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BACKGROUND: Although ambient temperature has been linked with injury incidence, there have been few nationwide studies to quantify the temperature-related risk and burden of cause-specific injury hospitalizations. Additionally, the impact of human-induced climate change to injury burden remains unknown. OBJECTIVES: Our objectives are to examine the associations between ambient temperature and injury hospitalizations from various causes and to quantify the contribution of human-induced warming to the heat-related burden. METHODS: We collected injury hospitalization data from a nationwide hospital-based registry in China during 2000–2019. Using a time-stratified case-crossover design, we investigated the associations between daily mean temperature (°C) and cause-specific injury hospitalizations. We also quantified the burden of heat-related injuries under the scenarios with and without anthropogenic forcing, using the Detection and Attribution Model Intercomparison Project to assess the contribution of human-induced warming. RESULTS: Our study included a total of 988,087 patients with hospitalization records for injuries. Overall, compared to the temperature at minimum risk of hospitalization (-12:1°C), the relative risk of hospitalization at extreme hot temperature (30.8°C, 97.5th percentile) was 1.18 [95% confidence interval (CI): 1.14, 1.22], with an approximately linear association between temperature and hospitalization. Vulnerability to heat-related injuries was more pronounced among males, young (<18 years of age) or middle-aged (45–64 years of age) individuals, and those living in the North. The heatrelated attributable fraction increased from 23.2% in the 2000s to 23.6% in the 2010s, with a corresponding increase in the contribution of humaninduced change over time. In the 2010s, the heat-related attributable fractions for specific causes of injury ranged from 12.4% to 54.4%, with humaninduced change accounting for 6.7% to 10.6% of the burden. DISCUSSION: This nationwide study presents new evidence of significant associations between temperature and cause-specific injury hospitalizations in China and highlights the increasing contribution of human-induced warming to the injury burden. [ABSTRACT FROM AUTHOR]

Background: The preoperative inflammatory condition significantly influences the prognosis of malignancies. We aimed to investigate the potential significance of preoperative inflammatory biomarkers in forecasting the long-term results of lung carcinoma after microwave ablation (MWA). Method: This study included patients who received MWA treatment for lung carcinoma from Jan. 2012 to Dec. 2020. We collected demographic, clinical, laboratory, and outcome information. To assess the predictive capacity of inflammatory biomarkers, we utilized the area under the receiver operating characteristic curve (AUC-ROC) and assessed the predictive potential of inflammatory biomarkers in forecasting outcomes through both univariate and multivariate Cox proportional hazard analyses. Results: A total of 354 individuals underwent MWA treatment, of which 265 cases were included in this study, whose average age was 69.1 ± 9.7 years. The AUC values for the Systemic Inflammatory Response Index (SIRI) to overall survival (OS) and disease-free survival (DFS) were 0.796 and 0.716, respectively. The Cox proportional hazards model demonstrated a significant independent association between a high SIRI and a decreased overall survival (hazard ratio [HR]=2.583, P<0.001). Furthermore, a high SIRI independently correlated with a lower DFS (HR=2.391, P<0.001). We developed nomograms utilizing various independent factors to forecast the extended prognosis of patients. These nomograms exhibited AUC of 0.900, 0.849, and 0.862 for predicting 1-year, 3-year, and 5-year OS, respectively. Additionally, the AUC values for predicting 1-year, 3-year, and 5-year DFS were 0.851, 0.873, and 0.883, respectively. Conclusion: SIRI has shown promise as a valuable long-term prognostic indicator for forecasting the outcomes of lung carcinoma patients following MWA. [ABSTRACT FROM AUTHOR]

Background: Previous research has yielded conflicting results on the link between epilepsy risk and lipid-lowering medications. The aim of this study is to determine whether the risk of epilepsy outcomes is causally related to lipidlowering medications predicted by genetics. Methods: We used genetic instruments as proxies to the exposure of lipidlowering drugs, employing variants within or near genes targeted by these drugs and associated with low-density lipoprotein cholesterol (LDL cholesterol) from a genome-wide association study. These variants served as controlling factors. Through drug target Mendelian randomization, we systematically assessed the impact of lipid-lowering medications, including HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and Niemann-Pick C1-like 1 (NPC1L1) inhibitors, on epilepsy. Results: The analysis demonstrated that a higher expression of HMGCR was associated with an elevated risk of various types of epilepsy, including all types (OR = 1.17, 95% CI:1.03 to 1.32, p = 0.01), focal epilepsy (OR = 1.24, 95% CI:1.08 to 1.43, p = 0.003), and focal epilepsy documented with lesions other than hippocampal sclerosis (OR = 1.05, 95% CI: 1.01 to 1.10, p = 0.02). The risk of juvenile absence epilepsy (JAE) was also associated with higher expression of PCSK9 (OR = 1.06, 95% CI: 1.02 to 1.09, p = 0.002). For other relationships, there was no reliable supporting data available. Conclusion: The drug target MR investigation suggests a possible link between reduced epilepsy vulnerability and HMGCR and PCSK9 inhibition. [ABSTRACT FROM AUTHOR]

Background: Several studies have pointed to the critical role of gut microbiota (GM) and their metabolites in Hirschsprung disease (HSCR) pathogenesis. However, the detailed causal relationship between GM and HSCR remains unknown. Methods: In this study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between GM and HSCR, based on the MiBioGen Consortium’s genome-wide association study (GWAS) and the GWAS Catalog’s HSCR data. Reverse MR analysis was performed subsequently, and the sensitivity analysis, Cochran’s Q-test, MR pleiotropy residual sum, outlier (MR-PRESSO), and the MR-Egger intercept were used to analyze heterogeneity or horizontal pleiotropy. 16S rDNA sequencing and targeted mass spectrometry were developed for initial validation. Results: In the forward MR analysis, inverse-variance weighted (IVW) estimates suggested that Eggerthella (OR: 2.66, 95%CI: 1.23–5.74, p =  0.01) was a risk factor for HSCR, while Peptococcus (OR: 0.37, 95%CI: 0.18–0.73, p =  0.004), Ruminococcus2 (OR: 0.32, 95%CI: 0.11–0.91, p =  0.03), Clostridiaceae1 (OR: 0.22, 95%CI: 0.06–0.78, p =  0.02), Mollicutes RF9 (OR: 0.27, 95%CI: 0.09– 0.8, p =  0.02), Ruminococcaceae (OR: 0.16, 95%CI: 0.04–0.66, p =  0.01), and Paraprevotella (OR: 0.45, 95%CI: 0.21–0.98, p =  0.04) were protective factors for HSCR, which had no heterogeneity or horizontal pleiotropy. However, reverse MR analysis showed that HSCR (OR: 1.02, 95%CI: 1–1.03, p =  0.049) is the risk factor for Eggerthella. Furthermore, some of the above microbiota and shortchain fatty acids (SCFAs) were altered in HSCR, showing a correlation. Conclusion: Our analysis established the relationship between specific GM and HSCR, identifying specific bacteria as protective or risk factors. Significant microbiota and SCFAs were altered in HSCR, underlining the importance of further study and providing new insights into the pathogenesis and treatment. [ABSTRACT FROM AUTHOR]

The economic and health significance of quinoa is steadily growing on a global scale. Nevertheless, the primary obstacle to achieving high yields in quinoa cultivation is pre-harvest sprouting (PHS), which is intricately linked to seed dormancy. However, there exists a dearth of research concerning the regulatory mechanisms governing PHS. The regulation of seed germination by various plant hormones has been extensively studied. Consequently, understanding the mechanisms underlying the role of endogenous hormones in the germination process of quinoa seeds and developing strategies to mitigate PHS in quinoa cultivation are of significant research importance. This study employed the HPLC-ESI-MS/MS internal standard and ELISA method to quantify 8 endogenous hormones. The investigation of gene expression changes before and after germination was conducted using RNA-seq analysis, leading to the discovery of 280 differentially expressed genes associated with the regulatory pathway of endogenous hormones. Additionally, a correlation analysis of 99 genes with significant differences identified 14 potential genes that may act as crucial "transportation hubs" in hormonal interactions. Through the performance of an analysis on the modifications in hormone composition and the expression of associated regulatory genes, we posit a prediction that implies the presence of a negative feedback regulatory mechanism of endogenous hormones during the germination of quinoa seeds. This mechanism is potentially influenced by the unique structure of quinoa seeds. To shed light on the involvement of endogenous hormones in the process of quinoa seed germination, we have established a regulatory network. This study aims to offer innovative perspectives on the breeding of quinoa varieties that exhibit resistance to PHS, as well as strategies for preventing PHS. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease characterized by extracellular senile plaques including amyloid-β peptides and intracellular neurofibrillary tangles consisting of abnormal Tau. Depression is one of the most common neuropsychiatric symptoms in AD, and clinical evidence demonstrates that depressive symptoms accelerate the cognitive deficit of AD patients. However, the underlying molecular mechanisms of depressive symptoms present in the process of AD remain unclear. Methods: Depressive-like behaviors and cognitive decline in hTau mice were induced by chronic restraint stress (CRS). Computational prediction and molecular experiments supported that an asparagine endopeptidase (AEP)- derived Tau fragment, Tau N368 interacts with peroxisome proliferator-activated receptor delta (PPAR-δ). Further behavioral studies investigated the role of Tau N368-PPAR-δ interaction in depressive-like behaviors and cognitive declines of AD models exposed to CRS. Results: We found that mitochondrial dysfunction was positively associated with depressive-like behaviors and cognitive deficits in hTau mice. Chronic stress increased Tau N368 and promoted the interaction of Tau N368 with PPAR-δ, repressing PPAR-δ-mediated transactivation in the hippocampus of mice. Then we predicted and identified the binding sites of PPAR-δ. Finally, inhibition of AEP, clearance of Tau N368 and pharmacological activation of PPAR-δ effectively alleviated CRS-induced depressive-like behaviors and cognitive decline in mice. Conclusion: These results demonstrate that Tau N368 in the hippocampus impairs mitochondrial function by suppressing PPAR-δ, facilitating the occurrence of depressive-like behaviors and cognitive decline. Therefore, our findings may provide new mechanistic insight in the pathophysiology of depression-like phenotype in mouse models of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Object: To investigate the efficacy and safety of tyrosine kinase inhibitors (TKIs: sorafenib and lenvatinib) plus PD-1 inhibitor (camrelizumab) versus TKIs alone in transarterial chemoembolization-refractory (TACE-refractory) hepatocellular carcinoma (HCC). Materials and methods: Data of TACE-refractory HCC patients treated with TACE+TKIs+PD-1 inhibitor (TACE+TKIs+PD-1group) (n=57) or TACE+TKIs (TACE +TKIs group) (n=50) from January 2019 to January 2022 were retrospectively collected and analyzed. The differences in overall survival (OS), progression-free survival (PFS), tumor responses (based on modified Response Evaluation Criteria in Solid Tumors) and adverse events (AEs) were compared between the two groups. Potential factors affecting OS and PFS were evaluated by univariate and multivariate analyses. Results: Compared with the TKIs group, both PFS and OS were prolonged in the TACE+TKIs+PD-1 group (median PFS: 7 months vs. 5 months, P=0.007; median OS: 17 months vs. 11 months, P=0.002). In multivariate analysis, tumor size and treatment were independent prognostic factors for PFS and OS. The incidence and severity of AEs related to the treatment between the two groups showed no significant difference. Conclusion: The treatment of TACE combined with TKIs plus camrelizumab demonstrated promising efficacy and safety in TACE-refractory HCC. [ABSTRACT FROM AUTHOR]

Background: Hepatoblastoma (HB) is the most common liver tumor in children with easy metastasis. The emergence of ferroptosis as a novel form of cell death has gained increased attention in various human cancers. However, the roles of ferroptosis-related (FR) genes in HB remain elusive Methods: The GSE133039, GSE131329, and GSE81928 datasets were utilized for screening core FR genes in HB. Through Lasso regression analysis and using the support vector machine recursive feature elimination (SVM-RFE) algorithm, three candidate FR genes were obtained for characterizing HB. Their expression patterns and their clinical associations were explored through the 'Limma' R package, and their diagnostic potential was evaluated using ROC curves. Nitric oxide synthase 2 (NOS2) emerged as a candidate for further analyses. The CIBERSORT algorithm and GSEA dataset were used to respectively investigate the immune and metabolism effects of NOS2; the former was validated through immunofluorescence. The GSDC database was employed to analyze the correlation between NOS2 expression and the therapeutic efficacy of multiple drugs. PCR, Western blotting, colony formation assays, and Transwell experiments, were used to determine biological functions of NOS2 in HB cells. Potential upstream transcription factors of NOS2 were predicted through the TRRUST, hTFtarget, GeneCards, and JASPAR databases. Results: NQO1, SLC1A4, and NOS2 were identified as potential genes in HB and found to be significantly upregulated in tumor samples. Nevertheless, only NOS2 was closely associated with HB clinicopathological characteristics; high NOS2 expression indicated poor prognosis, metastatic tendency, and late clinical stage. Immune analyses indicated that high NOS2 expression was concomitant with decreased infiltration levels of CD8+ T cells but increased infiltration levels of macrophages. GSEA revealed that NOS2 failed to affect the enrichments of glycolysis, fatty acid metabolism, and cholesterol biosynthesis in HB. Moreover, NOS2 was positively correlated with the IC50 values of trametinib, lapatinib, and cisplatin. NOS2 overexpression promoted the proliferation, migration and invasion of HepG2 and HuH-6 cells. JUND was identified as a potential transcriptional regulator of NOS2 by binding to its promoter (5'- TTCTGACTCTTTT-3'). Conclusion: NOS2 plays a significant role in HB clinical assessments and holds promise as a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Pre-harvest sprouting (PHS) will have a serious effect both on the yield and quality of quinoa (Chenopodium quinoa Willd.). It is crucial to select and breed quinoa varieties with PHS resistance and excellent agronomic traits for guidance production and utilization of quinoa. A comprehensive evaluation of the PHS resistance and agronomic traits of 37 species of quinoa resources was conducted in Chengdu Plain. The evaluation used various methods, including grain germination rate (GR), grain germination index (GI), total spike germination rate (SR), total grain germination index (SI), grey correlation analysis (GCA), cluster analysis and correlation analysis. Results showed significant differences in PHS resistance and agronomic traits amongst the 37 quinoa resources. CDU-23 was most resistant to PHS within 24 h, with a germination rate of 2.67% and 0% according to the GR and SR results, respectively. However, in the same time, CDU-31 showed the maximum susceptibility to PHS based on the SR of 31.07%, while CDU-34 was the most sensitive to PHS according to the GR of 100%. The comprehensive evaluation identified one and nine kinds of high resistance species for grain and whole spike germination, respectively. In both cases, the coefficients of variation (CV) for these parameters were 34.78% and 82.13%, respectively. GCA results showed that the magnitude of the association between each trait and yield in the thirty-seven quinoa resources was in the following order: thousand grain weight > seed length > seed area > seed width. Although the seed weight of CDU-18 reached 3.7010 g, the seed weight of CDU-5 was only 1.6030 g. However, the size of the seeds, their width and area did not correlate with their 1000-grain weight. There was a complex correlation between PHS resistance index and agronomic traits. Based on clustering analysis, thirty-seven quinoa resources were classified into three taxa. It was found that various taxa differed in PHS resistance and agronomic traits. Several comparisons of the aggregated data led to the selection of five varieties of quinoa, of which CDU-2 presented excellent agronomic qualities and strong PHS resistance. This study has provided a reference for breeding excellent quinoa varieties with PHS resistance. [ABSTRACT FROM AUTHOR]

Dual-specificity phosphatase 12 (DUSP12) is abnormally expressed under various pathological conditions and plays a crucial role in the pathological progression of disorders. however, the role of DUSP12 in cerebral ischaemia/reperfusion injury has not yet been investigated. this study explored the possible link between DUSP12 and cerebral ischaemia/reperfusion injury using an oxygen-glucose deprivation/ reoxygenation (OGD/R) model. Marked decreases in DUSP12 levels have been observed in cultured neurons exposed to OGD/R. DUSP12-overexpressed neurons were resistant to OGD/R-induced apoptosis and inflammation, whereas DUSP12-deficient neurons were vulnerable to OGD/R-evoked injuries. Further investigation revealed that DUSP12 overexpression or deficiency affects the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) in neurons under OGD/R conditions. Moreover, blockade of ASK1 diminished the regulatory effect of DUSP12 deficiency on JNK and p38 MAPK activation. in addition, DUsP12-deficiency-elicited effects exacerbating neuronal OGD/R injury were reversed by ASK1 blockade. in summary, DUSP12 protects against neuronal OGD/R injury by reducing apoptosis and inflammation through inactivation of the ASK1-JNK/p38 MAPK pathway. these findings imply a neuroprotective function for DUSP12 in cerebral ischaemia/reperfusion injury. [ABSTRACT FROM AUTHOR]

Numerous insects including pests and beneficial species undertake windborne migrations over hundreds of kilometers. In East Asia, climate-induced changes in large-scale atmospheric circulation systems are affecting wind-fields and precipitation zones and these, in turn, are changing migration patterns. We examined the consequences in a serious rice pest, the brown planthopper (BPH, Nilaparvata lugens) in East China. BPH cannot overwinter in temperate East Asia, and infestations there are initiated by several waves of windborne spring or summer migrants originating from tropical areas in Indochina. The East Asian summer monsoon, characterized by abundant rainfall and southerly winds, is of critical importance for these northward movements. We analyzed a 42-year dataset of meteorological parameters and catches of BPH from a standardized network of 341 light-traps in South and East China. We show that south of the Yangtze River during summer, southwesterly winds have weakened and rainfall increased, while the summer precipitation has decreased further north on the Jianghuai Plain. Together, these changes have resulted in shorter migratory journeys for BPH leaving South China. As a result, pest outbreaks of BPH in the key rice-growing area of the Lower Yangtze River Valley (LYRV) have declined since 2001. We show that these changes to the East Asian summer monsoon weather parameters are driven by shifts in the position and intensity of the Western Pacific subtropical high (WPSH) system that have occurred during the last 20 years. As a result, the relationship between WPSH intensity and BPH immigration that was previously used to predict the size of the immigration to the LYRV has now broken down. Our results demonstrate that migration patterns of a serious rice pest have shifted in response to the climate-induced changes in precipitation and wind pattern, with significant consequences for the population management of migratory pests. [ABSTRACT FROM AUTHOR]

Objective: Ginkgolide B (GB) possesses anti-inflammatory, antioxidant, and anti-apoptotic properties against neurotoxicity induced by amyloid beta (Aβ), but the potential neuroprotective effects of GB in Alzheimer's therapies remain elusive. We aimed to conduct proteomic analysis of Aβ1-42 induced cell injury with GB pretreatment to uncover the underlying pharmacological mechanisms of GB. Methods: Tandem mass tag (TMT) labeled liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was applied to analyze protein expression in Aβ1-42 induced mouse neuroblastoma N2a cells with or without GB pretreatment. Proteins with fold change >1.5 andp < 0.1 from two independent experiments were regarded as differentially expressed proteins (DEPs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to analyze the functional annotation information of DEPs. Two key proteins osteopontin (SPP1) and ferritin heavy chain 1 (FTH1) were validated in another three samples using western blot and quantitative real-time PCR. Results: We identified a total of 61 DEPs in GB treated N2a cells, including 42 upregulated and 19 downregulated proteins. Bioinformatic analysis showed that DEPs mainly participated in the regulation of cell death and ferroptosis by down-regulating SPP1 protein and up-regulating FTH1 protein. Conclusions: Our findings demonstrate that GB treatment provides neuroprotective effects on Aβ1-42 induced cell injury, which may be related to the regulation of cell death and ferroptosis. The research puts forward new insights into the potential protein targets of GB in the treatment of Alzheimer's disease (AD). [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually. The current treatment regime is long and expensive, and missed doses contribute to drug resistance. Therefore, development of new anti-TB drugs remains one of the highest public health priorities. Mtb has evolved a complex cell envelope that represents a formidable barrier to antibiotics. The Mtb cell envelop consists of four distinct layers enriched for Mtb specific lipids and glycans. Although the outer membrane, comprised of mycolic acid esters, has been extensively studied, less is known about the plasma membrane, which also plays a critical role in impacting antibiotic efficacy. The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. However, the role of PIMs in the structure and function of the membrane remains elusive. Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. To further validate the model, we tested known anti-TB drugs and demonstrated that our models agree with experimental results. Thus, our work sheds new light on the organization of the mycobacterial plasma membrane. This paves the way for future studies on antibiotic development and understanding Mtb membrane protein function. [ABSTRACT FROM AUTHOR]

Open-source software (OSS) licenses dictate the conditions, which should be followed to reuse, distribute, and modify software. Apart from widely-used licenses such as the MIT License, developers are also allowed to customize their own licenses (called custom license), whose descriptions are more flexible. The presence of such various licenses imposes challenges to understand licenses and their compatibility. To avoid financial and legal risks, it is essential to ensure license compatibility when integrating third-party packages or reusing code accompanied with licenses. In this work, we propose LiDetector, an effective tool that extracts and interprets OSS licenses (including both official licenses and custom licenses), and detects license incompatibility among these licenses. Specifically, LiDetector introduces a learning-based method to automatically identify meaningful license terms from an arbitrary license, and employs Probabilistic Context-Free Grammar (PCFG) to infer rights and obligations for incompatibility detection. Experiments demonstrate that LiDetector outperforms existing methods with 93.28% precision for term identification, and 91.09% accuracy for right and obligation inference, and can effectively detect incompatibility with 10.06% FP rate and 2.56% FN rate. Furthermore, with LiDetector, our large-scale empirical study on 1,846 projects reveals that 72.91% of the projects are suffering from license incompatibility, including popular ones such as the MIT License and the Apache License. We highlighted lessons learned from perspectives of different stakeholders and made all related data and the replication package publicly available to facilitate follow-up research. [ABSTRACT FROM AUTHOR]

Background: Preimplantation genetic test for monogenic disorders (PGT-M) has been used to select genetic disease-free embryos for implantation during in vitro fertilization (IVF) treatment. However, embryos tested by PGT-M have risks of harboring chromosomal aneuploidy. Hence, a universal method to detect monogenic diseases and genomic imbalances is required. Methods: Here, we report a novel PGT-A/M procedure allowing simultaneous detection of monogenic diseases and genomic imbalances in one experiment. Library was prepared in a special way that multiplex polymerase chain reaction (PCR) was integrated into the process of whole genome amplification. The resulting library was used for one-step low-pass whole genome sequencing (WGS) and high-depth target enrichment sequencing (TES). Results: The TAGs-seq PGT-A/M was first validated with genomic DNA (gDNA) and the multiple displacement amplification (MDA) products of a cell line. Over 90% of sequencing reads covered the whole-genome region with around 0.3-0.4 × depth, while around 5.4%-7.3% of reads covered target genes with >10000 × depth. Then, for clinical validation, 54 embryos from 8 women receiving PGT-M of β-thalassemia were tested by the TAGs-seq PGT-A/M. In each embryo, an average of 20.0 million reads with 0.3 × depth of the whole-genome region was analyzed for genomic imbalance, while an average of 0.9 million reads with 11260.0 × depth of the target gene HBB were analyzed for β-thalassemia. Eventually, 18 embryos were identified with genomic imbalance with 81.1% consistency to karyomapping results. 10 embryos contained β-thalassemia with 100% consistency to conventional PGT-M method. Conclusion: TAGs-seq PGT-A/M simultaneously detected genomic imbalance and monogenic disease in embryos without dramatic increase of sequencing data output. [ABSTRACT FROM AUTHOR]

Scoparone (SCO) is known to have curative effect of alleviating liver injury. The purpose of this study was to observe the therapeutic effect and possible mechanism of SCO against high-fat diet (HFD) induced non-alcoholic liver disease (NAFLD) through in vivo experiments and RNA sequencing. Male Kunming mice were fed with HFD for 8 weeks to establish a mouse model of NAFLD, and SCO was used to treat NAFLD. Histopathology and biochemical indicators were used to evaluate the liver injury and the efficacy of SCO. RNA sequencing analysis was performed to elucidate the hepatoprotective mechanism of SCO. Finally, the differentially expressed genes of cholesterol synthesis and fatty acid (triglyceride) synthesis pathways were verified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The histopathological results showed that HFD could lead to significant steatosis in mice, while SCO could alleviate liver steatosis remarkably in NAFLD mice. The determination of biochemical indicators showed that SCO could inhibit the increased serum transaminase activity and liver lipid level induced by HFD. RNA sequencing analysis of liver tissues found that 2742 and 3663 genes were significantly changed by HFD and SCO, respectively. SCO reversed the most of genes involved in cholesterol synthesis and fatty acid (triglyceride) metabolism induced by HFD. the results of the validation experiment were mostly consistent with the RNA sequencing. SCO alleviated liver injury and steatosis in NAFLD mice, which may be closely related to the regulation of cholesterol and fatty acid (triglyceride) metabolism. [ABSTRACT FROM AUTHOR]

Kinesiophobia is related with adverse outcomes in various diseases, but it has not been studied in chronic heart failure (CHF). Fatigue often causes movement avoidance in CHF patients, and thereby, leads to a worsening of condition and increasing severity of symptom burden. The purpose of this study was to explore kinesiophobia and its related factors and the relationship between the kinesiophobia and fatigue in CHF patients. We recruited (n = 236) inpatients with CHF from October 2020 to March 202 I and administered a self-designed demographic questionnaire, the Chinese version of the Tampa Scale for Kinesiophobia Heart (TSK-Heart-C), and the Multidimensional Fatigue Inventory (MFI-20), and collected related electronic medical record data. Findings revealed that 63% of participants had kinesiophobia. There was a moderate correlation between fatigue and kinesiophobia (r=.49, p <.01). Educational background, monthly family income, disease course, and fatigue explained 41%of the variance in kinesiophobia, of which fatigue independently accounted for 9%. [ABSTRACT FROM AUTHOR]

Purposes: We aimed to characterize the USH2A genotypic spectrum in a Chinese cohort and provide a detailed genetic profile for Chinese patients with USH2A-IRD. Methods: We designed a retrospective study wherein a total of 1,334 patients diagnosed with IRD were included as a study cohort, namely 1,278 RP and 56 USH patients, as well as other types of IEDs patients and healthy family members as a control cohort. The genotype-phenotype correlation of all participants with USH2A variant was evaluated. Results: Etiological mutations in USH2A, the most common cause of RP and USH, were found in 16.34% (n = 218) genetically solved IRD patients, with prevalences of 14.87% (190/1,278) and 50% (28/56). After bioinformatics and QC processing, 768 distinct USH2A variants were detected in all participants, including 136 disease-causing mutations present in 665 alleles, distributed in 5.81% of all participants. Of these 136 mutations, 43 were novel, nine were founder mutations, and two hot spot mutations with allele count =10. Furthermore, 38.5% (84/218) of genetically solved USH2A-IRD patients were caused by at least one of both c.2802T>G and c.8559-2 A>G mutations, and 36.9% and 69.6% of the alleles in the RP and USH groups were truncating, respectively. Conclusion: USH2A-related East Asian-specific founder and hot spot mutations were the major causes for Chinese RP and USH patients. Our study systematically delineated the genotype spectrum of USH2A-IRD, enabled accurate genetic diagnosis, and provided East Asian and other ethnicities with baseline data of a Chinese origin, which would better serve genetic counseling and therapeutic targets selection. [ABSTRACT FROM AUTHOR]

The education level and social participation of contemporary Chinese women have reached their historical peak; work is fast becoming the dominant theme of their lives. However, influenced by traditional attitudes, women are still expected to undertake the main family care tasks, thus, facing dual constraints of family and work, which seriously affect their life happiness. Based on the theory of subjective well-being and feminist geography, this study used the questionnaire survey and in-depth interview results of professional females in Dalian High-tech Industrial Zone as basic data to explore the life satisfaction and emotional cognition in intra- and extra-household life of professional females (Professional females: In this study, they are the women who have received formal education and currently have full-time and steady job (including regular employees in the national systems and those who have signed labor contracts with labor units).). The following results were obtained: (1) Most professional females reported higher life satisfaction in intra- rather than extra-household life, and it varied with individual attributes, reflecting the internal differences among them. (2) The positive emotions of professional females came from the company of family and friends in intra-household life, and satisfaction with the working environment and treatment in extra-household life. (3) The negative emotions came from the pressure of "marriage," "birth," and other traditional concepts in intra-household life. In extra-household life, it came from the health problems caused by working stress, interpersonal problems and gender inequality in the workplace, and the anxiety of age and future career development. Therefore, this study committed to revealing the living status and subjective feelings of contemporary professional females in China, hoping to improve women's life quality and enhance their life happiness from a theoretical and realistic perspective. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy frequently fails because most carcinomas have few T cells, suggesting that cancers can suppress T cell infiltration. Here, we show that cancer cells of human pancreatic ductal adenocarcinoma (PDA), colorectal cancer, and breast cancer are coated with transglutaminase-2 (TGM2)-dependent covalent CXCL12-keratin-19 (KRT19) heterodimers that are organized as filamentous networks. Since a dimeric form of CXCL12 suppresses the motility of human T cells, we determined whether this polymeric CXCL12-KRT19 coating mediated T cell exclusion. Mouse tumors containing control PDA cells exhibited the CXCL12-KRT19 coating, excluded T cells, and did not respond to treatment with anti-PD-1 antibody. Tumors containing PDA cells not expressing either KRT19 or TGM2 lacked the CXCL12-KRT19 coating, were infiltrated with activated CD8+ T cells, and growth was suppressed with anti-PD-1 antibody treatment. Thus, carcinomas assemble a CXCL12-KRT19 coating to evade cancer immune attack. [ABSTRACT FROM AUTHOR]

Nature-based climate solutions are playing an increasingly significant role under the long-term goal of carbon-neutrality. Carbon storage and sequestration are important service functions of the ecosystem, but these potential in neutralizing carbon emissions at provincial level is rarely evaluated. Here we take Qinghai province in northwest China to conduct a case study, as it possesses the country's best solar and wind energy resource, one of the largest ecosystem therefore great carbon sequestration potential, and has been strived to set off a carbon neutral pilot in China. We combine the carbon density observation database and the land use/cover change (LUCC) data with the InVEST model to study the spatiotemporal dynamics of the carbon stock for Qinghai's terrestrial ecosystem, which are then compared to the energy related carbon emissions. The results reveal a tale of two stages, as Qinghai transformed from being a fast growing carbon emitter during 2000e2015 to be a carbon neutral player during the 13th Five-Year Plan (2015e2020). Land management interventions can contribute to climate change mitigation through avoided emissions from ecosystem degradation, and through negative emissions via biomass growth and, soil carbon sequestration. The duel-effort of greening the power grid and enhancing the ecosystem carbon sequestration is critical in achieving Qinghai's transition. Practices like agrophotovoltaic power plant in the barren or degraded lands have demonstrated great synergies of harvesting solar energy and enhancing ecosystem carbon sequestration, and offer good example for regions alike. [ABSTRACT FROM AUTHOR]

We use the earnings forecast revisions during the period 2005–2019 to study the performance of confirmatory bias in China. As we have found, analysts are less likely to make earnings forecast revisions when the latest two signals are opposite or different from their previous beliefs. In addition, we find confirmatory bias has a significantly positive influence on analysts’ forecast dispersions, especially when new signals are negative. Finally, we extend the practical significance by combining confirmatory bias with pricing efficiency and find significant harms, especially in bull markets. Uninformed investors and market supervisors should take precautions to avoid this bias. [ABSTRACT FROM AUTHOR]

Volcanic radiative forcing reconstruction is an important part of paleoclimate simulation and attribution efforts, and the conversion factor used to transfer ice core-based sulfate observation into stratospheric volcanic aerosol loading (hereafter referred to as atmospheric-loading to icecap-deposition, 퐿푇퐷) is critical for such reconstruction. This study revisits the Pinatubo-based 퐿푇퐷 applied in the CMIP5 and CMIP6 volcanic forcing, by using 54 polar ice core records of Tambora deposition and a Monte Carlo sampling model. A set of Tambora-based 퐿푇퐷 with associated uncertainties are obtained, which corrects the bias of over-representing the west Antarctic. New 퐿푇퐷s for Pinatubo and Agung are calculated using 18 and 24 Antarctic ice core observations, respectively, and the uncertainties are evaluated against the Monte Carlo characterization with varying ice core numbers. The comparison of Southern Hemispheric 퐿푇퐷 among Tambora, Pinatubo and Agung suggests that, the conversion factor may vary significantly among different eruptions. Even larger uncertainty is revealed when compare the ice-core-based conversion factor with the model results. Both results suggest systematic and stochastic causes that are difficult to anticipate, and call for precaution when single conversion factor is used for reconstruction. [ABSTRACT FROM AUTHOR]

Catalytic hydrogen reduction appears to be a promising strategy for nitrate removal. However, the danger and low utilization of H2 are the disadvantages of catalytic hydrogen reduction. Sodium borohydride (NaBH4), considered a potential candidate for hydrogen storage, has been investigated as an electron source for the catalytic reduction of contaminants. However, extensive use of NaBH4 makes commercialization costly and causes environmental pollution. In this study, we prepared supported Cu/Pd bimetallic nanoparticles that could prestore hydrogen. No additional reducing agent was required during the nitrate reduction process. The performance and mechanism of Cu/Pd bimetallic nanoparticles for nitrate reduction are discussed. Good performance was obtained with high reactivity (99.04% nitrate removal efficiency) and high selectivity for N2 (94.71%). The Cu/Pd bimetallic catalyst could be recovered by NaBH4 for 5 cycles. Moreover, a 97.49% nitrate removal efficiency was obtained for actual wastewater, indicating good prospects for nitrate reduction applications. [ABSTRACT FROM AUTHOR]

Electromagnetic (EM) fields in the extremely low-frequency (ELF) domain that can be excited by the vertical electric dipole (VED) and propagated in the Earth-ionosphere spherical cavity have received tremendous attention owing to their exploitation in many fields such as communication, earthquake prediction, and geophysical investigations. Some researchers use the planar model and curvature correction terms to simulate EM fields in a spherical cavity, while others directly solve the differential functions and estimate the excited EM fields represented by spherical Bessel and associated Legendre functions. Regarding the divergence problem of a series when simulating EM fields, several numerical methods are available such as Watson transformation method, W. K. B. J method, and speeding algorithm. In this study, Pade approximant is utilized to estimate EM fields propagating in the Earth-ionosphere spherical cavity, where new asymptotic expansions of spherical Bessel functions are introduced for estimating their products for high orders. These EM fields are then interpreted as a sum of the dominant incident fields and the increase of multiple scattering fields. The convergence of series expressions of EM fields estimated by Pade approximant is theoretically guaranteed, with its computational complexity lower than that of the speeding algorithm. The EM fields are further verified by numerical tests. The effects of the height and conductivity of the ionosphere, the conductivity of air, the VED height, and the frequencies of the resonance phenomenon are also highlighted. The proposed method is helpful to capture the true nature of the field distribution within a spherical cavity. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Sign language is a form of communication and exchange of ideas by people who are hearing-impaired or unable to speak. Chinese fingerspelling is an important component of Chinese sign language, which is suitable for denoting terminology and using as the basis of gesture sign language learning. OBJECTIVES: We propose a nine-layer convolutional neural network (CNN) for the classification of Chinese sign language. METHODS: With self-learning and self-organization abilities, CNN is committed to processing data with similar network structure. CNN has a good application prospect in the aspect of image classification and plays a very important role in the classification of Chinese sign language. RESULTS: Through experiments on 1320 data samples of 30 categories, the results show that the classification accuracy based on the nine-layer convolutional neural network can reach up to 89.69± 2.10 %, it can be seen that this method can effectively classify Chinese gestures. CONCLUSION: We proposed a nine-layer convolutional neural network (CNN) that can classify Chinese sign language. [ABSTRACT FROM AUTHOR]

Inhibition of the chemokine receptor CXCR4 in combination with blockade of the PD-1/PD-L1 T cell checkpoint induces T cell infiltration and anticancer responses in murine and human pancreatic cancer. Here we elucidate the mechanism by which CXCR4 inhibition affects the tumor immune microenvironment. In human immune cell-based chemotaxis assays, we find that CXCL12- stimulated CXCR4 inhibits the directed migration mediated by CXCR1, CXCR3, CXCR5, CXCR6, and CCR2, respectively, chemokine receptors expressed by all of the immune cell types that participate in an integrated immune response. Inhibiting CXCR4 in an experimental cancer medicine study by 1-wk continuous infusion of the small-molecule inhibitor AMD3100 (plerixafor) induces an integrated immune response that is detected by transcriptional analysis of paired biopsies of metastases from patients with microsatellite stable colorectal and pancreatic cancer. This integrated immune response occurs in three other examples of immunemediated damage to noninfected tissues: Rejecting renal allografts, melanomas clinically responding to anti-PD1 antibody therapy, and microsatellite instable colorectal cancers. Thus, signaling by CXCR4 causes immune suppression in human pancreatic ductal adenocarcinoma and colorectal cancer by impairing the function of the chemokine receptors that mediate the intratumoral accumulation of immune cells. [ABSTRACT FROM AUTHOR]

Human flap endonuclease 1 (FEN1) is a structure-specific, multifunctional endonuclease essential for DNA replication and repair. Our previous study showed that in response to DNA damage, FEN1 interacts with the PCNA-like Rad9-Rad1-Hus1 complex instead of PCNA to engage in DNA repair activities, such as stalled DNA replication fork repair, and undergoes SUMOylation by SUMO-1. Here, we report that succinylation of FEN1 was stimulated in response to DNA replication fork-stalling agents, such as ultraviolet (UV) irradiation, hydroxyurea, camptothecin, and mitomycin C. K200 is a key succinylation site of FEN1 that is essential for gap endonuclease activity and could be suppressed by methylation and stimulated by phosphorylation to promote SUMO-1 modification. Succinylation at K200 of FEN1 promoted the interaction of FEN1 with the Rad9- Rad1-Hus1 complex to rescue stalled replication forks. Impairment of FEN1 succinylation led to the accumulation of DNA damage and heightened sensitivity to fork-stalling agents. Altogether, our findings suggest an important role of FEN1 succinylation in regulating its roles in DNA replication and repair, thus maintaining genome stability. [ABSTRACT FROM AUTHOR]

Objective: Through literature research, the distribution of TCM constitution of nonalcoholic fatty liver (NAFLD) was discussed, the common constitution types of the disease were determined, and medical evidence was provided for the prevention and treatment of NAFLD by traditional Chinese medicine. Methods: The literatures on the correlation between NAFLD and TCM constitution published in domestic journals from the database establishment to April 2020 were searched with "non-alcoholic fatty liver disease and TCM constitution" as the search term, and screening, quality evaluation and data extraction were conducted according to the na exclusion criteria. Statistical software stata16.0 was used for meta analysis of the included literature. Results: Sixteen studies were included. The results showed that the proportions of TCM constitution types and 95%CI of NAFLD patients were phlegmdampness0.28(0.24,0.31), moisture-heat0.16(0.13,0.20),qi-asthenia0.13(0.10,0.16),qistagnation0.11(0.06,0.17),qi-stagnation0.08(0.06,0.10),yi-stagnation0.08(0.06,0.10),yi- -stagnation0.08(0.06,0.10), blood stasis0.07(0.04, 0.08), yang-asthenia0.06(0.04,0.08),and special report 0.02(0.01,0.02). Conclusion: The common constitution types of patients with nonalcoholic fatty liver are phlegm-dam-pness, damp-heat, q-asthenia, and mild, especially phlegm-dampness, which are most closely related to nonalcoholic fatty liver. [ABSTRACT FROM AUTHOR]

Objective: Through literature research, the distribution of TCM constitution of nonalcoholic fatty liver (NAFLD) was discussed, the common constitution types of the disease were determined, and medical evidence was provided for the prevention and treatment of NAFLD by traditional Chinese medicine. Methods: The literatures on the correlation between NAFLD and TCM constitution published in domestic journals from the database establishment to April 2020 were searched with "non-alcoholic fatty liver disease and TCM constitution" as the search term, and screening, quality evaluation and data extraction were conducted according to the na exclusion criteria. Statistical software stata16.0 was used for meta analysis of the included literature. Results: Sixteen studies were included. The results showed that the proportions of TCM constitution types and 95%CI of NAFLD patients were phlegmdampness0.28(0.24,0.31), moisture-heat0.16(0.13,0.20),qi-asthenia0.13(0.10,0.16),qistagnation0.11(0.06,0.17),qi-stagnation0.08(0.06,0.10),yi-stagnation0.08(0.06,0.10),yi- -stagnation0.08(0.06,0.10), blood stasis0.07(0.04, 0.08), yang-asthenia0.06(0.04,0.08),and special report 0.02(0.01,0.02). Conclusion: The common constitution types of patients with nonalcoholic fatty liver are phlegm-dam-pness, damp-heat, q-asthenia and mild, especially phlegm-dampness, which are most closely related to nonalcoholic fatty liver. [ABSTRACT FROM AUTHOR]

[Objectives] To study the effect of total flavonoids extracted from Polygonum perfoliatum L.（TFP） on immune-mediated liver injury induced by bacillus Calmette-Guerin plus lipopolysaccharide（BCG+LPS） in mice, and to explore its action mechanism. [Methods] 60 Kunming mice were divided into normal group, model group, control group（bifendate） and TFP low, medium and high dose groups according to random number table method, with 10 mice in each group. On the first day of modeling, mice were injected with 0.2 mL of BCG solution（12.5 mg/mL） through the tail vein, and on the eleventh day, 0.2 mL of LPS（37.5 μg/mL） were injected into the tail vein to prepare a mouse model of immune-mediated liver injury; from the first day of modeling, the normal group and the model group were administered intragastrically with the corresponding volume of distilled water, and the bifendate group and the TFP high, medium, and low dose groups were administered intragastrically with the corresponding doses once a day for 11 d. After the last time administration, fasting but giving water for 16 h, took blood from eyes, then collected the liver tissue. The levels of alanine transaminase（ALT） and aspartate transaminase（AST） in serum were detected by biochemical method; transforming growth factor-β1（TGF-β1）, intercellular adhesion molecule-1（ICAM-1）, interleukin-6（IL-6） and interleukin-1β（IL-1β） expression levels in liver tissue were detected by enzyme-linked immunosorbent assay（ELISA）; phosphorylated protein tyrosine kinase JAK-2（p-JAK2）, phosphorylated signal transducer and activator of transcription 3（p-STAT3） protein expression levels were detected by Western Blot method; the degree of liver tissue lesions was detected by HE staining. [Results] Compared with the model group, the levels of ALT and AST in the serum of mice in each dose group of TFP（high dose 600 mg/kg, medium dose 400 mg/kg, and low dose 200 mg/kg） were reduced, and the activities of T-SOD and GSH-Px were increased; the content or expression of β1, ICAM-1, IL-6, IL-1β decreased, and the expression of p-JAK2 and p-STAT3 protein decreased; pathological sections showed that the degree of inflammatory necrosis and the degree of lesions in the liver tissues of each dose group of TFP were reduced by varying degrees. [Conclusions] TFP has a protective effect on BCG+LPS-induced immune-mediated liver injury in mice. The mechanism may be related to regulating the phosphorylation level of JAK2 and inhibiting the inflammatory reaction, thereby regulating the TGF-β1/STAT3 signaling pathway and improving the immune-mediated liver injury. [ABSTRACT FROM AUTHOR]

Objectives] To observe the effects of polysaccharides from Dicliptera chinensis（L.） Nees. on the expression of TLR/NF-κB pathway related proteins in HepG2 cells induced by oleic acid, and to explore the possible mechanism of polysaccharides from D. chinensis（L.） Nees. in the treatment of non-alcoholic fatty liver disease（NAFLD）. [Methods] HepG2 cells were induced with oleic acid to establish a non-alcoholic fatty liver cell model. After intervention with 0.25 and 0.5 mg/mL of D. chinensis（L.） Nees. polysaccharides, the ALT and AST activity and TG and TC contents were detected with kits, and the changes in the expression of CDK5, TLR4, p-NF-κB and NF-κB were analyzed using Western-blotting. [Results] In the HepG2 cells induced with oleic acid, the ALT and AST activity increased significantly, the TG and TC contents increased significantly, and the expression levels of CDK5, TLR4 and p-NF-κB proteins up-regulated significantly. In the HepG2 cells intervened with D. chinensis（L.） Nees. polysaccharides, the activity of ALT and AST, the contents of TG and TC, and the expression levels of CDK5, TLR4 and p-NF-κB proteins all reduced significantly. [Conclusions] Polysaccharides from D. chinensis（L.） Nees. may interfere with NAFLD by inhibiting the TLR4/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Objectives] To explore the protective effects and mechanism of Yinzhihuang combined with metformin on nonalcoholic fatty liver diseases（NAFLD） based on PPAR-α signaling pathway. [Methods] 54 male SD rats were randomly divided into 2 groups, namely normal group（12 rats） and high-fat feed group（42 rats）. After 8 weeks, 2 rats were randomly selected from each group. After pathological examination confirmed the success of the NAFLD model, the high-fat feed group was divided into model group, Yinzhihuang（9 000 mg/kg）, metformin group（200 mg/kg）, Yinzhihuang combined with metformin group（4 500 mg/kg+100 mg/kg）, 10 rats in each group. Except the normal group and the model group, the other groups were given treatment drugs at the same time, one time a day, on the fifth weekend of the experiment, at the last time of administration, fasting but giving water for 16 h, then collected blood and liver tissue. Biochemical method was used to detect AST and ALT in serum and SOD, MDA, GSH-px biochemical indicators in liver tissue; enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of TNF-α, IL-6 and TGF-β in liver tissue; Western blot was used to detect the expression of peroxisome proliferators-activated receptor-α（PPAR-α） protein in rat liver tissue. [Results] Compared with the model group, the serum levels of ALT, AST and MDA in liver tissue of model group rats were significantly increased; the levels of SOD and GSH-px in liver tissue were significantly increased; TNF-α and IL-6 and TGF-β contents in liver tissue were significantly increased. [Conclusions] Both Yinzhihuang and metformin have a therapeutic effect on NAFLD rats, and the effect of combined application of the two is significantly better than the intervention effect of Yinzhihuang or metformin alone, the mechanism is possibly associated with the regulation of PPAR-α signaling pathway. [ABSTRACT FROM AUTHOR]

The meteorological factors play an important role to influence the concentration of the particulate matters. The path analysis method is employed to investigate the influence of meteorological factors (including atmospheric temperature (AT), relative humidity (RH), and wind speed (WS)) on particulate matters (including PM2.5 and PM10) in Dazhou city. The following results are obtained: (1) The direct path coefficients of AT, RH, and WS to PM2.5 and PM10 are all negative, which means that the concentration of particulate matters would be declined following with the increasing of AT, RH, and WS. (2) The meteorological factors would explain about 17.43 and 16.52% variance of PM2.5 and PM10, respectively. However, 82.57% variance of PM2.5 and 83.48% variance of PM10 would be determined by non-meteorological factors. (3) AT and WS are the most important meteorological factors to modulate the concentration of particulate matters. AT would explain 12.73 and 8.78% variance of PM2.5 and PM10, respectively. WS would explain 6.54 and 8.69% variance of PM2.5 and PM10, respectively. (4) According to the absolute value of the determination coefficients, the main influence on the concentration of PM2.5 is the direct influence by AT and the impact on the concentration of PM10 is by the combined contribution of meteorological factors. [ABSTRACT FROM AUTHOR]