Miracle-dz/UniFAR-FTUs huggingface dataset:
Requirements for MRN endonuclease processing of topoisomerase II-mediated DNA damage in mammalian cells

During a normal topoisomerase II (TOP2) reaction, the enzyme forms a covalent enzyme DNA intermediate consisting of a 5′ phosphotyrosyl linkage between the enzyme and DNA. While the enzyme typically rejoins the transient breakage after strand passage, a variety of conditions including drugs targeting TOP2 can inhibit DNA resealing, leading to enzyme-mediated DNA damage. A critical aspect of the repair of TOP2-mediated damage is the removal of the TOP2 protein covalently bound to DNA. While proteolysis plays a role in repairing this damage, nucleolytic enzymes must remove the phosphotyrosyl-linked peptide bound to DNA. The MRN complex has been shown to participate in the removal of TOP2 protein from DNA following cellular treatment with TOP2 poisons. In this report we used an optimized ICE (In vivo Complex of Enzyme) assay to measure covalent TOP2/DNA complexes. In agreement with previous independent reports, we find that the absence or inhibition of the MRE11 endonuclease results in elevated levels of both TOP2α and TOP2β covalent complexes. We also examined levels of TOP2 covalent complexes in cells treated with the proteasome inhibitor MG132. Although MRE11 inhibition plus MG132 was not synergistic in etoposide-treated cells, ectopic overexpression of MRE11 resulted in removal of TOP2 even in the presence of MG132. We also found that VCP/p97 inhibition led to elevated TOP2 covalent complexes and prevented the removal of TOP2 covalent complexes by MRE11 overexpression. Our results demonstrate the existence of multiple pathways for proteolytic processing of TOP2 prior to nucleolytic processing, and that MRE11 can process TOP2 covalent complexes even when the proteasome is inhibited. The interactions between VCP/p97 and proteolytic processing of TOP2 covalent complexes merit additional investigation.
Diet drives the gut microbiome composition and assembly processes in winter migratory birds in the Poyang Lake wetland, China

The complex gut bacterial communities may facilitate the function, distribution, and diversity of birds. For migratory birds, long-distance traveling poses selection pressures on their gut microbiota, ultimately affecting the birds’ health, fitness, ecology, and evolution. However, our understanding of mechanisms that underlie the assembly of the gut microbiome of migratory birds is limited. In this study, the gut microbiota of winter migratory birds in the Poyang Lake wetland was characterized using MiSeq sequencing of 16S rRNA genes. The sampled bird included herbivorous, carnivorous, and omnivorous birds from a total of 17 species of 8 families. Our results showed that the gut microbiota of migratory birds was dominated by four major bacterial phyla: Firmicutes (47.8%), Proteobacteria (18.2%), Fusobacteria (12.6%), and Bacteroidetes (9.1%). Dietary specialization outweighed the phylogeny of birds as an important factor governing the gut microbiome, mainly through regulating the deterministic processes of homogeneous selection and stochastic processes of homogeneous dispersal balance. Moreover, the omnivorous had more bacterial diversity than the herbivorous and carnivorous. Microbial networks for the gut microbiome of the herbivorous and carnivorous were less integrated, i.e., had lower average node degree and greater decreased network stability upon node attack removal than those of the omnivorous birds. Our findings advance the understanding of host-microbiota interactions and the evolution of migratory bird dietary flexibility and diversification.
The nuclear-encoded plastid ribosomal protein L18s are essential for plant development

Plastid ribosomal proteins (PRPs) are necessary components for plastid ribosome biogenesis, playing essential roles in plastid development. The ribosomal protein L18 involved in the assemble of 5S rRNA and 23S rRNA, is vital for E. coli viability, but the functions of its homologs in plant plastid remain elusive. Here, we characterized the functions of the plant plastid ribosomal protein L18s (PRPL18s) in Arabidopsis and rice. AtPRPL18 was ubiquitously expressed in most of the plant tissues, but with higher expression levels in seedling shoots, leaves, and flowers. AtPRPL18 was localized in chloroplast. Genetic and cytological analyses revealed that a loss of function of AtPRPL18 resulted in embryo development arrest at globular stage. However, overexpression of AtPRPL18 did not show any visible phenotypical changes in Arabidopsis. The rice OsPRPL18 was localized in chloroplast. In contrast to AtPRPL18, knockout of OsPRPL18 did not affect embryo development, but led to an albino lethal phenotype at the seedling stage. Cytological analyses showed that chloroplast development was impaired in the osprpl18-1 mutant. Moreover, a loss-function of OsPRPL18 led to defects in plastid ribosome biogenesis and a serious reduction in the efficiency of plastid intron splicing. In all, these results suggested that PRPL18s play critical roles in plastid ribosome biogenesis, plastid intron splicing, and chloroplast development, and are essential for plant survival.
The dark side of university student entrepreneurship: Exploration of Chinese universities

The dark side of entrepreneurship, especially the dark side of student entrepreneurship, has received little attention from academia. This study tries to examine the dark side of entrepreneurship among students in Chinese universities. Employing qualitative method by conducting semi-structured interview with students at the universities. Our study identifies the unproductive and destructive factors that drive the dark side of student entrepreneurship. Entrepreneurship costs that accompany students in the process of entrepreneurship are usually time pressure, academic conflict, and even health damage. There is a huge discrepancy between the knowledge given to students by universities and the knowledge required for entrepreneurship, and college students frequently lack entrepreneurial knowledge and business logic. In China, the use of inappropriate policy tools has decoupled the student entrepreneurship policies it pursues from the purpose the policies are supposed to serve. In so doing, this study contributes to the micro-level of the notion of the dark side of student entrepreneurship.
Multivariate drought stress response of Norway spruce, silver fir and Douglas fir along elevational gradients in Southwestern Germany

The conifer tree species Norway spruce (Picea abies), silver fir (Abies alba) and Douglas fir (Pseudotsuga menziesii) are important elements in tree species composition and forest management of Central European forests, but their potential to thrive under anticipated climatic changes is still debated controversially. This study contributes a multivariate analysis of resilience components based on increment cores sampled at breast height of Norway spruce, silver fir and Douglas fir trees growing along elevational gradients in Southwestern Germany. We aimed to gain novel insights into the species-specific and elevational response of tree growth and wood density variables during the extreme drought events of the years 2003 and 2018. Our results for Norway spruce corroborate projections of its ongoing decline during climate change as the reductions of wood density and biomass production indicated high drought sensitivity at all elevations. Moreover, resilience indices of mean tree-ring density, maximum latewood density, tree-ring width and biomass production were even lower after the drought of 2018 compared to the previous drought of 2003. Silver fir, a potential substitute tree species for Norway spruce, showed unexpected results with resistance and resilience indices being significantly lower in 2018 compared to 2003 indicating that silver fir might be more vulnerable to drought than previously expected, especially at low elevations. In contrast, the superior growth rates and higher levels of drought tolerance of Douglas fir were especially pronounced during the drought of 2018 and visible across the entire elevational gradient, even though high coning intensity was present for all investigated tree species as a possible confounding factor to exacerbate the drought stress effects in the study region.
4-(2-Butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid inhibits angiogenesis via modulation of vascular endothelial growth factor receptor 2 signaling pathway

4-(2-Butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid (DCPIB), was discovered to be a potent and specific antagonist of volume-regulated anion channel that is closely linked to angiogenesis. However, the effect of DCPIB on angiogenesis remains unclear. Here, we found that DCPIB inhibited angiogenesis in the corneal suture and myocardial infarction in vivo model. In addition, DCPIB inhibited human umbilical vein endothelial cell migration, tube formation and proliferation in vitro. Moreover, DCPIB repressed the activation and expression of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream signaling pathway. Computer modeling further confirmed that DCPIB binds with high affinity to VEGFR2. Collectively, we present evidence supporting an antiangiogenic role of DCPIB by targeting VEGFR2 signaling pathway, which suggests that DCPIB is a valuable lead compound for the treatment of angiogenesis-related diseases.
Stimulating myocardial pyruvate dehydrogenase activity fails to alleviate cardiac abnormalities in a mouse model of human Barth syndrome

Barth syndrome (BTHS) is a rare genetic disorder due to mutations in the TAFAZZIN gene, leading to impaired maturation of cardiolipin and thereby adversely affecting mitochondrial function and energy metabolism, often resulting in cardiomyopathy. In a murine model of BTHS involving short-hairpin RNA mediated knockdown of Tafazzin (TazKD mice), myocardial glucose oxidation rates were markedly reduced, likely secondary to an impairment in the activity of pyruvate dehydrogenase (PDH), the rate-limiting enzyme of glucose oxidation. Furthermore, TazKD mice exhibited cardiac hypertrophy with minimal cardiac dysfunction. Because the stimulation of myocardial glucose oxidation has been shown to alleviate diabetic cardiomyopathy and heart failure, we hypothesized that stimulating PDH activity would alleviate the cardiac hypertrophy present in TazKD mice. In order to address our hypothesis, 6-week-old male TazKD mice and their wild-type (WT) littermates were treated with dichloroacetate (DCA; 70 mM in the drinking water), which stimulates PDH activity via inhibiting PDH kinase to prevent inhibitory phosphorylation of PDH. We utilized ultrasound echocardiography to assess cardiac function and left ventricular wall structure in all mice prior to and following 6-weeks of treatment. Consistent with systemic activation of PDH and glucose oxidation, DCA treatment improved glycemia in both TazKD mice and their WT littermates, and decreased PDH phosphorylation equivalently at all 3 of its inhibitory sites (serine 293/300/232). However, DCA treatment had no impact on left ventricular structure, or systolic and diastolic function in TazKD mice. Therefore, it is unlikely that stimulating glucose oxidation is a viable target to improve BTHS-related cardiomyopathy.
How does job insecurity cause unethical pro-organizational behavior? The mediating role of impression management motivation and the moderating role of organizational identification

This study aims to examine the effect of quantitative and qualitative job insecurity on unethical pro-organizational behavior (UPB), focusing on the mediating effect of impression management motivation and the moderating effect of organizational identification. A two-wave questionnaire survey is conducted, and data from 254 employees of Chinese enterprises are used to test the research hypotheses. Empirical results show that: (1) Quantitative job insecurity has a significant positive effect on UPB, while positive effect of qualitative job insecurity on UPB is insignificant. (2) Quantitative job insecurity positively affects impression management motivation and increases UPB. Although the direct effect of qualitative job insecurity on UPB is insignificant, it positively affects UPB through impression management motivation. (3) Organizational identification plays a positive moderation role in the relationship between impression management motivation and employees’ UPB, that is, high-degree organizational identification leads to a strong effect of impression management motivation on UPB; furthermore, organizational identification moderates the mediating role of impression management motivation in the relationships between quantitative, qualitative job insecurity, and UPB, such that the effect is strong when organizational identification is high, rather than low. This study compares the effect of quantitative and qualitative job insecurity on employees’ UPB, reveals that impression management motivation is the key mechanism of quantitative and qualitative job insecurity affecting UPB, and points out the moderating effect of organizational identification, which offers implications for organizational management practices.
Reclassification of endometrial cancer and identification of key genes based on neural-related genes

Endometrial cancer (EC) is the most common gynecologic malignancy, and its incidence has been increasing every year. Nerve signaling is part of the tumor microenvironment and plays an active role in tumor progression and invasion. However, the relationship between the expression of neural-related genes (NRGs) and prognosis in endometrial cancer remains unknown. In this study, we obtained RNA sequencing data of EC from The Cancer Genome Atlas (TCGA). Endometrial cancer was classified into two subtypes based on the expression of neural-associated genes (NRGs), with statistical differences in clinical stage, pathological grading, and prognosis. A prognostic prediction model was established by LASSO-Cox analysis, and the results showed that high expression of NRGs was associated with poor survival prognosis. Further, CHRM2, GRIN1, L1CAM, and SEMA4F were found to be significantly associated with clinical stage, immune infiltration, immune response, and important signaling pathways in endometrial cancer. The reclassification of endometrial cancer based on NRG expression would be beneficial for future clinical practice. The genes CHRM2, GRIN1, L1CAM, and SEMA4F might serve as potential biomarkers of EC prognosis.
EFMSDTI: Drug-target interaction prediction based on an efficient fusion of multi-source data

Accurate identification of Drug Target Interactions (DTIs) is of great significance for understanding the mechanism of drug treatment and discovering new drugs for disease treatment. Currently, computational methods of DTIs prediction that combine drug and target multi-source data can effectively reduce the cost and time of drug development. However, in multi-source data processing, the contribution of different source data to DTIs is often not considered. Therefore, how to make full use of the contribution of different source data to predict DTIs for efficient fusion is the key to improving the prediction accuracy of DTIs. In this paper, considering the contribution of different source data to DTIs prediction, a DTIs prediction approach based on an effective fusion of drug and target multi-source data is proposed, named EFMSDTI. EFMSDTI first builds 15 similarity networks based on multi-source information networks classified as topological and semantic graphs of drugs and targets according to their biological characteristics. Then, the multi-networks are fused by selective and entropy weighting based on similarity network fusion (SNF) according to their contribution to DTIs prediction. The deep neural networks model learns the embedding of low-dimensional vectors of drugs and targets. Finally, the LightGBM algorithm based on Gradient Boosting Decision Tree (GBDT) is used to complete DTIs prediction. Experimental results show that EFMSDTI has better performance (AUROC and AUPR are 0.982) than several state-of-the-art algorithms. Also, it has a good effect on analyzing the top 1000 prediction results, while 990 of the first 1000DTIs were confirmed. Code and data are available at https://github.com/meng-jie/EFMSDTI.
Efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations: Results from phase II and III trials

Objectives The addition of novel β-lactamase inhibitors to carbapenems restores the activity against multidrug-resistant Gram-negative bacteria. The aim of this study was to summarize the evidence on the efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations. Methods We conducted a meta-analysis of clinical trials comparing novel carbapenem–β-lactamase inhibitor combinations with comparators to assess the clinical and microbiological responses, mortality, and adverse events (AEs). Results A total of 1,984 patients were included. The pooled risk ratios (RRs) of clinical cure, microbiological eradication, all-cause mortality, and 28-day mortality were 1.11 (95% CI: 0.98–1.26), 0.98 (95% CI: 0.82–1.16), 0.90 (95% CI: 0.49–0.94), and 0.68 (95% CI: 0.49–0.94) between the novel carbapenem–β-lactamase inhibitor combinations and control groups. Sensitivity analysis revealed that the phase II trial of imipenem–cilastatin/relebactam (ICR) against complicated urinary tract infections could be the most important factor of heterogeneity for the microbiological response. The therapeutic effect of novel carbapenem–β-lactamase inhibitor combinations was better in meropenem–vaborbactam (MEV), phase III trials, and number of patients less than 200. The RRs of AEs from any cause and serious adverse events (SAEs) for patients receiving novel carbapenem–β-lactamase inhibitor combinations were 0.98 (95% CI: 0.93–1.04) and 1.01 (95% CI: 0.75–1.36), respectively. Conclusions ICR and MEV were superior to comparators for clinical cure and survival rate in the treatment of complicated infections, and both were as tolerable as the comparators.
Unique profile of predominant CCR5-tropic in CRF07_BC HIV-1 infections and discovery of an unusual CXCR4-tropic strain

CRF07_BC is one of the most prevalent HIV-1 strains in China, which contributes over one-third of the virus transmissions in the country. In general, CRF07_BC is associated with slower disease progression, while the underlying mechanisms remain unclear. Our study focused on envelope proteins (Env) and its V3 loop which determine viral binding to co-receptors during infection of cells. We studied a large dataset of 3,937 env sequences in China and found that CRF07_BC had a unique profile of predominantly single CCR5 tropism compared with CCR5 and CXCR4 dual tropisms in other HIV-1 subtypes. The percentages of the CXCR4-tropic virus in B (3.7%) and CRF01_AE (10.4%) infection are much higher than that of CRF07_BC (0.1%), which is supported by median false-positive rates (FPRs) of 69.8%, 25.5%, and 13.4% for CRF07_BC, B, and CRF01_AE respectively, with a cutoff FPR for CXCR4-tropic at 2%. In this study, we identified the first pure CXCR4-tropic virus from one CRF07_BC-infected patient with an extremely low CD4+T cell count (7 cells/mm3). Structural analysis found that the V3 region of this virus has the characteristic 7T and 25R and a substitution of conserved “GPGQ” crown motif for “GPGH”. This study provided compelling evidence that CRF07_BC has the ability to evolve into CXCR4 strains. Our study also lay down the groundwork for studies on tropism switch, which were commonly done for other HIV-1 subtypes, for the long-delayed CRF07_BC.
Factors of suicidal behavior among inpatients with major depressive disorder: A retrospective case series

Objective Previous studies indicate that more than half of those who died by suicide had a depressive disorder. When discussing the factors associated to suicidal behavior (SB) among patients with major depressive disorder (MDD), sociocultural contexts should also be carefully considered. This case series study explored the factors correlated to SB among MDD patients in Beijing, China. Methods The patient information sheets were retrieved from an electronic database that comprised patient medical information. Three forms of binary logistic regression equations were conducted to explore the factors associated to SB among patients with MDD. For the inconsistent variables produced by the three regression models, the propensity score matching (PSM) analysis was done for further verification. Results In this retrospective study, 1,091 depressed cases were enrolled. The difference between the SB group and non-SB group in gender, impulsivity, the severity of depression, history of major mental trauma, and family history of suicide were statistically significant in univariate comparisons (P < 0.05); the binary logistic regression analysis and the PSM analysis showed that female gender, history of major mental trauma, impulsivity, family history of suicide and severity of depression were factors correlated to SB among patients with MDD (odds ratios >1). Conclusions Female gender, the history of major mental trauma, impulsivity, the severity of depression, and family history of suicide were independently associated with the appearance of SB among MDD patients in Beijing, China. Inevitably, these findings should be viewed with particular caution due to the inherent drawbacks of a retrospective nature. More prospective longitudinal research should be conducted to examine those dynamic alterations in the corresponding confounders.
The study of new energy vehicle choice in China from the perspective of complex neural network

China has become the world’s largest market for the production and sales of new energy vehicles. In the Internet era, online review data is becoming more and more important, and it is a great challenge for new energy vehicle manufacturers and consumers to quickly obtain and find out the effective information in the review data. In view of the above understanding, this study uses the Bert-wwm-ext model structure, data mining, and deep learning to study the new energy vehicle selection, and also analyzes the positioning of domestic and foreign new energy vehicle brands and their brand development from the perspective of complex networks. The research results found that: 1) Consumers pay more and more attention to the quality of new energy vehicles. 2) The comparative analysis of BEV and PHEV reveals that consumers’ evaluation of both types of vehicles is roughly comparable, but the difference in satisfaction with the endurance of both types of vehicles is very obvious. 3) Most of the brands of new energy vehicles are concentrated in the price range of RMB80,000 to RMB350,000, and within this range, consumers’ evaluation is positively correlated with the price of the vehicle. Among the new energy vehicle brands over RMB350,000, consumer evaluation does not rise with the price of the vehicle. 4) The head effect of Chinese brands is significant, Foreign brands have formed strong brands with high brand premiums.