Research on China's Population Structure in the New Situation

To analyze the impact of the “two-child policy” on the population size and structure, first of all, the birth rate, the ratio of men and women, and the ratio of urban and rural population are used as indicators. Before and after the dispersion, then establish a PDE model, and compare it with the population predicted by the gray forecast to analyze the mitigation of the ageing of the second child policy; continue to analyze the impact of changes in the population structure on the national economy, and select the male and female ratio and the labor population The urban-rural population ratio is used as an index to establish a multiple regression equation for analysis, and a related regression equation is obtained. Finally, the future marriage problem is analyzed, considering only the difference in the number of men and women entering the marriageable period at the same time. The difference in the number of marriageable populations is analyzed through the difference in the number of men and women born at birth, focusing on a dynamic perspective

Study on reasonable advancing speed of fully-mechanized top-coal caving face in mining contugous extra-thick coal seams in rockburst mine

In view of the rock burst problem caused by too fast advancing speed of the working face, taking the mining of W1123 fully mechanized top coal caving face in contugous extra-thick coal seam in Kuangou Coal Mine as the background, the comprehensive analysis method of numerical simulation and theoretical analysis is adopted. By studying the mining stress and energy evolution characteristics of coal and rock under the influence of different advancing speeds, the characteristics of overlying strata movement and breaking at different advancing speeds are analyzed, and the burst risk of coal and rock mass under the influence of different advancing speeds is evaluated. The reasonable advancing speed of the working face is determined by comprehensive research. The results show that the peak stress of front abutment pressure caused by mining in the working face shows an obvious nonlinear increase trend with the increase of advancing speed, and its increase rate gradually increases. The mining stress level under solid coal is obviously higher than that under goaf, and the front abutment pressure shows an obvious double peak shape. With the increase of advancing speed, the initial breaking distance of overburden and the elastic energy accumulated in overburden obviously increase, and the strain energy density also gradually increases. The displacement of overlying strata increases sharply with the advancing speed, and the damage range is large, showing obvious discontinuous deformation characteristics. At the same time, the faster the advancing speed, the larger the influence range of overlying strata breakage, and the more severe the migration evolution. With the increase of advancing speed, the burst risk index of coal and rock in working face increases obviously, and the risk of mining under solid coal is far greater than that under goaf. The burst risk index of 100 m behind the setup room of overlying coal seam rises sharply with the increase of advancing speed, which is a high-risk area with bursts. According to the results of numerical simulation, it is considered that the relative suitable advancing speed of W1123 working face should be no more than 6.4 m/d on the premise of ensuring safe and efficient production. The research results provide scientific guidance for safe and efficient mining of rock burst prone mines in coal seams occur in close proximity

Single-Cell RNA Sequencing Maps Immune Cell Heterogeneity in Mice with Allogeneic Cardiac Transplantation

Objective: Immune cells play important roles in mediating allograft rejection and tolerance after cardiac transplantation. However, immune cell heterogeneity at the single-cell level, and how immune cell states shape transplantation immunity, remain incompletely characterized. Methods: We performed single-cell RNA sequencing (scRNA-seq) on immune cells in LNs from a mouse syngeneic and allogeneic cardiac transplantation model. Nine T cell clusters were identified through unsupervised analysis. Pathway enrichment analysis was used to explore the functional differences among cell subpopulations and to characterize the metabolic heterogeneity of T cells. Results: We comprehensively determined the transcriptional landscape of immune cells, particularly T cells, and their metabolic transcriptomes in LNs during mouse cardiac transplantation. On the basis of molecular and functional properties, we also identified T cell types associated with transplantation-associated immune processes, including cytotoxic CD8 + T cells, activated conventional CD4 + T cells, and dysfunctional Tregs. We further elucidated the contribution of JunB to the induction of Th17 cell differentiation and restriction of Treg development, and identified that HIF-1a participates in T cell metabolism and function. Conclusions: We present the first systematic single-cell analysis of transcriptional variation within the T cell population, providing new insights for the development of novel therapeutic targets for allograft rejection

The protective role of DOT1L in UV-induced melanomagenesis

The DOT1L histone H3 lysine 79 (H3K79) methyltransferase plays an oncogenic role in MLL-rearranged leukemogenesis. Here, we demonstrate that, in contrast to MLL-rearranged leukemia, DOT1L plays a protective role in ultraviolet radiation (UVR)-induced melanoma development. Specifically, the DOT1L gene is located in a frequently deleted region and undergoes somatic mutation in human melanoma. Specific mutations functionally compromise DOT1L methyltransferase enzyme activity leading to reduced H3K79 methylation. Importantly, in the absence of DOT1L, UVR-induced DNA damage is inefficiently repaired, so that DOT1L loss promotes melanoma development in mice after exposure to UVR. Mechanistically, DOT1L facilitates DNA damage repair, with DOT1L-methylated H3K79 involvement in binding and recruiting XPC to the DNA damage site for nucleotide excision repair (NER). This study indicates that DOT1L plays a protective role in UVR-induced melanomagenesis

Gene-SGAN: a method for discovering disease subtypes with imaging and genetic signatures via multi-view weakly-supervised deep clustering

Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Herein, we describe Gene-SGAN - a multi-view, weakly-supervised deep clustering method - which dissects disease heterogeneity by jointly considering phenotypic and genetic data, thereby conferring genetic correlations to the disease subtypes and associated endophenotypic signatures. We first validate the generalizability, interpretability, and robustness of Gene-SGAN in semi-synthetic experiments. We then demonstrate its application to real multi-site datasets from 28,858 individuals, deriving subtypes of Alzheimer's disease and brain endophenotypes associated with hypertension, from MRI and SNP data. Derived brain phenotypes displayed significant differences in neuroanatomical patterns, genetic determinants, biological and clinical biomarkers, indicating potentially distinct underlying neuropathologic processes, genetic drivers, and susceptibility factors. Overall, Gene-SGAN is broadly applicable to disease subtyping and endophenotype discovery, and is herein tested on disease-related, genetically-driven neuroimaging phenotypes

The protective role of DOT1L in UV-induced melanomagenesis

The DOT1L histone H3 lysine 79 (H3K79) methyltransferase plays an oncogenic role in MLL-rearranged leukemogenesis. Here, we demonstrate that, in contrast to MLL-rearranged leukemia, DOT1L plays a protective role in ultraviolet radiation (UVR)-induced melanoma development. Specifically, the DOT1L gene is located in a frequently deleted region and undergoes somatic mutation in human melanoma. Specific mutations functionally compromise DOT1L methyltransferase enzyme activity leading to reduced H3K79 methylation. Importantly, in the absence of DOT1L, UVR-induced DNA damage is inefficiently repaired, so that DOT1L loss promotes melanoma development in mice after exposure to UVR. Mechanistically, DOT1L facilitates DNA damage repair, with DOT1L-methylated H3K79 involvement in binding and recruiting XPC to the DNA damage site for nucleotide excision repair (NER). This study indicates that DOT1L plays a protective role in UVR-induced melanomagenesis

Mechanism of Rock Burst and Its Dynamic Control Measures in Extra-Thick Coal Seam Mining from below the Residual Coal Seam to below the Gob

AbstractIn this paper, aiming at the mechanism and regulation of overburden breakage induced by mining from the residual coal seam to the mined-out area, taking Kuangou Coal Mine as the background, the mechanism of rock burst from the residual coal seam to the mined-out area was revealed through the laws of overburden breakage and its structural evolution, ground pressure appearance, and energy release. The impact risk area is determined by the comprehensive evaluation results of multimethod face impact risk. A roof pressure relief and impact prevention control method using large-diameter empty hole combined with advanced deep hole blasting was formed, and the field verification was completed. The research results show that an obvious inverted trapezoid structure is formed when the residual coal seam of the W1123 working face is mined to the working face under the gob, which is related to the energy release caused by the occurrence of periodic pressure and the rupture of the critical layer. The shock ground pressure of the working face predicted by the neural network is mainly weak shock and medium shock risk; the numerical simulation analysis shows that the shock hazard area of the W1123 face below the solid coal is mainly located in the lower part of the working face near the transportation roadway and the shock below the W1145 gob. The dangerous area is about 32~72 m away from the return air alley. Through the plastic zone distribution and the orthogonal test, the optimal pressure relief scheme for large-diameter holes is 12 m in depth, 300 mm in diameter, and 2 m in spacing. When the blasting angle is consistent with the overlying rock fracture angle obtained from the simulation experiment, a better pressure relief can be achieved. When the bursting angle is consistent with the simulated overburden rupture angle, it has a better pressure relief effect. The pressure relief and anti-scour control method of large-diameter holes combined with advanced deep hole blasting reduce the daily average vibration frequency, energy, incoming pressure, and step distance of working face mining. The safe and efficient mining has a certain reference effect

Prediction of protein-ligand binding affinity with deep learning

The prediction of binding affinities between target proteins and small molecule drugs is essential for speeding up the drug research and design process. To attain precise and effective affinity prediction, computer-aided methods are employed in the drug discovery pipeline. In the last decade, a variety of computational methods has been developed, with deep learning being the most commonly used approach. We have gathered several deep learning methods and classified them into convolutional neural networks (CNNs), graph neural networks (GNNs), and Transformers for analysis and discussion. Initially, we conducted an analysis of the different deep learning methods, focusing on their feature construction and model architecture. We discussed the advantages and disadvantages of each model. Subsequently, we conducted experiments using four deep learning methods on the PDBbind v.2016 core set. We evaluated their prediction capabilities in various affinity intervals and statistically and visually analyzed the samples of correct and incorrect predictions for each model. Through visual analysis, we attempted to combine the strengths of the four models to improve the Root Mean Square Error (RMSE) of predicted affinities by 1.6% (reducing the absolute value to 1.101) and the Pearson Correlation Coefficient (R) by 2.9% (increasing the absolute value to 0.894) compared to the current state-of-the-art method. Lastly, we discussed the challenges faced by current deep learning methods in affinity prediction and proposed potential solutions to address these issues

Expression of adhA from different organisms in Clostridium thermocellum

Abstract Background Clostridium thermocellum is a cellulolytic anaerobic thermophile that is a promising candidate for consolidated bioprocessing of lignocellulosic biomass into biofuels such as ethanol. It was previously shown that expressing Thermoanaerobacterium saccharolyticum adhA in C. thermocellum increases ethanol yield.In this study, we investigated expression of adhA genes from different organisms in Clostridium thermocellum. Methods Based on sequence identity to T. saccharolyticum adhA, we chose adhA genes from 10 other organisms: Clostridium botulinum, Methanocaldococcus bathoardescens, Thermoanaerobacterium ethanolicus, Thermoanaerobacter mathranii, Thermococcus strain AN1, Thermoanaerobacterium thermosaccharolyticum, Caldicellulosiruptor saccharolyticus, Fervidobacterium nodosum, Marinitoga piezophila, and Thermotoga petrophila. All 11 adhA genes (including T. saccharolyticum adhA) were expressed in C. thermocellum and fermentation end products were analyzed. Results All 11 adhA genes increased C. thermocellum ethanol yield compared to the empty-vector control. C. botulinum and T. ethanolicus adhA genes generated significantly higher ethanol yield than T. saccharolyticum adhA. Conclusion Our results indicated that expressing adhA is an effective method of increasing ethanol yield in wild-type C. thermocellum, and that this appears to be a general property of adhA genes