2 and SLE. A total of 1,710 Han Chinese women comprising 567 SLE patients and 1,143 controls were recruited to genotype 20 selected tagging SNPs. We tested the potential association between 13 clinical variables of SLE and the significant polymorphisms related to SLE. The eQTL data were extracted from the GTEx database to examine the functional consequences of the targeted SNPs. A significant association signal was identified between rs36023980 and SLE in both genotypic and allelic analyses (OR = 0.61, P = 0.0003). Complement inhibition was shown to be significantly associated with the genotypes of SNP rs36023980 in SLE patients (Pgenotype = 0.003). Further stratification analyses showed that the genetic association signal of SNP rs36023980 on SLE could only be identified in cases with complement inhibition. SNP rs36023980 was also identified to be significantly associated with the expression of GRB2 in whole blood and sun-exposed skin. In conclusion, our findings confirm the results from the previous GWAS and are the first to report the association of GRB2 with SLE in Han Chinese population. [ABSTRACT FROM AUTHOR]

Metal pollution in drinking water source has been under scrutiny as it seriously affects human health. This work examined 12 dissolved metals in the surface and overlying water of the Xiangjiang River, an important drinking water source in southern China, and characterized their distribution, identified their possible sources, assessed their toxicity load, and determined their potential ecological and health risk. No significant difference was found in the metal concentration between surface and overlying water. The average metal concentration fell in the order of Mg > Mn > Ba > Fe > Zn > As > Sb > Ni > Cd > V > Cr > Co, and all was lower than the safety threshold in the drinking water guideline of China. Anthropogenic activities were found to be the main source of metals from correlation analysis, principal component analysis (PCA), and cluster analysis (CA). According to the total heavy metal toxicity load (HMTL), 98.20%, 71.54%, 68.88%, and 7.97% of As, Cd, Sb, and Mn should be removed from the surface water to ensure safety. Most water samples from the surveyed area were found to have high ecological risk as was measured by the ecological risk index (RI). Health risk assessment showed that children are more susceptible than adults to the non-carcinogenic risk of dissolved metals, and the potential carcinogenic risk (CR) of As and Cd should be addressed. The results provide guidance for controlling the metal pollution of the Xiangjiang River and improving its quality as a drinking water source. [ABSTRACT FROM AUTHOR]

Metal pollution in drinking water source has been under scrutiny as it seriously affects human health. This work examined 12 dissolved metals in the surface and overlying water of the Xiangjiang River, an important drinking water source in southern China, and characterized their distribution, identified their possible sources, assessed their toxicity load, and determined their potential ecological and health risk. No significant difference was found in the metal concentration between surface and overlying water. The average metal concentration fell in the order of Mg > Mn > Ba > Fe > Zn > As > Sb > Ni > Cd > V > Cr > Co, and all was lower than the safety threshold in the drinking water guideline of China. Anthropogenic activities were found to be the main source of metals from correlation analysis, principal component analysis (PCA), and cluster analysis (CA). According to the total heavy metal toxicity load (HMTL), 98.20%, 71.54%, 68.88%, and 7.97% of As, Cd, Sb, and Mn should be removed from the surface water to ensure safety. Most water samples from the surveyed area were found to have high ecological risk as was measured by the ecological risk index (RI). Health risk assessment showed that children are more susceptible than adults to the non-carcinogenic risk of dissolved metals, and the potential carcinogenic risk (CR) of As and Cd should be addressed. The results provide guidance for controlling the metal pollution of the Xiangjiang River and improving its quality as a drinking water source. [ABSTRACT FROM AUTHOR]

Rheum emodi is a perennial herb and an important medicinal plant, with anthraquinones and flavonoids as its main bioactive compounds. However, there is little knowledge about the biosynthetic pathway of anthraquinones in rhubarbs. In this study, we qualitatively and quantitatively assessed 62 pharmacological metabolites in rhubarb using dynamic multiple reaction monitoring (dMRM) of triple-quadrupole mass spectrometry (QqQ-MS), including 21 anthraquinones, 17 flavonoids, 6 stilbenes, 12 gallate esters, 3 tannins, and 3 others. Besides, the metabolomics results showed significant differences among all the 60 metabolites, except for gallic acid and piceatannol-O-β-glucoside. The combined transcriptome data of R. palmatum L. (RPL) and R. officinale Baill. (ROB) showed that 21,691 unigenes were annotated in the metabolic pathways. Taken together, 17 differentially expressed genes (DEGs) were associated with the anthraquinone biosynthetic pathway. Additionally, a significant correlation between anthraquinone peak intensity and DEG expression level existed, validating that DEGs contribute to the anthraquinone biosynthetic pathway. RT-qPCR results showed that the cluster-14354.38156 gene may catalyze the O-methylation of emodin to produce physcion. This study provides a useful resource for further studies on secondary metabolism in rhubarb and the combination analysis of transcriptome and metabolome, which can help with the discovery of enzyme genes involved in metabolite biosynthesis. [ABSTRACT FROM AUTHOR]

This meta-analysis aims to determine the efficacy of Epigallocatechin gallate (EGCG) in the treatment of myocardial ischemia–reperfusion injury (MIRI) and summarize the mechanisms involved. Literature from six databases including Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wan-Fang database, and VIP database (VIP) were systematically searched. All the analysis were conducted by R. Twenty-five eligible studies involving 443 animals were included in this meta-analysis. The results indicated that compared to controls, EGCG exerts a cardioprotective effect by reducing myocardial infarct size (SMD = −4.06; 95% CI: −5.17, −2.94; P < 0.01; I2 = 77%). The funnel plot revealed publication bias. Moreover, EGCG significantly improves cardiac function, serum myocardial injury enzyme, and oxidative stress levels in MIRI animal models. This meta-analysis demonstrates that EGCG exhibits therapeutic promise in animal models of MIRI. However, further validation is still needed in large animal models and large clinical studies. [ABSTRACT FROM AUTHOR]

Approximately 20% of aged captive giant pandas (Ailuropoda melanoleuca) have cataracts that impair their quality of life. To identify potential biomarkers of cataract formation, we carried out a quantitative proteomics analysis of 10 giant pandas to find proteins differing in abundance between healthy and cataract-bearing animals. We identified almost 150 proteins exceeding our threshold for differential abundance, most of which were associated with GO categories related to extracellular localization. The most significant differential abundance was associated with components of the proteasome and other proteins with a role in proteolysis or its regulation, most of which were depleted in pandas with cataracts. Other modulated proteins included components of the extracellular matrix or cytoskeleton, as well as associated signaling proteins and regulators, but we did not find any differentially expressed transcription factors. These results indicate that the formation of cataracts involves a complex post-transcriptional network of signaling inside and outside lens cells to drive stress responses as a means to address the accumulation of protein aggregates triggered by oxidative damage. The modulated proteins also indicate that it should be possible to predict the onset of cataracts in captive pandas by taking blood samples and testing them for the presence or absence of specific protein markers. [ABSTRACT FROM AUTHOR]

Stressful life events (SLEs) closely correlates with depressive symptoms. Although vulnerability-stress model suggests SLEs interacted with dysfunctional attitudes (DA) to predict depression, the mediation role of DA is poorly understood. Therefore, this study intended to investigate the mediating role of DA and the moderating role of sex between SLEs and self-reported depression. A cross-sectional survey was conducted with a sample of 7769 Chinese college students. Participants were assessed in terms of self-reported SLEs, DA and depression variables. Results showed that there were significant sex differences in both SLE and DA. DA mediated the association between SLE and self-reported depression. The moderated mediation model analysis showed that the interaction of SLEs and sex significantly predicted DA in mediator variable model and self-reported depression in dependent variable model. Results indicated that DA partially mediated the association between SLEs and self-reported depression, and sex moderates the association between SLEs and both DA and self-reported depression, which females have bigger changes of DA and depressive symptoms across low and high levels of SLEs than males. [ABSTRACT FROM AUTHOR]

Northern dynasties (386–581 CE) of China witnessed extensive cultural contacts with the outside world. Several gold objects of this period indicate multiple culture influences. However, very few of them were testified by metallurgic analysis. The gold jewellery including a finger ring and an earring with exotic features were uncovered from the joint elite Sogdian tomb of Shi Jun and his wife of the Northern Zhou dynasty (557–581 CE) in Xi'an. The current study applied multiple non-destructive analyses to investigate the decorative techniques and materials of the two objects. The results showed that both ornaments were made of refined gold. Autogenous welding and brazing were employed for joining the granules of the earring, indicating different technical choices. More interestingly, niello made of silver sulfide was identified as an innovative technology to decorate the finger ring, presenting the earliest evidence of niello inlay in ancient China. It is noteworthy that powders of silver and sulfur were applied separately, deferring from the traditional method of silver sulfide being synthesised prior to being used. These findings help us gain insights into understanding the technical features of early Medieval gold jewellery, as well as the goldsmith's methods and intentions. [ABSTRACT FROM AUTHOR]

Convolvulus arvensis is a troublesome weed that is naturally tolerant to glyphosate. This weed tolerates glyphosate at a rate 5.1 times higher than that of glyphosate-susceptible Calystegia hederacea. Glyphosate-treated C. arvensis plants accumulated less shikimic acid than C. hederacea plants. The overexpression of EPSPS genes from the two species in transgenic Arabidopsis thaliana resulted in similar glyphosate tolerance levels. qPCR of genomic DNA revealed that the EPSPS copy number in C. arvensis was approximately 2 times higher than that in C. hederacea. Moreover, glyphosate treatment caused a marked increase in EPSPS mRNA in C. arvensis compared to C. hederacea. GUS activity analysis showed that the promoter of CaEPSPS (CaEPSPS-P) highly improved GUS expression after glyphosate treatment, while no obvious differential GUS expression was observed in ChEPSPS-P transgenic A. thaliana in the presence or absence of glyphosate. Based on the obtained results, two coexisting mechanisms may explain the natural glyphosate tolerance in C. arvensis: (i) high EPSPS copy number and (ii) specific promoter-mediated overexpression of EPSPS after glyphosate treatment. [ABSTRACT FROM AUTHOR]

To determine whether the traditional Chinese medicine Tongxinluo (TXL) is efficacious at retarding the progression of carotid atherosclerotic lesions, a total of 1,212 patients with a focal intima-media thickness (IMT) of ≥1.2 mm of the carotid arteries received TXL or placebo capsules in addition to current routine therapy. The primary outcome was between-group differences in annualized change in mean IMT of 12 sites of bilateral carotid arteries over 24 months. The secondary outcomes were between-group differences in plaque area, vascular remodeling index (RI), serum levels of lipids and high-sensitivity C-reactive protein, and a composite of first major cardiovascular events. The results showed that the annualized change in mean IMT in the TXL and placebo groups was −0.00095 (95% CI, −0.00330 to 0.00141) mm and 0.01312 (95% CI, 0.01076 to 0.01548) mm, respectively, with a difference between the two groups of −0.01407 (95% CI, −0.01740 to −0.01073) mm (P < 0.001). Compared with placebo, TXL treatment significantly reduced the change from baseline in the plaque area and RI, as well as the first major cardiovascular events. In conclusion, TXL retarded the progression of mean IMT, plaque area and vascular remodeling of the carotid artery with a good safety profile. [ABSTRACT FROM AUTHOR]

Vitiligo is a skin disease that affects 1% of the population worldwide. Both environmental and genetic factors contribute to the risk of vitiligo. GZMB encodes the enzyme Granzyme B, which plays an important role in cytotoxic T cell-induced apoptosis, and it has been considered one of the candidate genes for vitiligo because of its connections with human immune system. Overall, 3,120 study subjects with Chinese Han ancestry were recruited, and 15 pre-selected SNPs of GZMB were genotyped. Genetic association analyses were performed to evaluate the genetic risk of these SNPs to vitiligo. Further bioinformatic analyses were conducted to examine the potential biological function of targeted SNPs. The SNP rs8192917, a non-synonymous coding SNP, was identified to be significantly associated with the disease status of vitiligo, with OR = 1.39 and P = 1.92 × 10−8. Differences in the association signal can be observed in the stratification analyses of multiple clinical variables. Our positive results provide additional supportive evidence that GZMB gene is an important locus for vitiligo in Han Chinese population. [ABSTRACT FROM AUTHOR]

A single base changes causing a change to the amino acid sequence of the encoded protein, which is defined as non-synonymous single nucleotide polymorphisms (nsSNPs). Many of the nsSNPs can cause disease, and these nsSNPs are considered as pathogenic mutations. In the study, the high-risk nsSNPs of WFS1 and their influence on the structure and function of wolframin protein were predicted by multiple bioinformatics software. We obtained 13 high-risk nsSNPs of WFS1. All the 13 high-risk nsSNPs are highly conserved residues with a conservative score of 9 or 8 and mostly may cause a decrease in protein stability. The high-risk nsSNPs have an important effect on not only amino acid size, charge and hydrophobicity, but also protein's spatial structure. Among these, 11 nsSNPs had been previously published or cited and 2 nsSNPs (G695S and E776K) had not been reported to date. The two novel variants increased or decreased hydrogen bonds. In conclusion, through different computational tools, it is presumed that the mechanism of pathogenic WFS1 nsSNPs should include the changes of physicochemical properties, significant structural changes and abnormal binding with functional partners. We accomplished the computational-based screening and analysis for deleterious nsSNPs in WFS1, which had important reference value and could contribute to further studies of the mechanism of WFS1 related disease. The computational analysis has many advantages, but the results should be identified by further experimental studies in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Soybean agglutinin (SBA) is a main anti-nutritional factor in soybean. SBA exhibits its anti-nutritional functions by binding to intestinal epithelial cells. Keratin8 (KRT8), Keratin18 (KRT18) and Actin (ACTA) are the representative SBA-specific binding proteins. Such cytoskeletal proteins act a crucial role in different cell activities. However, limited reports reveal what the signal transduction pathway of apoptosis caused by SBA when binding to KRT8, KRT18 and ACTA. We aimed to evaluate the effects of SBA on cell apoptosis and the expression of the cytoskeletal protein (KRT8, KRT18 and ACTA), reveal the roles of these cytoskeletal proteins or their combinations on SBA-induced cell apoptosis in IPEC-J2 cell line, evaluate the influences of SBA on the mitochondria, endoplasmic reticulum stress and death receptor-mediated apoptosis signal pathway and to show the roles of KRT8, KRT18 and ACTA in different apoptosis signal pathways induced by SBA. The results showed that SBA induced the IPEC-J2 cell apoptosis and decreased the mRNA expression of KRT8, KRT18 and ACTA (p < 0.05). The degree of effect of three cytoskeleton proteins on cell apoptosis was ACTA > KRT8 > KRT18. The roles of these three cytoskeletal proteins on IPEC-J2 apoptotic rates had a certain accumulation effect. SBA up-regulated mitochondrial fission variant protein (FIS1) and fusion protein (Mfn2) promoted CytC and AIF in mitochondria to enter the cytoplasm, activated caspase-9 and caspase-3, damaged or declined mitochondrial function and reduced ATP synthesis (p < 0.05). Also, SBA up-regulated the expression of GRP78, XBP-1, eIF2α, p-eIF2α and CHOP (p < 0.05), down-regulated the expression level of ASK1 protein (p < 0.05). SBA led to the recruitment of FADD to the cytoplasmic membrane and increased the expression of FasL, resulting in caspase-8 processing. SBA up-regulated the expression level of Bax protein and decreased cytosolic Bcl-2 and Bid (p < 0.05). In addition, there was a significant negative correlation between the gene expression of cytoskeleton proteins and apoptosis, as well as the expression of key proteins of apoptosis-related signal transduction pathways. In conclusion, SBA induced the activation of the mitochondria, endoplasmic reticulum stress and the death receptor-mediated apoptosis signal pathway and the crosstalk between them. The effect of SBA on these three pathways was mainly exhibited via down-regulation of the mRNA expression of the three cytoskeletal expressions. This study elucidates the molecular mechanism and signaling pathway of SBA that lead to apoptosis from the perspective of cell biology and molecular biology and provides a new perspective on the toxicity mechanism of other food-derived anti-nutrients, medical gastrointestinal health and related cancer treatment. [ABSTRACT FROM AUTHOR]