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The research objectives are to reveal the eco-environmental quality of surface mining areas in semi-arid grasslands, separate the ecological cumulative effects of anthropogenic activities and examine their evolving trends. Based on the concept of ecological cumulative effects in mining areas, an assessment index called Surface Mining Areas Eco-environmental Evaluation Index (SMAEEI) and a quantitative evaluation model of ecological cumulative effects in mining areas suitable for semi-arid grasslands were developed. The Shengli Coalfield in Inner Mongolia was selected as the study site to analyze the spatiotemporal distribution patterns of regional eco-environmental quality and ecological cumulative effects from 1986 to 2020, and the differences between cumulative effects caused by major anthropogenic activities. The results show that: ① the SMAEEI is applicable to the surface mining areas in semi-arid grasslands and can objectively rank the eco-environmental quality across different land-cover types. The study area exhibited an extremely significant decline in eco-environmental quality over the past 35 years, with diminishing spatial differences. Open-pit mines, expanding urban areas, Xilin River wetlands, and northern grasslands experienced extremely significant or significant degradation trends. ② The quantitative evaluation model of ecological cumulative effects for the surface mining areas in semi-arid grasslands can exclude the influence of climate factors on ecosystems, effectively quantify the cumulative effects of human activities on mining area ecosystems, and reveal their direction, magnitude, and spatial extent. The Change of Ecosystem Service Value Cumulant (COESVC) in the study area decreased by a total of 11 861.570 3 million yuan, indicating a negative ecological cumulative effect and a decline in ecosystem services and functions. Areas with high and medium levels of negative accumulation were concentrated in degraded wetlands, grasslands, urban regions, and open-pit mines. ③ Surface mining and urban development exerted the most pronounced negative ecological cumulative effects per unit area. The former exhibited the most severe negative changes per unit time, and the latter had the greatest local impact and deviation in negative cumulative effects. Grazing resulted in negative ecological cumulative effects over a wider range and in larger quantities but with the least local impact. Compared with other human activities, the ecosystem services and functions were more stable in relation to grazing. The research outcomes facilitate the shift from the physical quantity changes of the ecological environment caused by human activities in mining areas to value-based descriptions, providing a feasible method for estimating the environmental damage costs of regional production and living behaviors in monetary terms.

Abstract Traditional decomposition integration models decompose the original sequence into subsequences, which are then proportionally divided into training and testing periods for modeling. Decomposition may cause data aliasing, then the decomposed training period may contain part of the test period data. A more effective method of sample construction is sought in order to accurately validate the model prediction accuracy. Semi-stepwise decomposition (SSD), full stepwise decomposition (FSD), single model semi-stepwise decomposition (SMSSD), and single model full stepwise decomposition (SMFSD) techniques were used to create the samples. This study integrates Variational Mode Decomposition (VMD), African Vulture Optimization Algorithm (AVOA), and Least Squares Support Vector Machine (LSSVM) to construct a coupled rainfall prediction model. The influence of different VMD parameters α is examined, and the most suitable stepwise decomposition machine learning coupled model algorithm for various stations in the North China Plain is selected. The results reveal that SMFSD is relatively the most suitable tool for monthly precipitation forecasting in the North China Plain. Among the predictions for the five stations, the best overall performance is observed at Huairou Station (RMSE of 18.37 mm, NSE of 0.86, MRE of 107.2%) and Jingxian Station (RMSE of 24.74 mm, NSE of 0.86, MRE of 51.71%), while Hekou Station exhibits the poorest performance (RMSE of 25.11 mm, NSE of 0.75, MRE of 173.75%).

Abstract Background Allogeneic Blood transfusion is common in hip surgery but is associated with increased morbidity. Accurate prediction of transfusion risk is necessary for minimizing blood product waste and preoperative decision-making. The study aimed to develop machine learning models for predicting perioperative blood transfusion in hip surgery and identify significant risk factors. Methods Data of patients undergoing hip surgery between January 2013 and October 2021 in the Peking Union Medical College Hospital were collected to train and test predictive models. The primary outcome was perioperative red blood cell (RBC) transfusion within 72 h of surgery. Fourteen machine learning algorithms were established to predict blood transfusion risk incorporating patient demographic characteristics, preoperative laboratory tests, and surgical information. Discrimination, calibration, and decision curve analysis were used to evaluate machine learning models. SHapley Additive exPlanations (SHAP) was performed to interpret models. Results In this study, 2431 hip surgeries were included. The Ridge Classifier performed the best with an AUC = 0.85 (95% CI, 0.81 to 0.88) and a Brier score = 0.21. Patient-related risk factors included lower preoperative hemoglobin, American Society of Anesthesiologists (ASA) Physical Status > 2, anemia, lower preoperative fibrinogen, and lower preoperative albumin. Surgery-related risk factors included longer operation time, total hip arthroplasty, and autotransfusion. Conclusions The machine learning model developed in this study achieved high predictive performance using available variables for perioperative blood transfusion in hip surgery. The predictors identified could be helpful for risk stratification, preoperative optimization, and outcomes improvement.

Abstract Background The presence of mesenchymal stem cells has been confirmed in some solid tumors where they serve as important components of the tumor microenvironment; however, their role in cancer has not been fully elucidated. The aim of this study was to investigate the functions of mesenchymal stem cells isolated from tumor tissues of patients with non-small cell lung cancer. Results Human lung cancer-derived mesenchymal stem cells displayed the typical morphology and immunophenotype of mesenchymal stem cells; they were nontumorigenic and capable of undergoing multipotent differentiation. These isolated cells remarkably enhanced tumor growth when incorporated into systems alongside tumor cells in vivo. Importantly, in the presence of mesenchymal stem cells, the ability of peripheral blood mononuclear cell-derived natural killer and activated T cells to mediate tumor cell destruction was significantly compromised. Conclusion Collectively, these data support the notion that human lung cancer-derived mesenchymal stem cells protect tumor cells from immune-mediated destruction by inhibiting the antitumor activities of natural killer and T cells.

Background: Breast cancer is the most widespread malignant tumor worldwide. Single-cell sequencing technology offers novel insights and methods to understand the onset, progression, and treatment of tumors. Nevertheless, there is currently an absence of a thorough and unbiased report on the comprehensive research status of single-cell sequencing in breast cancer. This study seeks to summarize and quantify the dynamics and trends of research on breast cancer single-cell sequencing by bibliometric analysis. Methods: Research articles and reviews related to breast cancer single-cell sequencing were selected from the WoSCC database. Visualization of data regarding countries, institutions, authors, references, and keywords was performed by CiteSpace and VOSviewer software. Results: 583 articles and reviews were analyzed in this study. The quantity of publications related to breast cancer single-cell sequencing has been increasing annually. These studies originate from 302 institutions in 46 countries, with YMAX S WICHA producing the most publications and WANG Y being the most cited author. Nature Communications is the most researched journal, while Nature holds the highest number of citations. These journals predominantly cover topics in the molecular/biological/immunological fields. Moreover, an analysis of reference and keyword bursts revealed that current research trends in this area are primarily centered on “clonal evolution,” “tumor microenvironment,” and “immunotherapy.” Conclusion: Breast cancer single-cell sequencing is a rapidly growing area of scientific interest. Future research requires more frequent and in-depth collaborations among countries, institutions, and authors. Furthermore, “clonal evolution,” “tumor microenvironment,” and “immunotherapy” are likely to become major focal points in upcoming research on breast cancer single-cell sequencing.

Transcatheter aortic valve implantation (TAVI) was originally devised as a treatment for patients with aortic stenosis (AS). It has since emerged as a beneficial alternative to surgical aortic valve replacement (SAVR), extending its reach to a broader array of patients. Our objective was to illustrate the developmental trends and focus areas in TAVI research. We sourced a total of 11,480 research papers on TAVI, published between 1994 and 2022, from the Web of Science Core Collection (WoSCC) database. We conducted a bibliometric analysis of these publications, generating cooperation maps, performing co-citation analysis of journals and references, and carrying out a cluster analysis of keywords. Our findings indicate that TAVI research grapples with numerous clinical challenges. We created knowledge maps that highlight contributing countries/institutions, authors, journals with high publication and citation rates, and notable references in this domain. North America and Europe have been at the forefront of research within the TAVI field. The institutions and authors from these regions exert significant influence in this area of study. Beginning in 2009, China has progressively expanded its research on TAVI over the past two decades. We anticipate that future research will increasingly focus on three key areas: implementation scope, lifelong management, outcomes and predicting the risk of TAVI. Research on TAVI is flourishing. Cooperation among different countries and institutions in this field must be strengthened in the future, especially for developing counties.

Abstract Temperature as an important indicator of climate change, accurate temperature prediction has important guidance and application value for agricultural production, energy management and disaster warning. Based on the advantages of CEEMDAN model in effectively extracting the time–frequency characteristics of nonlinear and nonsmooth signals, BO algorithm in optimizing the objective function within a limited number of iterations, and BiLSTM model in revealing the connection between the current data, the previous data and the future data, a monthly average temperature prediction model based on CEEMDAN–BO–BiLSTM is established. A CEEMDAN–BO–BiLSTM-based monthly average temperature prediction model is developed and applied to the prediction of monthly average temperature in Jinan City, Shandong Province. The results show that the constructed monthly mean temperature prediction model based on CEEMDAN–BO–BiLSTM is feasible; the constructed CEEMDAN–BO–BiLSTM model has an average absolute error of 1.17, a root mean square error of 1.43, an average absolute percentage error of 0.31%, which is better than CEEMDAN–BiLSTM, EMD–BiLSTM, and BiLSTM models in terms of prediction accuracy and shows better adaptability; the constructed CEEMDAN–BO–BiLSTM model illustrates that the model is not over-modeled and adds complexity using Friedman’s test and performance comparisons between model run speeds. The model provides insights for effective forecasting of monthly mean temperatures.

Pancreatic ductal adenocarcinoma (PDAC) is the prototypical aggressive cancer that develops in nutrient-deficient and hypoxic microenvironment. PDAC overcomes these restrictions by employing unconventional tactics for the procurement and usage of fuel sources. The substantial reprogramming of PDAC cell metabolism is driven by oncogene-mediated cell-autonomous pathways. PDAC cells use glucose, glutamine, and lipids for energy and depend on autophagy and macropinocytosis for survival and growth. They also interact metabolically with non-cancerous cells, aiding tumor progression. Many clinical trials focusing on altered metabolism are ongoing. Understanding the metabolic regulation of PDAC cells will not only help to increase understanding of the mechanisms of disease progression but also provide insights for the development of new diagnostic and therapeutic approaches.

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Others and our studies have shown that mechanical stresses (forces) including shear stress and cyclic stretch, occur in various pathological conditions, play significant roles in the development and progression of CVDs. Mitochondria regulate the physiological processes of cardiac and vascular cells mainly through adenosine triphosphate (ATP) production, calcium flux and redox control while promote cell death through electron transport complex (ETC) related cellular stress response. Mounting evidence reveal that mechanical stress-induced mitochondrial dysfunction plays a vital role in the pathogenesis of many CVDs including heart failure and atherosclerosis. This review summarized mitochondrial functions in cardiovascular system under physiological mechanical stress and mitochondrial dysfunction under pathological mechanical stress in CVDs (graphical abstract). The study of mitochondrial dysfunction under mechanical stress can further our understanding of the underlying mechanisms, identify potential therapeutic targets, and aid the development of novel treatments of CVDs.

In this article, a fault diagnosis method is presented for identifying multi-point grounding faults in transformer cores. Based on the finite element method (FEM), the method aims to achieve non-invasive localization of these faults, thereby minimizing loss attributed to troubleshooting and maintenance downtime. Firstly, as a prerequisite for solving the coupled temperature field, an applied circuit method is employed to ascertain the internal loss of the transformer. This determination relies on investigating the influence of internal loss in the oil-immersed transformers for diagnosing under rated operating conditions. Secondly, the internal temperature distribution within the transformer and the condition of the transformer oil are comprehensively analyzed and validated by using an electromagnetic-fluid-solid coupled finite element simulation. Lastly, relying on the simulation outcomes under fault-free conditions, a fault model of the transformer core is established. Subsequently, the output data of the model are classified and localized using deep belief networks. This approach resolves the problems associated with masking transformer fault data signals and acquiring data. The results indicate that the temperature data obtained from the temperature field simulation exhibit an error of less than 2.6% when compared to actual values. The fault localization accuracy for multiple grounding points in the iron core of oil-immersed transformers reaches 96.4%, confirming the practicality and effectiveness of this method.

Abstract Objectives This study intends to build an artificial intelligence model for obstetric cesarean section surgery to evaluate the intraoperative blood transfusion volume before operation, and compare the model prediction results with the actual results to evaluate the accuracy of the artificial intelligence prediction model for intraoperative red blood cell transfusion in obstetrics. The advantages and disadvantages of intraoperative blood demand and identification of high-risk groups for blood transfusion provide data support and improvement suggestions for the realization of accurate blood management of obstetric cesarean section patients during the perioperative period. Methods Using a machine learning algorithm, an intraoperative blood transfusion prediction model was trained. The differences between the predicted results and the actual results were compared by means of blood transfusion or not, blood transfusion volume, and blood transfusion volume targeting postoperative hemoglobin (Hb). Results Area under curve of the model is 0.89. The accuracy of the model for blood transfusion was 96.85%. The statistical standard for the accuracy of the model blood transfusion volume is the calculation of 1U absolute error, the accuracy rate is 86.56%, and the accuracy rate of the blood transfusion population is 45.00%. In the simulation prediction results, 93.67% of the predicted and actual cases in no blood transfusion surgery; 63.45% of the same predicted blood transfusion in blood transfusion surgery, and only 20.00% of the blood transfusion volume is the same. Conclusions In conclusion, this study used machine learning algorithm to process, analyze and predict the results of a large sample of cesarean section clinical data, and found that the important predictors of blood transfusion during cesarean section included preoperative RBC, surgical method, the site of surgery, coagulation-related indicators, and other factors. At the same time, it was found that the overall accuracy of the AI model was higher than actual blood using. Although the prediction of blood transfusion volume was not well matched with the actual blood using, the model provided a perspective of preoperative identification of high blood transfusion risks. The results can provide good auxiliary decision support for preoperative evaluation of obstetric cesarean section, and then promote the realization of accurate perioperative blood management for obstetric cesarean section patients.

Abstract Purpose To develop a deep learning radiomics of multiparametric magnetic resonance imaging (DLRMM)‐based model that incorporates preoperative and postoperative signatures for prediction of local tumor progression (LTP) after thermal ablation (TA) in hepatocellular carcinoma (HCC). Methods From May 2017 to October 2021, 417 eligible patients with HCC were retrospectively enrolled from three hospitals (one primary cohort [PC, n = 189] and two external test cohorts [ETCs][n = 135, 93]). DLRMM features were extracted from T1WI + C, T2WI, and DWI using ResNet18 model. An integrative model incorporating the DLRMM signature with clinicopathologic variables were further built to LTP risk stratification. The performance of these models were compared by areas under receiver operating characteristic curve (AUC) using DeLong test. Results A total of 1668 subsequences and 31,536 multiparametric MRI slice including T1WI, T2WI, and DWI were collected simultaneously. The DLRMM signatures were extracted from tumor and ablation zone, respectively. Ablative margin, multiple tumors, and tumor abutting major vessels were regarded as risk factors for LTP in clinical model. The AUC of DLRMM model were 0.864 in PC, 0.843 in ETC1, and 0.858 in ETC2, which was higher significantly than those in clinical model (p

Abstract Lipid metabolism disorders are considerably involved in the pathology of atherosclerosis; nevertheless, the fundamental mechanism is still largely unclear. This research sought to examine the function of lipophagy in lipid metabolism disorder-induced atherosclerosis and its fundamental mechanisms. Previously, Sirt6 has been reported to stimulate plaque stability by promoting macrophage autophagy. However, its role in macrophage lipophagy and its relationship with Wnt1 remains to be established. In this study, ApoE−/−: Sirt6−/− and ApoE−/−: Sirt6Tg mice were used and lipid droplets were analysed via transmission electron microscopy and Bodipy 493/503 staining in vitro. Atherosclerotic plaques in ApoE−/−: Sirt6−/− mice showed greater necrotic cores and lower stability score. Reconstitution of Sirt6 in atherosclerotic mice improved lipid metabolism disorder and prevented the progression of atherosclerosis. Furthermore, macrophages with Ac-LDL intervention showed more lipid droplets and increased expression of adipophilin and PLIN2. Reconstitution of Sirt6 recruited using SNF2H suppressed Wnt1 expression and improved lipid metabolism disorder by promoting lipophagy. In addition, downregulation of Sirt6 expression in Ac-LDL-treated macrophages inhibited lipid droplet degradation and stimulated foam cell formation. Innovative discoveries in the research revealed that atherosclerosis is caused by lipid metabolism disorders due to downregulated Sirt6 expression. Thus, modulating Sirt6’s function in lipid metabolism might be a useful therapeutic approach for treating atherosclerosis.

Abstract Addressing the current complexities, costs, and adherence issues in the detection of forward head posture (FHP), our study conducted an exhaustive epidemiologic investigation, incorporating a comprehensive posture screening process for each participant in China. This research introduces an avant-garde, machine learning-based non-contact method for the accurate discernment of FHP. Our approach elevates detection accuracy by leveraging body landmarks identified from human images, followed by the application of a genetic algorithm for precise feature identification and posture estimation. Observational data corroborates the superior efficacy of the Extra Tree Classifier technique in FHP detection, attaining an accuracy of 82.4%, a specificity of 85.5%, and a positive predictive value of 90.2%. Our model affords a rapid, effective solution for FHP identification, spotlighting the transformative potential of the convergence of feature point recognition and genetic algorithms in non-contact posture detection. The expansive potential and paramount importance of these applications in this niche field are therefore underscored.

Junctional adhesion molecule-A (JAM-A), also known as F11 receptor (F11R), is a transmembrane glycoprotein that is involved in various biological processes, including cancer initiation and progression. However, the functional characteristics and significance of JAM-A in pan-cancer remain unexplored. In this study, we used multiple databases to gain a comprehensive understanding of JAM-A in human cancers. JAM-A was widely expressed in various tissues, mainly located on the microtubules and cell junctions. Aberrant expression of JAM-A was detected in multiple cancers at both mRNA and protein levels, which can be correlated with poorer prognosis and may be attributed to genetic alterations and down-regulated DNA methylation. JAM-A expression was also associated with immune infiltration and may affect immunotherapy responses in several cancers. Functional enrichment analysis indicated that JAM-A participated in tight junction and cancer-related pathways. In vitro experiments verified that JAM-A knockdown suppressed the proliferation and migration abilities of breast cancer cells and liver cancer cells. Overall, our study suggests that JAM-A is a pan-cancer regulator and a potential biomarker for predicting prognosis and immune-therapeutic responses for different tumors.

Objective To investigate the compatibility of human albumin and its internal packaging materials of Sinopharm Lanzhou Biopharmaceutical Co., Ltd. Methods One batch of inner packaging materials (medium borosilicate glass-molded injection bottle and halogenated butyl rubber plug for injection) was extracted with 4 extraction solvents to conduct the toxicological evaluation of potential inner packaging extracts. Through the simulated acceleration test, the trend analysis of the elements in the sample and the inner surface of the glass bottle were observed, and the routine drug inspection items during the long-term stability test process were determined. Results The detection results of the leaching elements of the internal packaging materials did not exceed the limit of 50%, and the organic matter safety threshold (margin of safety, MOS) was greater than 1.0, indicating that both the leaching elements and the organic matter had no safety risk to the user under the current exposure. The results of the simulated acceleration test show that the drug will not have the risk of peeling tablets after the long-term stability condition was placed for a period of time, and the routine inspection items of the long-term stability test drugs all meet the requirements of the pharmacopoeia. Conclusion The inner packaging material has no significant impact on the quality of drugs and has good overall compatibility, making it suitable for packaging human albumin.

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet–induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1–WIPI2 axis may be a novel therapeutic strategy for NASH.

To investigate the wall cooling of the thrust chamber in an engine, two film-cooling structures, namely, a circular hole structure and a slot structure, were designed. Numerical simulations were performed to study the coupled flow and regenerative cooling heat transfer in thrust chambers with different structures. The influences of parameters such as the film mass flow rate and film hole size on wall cooling were analyzed. Experiments were conducted in a thrust chamber to validate the accuracy of the numerical calculation method. The results indicate that the slot-structured film adheres better to the wall than the circular-hole-structured film, and the film closely adhering to the wall provides better insulation against hot gas, resulting in a reduction of approximately 6% in wall temperature. When the film hole size changes, the change in circumferential wall temperature in the upstream region of the slot-structured film is more pronounced. This paper aims to provide a reference for the design of the cooling structure at the head of the thrust chamber in engineering and suggests directions for optimization and improvement.

Over the past few decades, marine current energy utilization has transitioned from conceptual demonstrations to industrial-scale prototypes. This progression now approaches a crucial phase emphasizing the need for industrialization and commercialization. This paper provides an in-depth examination of the developmental status of large-scale marine current turbines and arrays, underscoring the promising prospects for marine current energy systems. Despite the significant advancements, the deployment of these systems has revealed several challenges, including blade design optimization, transmission system selection, and the establishment of appropriate test sites. Addressing these issues is essential for technological maturity and economic feasibility, which will foster the next wave of innovation in marine energy systems. Furthermore, the paper offers various perspectives for future applications.

Plasma-initiated polymerization (PIP) is generally attributed to a radical process due to its inhibiting property. However, its unique polymerization behaviors like long-lived radical and solvent effect do not comply well with the traditional radical mechanism. Herein, the PIP of methyl methacrylate (MMA) was conducted in a high-voltage DC electric field to investigate the charged nature of its radicals. Consequently, the polymerization presented a preferential distribution of polymers at the anode but not the cathode, revealing the negatively charged nature of the growing radicals. An acceleration phenomenon, accompanied by the growth in molecular weights and the reduction in molecular weight distributions (Ð), was observed at the voltages above 16 kV, suggesting the dissociation of ion pairs of growing radicals. The PIP yielded PMMA with analogous chemical and steric structures to those of PMMA from traditional radical initiation, whether in the presence or absence of the external electric field. This work offers new insights into the PIP of vinyl monomers, wherein a one-electron transfer reaction is inferred to be involved in the monomer activation.

Frequent spontaneous combustion activities restrict ecological restoration of coal waste dumps after reclamation. Effective monitoring of vegetation restoration is important for ensuring land reclamation success and preserving the ecological environment in mining areas. Development of unmanned aerial vehicle (UAV) technology has enabled fine-scale vegetation monitoring. In this study, we focused on Medicago sativa L. (alfalfa), a representative herbaceous vegetation type, in a coal waste dump after reclamation in Shanxi province, China. The alfalfa aboveground biomass (AGB) was used as an indicator for assessing vegetation restoration. The objective of this study was to evaluate the capacity of UAV-based fusion of RGB, multispectral, and thermal infrared information for estimating alfalfa AGB using various regression models, including random forest regression (RFR), gradient boosting decision tree (GBDT), K-nearest neighbor (KNN), support vector regression (SVR), and stacking models. The main results are as follows: (i) UAV multi-source data fusion improved alfalfa AGB estimation accuracy, although the enhancement diminished with the increasing number of sensor types. (ii) The stacking model consistently outperformed RFR, GBDT, KNN, and SVR regression models across all feature fusion combinations. It achieved high accuracy with R2 of 0.86–0.88, RMSE of 80.06–86.87 g/m2, and MAE of 60.24–62.69 g/m2. Notably, the stacking model based on only RGB imagery features mitigated the accuracy loss from limited types of features, potentially reducing equipment costs. This study demonstrated the potential of UAV in improving vegetation restoration management of coal waste dumps after reclamation.

Triboelectric nanogenerator has extensive applicability because of its capability of harvesting mechanical energy and flexible working modes. To research the optimum pressure and improve the recovered energy of the sliding-mode triboelectric nanogenerator, a contact model of the Al/PTFE tribo-pair is studied by ab initio calculation and finite element simulation. The F-atom of PTFE is proved to be the electron accepter and the charges transferred can be predicted by Bader charge analysis. The mathematical relation between interfacial distance, charges transferred and contact pressure can be fitted. By Gauss’s law, the electric field is simulated and the regeneration energy of the sliding-mode triboelectric nanogenerator can be evaluated by the total electric energy and friction loss. Finally, an optimum pressure can be set to the upper or lower limit of working pressure corresponding to larger recovered energy. And less friction coefficient and larger contact area are also effective methods for recovering energy.

Abstract Background Acute myocardial infarction is a major health problem and is the leading cause of death worldwide. Myocardial apoptosis induced by myocardial infarction injury is involved in the pathophysiology of heart failure. Therapeutic stem cell therapy has the potential to be an effective and favorable treatment for ischemic heart disease. Exosomes derived from stem cells have been shown to effectively repair MI injury-induced cardiomyocyte damage. However, the cardioprotective benefits of adipose tissue-derived mesenchymal stem cell (ADSC)-Exos remain unknown. This study aimed to investigate the protective effects of exosomes from ADSC on the hearts of MI-treated mice and to explore the underlying mechanisms. Methods Cellular and molecular mechanisms were investigated using cultured ADSCs. On C57BL/6J mice, we performed myocardial MI or sham operations and assessed cardiac function, fibrosis, and angiogenesis 4 weeks later. Mice were intramyocardially injected with ADSC-Exos or vehicle-treated ADSCs after 25 min following the MI operation. Results Echocardiographic experiments showed that ADSC-Exos could significantly improve left ventricular ejection fraction, whereas ADSC-Exos administration could significantly alleviate MI-induced cardiac fibrosis. Additionally, ADSC-Exos treatment has been shown to reduce cardiomyocyte apoptosis while increasing angiogenesis. Molecular experiments found that exosomes extracted from ADSCs can promote the proliferation and migration of microvascular endothelial cells, facilitate angiogenesis, and inhibit cardiomyocytes apoptosis through miRNA-205. We then transferred isolated exosomes from ADSCs into MI-induced mice and observed decreased cardiac fibrosis, increased angiogenesis, and improved cardiac function. We also observed increased apoptosis and decreased expression of hypoxia-inducible factor-1α and vascular endothelial growth factor in HMEC-1 transfected with a miRNA-205 inhibitor. Conclusion In summary, these findings show that ADSC-Exos can alleviate cardiac injury and promote cardiac function recovery in MI-treated mice via the miRNA-205 signaling pathway. ADSC-Exos containing miRNA205 have a promising therapeutic potential in MI-induced cardiac injury.

The distribution of measurement noise is usually assumed to be Gaussian in the optimal phasor measurement unit (PMU) placement (OPP) problem. However, this is not always accurate in practice. This paper proposes a new OPP method for smart grids in which the effects of conventional measurements, limited channels of PMUs, zero-injection buses (ZIBs), single PMU loss contingency, state estimation error (SEE), and the maximum SEE variance (MSEEV) are considered. The SEE and MSEEV are both obtained using a robust $t$-distribution maximum likelihood estimator (MLE) because $t$-distribution is more flexible for modeling both Gaussian and non-Gaussian noises. The A- and G-optimal experimental criteria are utilized to form the SEE and MSEEV constraints. This allows the optimization problem to be converted into a linear objective function subject to linear matrix inequality observability constraints. The performance of the proposed OPP method is verified by the simulations of the IEEE 14-bus, 30-bus, and 118-bus systems as well as the 188-bus practical distribution system in China.

The geostationary orbit microwave multi-channel radiometer has the advantages of high real-time performance and large coverage, which plays an important role in typhoon, strong precipitation detection, and medium-to-short-term meteorological/oceanic forecasting. However, due to the difficulty in engineering development of the payload, its application on-orbit has not yet been achieved at present. To satisfy the requirements of fine and quantitative application of satellite observation data, a geostationary orbit microwave multi-channel radiometer with a 10-m-caliber is developed, in which the spatial resolution at horizontal polarization is better than 24 km at 54 GHz. In geostationary orbit microwave multi-channel radiometer, a quasi-optical feed network covering nearly 28 frequency octave bands and ranging from 23.8 to 664 GHz is proposed to solve the technical problem of multi-frequency sharing in the system. Meanwhile, a high-precision reflector preparation method and a high-precision unfolding scheme are proposed, which are considered as a solution for the large-diameter reflector with a high maintaining surface accuracy. A high-precision antenna prototype with 0.54-m is developed, and the tests are performed to verify the key technologies, such as the preparation of high-precision grating reflectors at the micron level, high surface accuracy detection, and sub-millimeter wave antenna electrical performance testing. The results indicate that measured main beam efficiency of the 664 GHz antenna is better than 95.5%. In addition, the system sensitivity is greater than 1.5 K, and the calibration accuracy is better than 1.8 K, according to the results of an analysis of the multi-channel radiometer’s essential parameters and calibration errors.

Abstract Opencast coal mining has a large impact on the land surface, both at the mining pits themselves and at waste sites. After artificial management is stopped, a reclaimed opencast coal mine dump is affected by wind and water erosion from natural processes, resulting in land degradation and even safety incidents. In this paper, the soil erosion and land degradation after 5 years of such natural processes, at the Xilinhot opencast coal mine dump in Inner Mongolia, were investigated. A multi-source data acquisition method was applied: the vegetation fraction coverage (VFC) was extracted from GF-1 satellite imagery, high-precision terrain characteristics and the location and degree of soil erosion were obtained using a drone, and the physical properties of the topsoil were obtained by field sampling. On this basis, the degree and spatial distribution of erosion cracks were identified, and the causes of soil erosion and land degradation were analyzed using the geographical detector. The results show that (1) multi-source data acquisition method can provide effective basic data for the quantitative evaluation of the ecological environment at dumps, and (2) slope aspect and VFC are the main factors affecting the degree of degradation and soil erosion. Based on above analysis, several countermeasures are proposed to mitigate land degradation: (1) The windward slope be designed to imitate the natural landform. (2) Reasonable engineering measures should be applied at the slope to restrain soil erosion. (3) The Pioneer plants should be widely planted on the platform at the early stage of reclamation.

Summary: To date, genome-wide association studies (GWAS) have revealed over 200 genetic risk loci associated with prostate cancer; yet, true disease-causing variants remain elusive. Identification of causal variants and their targets from association signals is complicated by high linkage disequilibrium and limited availability of functional genomics data for specific tissue/cell types. Here, we integrated statistical fine-mapping and functional annotation from prostate-specific epigenomic profiles, 3D genome features, and quantitative trait loci data to distinguish causal variants from associations and identify target genes. Our fine-mapping analysis yielded 3,395 likely causal variants, and multiscale functional annotation linked them to 487 target genes. We prioritized rs10486567 as a genome-wide top-ranked SNP and predicted HOTTIP as its target. Deletion of the rs10486567-associated enhancer in prostate cancer cells decreased their capacity for invasive migration. HOTTIP overexpression in enhancer-KO cell lines rescued defective invasive migration. Furthermore, we found that rs10486567 regulates HOTTIP through allele-specific long-range chromatin interaction.

Ecological risk assessment plays an important role in ecosystem management and conservation. Conventional landscape-level assessment can only estimate the ecological risk level. It does not define ecological risk types, resulting in a lack of targeted regulation methods. This study establishes a model for identifying ecological risk-related “source-sink” landscape functions according to (1) “source-sink” landscape theory, (2) the responses of landscape types to ecological risks, and (3) the key influences on ecological risk. Four ecological risk “source-sink” landscape functions were mapped as a grid to understand their distribution. Natural and human activity factors were analyzed to determine their effects. After comprehensively considering the ecological risk levels, types of ecological risk, “source-sink” landscape functions, and their influencing factors, six principles and twenty-four targeted regulation strategies were proposed. Take the Liaoning province, China, as an example. The results prove that more than 80% of the grids were affected by the ecological risk “sink” landscape function for different and multiple ecological risks in the study area. Landscapes with the “source” function were mainly located in central cities and coastal areas. About 65% of the grids with “sink” landscape functions had medium, moderate-high, and high ecological risks. More than 75% of the grids with “source” landscape functions had medium, moderate-low, and low ecological risks. Local terrain features, vegetation, and climate were closely related to the “source” or “sink” landscape function of a grid. The land use type converted to artificial surface had the highest driving effects (q value) on multiple ecological risk “source-sink” landscape functions, and had a significant difference between other factors. The driving effects of land use type converted to artificial surface and road network density gradually increased with the risk level. The influences of GDP and population density gradually weakened with the level. The influence of interaction between any two factors was stronger than the influence of a single factor on ecological risk. The proposed assessment model can help to identify specific ecological risk at the grid level, and combined with the regulation strategy, the scientific basis can be provided for the regulation and management of different ecological risks.

Two new β-type titanium (β-Ti) alloys of Ti-10.5Cr-5.4Mn-2.4Zr-0.9Al and Ti-15.6Cr-12Mn-3.3Zr were designed with the same bond order value 2.79 and different d-orbital energy level values of 2.28 and 2.16, respectively. The effect of intermetallic compounds (IMCs) and the segregation behaviors of β-Ti alloys were discussed by adding excessive and normal alloying elements to alloys under both as-cast and solution-treated conditions. The mono-β phase in the Ti-10.5Cr-5.4Mn-2.4Zr-0.9Al alloy and β+intermetallic compounds (IMCs) in the Ti-15.6Cr-12Mn-3.3Zr alloy were identified and observed. The as-cast and solution-treated alloys showed their ultimate tensile strength and fracture strain; these were 982 and 1002 MPa, with 9.82 and 9.89% for Ti-10.5Cr-5.4Mn-2.4Zr-0.9Al, and 448 and 296 MPa, with 0.12 and 0.11% for Ti-15.6Cr-12Mn-3.3Zr, respectively. Moreover, the Vickers hardness values of the as-cast and solution-treated alloys were 345 and 355 for Ti-10.5Cr-5.4Mn-2.4Zr-0.9Al, and 422 and 466 for Ti-15.6Cr-12Mn-3.3Zr, respectively.

Abstract Penetration of immune cells into tumor cells was believed to be immune-suppressive via cell-in-cell (CIC) mediated death of the internalized immune cells. We unexpectedly found that CIC formation largely led to the death of the host tumor cells, but not the internalized immune cells, manifesting typical features of death executed by NK cells; we named this “in-cell killing” which displays the efficacy superior to the canonical way of “kiss-killing” from outside. By profiling isogenic cells, CD44 on tumor cells was identified as a negative regulator of “in-cell killing” via inhibiting CIC formation. CD44 functions to antagonize NK cell internalization by reducing N-cadherin-mediated intercellular adhesion and by enhancing Rho GTPase-regulated cellular stiffness as well. Remarkably, antibody-mediated blockade of CD44 signaling potentiated the suppressive effects of NK cells on tumor growth associated with increased heterotypic CIC formation. Together, we identified CIC-mediated “in-cell killing” as a promising strategy for cancer immunotherapy.

Abstract The self‐assembling preparation accompanied with template auto‐catalysis loop and the ability to gather energy, induces the appearance of chirality and entropy reduction in biotic systems. However, an abiotic system with biotic characteristics is of great significance but still missing. Here, it is demonstrated that the molecular evolution is characteristic of ultralong carbon nanotube preparation, revealing the advantage of chiral assembly through template auto‐catalysis growth, stepwise‐enriched chirality distribution with decreasing entropy, and environmental effects on the evolutionary growth. Specifically, the defective and metallic nanotubes perform inferiority to semiconducting counterparts, among of which the ones with double walls and specific chirality (n, m) are more predominant due to molecular coevolution. An explicit evolutionary trend for tailoring certain layer chirality is presented toward perfect near‐(2n, n)‐containing semiconducting double‐walled nanotubes. These findings extend our conceptual understanding for the template auto‐catalysis assembly of abiotic carbon nanotubes, and provide an inspiration for preparing chiral materials with kinetic stability by evolutionary growth.

Abstract Through the improvement of supporting structure and the utilization of the interaction between surrounding rock and supporting structure, the synergistic system of energy-absorbing yielding anti-impact supporting structure and surrounding rock is established. The process of energy absorption device, energy-absorbing yielding anti-impact supporting structure and synergistic system under impact is simulated to analyze the properties of them. The following conclusions could be drawn. The deformation and yielding process under compression of energy absorption device is divided into five stages. Compared with the traditional supporting structure, the energy-absorbing yielding anti-impact supporting structure has the reaction force with lower value and smaller fluctuation range before the deformation of the energy absorption device reaches the third ascending section. The synergy between surrounding rock and supporting structure plays an important role in roadway support. Compared with the supporting structure without surrounding rock, the reaction force of the supporting structure in the synergistic system is lower, and a stationary stage is added in the early stage of the reaction force curve.

Abstract Industrial parks contribute greatly to China’s economic development while emitting huge air pollutants. It is necessary to study the characteristics of air pollutant emissions in industrial parks. In this study, emission inventories for 11 industrial parks were established. Meanwhile, the source emission and spatial distribution characteristics of the industrial park were analyzed. The cluster analysis was used to classify these parks into “4Hs”, “Mixed” and “4Ls” parks. “4Hs”, “Mixed” and “4Ls” represent that the levels of energy intensity, economic proportion of energy-intensive industries, coal proportion and pollution performance value are high, medium and low in turn. Then three emission reduction measures were set up to estimate the emission reduction potential and environmental impacts. The results show that: (1) the emissions of SO2, NOx, CO, PM10, PM2.5, VOCs and NH3 of 11 industrial parks in 2017 were 11.2, 23.1, 30.8, 8.3, 3.5, 5.1, and 1.1 kt, respectively. (2) Power plants were the largest source of SO2 and NOx emissions, and industrial processes were the largest emission source of CO, PM10, PM2.5, VOCs and NH3. (3) “4Hs” parks with traditional energy-intensive industries as the leading industries should be the emphasis of air pollutant emission reduction. (4) Through the optimal emission reduction measures, SO2, NOx, PM10, PM2.5 and VOCs were reduced by 81, 46, 51, 46 and 77%, respectively. Environmental impact reductions include 1.6 kt SO2eq acidified gas emissions, 1.4 kt PO4 3−eq eutrophication substances, 4.2 kt PM10eq atmospheric particulate emissions, 7.0 kt 1,4-DCEeq human toxic substances, and 5.2 kt PM2.5 eq breathing Inorganic. This study is helpful to understand the characteristics of air pollutants emissions in industrial parks and promotes the proposal and implementation of air pollutant emissions reduction strategies.

Mitotic spindle assembly is required for proper cell division, but many underlying mechanisms remain unclear. Here, the authors show that NuMa undergoes liquid-liquid phase separation, condensing on spindle poles during mitotic entry and enriching critical components to promote spindle assembly.

Overlying strata movement has an important effect on the stability of coal along goaf. In order to study the impact of overlying strata movement on the stability of coal during fully mechanized top-coal caving mining, a simulation experiment was conducted on the Liuxiang Coal Mine using digital image correlation (DIC) and stress electric measurement methods. The characteristics of overlying strata movement, stress concentration and deformation evolution of coal, and interlayer sliding between coal and rock are analyzed. The following conclusions could be drawn. The movement of overlying strata can be classified into two stages: the first stage is characterized by vertical displacement, while the second stage is characterized by horizontal displacement. In the first stage, the vertical movement of overlying strata causes the vertical stress concentration of the coal. In the second stage, the horizontal movement causes frictional sliding between coal and rock, which produces a shearing effect on the coal. Under these two effects, the coal along goaf gradually reaches its strength limit, and local deformation occurs, and the micro-cracks are further concentrated and fused in this area. When macro-cracks are formed, occur and expand unstable, the elastic energy is released suddenly, which will lead to dynamic disasters such as rock bursts.

Abstract SARS-CoV-2 infection could cause severe acute respiratory syndrome, largely attributed to dysregulated immune activation and extensive lung tissue damage. However, the underlying mechanisms are not fully understood. Here, we reported that viral infection could induce syncytia formation within cells expressing ACE2 and the SARS-CoV-2 spike protein, leading to the production of micronuclei with an average rate of about 4 per syncytium (> 93%). Remarkably, these micronuclei were manifested with a high level of activation of both DNA damage response and cGAS-STING signaling, as indicated by micronucleus translocation of γH2Ax and cGAS, and upregulation of their respective downstream target genes. Since activation of these signaling pathways were known to be associated with cellular catastrophe and aberrant immune activation, these findings help explain the pathological effects of SARS-CoV-2 infection at cellular and molecular levels, and provide novel potential targets for COVID-19 therapy.

BackgroundsCisplatin-based chemotherapy has been considered as the pivotal option for treating cervical cancer. However, some patients may present a poor prognosis due to resistance to chemotherapy. As a metabolite of natural products, sodium butyrate (NaB) could inhibit the proliferation of several malignant cells, but little is known about its combination with cisplatin in the treatment of cervical cancer.Materials and methodsFlow cytometry, CCK-8 assay, and Transwell assay were utilized to analyze the cellular apoptosis, viability, cellular migration and invasion upon treating with NaB and/or cisplatin. The allograft mice model was established, followed by evaluating the tumor volume and necrotic area in mice treated with NaB and/or cisplatin. Western blot was performed for detecting protein expression involved in epithelial-mesenchymal transition (EMT) and the expression of MMPs. Immunohistochemical staining was conducted with the tumor sections. The transcription, expression, and cellular translocation of β-catenin were determined using luciferase reporter gene assay, Real-Time PCR, Western blot, and confocal laser scanning microscope, respectively.ResultsNaB combined with cisplatin inhibited cell viability by promoting apoptosis of cervical cancer cells. In vivo experiments indicated that NaB combined with cisplatin could inhibit tumor growth and induce cancer cell necrosis. Single application of NaB activated the Wnt signaling pathway and induced partial EMT. NaB alone up-regulated MMP2, MMP7 and MMP9 expression, and promoted the migration and invasion of cervical cancer cells. The combination of cisplatin and NaB inhibited cellular migration and invasion by abrogating the nuclear transition of β-catenin, reverse EMT and down-regulate MMP2, MMP7 and MMP9. Immunohistochemical staining indicated that NaB combined with cisplatin up-regulated the expression of E-cadherin and reverse the EMT phenotype in the mice model.ConclusionsNaB serves as a sensitizer for cisplatin, which may be a promising treatment regimen for cervical cancer when combined both. NaB alone should be utilized with caution for treating cervical cancer as it may promote the invasion and migration of cervical cancer cells.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. This tumor presents with an insidious onset, rapid progression, and frequent recurrence. Ferroptosis is a newly discovered mode of programmed cell death that may play a key role in the progression of HCC. This study aimed to investigate the prognostic value of ferroptosis-related genes (FRGs) in HCC and their impact on tumor immune function, thereby providing new insights into targeted therapy for HCC. First, 43 differentially expressed FRGs were identified using the TCGA database, and four prognostically relevant methylation-driven FRGs (G6PD, HELLS, RRM2, and STMN1) were screened via survival and methylation analyses. Gene co-expression, mutation, and clinicopathological characterization indicated that these four pivotal FRGs play essential roles in tumor progression. We also validated these four genes using transcriptomic and proteomic data as well as cohort samples from our patients. Moreover, receiver operator characteristic (ROC) curves confirmed that the signatures of the four FRGs were independent prognostic factors in HCC. Gene set enrichment analysis of the four FRGs showed statistically significant associations with pathways related to HCC proliferation. Finally, the TIMER and TISIDB databases indicated that the four FRGs were statistically significantly correlated with tumor-infiltrating immune cells and immune checkpoint expression. Taken together, this study provides information guiding a novel therapeutic strategy targeting FRGs for HCC treatment.

BackgroundDiabetes mellitus (DM) is a global health problem, and it has become a shocking threat in the contemporary era. The objective of this study was to analyze the safety of sotagliflozin in patients with DM systematically and intuitively.MethodsOn November 15, 2021, literature retrieval was performed on PubMed, Web of Science, EBSCO, and Cochrane libraries. The meta-analysis results included genital mycotic infection, related-to-acidosis events, and other related adverse events, including diarrhea, severe nocturnal hypoglycemia event, and volume depletion. In addition, a subgroup analysis was also conducted based on different doses of sotagliflozin. Moreover, the patient-treated years analyzed in the study were 12 weeks, 24 weeks, and 52 weeks, respectively, for type 1 diabetes, and were 12 weeks, 22 weeks, and 52 weeks, respectively, for type 2 diabetes.ResultsThe results of this meta-analysis illustrated that sotagliflozin could increase the risk of genital mycotic infection for patients with T1D and T2D (RR: 3.49, 95% Cl: 2.54-4.79, p < 0.001; RR: 2.83, 95% Cl: 2.04-3.93, p < 0.001; respectively). In addition, the subgroup analysis showed that the drug doses that could increase the risk of genital mycotic infection were 400 mg and 200 mg (RR: 3.63, 95% Cl: 2.46-5.36, p < 0.001; RR: 3.21, 95% Cl: 1.84-5.62, p < 0.001; respectively) in T1D. Moreover, sotagliflozin could increase the risk of events related to acidosis in the patients of T1D, including acidosis-related adverse events, positively adjudicated diabetic ketoacidosis, acidosis-related event, and diabetic ketoacidosis (RR: 7.49, 95% Cl: 3.20-17.52, p < 0.001; RR: 6.05, 95% Cl: 2.56-14.30, p < 0.001; RR: 4.83, 95% Cl: 3.13-7.45, p < 0.001; RR: 8.12, 95% Cl: 3.06-21.52, p < 0.001; respectively). In the patients of T2D, sotagliflozin could not increase the risk of DKA (RR: 1.30, 95% Cl: 0.34-4.99, p = 0.70). About serious of acidosis-related adverse events, positively adjudicated diabetic ketoacidosis (DKA) and acidosis-related event, the included studies were not reported for T2D patients. As for the other related adverse events, sotagliflozin was found to be a risk factor for diarrhea and volume depletion in T1D patients (RR: 1.44, 95% Cl: 1.09-1.90, p = 0.01; RR: 2.50, 95% Cl: 1.33-4.69, p < 0.01; respectively) and T2D patients (RR: 1.44, 95% Cl: 1.26-1.64, p < 0.001; RR: 1.25, 95% Cl: 1.07-1.45, p < 0.01; respectively).ConclusionsThis meta-analysis showed that the adverse events of sotagliflozin were tolerable to patients with DM, in terms of the incidence of genital mycotic infection, related-to-acidosis events, diarrhea, volume depletion, and severe nocturnal hypoglycemia events. In addition, the subgroup analysis of sotagliflozin dosage is considered to have great clinical significance for future guidance of sotagliflozin application in patients with DM.

Objective: We aimed to develop a novel anti-HIF-1α intrabody to decrease gemcitabine resistance in pancreatic cancer patients. Methods: Surface plasmon resonance and glutathione S-transferase pull-down assays were conducted to identify the binding affinity and specificity of anti-HIF-1α VHH212 [a single-domain antibody (nanobody)]. Molecular dynamics simulation was used to determine the protein-protein interactions between hypoxia-inducible factor-1α (HIF-1α) and VHH212. The real-time polymerase chain reaction (PCR) and Western blot analyses were performed to identify the expressions of HIF-1α and VEGF-A in pancreatic ductal adenocarcinoma cell lines. The efficiency of the VHH212 nanobody in inhibiting the HIF-1 signaling pathway was measured using a dual-luciferase reporter assay. Finally, a PANC-1 xenograft model was developed to evaluate the anti-tumor efficiency of combined treatment. Immunohistochemistry analysis was conducted to detect the expressions of HIF-1α and VEGF-A in tumor tissues. Results: VHH212 was stably expressed in tumor cells with low cytotoxicity, high affinity, specific subcellular localization, and neutralization of HIF-1α in the cytoplasm or nucleus. The binding affinity between VHH212 and the HIF-1α PAS-B domain was 42.7 nM. Intrabody competitive inhibition of the HIF-1α heterodimer with an aryl hydrocarbon receptor nuclear translocator was used to inhibit the HIF-1/VEGF pathway in vitro. Compared with single agent gemcitabine, co-treatment with gemcitabine and a VHH212-encoding adenovirus significantly suppressed tumor growth in the xenograft model with 80.44% tumor inhibition. Conclusions: We developed an anti-HIF-1α nanobody and showed the function of VHH212 in a preclinical murine model of PANC-1 pancreatic cancer. The combination of VHH212 and gemcitabine significantly inhibited tumor development. These results suggested that combined use of anti-HIF-1α nanobodies with first-line treatment may in the future be an effective treatment for pancreatic cancer.

Evidence suggests that English speakers use pronouns when referring to the grammatical subject and predictable thematic role. We tested how grammatical role and thematic role predictability affect different types of referential forms, namely, overt pronouns and null pronouns in Mandarin Chinese. We found that both overt and null pronouns were sensitive to grammatical role. However, we did not find any evidence that overt and null pronouns were sensitive to thematic role predictability. Although null pronouns were influenced by grammatical role, the rate of null pronouns for subject reference was very low compared to that of overt pronouns. Given the frequent occurrence of null pronouns in Mandarin, our results suggest that the use of null pronouns may not be explained by a simple grammatical role mechanism.

BackgroundBehcet’s disease (BD) is a chronic immune disease that involves multiple systems. As the pathogenesis of BD is not clear, and new treatments are needed, we used bioinformatics to identify potential drugs and validated them in mouse models.MethodsBehcet’s disease-related target genes and proteins were screened in the PubMed and UVEOGENE databases. The biological functions and pathways of the target genes were analyzed in detail by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed by the STRING database, and hub genes were identified by the Cytoscape plug-in CytoHubba. Gene-drug interactions were identified from the DGIdb database. Experimental autoimmune uveitis (EAU) mice were used as an animal model for drug validation.ResultsA total of 249 target genes and proteins with significant differences in BD were screened, and the results of functional enrichment analysis suggested that these genes and proteins were more located on the cell membrane, involved in regulating the production of cytokines and affecting the activity of cytokines. They mainly regulated “Cytokine- Cytokine receptor interaction”, “Inflammatory bowel disease (IBD)” and “IL-17 signaling Pathway”. In addition, 10 hub genes were obtained through PPI network construction and CytoHubba analysis, among which the top 3 hub genes were closely related to BD. The DGIdb analysis enriched seven drugs acting together on the top 3 hub genes, four of which were confirmed for the treatment of BD or its complications. There is no evidence in the research to support the results in omeprazole, rabeprazole, and celastrol. However, animal experiments showed that rabeprazole and celastrol reduced anterior chamber inflammation and retinal inflammation in EAU mice.ConclusionsThe functional analysis of genes and proteins related to BD, identification of hub genes, and validation of potential drugs provide new insights into the disease mechanism and potential for the treatment of BD.

Abstract Background Human papillomavirus (HPV) infection is currently the main cause of cervical cancer and precancerous lesions in female patients. By analyzing 6-year patient data from Shanghai Zhoupu Hospital in China, we retrospectively analyzed the epidemiological characteristics of women to determine the relationship between HPV genotype and cytological test results. Methods From 2014 to 2019, 23,724 cases of cervical shedding were collected from Zhoupu Hospital in Shanghai, China. By comparing the results of HPV and ThinPrep cytology test (TCT), the HPV infection rate of patients was retrospectively analyzed. HPV genotyping using commercial kits can detect 21 HPV subtypes (15 high-risk and 6 low-risk). According to the definition of the Bethesda system, seven types of cervical cytology results were involved. Results 3816 among 23,724 women, nearly 16.08%, were infected with HPV. The top three highest HPV prevalence rates were high-risk type infection, including HPV52 (3.19%), 58 (2.47%) and 16 (2.34%). The number of single-type HPV infections (3480 (91.20%)) was much larger than the number of multi-type ones (336 (8.8%)). Single-type infections were mainly in women aged 50–60 (16.63%) and women under 30 (15.37%), while multi-type infections were more common in women over 60 (2.67%). By analyzing the long-term trends, between 2014 and 2019, HPV52, 58, and 16 subtypes changed significantly, and the HPV positive rate also changed significantly during this period. Among 4502 TCT positive women, 15 (4.04%), 125 (2.64%),159 (1.54%), 4202 (17.71%) and 1 (0.004%) had atypical glandular cells (AGC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), atypical squamous cells (ASC)and cervical adenocarcinoma, respectively. The HPV infection rates were 66.08%, 63.99%, 115.20%, 119.50%, and 31.72% for NILM, AGCs, HSILs LSILs and ASCs, respectively. Conclusions HPV and TCT screening were very important steps in the secondary prevention of cervical cancer. Through the tracking and analysis of HPV and TCT results in this study, it can provide valuable information for Shanghai's HPV screening and prevention strategies, and provide references for clinical decision-making in the treatment of cervical cancer and precancerous lesions.

Abstract Interactions among the environment, humans and language underlie many of the most pressing challenges we face today. This study investigates the use of different verbs to encode various weather events in Sinitic languages, a language family spoken over a wide range of climates and with 3000 years of continuous textual documentation. We propose to synergise the many concepts of kinesis that grew from Aristotle’s original ideas to account for the correlation between meteorological events and their linguistic encoding. It is observed that the two most salient key factors of weather events, i.e., mass of weather substances and speed of weather processes, are the two contributing components of kinetic energy. Leveraging the linguistic theory that kinesis underpins conceptualisation of verb classes, this paper successfully accounts for the selection of verbs for different meteorological events in all Sinitic languages in terms of both language variations and changes. Specifically, weather events with bigger weather substances and faster weather processes tend to select action verbs with high transitivity. The kinesis driven accounts also predict the typological variations between verbal and nominal constructions for weather expressions. The correlation between kinesis and the selection of verbs is further corroborated by an experiment on the perception of native Sinitic language speakers, as well as analyses of regional variations of verb selections that do not follow general typological patterns. It is found that such typological exceptions generally correspond to variations in meteorological patterns. By explicating the pivotal role of kinesis in bridging weather events and the linguistic encoding of weather, this study underlines the role of cognition as the conceptualisation of physical and sensory inputs to sharable knowledge encoded by language.

Abstract The nonautonomous cell death by entosis was mediated by the so-called cell-in-cell structures, which were believed to kill the internalized cells by a mechanism dependent on acidified lysosomes. However, the precise values and roles of pH critical for the death of the internalized cells remained undetermined yet. We creatively employed keima, a fluorescent protein that displays different excitation spectra in responding to pH changes, to monitor the pH dynamics of the entotic vacuoles during cell-in-cell mediated death. We found that different cells varied in their basal intracellular pH, and the pH was relatively stable for entotic vacuoles containing live cells, but sharply dropped to a narrow range along with the inner cell death. In contrast, the lipidation of entotic vacuoles by LC3 displayed previously underappreciated complex patterns associated with entotic and apoptotic death, respectively. The pH decline seemed to play distinct roles in the two types of inner cell deaths, where apoptosis is preceded with moderate pH decline while a profound pH decline is likely to be determinate for entotic death. Whereas the cancer cells seemed to be lesser tolerant to acidified environments than noncancerous cells, manipulating vacuolar pH could effectively control inner cell fates and switch the ways whereby inner cell die. Together, this study demonstrated for the first time the pH dynamics of entotic vacuoles that dictate the fates of internalized cells, providing a rationale for tuning cellular pH as a potential way to treat cell-in-cell associated diseases such as cancer.

Phosphorus is one of the main causes of water eutrophication. Hard biochar is considered a promising phosphate adsorbent, but its application is limited by its textural properties and low adsorption capacity. Here, an adhesion approach in a mixed suspension containing egg white is proposed for preparing the hybrid material of Mg/Al-layered double hydroxide (LDH) and almond shell biochar (ASB), named L-AE or L-A (with or without egg white). Several techniques, including XRD, SEM/EDS, FTIR and N2 adsorption/desorption, were used to characterize the structure and adsorption behavior of the modified adsorbents. The filament-like material contained nitrogen elements at a noticed level, indicating that egg white was the crosslinker that mediated the formation of the L-AE hybrid material. The L-AE had a higher phosphate adsorption rate with a higher equilibrium adsorption capacity than the L-A. The saturation phosphate adsorption capacity of L-AE was nearly three times higher than that of L-A. Furthermore, the number of surface groups and the density of the positively charged surface sites follow the ASB < L-A < L-AE order, which is consistent with their phosphate adsorption performance. The study may offer an efficient approach to improving hard biochar’s adsorption performance in wastewater treatment.

The bin packing problem has a wide range of applications in industry. With the upgrade of the task difficulty, the traditional 2d rectangular layout algorithm can no longer meet the needs of modern industry, such as express packing task and exoplanet ore collection task. The express or ore samples come in heterogeneous shapes so they cannot all be treated as rectangular pieces. In this paper, we propose a three-stage method called covering, corner-searching and occupying (C,S&O) to solve the two-dimensional multishape part packing problem. The objective of the packing problem variant is to ensure maximum use of the raw material and minimize the trim loss. The algorithm cannot make use of information about the sequence of future objects that are going to arrive, only knowing the shape and size of the coming one, and the coming part must be packed into the bin immediately after its arrival without buffering or readjusting. The method of C,S&O hybridizes the idea of “gold corners, silver edges and grass belly” in the Chinese game Go and the method of finding picture corners in machine vision. In the first stage, the rectangular bin and the coming part are transformed into matrix representation, and generating the position matrix that indicates possible ways of packing the part into the bin. In the second stage, the suitable layout position of the coming part is obtained using machine vision image processing technology for reference. The third stage is calculating the environment matching degree to determine the current optimal placement orientation. In order to facilitate the display of the simulation results, only three shapes of parts are considered in the simulation, rectangle, circle and triangle. The experimental results show the effectiveness of this method. Consulting the literature, it is found that this paper is the first to propose a layout method for multishape manufacturing parts.