Geomorphic impacts within Red River Fault and island shifting as witnessed by the phylogeography of the largest water strider.

Palaeogeological events and climate oscillations profoundly impact the demographics and distributions of small-range species, increasing the extinction risk. The largest water strider worldwide, Gigantometra gigas (Hemiptera: Gerridae), exhibits restricted distributions in Vietnam and southern China. Herein, we generated three genomic datasets (mitogenomes, 146 nuclear protein-coding genes and single nucleotide polymorphisms) with ecological niche modelling (ENM) to explicitly test whether the present-day distribution of G. gigas actually resulted from geographical and climatic effects. We found that the origin of this largest water strider reached the divergence time of the genus within Gerridae, providing a greater opportunity to explore its response to geographic movements. The right-lateral motion of the Red River Fault facilitated the divergence of two phylogeographic lineages, resulting in the "north-south component" genetic pattern in G. gigas. The Hainan and southeast Vietnam populations of the southern linage were completely separated by the Beibu Gulf but exhibited similar genetic compositions, confirming that Hainan had a continental origin and that Hainan Island joined with the Indo-China Peninsula to promote gene exchange among populations. Additionally, we noticed the low genetic diversity but long demographic history of the northern lineage, which displayed population dynamics opposite to those of other organisms. Integrating the demographic changes and ENM findings revealed that suitable habitat contraction and rapid demographic decline during the Last Glacial Maximum (LGM) triggered the low genetic diversity of the northern lineage. Overall, the demographic history of the largest water strider was mainly shaped by geographical features, and first provided evidence from the phylogeographic perspective of aquatic insects to support the hypothesis of Hainan Island shifting.

Local false discovery rate estimation with competition-based procedures for variable selection.

Multiple hypothesis testing has been widely applied to problems dealing with high-dimensional data, for example, the selection of important variables or features from a large number of candidates while controlling the error rate. The most prevailing measure of error rate used in multiple hypothesis testing is the false discovery rate (FDR). In recent years, the local false discovery rate (fdr) has drawn much attention, due to its advantage of accessing the confidence of individual hypotheses. However, most methods estimate fdr through P $$ P $$ -values or statistics with known null distributions, which are sometimes unavailable or unreliable. Adopting the innovative methodology of competition-based procedures, for example, the knockoff filter, this paper proposes a new approach, named TDfdr, to fdr estimation, which is free of P $$ P $$ -values or known null distributions. Extensive simulation studies demonstrate that TDfdr can accurately estimate the fdr with two competition-based procedures. We applied the TDfdr method to two real biomedical tasks. One is to identify significantly differentially expressed proteins related to the COVID-19 disease, and the other is to detect mutations in the genotypes of HIV-1 that are associated with drug resistance. Higher discovery power was observed compared to existing popular methods.

PARP1 modulates METTL3 promoter chromatin accessibility and associated LPAR5 RNA m6A methylation to control cancer cell radiosensitivity.

Chromatin remodeling and N6-methyladenosine (m6A) modification are two critical layers in controlling gene expression and DNA damage signaling in most eukaryotic bioprocesses. Here, we report that poly(ADP-ribose) polymerase 1 (PARP1) controls the chromatin accessibility of METTL3 to regulate its transcription and subsequent m6A methylation of poly(A)+ RNA in response to DNA damage induced by radiation. The transcription factors nuclear factor I-C (NFIC) and TATA binding protein (TBP) are dependent on PARP1 to access the METTL3 promoter to activate METTL3 transcription. Upon irradiation or PARP1 inhibitor treatment, PARP1 disassociated from METTL3 promoter chromatin, which resulted in attenuated accessibility of NFIC and TBP and, consequently, suppressed METTL3 expression and RNA m6A methylation. Lysophosphatidic Acid Receptor 5 (LPAR5) mRNA was identified as a target of METTL3, and m6A methylation was located at A1881. The level of m6A methylation of LPAR5 significantly decreased, along with METTL3 depression, in cells after irradiation or PARP1 inhibition. Mutation of the LPAR5 A1881 locus in its 3' UTR results in loss of m6A methylation and, consequently, decreased stability of LPAR5 mRNA. METTL3-targeted small-molecule inhibitors depress murine xenograft tumor growth and exhibit a synergistic effect with radiotherapy in vivo. These findings advance our comprehensive understanding of PARP-related biological roles, which may have implications for developing valuable therapeutic strategies for PARP1 inhibitors in oncology.

Aberrant DNA Methylation Profile of Dickkopf-1 in Ankylosing Spondylitis.

In recent years, the impact of methylation modifications on Dickkopf-1 (DKK1) in relation to ankylosing spondylitis (AS) has remained elusive. Our objective was to investigate the potential link between DKK1 methylation patterns and transcript levels and AS susceptibility. DNA methylation level of DKK1 was measured in 82 AS and 82 healthy controls (HCs) using targeted bisulfite sequencing. In addition, the transcript level of DKK1 in peripheral blood mononuclear cells from 35 AS patients and 35 HCs was detected using real-time quantitative transcription-polymerase chain reaction. Our study showed that the DKK1 was significantly hypomethylated in AS patients (P < 0.001). The Receiver operating characteristic curve (ROC) showed that DKK1 methylation may be a potential biomarker. The results showed that the difference in DKK1 transcript levels between AS and HCs was not statistically significant. Further analysis showed that DKK1 methylation levels were positively correlated with age and negatively correlated with C-reactive protein levels, neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR). The methylation level of DKK1 in PBMC of AS patients was significantly lower than that of HCs, and DKK1 methylation may be associated with susceptibility to AS. In addition, DNA methylation levels of DKK1 were negatively correlated with the level of inflammation in AS patients.

RNA N6-Methyladenosine Modification in DNA Damage Response and Cancer Radiotherapy.

The N6-methyladenosine (M6A) modification is the most common internal chemical modification of RNA molecules in eukaryotes. This modification can affect mRNA metabolism, regulate RNA transcription, nuclear export, splicing, degradation, and translation, and significantly impact various aspects of physiology and pathobiology. Radiotherapy is the most common method of tumor treatment. Different intrinsic cellular mechanisms affect the response of cells to ionizing radiation (IR) and the effectiveness of cancer radiotherapy. In this review, we summarize and discuss recent advances in understanding the roles and mechanisms of RNA M6A methylation in cellular responses to radiation-induced DNA damage and in determining the outcomes of cancer radiotherapy. Insights into RNA M6A methylation in radiation biology may facilitate the improvement of therapeutic strategies for cancer radiotherapy and radioprotection of normal tissues.

DNA methylation and transcriptome signatures of the PDCD1 gene in ankylosing spondylitis.

Ankylosing spondylitis (AS) is an autoimmune-related inflammatory arthritis. The association between the DNA methylation and mRNA expression of PDCD1 gene with the susceptibility to AS remains unclear. In this case-control study, the methylation level of PDCD1 promoter was detected in 80 AS patients and 80 healthy controls by MethylTarget method. The transcriptional level of PDCD1 gene was measured in 47 AS patients and 47 healthy controls by real-time quantitative PCR. Finally, 17 methylation sites mapped to one CpG island were detected. Compared to healthy controls, the promoter of PDCD1 was hypermethylated (p < 0.001) and the mRNA expression was downregulated (p < 0.001) in AS patients. Significantly negative correlation was identified between the DNA methylation and mRNA expression of PDCD1 gene (rs = -0.470, p < 0.001). The receiver operating characteristic (ROC) results showed that PDCD1 island had a sensitivity of 61.3% and a specificity of 82.5%, and PDCD1 mRNA had a sensitivity of 87.2% and a specificity of 89.0%. The methylation level of PDCD1 was positively correlated with the ESR, CRP and ASDAS of AS, and was not affected by HLA-B27 status, gender or medicine intake.

NIPSNAP1 directs dual mechanisms to restrain senescence in cancer cells.

BACKGROUND: Although the executive pathways of senescence are known, the underlying control mechanisms are diverse and not fully understood, particularly how cancer cells avoid triggering senescence despite experiencing exacerbated stress conditions within the tumor microenvironment. METHODS: Mass spectrometry (MS)-based proteomic screening was used to identify differentially regulated genes in serum-starved hepatocellular carcinoma cells and RNAi employed to determine knockdown phenotypes of prioritized genes. Thereafter, gene function was investigated using cell proliferation assays (colony-formation, CCK-8, Edu incorporation and cell cycle) together with cellular senescence assays (SA-ß-gal, SAHF and SASP). Gene overexpression and knockdown techniques were applied to examine mRNA and protein regulation in combination with luciferase reporter and proteasome degradation assays, respectively. Flow cytometry was applied to detect changes in cellular reactive oxygen species (ROS) and in vivo gene function examined using a xenograft model. RESULTS: Among the genes induced by serum deprivation, NIPSNAP1 was selected for investigation. Subsequent experiments revealed that NIPSNAP1 promotes cancer cell proliferation and inhibits P27-dependent induction of senescence via dual mechanisms. Firstly, NIPSNAP1 maintains the levels of c-Myc by sequestering the E3 ubiquitin ligase FBXL14 to prevent the proteasome-mediated turnover of c-Myc. Intriguingly, NIPSNAP1 levels are restrained by transcriptional repression mediated by c-Myc-Miz1, with repression lifted in response to serum withdrawal, thus identifying feedback regulation between NIPSNAP1 and c-Myc. Secondly, NIPSNAP1 was shown to modulate ROS levels by promoting interactions between the deacetylase SIRT3 and superoxide dismutase 2 (SOD2). Consequent activation of SOD2 serves to maintain cellular ROS levels below the critical levels required to induce cell cycle arrest and senescence. Importantly, the actions of NIPSNAP1 in promoting cancer cell proliferation and preventing senescence were recapitulated in vivo using xenograft models. CONCLUSIONS: Together, these findings reveal NIPSNAP1 as an important mediator of c-Myc function and a negative regulator of cellular senescence. These findings also provide a theoretical basis for cancer therapy where targeting NIPSNAP1 invokes cellular senescence.

Tea consumption and risk of lower respiratory tract infections: a two-sample mendelian randomization study.

BACKGROUND: Observational studies have reported the association between tea consumption and the risk of lower respiratory tract infections (LRTIs). However, a consensus has yet to be reached, and whether the observed association is driven by confounding factors or reverse causality remains unclear. METHOD: A two-sample Mendelian randomization (MR) analysis was conducted to determine whether genetically predicted tea intake is causally associated with the risk of common LRTI subtypes. Genome-wide association study (GWAS) from UK Biobank was used to identify single-nucleotide polymorphisms (SNPs) associated with an extra cup of tea intake each day. The summary statistics for acute bronchitis, acute bronchiolitis, bronchiectasis, pneumonia, and influenza and pneumonia were derived from the FinnGen project. RESULTS: We found that genetically predicted an extra daily cup of tea intake was causally associated with the decreased risk of bronchiectasis [odds ratio (OR) = 0.61, 95% confidence interval (CI) = 0.47-0.78, P < 0.001], pneumonia (OR = 0.90, 95% CI = 0.85-0.96, P = 0.002), influenza and pneumonia (OR = 0.91, 95% CI = 0.85-0.97, P = 0.002), but not with acute bronchitis (OR = 0.91, 95% CI = 0.82-1.01, P = 0.067) and acute bronchiolitis (OR = 0.79, 95% CI = 0.60-1.05, P = 0.100). Sensitivity analyses showed that no heterogeneity and pleiotropy could bias the results. CONCLUSIONS: Our findings provided new evidence that genetically predicted an extra daily cup of tea intake may causally associated with a decreased risk of bronchiectasis, pneumonia, and influenza and pneumonia.

Astaxanthin alleviates PM2.5-induced cardiomyocyte injury via inhibiting ferroptosis.

BACKGROUND: Long-term exposure of humans to air pollution is associated with an increasing risk of cardiovascular diseases (CVDs). Astaxanthin (AST), a naturally occurring red carotenoid pigment, was proved to have multiple health benefits. However, whether or not AST also exerts a protective effect on fine particulate matter (PM2.5)-induced cardiomyocyte damage and its underlying mechanisms remain unclear. METHODS: In vitro experiments, the H9C2 cells were subjected to pretreatment with varying concentrations of AST, and then cardiomyocyte injury model induced by PM2.5 was established. The cell viability and the ferroptosis-related proteins expression were measured in different groups. In vivo experiments, the rats were pretreated with different concentrations of AST for 21 days. Subsequently, a rat model of myocardial PM2.5 injury was established by intratracheal instillation every other day for 1 week. The effects of AST on myocardial tissue injury caused by PM2.5 indicating by histological, serum, and protein analyses were examined. RESULTS: AST significantly ameliorated PM2.5-induced myocardial tissue injury, inflammatory cell infiltration, the release of inflammatory factors, and cardiomyocyte H9C2 cell damage. Mechanistically, AST pretreatment increased the expression of SLC7A11, GPX4 and down-regulated the expression of TfR1, FTL and FTH1 in vitro and in vivo. CONCLUSIONS: Our study suggest that ferroptosis plays a significant role in the pathogenesis of cardiomyocyte injury induced by PM2.5. AST may serve as a potential therapeutic agent for mitigating cardiomyocyte injury caused by PM2.5 through the inhibition of ferroptosis.

Research on the relationship between common metabolic syndrome and meteorological factors in Wuhu, a subtropical humid city of China.

As climate conditions deteriorate, human health faces a broader range of threats. This study aimed to determine the risk of death from metabolic syndrome (MetS) due to meteorological factors. We collected daily data from 2014 to 2020 in Wuhu City, including meteorological factors, environmental pollutants and death data of common MetS (hypertension, hyperlipidemia and diabetes), as well as a total number of 15,272 MetS deaths. To examine the relationship between meteorological factors, air pollutants, and MetS mortality, we used a generalized additive model (GAM) combined with a distributed delay nonlinear model (DLNM) for time series analysis. The relationship between the above factors and death outcomes was preliminarily evaluated using Spearman analysis and structural equation modeling (SEM). As per out discovery, diurnal temperature range (DTR) and daily mean temperature (T mean) increased the MetS mortality risk notably. The ultra low DTR raised the MetS mortality risk upon the general people, with the highest RR value of 1.033 (95% CI: 1.002, 1.065) at lag day 14. In addition, T mean was also significantly associated with MetS death. The highest risk of ultra low and ultra high T mean occured on the same day (lag 14), RR values were 1.043 (95% CI: 1.010, 1.077) and 1.032 (95% CI: 1.003, 1.061) respectively. Stratified analysis's result showed lower DTR had a more pronounced effect on women and the elderly, and ultra low and high T mean was a risk factor for MetS mortality in women and men. The elderly need to take extra note of temperature changes, and different levels of T mean will increase the risk of death. In warm seasons, ultra high RH and T mean can increase the mortality rate of MetS patients.

Burnout, moral injury, and suicidal/self-harm ideation among healthcare professionals in Mainland China: Insights from an online survey during the COVID-19 pandemic.

OBJECTIVE: This survey aimed to explore the relationships between burnout, moral injury, and suicidal/self-harm ideation among Chinese health professionals to provide a reference for protecting their mental health. METHOD: Health professionals were surveyed online using the Maslach Burnout Inventory-Human Services Survey for Medical Personnel, Patient Health Questionnaire-9, and the Moral Injury Symptoms Scale-Health Professional. RESULTS: In the analysis, 6146 eligible respondents were included in the study. The average participant age was 34.9 ± 8.5 years, and suicidal/self-harm ideation was detected in 2338 participants (38.0%). The prevalence of suicidal/self-harm ideation among those with severe burnout in the dimensions of emotional exhaustion, depersonalisation, and decreased personal accomplishment was significantly higher than those with mild burnout. The prevalence of suicidal/self-harm ideation among those with significant moral injury symptoms was higher than those without moral injury. Unconditional logistic regression analysis showed that those with moderate or severe emotional exhaustion, moderate or severe reduced sense of professional accomplishment and moderate or severe depersonalisation had increased risks of suicidal/self-harm ideation. CONCLUSIONS: Structural equation modelling demonstrated that burnout significantly mediated the relationship between moral injury and suicidal/self-harm ideation. The proportion of mediation (PM) by burnout was 43.0%. Burnout and moral injury were potential predictors of suicidal/self-harm ideation among health professionals. Both moral injury and burnout had positive and direct effects on suicidal/self-harm ideation, and burnout was a mediator in this relationship among Chinese health professionals. Therefore, to alleviate the moral injury and subsequent burnout of healthcare workers and enhance their mental qualities, active interventions should be developed in the future.

Cytosolic Release of Mitochondrial DNA and Associated cGAS Signaling Mediates Radiation-Induced Hematopoietic Injury of Mice.

Mitochondrion is an important organelle of eukaryotic cells and a critical target of ionizing radiation (IR) outside the nucleus. The biological significance and mechanism of the non-target effect originating from mitochondria have received much attention in the field of radiation biology and protection. In this study, we investigated the effect, role, and radioprotective significance of cytosolic mitochondrial DNA (mtDNA) and its associated cGAS signaling on hematopoietic injury induced by IR in vitro culture cells and in vivo total body irradiated mice in this study. The results demonstrated that γ-ray exposure increases the release of mtDNA into the cytosol to activate cGAS signaling pathway, and the voltage-dependent anion channel (VDAC) may contribute to IR-induced mtDNA release. VDAC1 inhibitor DIDS and cGAS synthetase inhibitor can alleviate bone marrow injury and ameliorate hematopoietic suppression induced by IR via protecting hematopoietic stem cells and adjusting subtype distribution of bone marrow cells, such as attenuating the increase of the F4/80+ macrophage proportion in bone marrow cells. The present study provides a new mechanistic explanation for the radiation non-target effect and an alternative technical strategy for the prevention and treatment of hematopoietic acute radiation syndrome.

LPAR5 confers radioresistance to cancer cells associated with EMT activation via the ERK/Snail pathway.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a critical event contributing to more aggressive phenotypes in cancer cells. EMT is frequently activated in radiation-targeted cells during the course of radiotherapy, which often endows cancers with acquired radioresistance. However, the upstream molecules driving the signaling pathways of radiation-induced EMT have not been fully delineated. METHODS: In this study, RNA-seq-based transcriptome analysis was performed to identify the early responsive genes of HeLa cells to γ-ray irradiation. EMT-associated genes were knocked down by siRNA technology or overexpressed in HeLa cells and A549 cells, and the resulting changes in phenotypes of EMT and radiosensitivity were assessed using qPCR and Western blotting analyses, migration assays, colony-forming ability and apoptosis of flow cytometer assays. RESULTS: Through RNA-seq-based transcriptome analysis, we found that LPAR5 is downregulated in the early response of HeLa cells to γ-ray irradiation. Radiation-induced alterations in LPAR5 expression were further revealed to be a bidirectional dynamic process in HeLa and A549 cells, i.e., the early downregulating phase at 2 ~ 4 h and the late upregulating phase at 24 h post-irradiation. Overexpression of LPAR5 prompts EMT programing and migration of cancer cells. Moreover, increased expression of LPAR5 is significantly associated with IR-induced EMT and confers radioresistance to cancer cells. Knockdown of LPAR5 suppressed IR-induced EMT by attenuating the activation of ERK signaling and downstream Snail, MMP1, and MMP9 expression. CONCLUSIONS: LPAR5 is an important upstream regulator of IR-induced EMT that modulates the ERK/Snail pathway. This study provides further insights into understanding the mechanism of radiation-induced EMT and identifies promising targets for improving the effectiveness of cancer radiation therapy.

Comprehensive 16S rDNA Sequencing and LC-MS/MS-Based Metabolomics to Investigate Intestinal Flora and Metabolic Profiles of the Serum, Hypothalamus and Hippocampus in p­Chlorophenylalanine-Induced Insomnia Rats Treated with Lilium brownie.

Gut microbiota homeostasis in the organism and insomnia have been reported to influence each other. In the study, a method of 16S rRNA gene sequencing combined with ultra-high performance liquid chromatography-mass/mass spectrometry was adopted to evaluate the effects of Lilium brownie (LB) on intestinal flora and metabolic profiles of serum, hypothalamus and hippocampus in insomnia rat induced by p­chlorophenylalanine (PCPA). It was observed that the imbalance in the diversity and abundance of gut microbiota induced by PCPA was restored after LB intervention. Among these, the Porphyromonadaceae, Lactobacillus and Escherichia were significantly adjusted at the genus level by PCPA and LB, respectively. It was also found that the most of metabolic phenotypes in serum, hypothalamus and hippocampus perturbed by PCPA were regulated towards normal after LB intervention, especially 5-hydroxy-L-tryptophan of the hypothalamus involving in 5-HT metabolism. Moreover, the arachidonic acid metabolism in serum, hypothalamus and hippocampus, and the serotonergic synapse in hypothalamus and hippocampus were the most fundamentally and significantly affected pathways after LB intervention. The results of correlation analysis showed that several floras including Pseudoruegeria have an outstanding contribution to the change of differential metabolites. In brief, the results confirm that gut microbiota is significantly returned to normal and may interact with the corresponding metabolites to relieve insomnia under LB intervention.

Diversification of the phytophagous lineages of true bugs (Insecta: Hemiptera: Heteroptera) shortly after that of the flowering plants.

More than 95% of phytophagous true bug (Hemiptera: Heteroptera) species belong to four superfamilies: Miroidea (Cimicomorpha), Pentatomoidea, Coreoidea, and Lygaeoidea (all Pentatomomorpha). These iconic groups of highly diverse, overwhelmingly phytophagous insects include several economically prominent agricultural and silvicultural pest species, though their evolutionary history has not yet been well resolved. In particular, superfamily- and family-level phylogenetic relationships of these four lineages have remained controversial, and the divergence times of some crucial nodes for phytophagous true bugs have hitherto been little known, which hampers a better understanding of the evolutionary processes and patterns of phytophagous insects. In the present study, we used 150 species and concatenated nuclear and mitochondrial protein-coding genes and rRNA genes to infer the phylogenetic relationships within the Terheteroptera (Cimicomorpha + Pentatomomorpha) and estimated their divergence times. Our results support the monophyly of Cimicomorpha, Pentatomomorpha, Miroidea, Pentatomoidea, Pyrrhocoroidea, Coreoidea, and Lygaeoidea. The phylogenetic relationships across phytophagous lineages are largely congruent at deep nodes across the analyses based on different datasets and tree-reconstructing methods with just a few exceptions. Estimated divergence times and ancestral state reconstructions for feeding habit indicate that phytophagous true bugs explosively radiated in the Early Cretaceous-shortly after the angiosperm radiation-with the subsequent diversification of the most speciose clades (Mirinae, Pentatomidae, Coreinae, and Rhyparochromidae) in the Late Cretaceous.

Natural source, bioactivity and synthesis of 3-Arylcoumarin derivatives.

3-arylcoumarins with different pharmacological properties widely exist in a variety of natural plants. The extensive research on 3-arylcoumarins was attributed to its therapeutic and relatively easy isolation. Therefore, 3-arylcoumarins can be recognised as useful structures for the design of novel compounds with potential pharmacological interest, particularly in the fields of anti-inflammatory, anti-cancer, antioxidant, Monoamine oxidase (MAO) enzyme inhibition, etc. The current review highlights the biological activities, design, and chemical synthetic methods of 3-arylcoumarins derivatives as well as their important natural product sources.

CircSRSF4 Enhances Proliferation, Invasion, and Migration to Promote the Progression of Osteosarcoma via Rac1.

(1) Background: At present, cancer cell metastasis is the main cause of death in patients with malignant tumors, and up to 23% of osteosarcoma patients have died due to lung and lymph node metastasis. Therefore, finding new molecules involved in tumor development can provide new strategies for the diagnosis and treatment of osteosarcoma patients. Circular RNAs (circRNAs) are a type of RNA molecule that are connected head-to-tail to form a closed ring. There is increasing evidence that circRNAs are RNA molecules with many biological functions in various diseases. However, the role and mechanism of circRNAs in osteosarcoma have rarely been reported. (2) Methods: The expression of circSRSF4 in osteosarcoma tissues and cell lines was detected by quantitative real-time PCR (RT-qPCR), and the result of high-throughput sequencing was verified. In order to explore the effect of circSRSF4 on tumor proliferation, invasion, and migration, a dual-luciferase reporter assay, RNA binding protein immunoprecipitation assay, cell counting kit-8 (CCK-8), transwell assay, scratch wound healing assay, Western blot analysis, and other experiments were carried out in vitro. Rescue experiments and a xenograft model confirmed that circSRSF4 directly acted on miR-224 to regulate Rac1 expression. (3) Results: The expression of circSRSF4 was significantly higher in osteosarcoma tissues and cell lines. Down-regulating the expression of circSRSF4 in vitro significantly inhibited the proliferation, invasion, and migration of cells, and also reduced the expression of Rac1, while the overexpression of Rac1 and miR-224 inhibition could reverse these effects. The inhibition of circSRSF4 expression in vivo also attenuated tumor growth. A mechanistic study showed that circSRSF4 can be used as an miR-224 sponge to up-regulate the expression of Rac1, thereby promoting the development of osteosarcoma. (4) Conclusions: CircSRSF4 acting as a ceRNA promotes the malignant behavior of osteosarcoma through the circSRSF4/miR-224/Rac1 axis, which provides a new theoretical basis for the clinical prevention and treatment of osteosarcoma and the study of related markers and intervention targets.

Psychological Strain and Suicidal Behaviors Among Medical Students in Northwest, China: The Mediating Effect of Psychological Distress and Hopelessness.

ABSTRACT: Although most studies have shown the psychological strains associated with increased risk of suicidal behaviors, how psychological strains are linked to suicidal behaviors is still unclear. The current study examines the possible mediation effect of psychological distress and hopelessness on the relationship between psychological strains and suicidal behaviors among Chinese medical college students. A cross-sectional survey was conducted from November 2017 to March 2018 involving 5703 medical college students, and the 12-month prevalence of suicidal behaviors was 12.89%. Psychological strains significantly associated with suicidal behaviors, and psychological distress and hopelessness partially explained this relationship. A positive psychological intervention program is needed to buffer the psychological strains, which is a crucial predictor for suicidal behaviors among Chinese medical college students.

Synthesis and biological evaluation of 2-arylbenzofuran derivatives as potential anti-Alzheimer's disease agents.

Alzheimer's disease (AD) is a type of progressive dementia caused by degeneration of the nervous system. A single target drug usually does not work well. Therefore, multi-target drugs are designed and developed so that one drug can specifically bind to multiple targets to ensure clinical effectiveness and reduce toxicity. We synthesised a series of 2-arylbenzofuran derivatives and evaluated their in vitro activities. 2-Arylbenzofuran compounds have good dual cholinesterase inhibitory activity and ß-secretase inhibitory activity. The IC50 value of compound 20 against acetylcholinesterase inhibition (0.086 ± 0.01 µmol·L-1) is similar to donepezil (0.085 ± 0.01 µmol·L-1) and is better than baicalein (0.404 ± 0.04 µmol·L-1). And most of the compounds have good BACE1 inhibitory activity, of which 3 compounds (8, 19 and 20) show better activity than baicalein (0.087 ± 0.03 µmol·L-1). According to experimental results, 2-arylbenzofuran compounds provide an idea for drug design to develop prevention and treatment for AD.

Integrate Candidate Answer Extraction with Re-Ranking for Chinese Machine Reading Comprehension.

Machine Reading Comprehension (MRC) research concerns how to endow machines with the ability to understand given passages and answer questions, which is a challenging problem in the field of natural language processing. To solve the Chinese MRC task efficiently, this paper proposes an Improved Extraction-based Reading Comprehension method with Answer Re-ranking (IERC-AR), consisting of a candidate answer extraction module and a re-ranking module. The candidate answer extraction module uses an improved pre-training language model, RoBERTa-WWM, to generate precise word representations, which can solve the problem of polysemy and is good for capturing Chinese word-level features. The re-ranking module re-evaluates candidate answers based on a self-attention mechanism, which can improve the accuracy of predicting answers. Traditional machine-reading methods generally integrate different modules into a pipeline system, which leads to re-encoding problems and inconsistent data distribution between the training and testing phases; therefore, this paper proposes an end-to-end model architecture for IERC-AR to reasonably integrate the candidate answer extraction and re-ranking modules. The experimental results on the Les MMRC dataset show that IERC-AR outperforms state-of-the-art MRC approaches.