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Non-contact remote sensing techniques, such as terrestrial laser scanning (TLS) and unmanned aerial vehicle (UAV) photogrammetry, have been globally applied for landslide monitoring in high and steep mountainous areas. These techniques acquire terrain data and enable ground deformation monitoring. However, practical application of these technologies still faces many difficulties due to complex terrain, limited access and dense vegetation. For instance, monitoring high and steep slopes can obstruct the TLS sightline, and the accuracy of the UAV model may be compromised by absence of ground control points (GCPs). This paper proposes a TLS- and UAV-based method for monitoring landslide deformation in high mountain valleys using traditional real-time kinematics (RTK)-based control points (RCPs), low-precision TLS-based control points (TCPs) and assumed control points (ACPs) to achieve high-precision surface deformation analysis under obstructed vision and impassable conditions. The effects of GCP accuracy, GCP quantity and automatic tie point (ATP) quantity on the accuracy of UAV modeling and surface deformation analysis were comprehensively analyzed. The results show that, the proposed method allows for the monitoring accuracy of landslides to exceed the accuracy of the GCPs themselves by adding additional low-accuracy GCPs. The proposed method was implemented for monitoring the Xinhua landslide in Baoxing County, China, and was validated against data from multiple sources.

Low-cadmium (Cd)-accumulating rice (Oryza sativa L.) cultivated by OsNRAMP5 mutation is a promising approach for ensuring food safety and human health. However, the impacts of reduced manganese (Mn) uptake caused by OsNRAMP5 mutation on rice growth and Cd accumulation under varying Mn levels remains unknown. Here, hydroponics and pot experiments were used to investigate the growth and Cd accumulation of an OsNRAMP5 mutant rice, Zhong’an 7 (ZA7), and the wild type, Zhongzao 35 (ZZ35), under different Mn supply conditions, and the Mn thresholds for ZA7 were determined. There was lower biomass of ZA7 than ZZ35 under hydroponic conditions with 0–0.05 μM Mn supply, and this was alleviated at Mn concentrations ranging from 1 to 200 μM. In pot Experiment I the grain yields of ZA7 in five soils increased from 5.92 to 15.0 g pot−1 as the inherent soil available Mn ranged from 3.17 to 400 mg kg−1. In pot Experiment II the exogenous MnSO4 significantly increased ZA7 grain yields by 135–173 % and reduced grain Cd concentrations by 50.3–72.9 % (p

Background: The electrocardiogram (ECG) is a valuable, noninvasive tool for monitoring heart-related conditions, providing critical insights. However, the interpretation of ECG data alongside patient information demands substantial medical expertise and resources. While deep learning methods help streamline this process, they often fall short in integrating patient data with ECG readings and do not provide the nuanced clinical suggestions and insights necessary for accurate diagnosis. Methods: Although recent advancements in multi-modal large language modeling have propelled their application scope beyond the natural language processing domain, their applicability to ECG processing remains largely unexplored, partly due to the lack of text–ECG data. To this end, we develop ECG-Language Model (ECG-LM), the first multi-modal large language model able to process natural language and understand ECG signals. The model employs a specialized ECG encoder that transforms raw ECG signals into a high-dimensional feature space, which is then aligned with the textual feature space derived from the large language model. To address the scarcity of text–ECG data, we generated text–ECG pairs by leveraging detailed ECG pattern descriptions from medical guidelines, creating a robust dataset for pre-training ECG-LM. Additionally, we fine-tune ECG-LM with public clinical conversation datasets and build an additional supervised fine-tuning dataset based on real clinical data from the hospital, aiming to provide a more comprehensive and customized user experience. Results: ECG-LM outperforms existing few-shot and zero-shot solutions in cardiovascular disease detection across all 3 tasks (diagnostic, rhythm, and form) while also demonstrating strong potential in ECG-related question answering. Conclusions: The results across various tasks demonstrate that ECG-LM effectively captures the intricate features of ECGs, showcasing its versatility in applications such as disease prediction and advanced question answering.

Studies based on metal isotope changes at micro-scale interfaces within soils (i.e., between aggregates of different size fractions) can provide further insight into soil-plant interactions during long-term phytoextraction. Here, aggregate size separation was conducted on two contaminated soils that underwent phytoextraction using Zn/Cd hyperaccumulator Sedum plumbizincicola over six consecutive seasons. The dynamic changes in Zn and Cd concentrations, chemical fractionations and isotope compositions in soil aggregates were investigated. As phytoextraction proceeded from the first (C1) to the sixth (C6) season, shoot Zn displayed a marginally heavier isotope composition despite the essentially constant Zn isotope composition of bulk soils and the 50–250, 5–50, 1–5, and

Abstract With the increase in the aging population, senile osteoporosis (SOP) has become a major global public health concern. Here, it is found that Prx1 and Bmi‐1 co‐localized in trabecular bone, bone marrow cavity, endosteum, and periosteum. Prx1‐driven Bmi‐1 knockout in bone‐marrow mesenchymal stem cells (BMSCs) reduced bone mass and increased bone marrow adiposity by inhibiting osteoblastic bone formation, promoting osteoclastic bone resorption, downregulating the proliferation and osteogenic differentiation of BMSCs, and upregulating the adipogenic differentiation of BMSCs. However, Prx1‐driven Bmi‐1 overexpression showed a contrasting phenotype to Prx1‐driven Bmi‐1 knockout in BMSCs. Regarding mechanism, Bmi‐1‐RING1B bound to DNMT3A and promoted its ubiquitination and inhibited DNA methylation of Runx2 at the region from 45047012 to 45047313 bp, thus promoting the osteogenic differentiation of BMSCs. Moreover, Bmi‐1‐EZH2 repressed the transcription of Cebpa by promoting H3K27 trimethylation at the promoter region −1605 to −1596 bp, thus inhibiting the adipogenic differentiation of BMSCs. It is also found that Prx1‐driven Bmi‐1 overexpression rescued the SOP induced by Prx1‐driven Bmi‐1 knockout in BMSCs. Thus, Bmi‐1 functioned as a hub protein in the epigenetic regulation of BMSCs differentiation to delay bone aging. The Prx1‐driven Bmi‐1 overexpression in BMSCs can be used as an approach for the translational therapy of SOP.

Liver ischemia-reperfusion (I/R) injury is a clinically relevant pathophysiological process that determines the effectiveness of life-saving liver transplantation, to which aberrant ROS accumulation plays a key role. In the present study we investigated the role of SUV39H1, a lysine methyltransferases, in this process focusing on regulatory mechanism and translational potential. We report that SUV39H1 expression was up-regulated in the liver tissues of mice subjected to ischemia-reperfusion and in hepatocytes exposed to hypoxia-reoxygenation (H/R) in a redox-sensitive manner. Mechanistically, coactivator associated arginine methyltransferases 1 (CARM1) mediated redox-sensitive Suv39h1 trans-activation by promoting histone H3R17 methylation. Consistently, pharmaceutical CARM1 inhibition attenuated liver I/R injury. In addition, global or hepatocyte conditional Suv39h1 KO mice were protected from liver I/R injury. RNA-seq revealed that aldehyde dehydrogenase 1 family 1a (Aldh1a1) as a novel target for SUV39H1. SUV39H1 directly bound to the Aldh1a1 promoter and repressed Aldh1a1 transcription in H/R-challenged hepatocytes. ALDH1A1 silencing abrogated the protective effects of SUV39H1 deficiency on H/R-inflicted injuries whereas ALDH1A1 over-expression mitigated liver I/R injury in mice. Importantly, administration of a small-molecule SUV39H1 inhibitor achieved similar hepatoprotective effects as SUV39H1 deletion. Finally, increased Suv39h1 expression and decreased Aldh1a1 expression were observed in liver I/R specimens in humans. In conclusion, our data uncover a regulatory role for SUV39H1 in liver I/R injury and serve as proof-of-concept that targeting the SUV39H1-ALDH1A1 axis might be considered as a reasonable approach for the intervention of liver I/R injury.

Landslides are one of the geological disasters with wide distribution, high impact and serious damage around the world. Landslide risk assessment can help us know the risk of landslides occurring, which is an effective way to prevent landslide disasters in advance. In recent decades, artificial intelligence (AI) has developed rapidly and has been used in a wide range of applications, especially for natural hazards. Based on the published literatures, this paper presents a detailed review of AI applications in landslide risk assessment. Three key areas where the application of AI is prominent are identified, including landslide detection, landslide susceptibility assessment, and prediction of landslide displacement. Machine learning (ML) containing deep learning (DL) has emerged as the primary technology which has been considered successfully due to its ability to quantify complex nonlinear relationships of soil structures and landslide predisposing factors. Among the algorithms, convolutional neural networks (CNNs) and recurrent neural networks (RNNs) are two models that are most widely used with satisfactory results in landslide risk assessment. The generalization ability, sampling training strategies, and hyper-parameters optimization of these models are crucial and should be carefully considered. The challenges and opportunities of AI applications are also fully discussed to provide suggestions for future research in landslide risk assessment.

Objective To reveal the deformation evolution of the Xinhua landslide in Luding County, Sichuan Province under the comprehensive effects of reservoir impoundment, reservoir water level fluctuations and seasonal rainfall, and to explore the progressive cumulative effect of the strength degradation of the landslide rock and soil mass under the coupling of multiple factors. Methods In this paper, based on a field investigation and multisource long sequence monitoring data analysis of the Xinhua landslide in the reservoir area of the hydropower project, combined with the three-stage evolution characteristics of the landslide cumulative deformation-time (S-t) curve and the measured S-t curve of the Xinhua landslide, the evolution stages of the three-step deformation cycles of the Xinhua landslide are identified and divided. At the same time, the improved tangent angle method is used for calculation and analysis, and a quantitative classification standard for Xinhua landslide classification early warning based on the improved displacement tangent angle early warning threshold is constructed. Results The results show that the short-term large increase of water level during the initial impoundment period, the rapid decrease of water level during the reservoir operation period and the influence of seasonal heavy rainfall are the main factors to accelerate the deformation of the Xinhua landslide. Conclusion According to the analysis and discussion, the improved displacement tangent angle early warning threshold can provide guidance for identifying the current stability state and potential risks of the Xinhua landslide to a certain extent, but multiple early warning indicators should still be considered, and the signs of macroscopic deformation and failure of landslides should be integrated for judgement.

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Chitosan-pectin gel beads (CPB) have high potential for removing heavy metals from food. This study aimed to improve their stability, recyclability, and adsorption capacity by modified CPB with gelatin (Gel) and carboxymethyl cellulose sodium (CMC). The structural characteristics of the modified CPBs were characterized using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG), Zeta potential, scanning electron microscopy (SEM), pore size distribution analysis (BET), X-ray photoelectron spectroscopy (XPS), specific surface area analysis. The adsorption-resolution conditions of modified CPB were optimized, and their actual removal efficiency for Pb(II) in C-phycocyanin was evaluated. Results showed that CMC-modified CPB (CMC-CPB) had higher thermal stability, rougher and more porous surface, larger specific surface area (20.28±1.35 m2/g), lower zeta potential, stronger metal ion adsorption capacity, and higher regeneration efficiency compared with CPB and Gel-CPB. FTIR showed the functional group of CPB had significant difference after modification, and the main group in CPB were carboxyl, hydroxyl, and amino groups. TG analysis presented the thermal stability of CMC-CPB was higher than that of CPB and Gel-CPB. XPS analysis showed CMC-CPB had the strongest absorption peak for Pb(II). The optimal pH and temperature for the three adsorbents (CPB, Gel-CPB, and CMC-CPB) to remove Pb(II) were 6.0 and 60 ℃, respectively. The Pb(II) adsorption process of all three adsorbents fit the Langmuir isotherm model (R2=0.9543~0.9811) and the pseudo-second-order kinetic model (R2=0.9963~0.9991), and the adsorption process belonged to the monolayer chemical adsorption, involving the complexation of -COO, -OH, -CO-NH, and Pb(II). Based on the Langmuir model curve, the maximum adsorption capacity (qmax) of CMC-CPB for Pb(II) was 69.37 mg/g, significantly higher than that of Gel-CPB and CPB (P

Abstract The sessile nature of plants confines their responsiveness to changing environmental conditions. Gene expression regulation becomes a paramount mechanism for plants to adjust their physiological and morphological behaviors. Alternative polyadenylation (APA) is known for its capacity to augment transcriptome diversity and plasticity, thereby furnishing an additional set of tools for modulating gene expression. APA has also been demonstrated to exhibit intimate associations with plant stress responses. In this study, we review APA dynamic features and consequences in plants subjected to both biotic and abiotic stresses. These stresses include adverse environmental stresses, and pathogenic attacks, such as cadmium toxicity, high salt, hypoxia, oxidative stress, cold, heat shock, along with bacterial, fungal, and viral infections. We analyzed the overarching research framework employed to elucidate plant APA response and the alignment of polyadenylation site transitions with the modulation of gene expression levels within the ambit of each stress condition. We also proposed a general APA model where transacting factors, including poly(A) factors, epigenetic regulators, RNA m6A modification factors, and phase separation proteins, assume pivotal roles in APA related transcriptome plasticity during stress response in plants. Graphical Abstract

Local geometric information and discontinuity features are key aspects of the analysis of the evolution and failure mechanisms of unstable rock blocks in rock tunnels. This study demonstrates the integration of terrestrial laser scanning (TLS) with distinct element method for rock mass characterization and stability analysis in tunnels. TLS records detailed geometric information of the surrounding rock mass by scanning and collecting the positions of millions of rock surface points without contact. By conducting a fuzzy K-means method, a discontinuity automatic identification algorithm was developed, and a method for obtaining the geometric parameters of discontinuities was proposed. This method permits the user to visually identify each discontinuity and acquire its spatial distribution features (e.g. occurrences, spacings, trace lengths) in great detail. Compared with hand mapping in conventional geotechnical surveys, the geometric information of discontinuities obtained by this approach is more accurate and the identification is more efficient. Then, a discrete fracture network with the same statistical characteristics as the actual discontinuities was generated with the distinct element method, and a representative numerical model of the jointed surrounding rock mass was established. By means of numerical simulation, potential unstable rock blocks were assessed, and failure mechanisms were analyzed. This method was applied to detection and assessment of unstable rock blocks in the spillway and sand flushing tunnel of the Hongshiyan hydropower project after a collapse. The results show that the noncontact detection of blocks was more labor-saving with lower safety risks compared with manual surveys, and the stability assessment was more reliable since the numerical model built by this method was more consistent with the distribution characteristics of actual joints. This study can provide a reference for geological survey and unstable rock block hazard mitigation in tunnels subjected to complex geology and active rockfalls.

Abstract Spinal cord injury (SCI) can result in irreversible sensory and motor disability with no effective treatment currently. After SCI, infiltrated macrophages accumulate in epicenter through destructed blood-spinal cord barrier (BSCB). Further, great majority of macrophages are preferentially polarized to M1 phenotype, with only a few transient M2 phenotype. The purpose of this study was to explore roles of vascular endothelial cells in microglia/macrophages polarization and the underlying mechanism. Lipopolysaccharide (LPS) was used to pretreat BV2 microglia and RAW264.7 macrophages followed by administration of conditioned medium from microvascular endothelial cell line bEnd.3 cells (ECM). Analyses were then performed to determine the effects of exosomes on microglia/macrophages polarization and mitochondrial function. The findings demonstrated that administration of ECM shifted microglia/macrophages towards M2 polarization, ameliorated mitochondrial impairment, and reduced reactive oxygen species (ROS) production in vitro. Notably, administration of GW4869, an exosomal secretion inhibitor, significantly reversed these observed benefits. Further results revealed that exosomes derived from bEnd.3 cells (Exos) promote motor rehabilitation and M2 polarization of microglia/macrophages in vivo. Ubiquitin-specific protease 13 (USP13) was shown to be significantly enriched in BV2 microglia treated with Exos. USP13 binds to, deubiquitinates and stabilizes the NF-κB inhibitor alpha (IκBα), thus regulating microglia/macrophages polarization. Administration of the selective IκBα inhibitor betulinic acid (BA) inhibited the beneficial effect of Exos in vivo. These findings uncovered the potential mechanism underlying the communications between vascular endothelial cells and microglia/macrophages after SCI. In addition, this study indicates exosomes might be a promising therapeutic strategy for SCI treatment.

Water-induced landslides in hydropower reservoirs pose a great threat to both project operation and human life. This paper examines three large reservoirs in Sichuan Province, China. Field surveys, site monitoring data analyses and numerical simulations are used to analyze the spatial distribution and failure mechanisms of water-induced landslides in reservoir areas. First, the general rules of landslide development in the reservoir area are summarized. The first rule is that most of the landslides have rear edge elevations of 100–500 m above the normal water level of the reservoir, with volumes in the range of 106–107 m3. When the volume exceeds a certain amount, the number of sites at which the landscape can withstand landslides is greatly reduced. Landslide hazards mainly occur in the middle section of the reservoir and less in the annex of the dam site and the latter half of the reservoir area. The second rule is that sedimentary rocks such as sandstone are more prone to landslide hazards than other lithologies. Then, the failure mechanism of changes in the water level that reduces the stability of the slope composed of different geomaterials is analyzed by a proposed slope stability framework that considers displacement and is discussed with the monitoring results. Permeability is an essential parameter for understanding the diametrically opposed deformation behavior of landslides experiencing filling-drawdown cycles during operation. This study seeks to provide inspiration to subsequent researchers, as well as guidance to technicians, on landslide prevention and control in reservoir areas.

Background: Osteoarthritis (OA), a degenerative disease prevalent among the elderly, poses significant challenges due to its high incidence and disability rates. Regrettably, there exists a lack of effective regenerative therapies for the irreversible degradation of cartilage in OA. Mesenchymal stem cells (MSCs), known for their robust differentiation and immune regulatory capabilities, have emerged as promising candidates for OA treatment. MSCs sourced from perinatal tissues offer the dual advantage of convenience in extraction and ethical non-controversy. However, the heterogeneous nature of MSCs derived from different perinatal tissue sources gives rise to varying therapeutic indications. Moreover, the immune response of MSCs may be modulated under the influence of inflammatory factors.Methods: In this study, we isolated mesenchymal stem cells from distinct parts of human perinatal tissue: umbilical cord-derived MSCs (UC-MSCs), fetal placenta-derived MSCs (FP-MSCs), and umbilical cord placental junction-derived MSCs (CPJ-MSCs). These cells were cultured in vitro and subjected to a 24-hour treatment with the inflammatory mediator Interleukin-1β (IL-1β). Subsequently, the MSCs were evaluated for changes in proliferation, migration, and regulatory capabilities. To assess the comparative anti-injury potential of MSCs from different sources, primary articular chondrocytes (ACs) were exposed to H2O2-induced injury and co-cultured with IL-1β-primed MSCs. Changes in the proliferation, migration, and regulatory abilities of ACs resembling those observed in OA were examined.Results: Following IL-1β treatment, all three types of MSCs displayed decreased rates of proliferation and migration. Notably, their chondrogenic differentiation capacities exhibited an enhancement. Additionally, diverse MSCs exhibited a degree of efficacy in restoring damaged ACs in vitro. Among these, CPJ-MSCs demonstrated superior potential in promoting cartilage cell proliferation, while FP-MSCs displayed notable anti-inflammatory effects.Conclusion: Our findings underscore the substantial capacity of primed FP-MSCs and CPJ-MSCs to alleviate the injury in OA-like ACs. Consequently, this study advocates for the prospective use of preconditioning strategies involving FP-MSCs and CPJ-MSCs in forthcoming OA therapies.

Background Chronic changes caused by a high‐fat diet (HFD) may be associated with weakened lung function in obese patients. However, few studies have focused on the role of senescent cells in HFD‐induced pulmonary fibrosis. This study aimed to determine whether (i) obesity causes the accumulation of aging cells in the lungs, (ii) p16 accumulation in aging epithelial cells or fibroblasts exacerbates long‐term HFD‐induced senescence‐associated pulmonary fibrosis (SAPF) and (iii) p16 deletion or clearance of aging cells ameliorates HFD‐induced SAPF through inactivation of the inflammasome and metabolic remodelling. Methods Twelve‐month old male mice of p16INK4a (hereafter p16) knockout (p16−/−) and wild‐type (WT), ApoE knockout (ApoE−/−) and ApoE−/−p16−/− were fed a HFD to induce obesity, and the effects of treatment with the senolytic drug ABT263 or the SGK1 specific inhibitor EMD638683 on fibrosis, inflammaging, gene expression, integrin‐inflammasome signalling and metabolism were examined. A549 and IMR‐90 cells were transduced with p16‐overexpressing adenovirus, and treated with palmitic and oleic acids (P&O) to induce steatosis in vitro. Results We found that long‐term HFD promoted the expression of p16 and the increase of senescent cells in the lung. P16 knockout or ABT263 treatment alleviated pulmonary fibrosis, the increase of senescent cells and senescence‐associated secretory phenotype (SASP) in HFD‐fed mice, as well as in P&O‐treated A549 and IMR‐90 cells. RNA sequencing and bioinformatics analyses revealed that p16 knockout inhibited activation of the integrin‐inflammasome pathway and cellular glycolysis. Mass spectrometry, co‐immunoprecipitation and GST pull‐down assays demonstrated that p16 bound to the N‐terminal of SGK1, thereby interfering with the interaction between the E3 ubiquitin ligase NEDD4L and SGK1, and subsequently inhibiting K48‐polyubiquitin‐dependent degradation of SGK1 mediated by the NEDD4L–Ubch5 complex. EMD638683 was found to alleviate HFD‐induced pulmonary fibrosis and activation of the integrin‐inflammasome pathway. Conclusion P16 accumulation promoted activation of integrin– inflammasome pathway and cell glycolysis by binding to the N– terminal of SGK1, intefering with the interaction between the E3 ubiquitin ligase NEDD4L and SGK1, thereby inhibiting K48– polyubiquitin– dependent degradation of SGK1 mediated by the NEDD4L–Ubch5 complex. ABT263 or EMD638683 could be used as potential drugs to treat pulmonary fibrosis in obese patients.

The stability of the surrounding rocks of large underground powerhouses is always emphasized during the construction process, especially in large-scale underground projects under construction, such as the Baihetan hydropower station in China. According to field investigations, numerical simulations and monitoring data analysis, we present a comparative analysis of the deformation and failure characteristics of the surrounding rocks of underground powerhouses on the left and right banks of the Baihetan hydropower station. The failure characteristics and deformation magnitude of the underground powerhouses on the left and right banks are quite different. Under the disadvantageous condition where the maximum principal stress intersects the axis of the powerhouse at a large angle, the left bank underground powerhouse shows prominent stress-controlled failure characteristics such as spalling, slack collapse and concrete cracking. Although the maximum principal stress is in the favorable condition which intersects the right bank powerhouse at a small angle, the relatively high intermediate principal stress with an angle subvertical to the right bank powerhouse plays an essential role in its deformation and failure, indicating that the influence of high intermediate principal stress cannot be ignored. In addition, structural plane-controlled failure and large deformation are also more evident on the right bank due to the extensive distribution of weak structural planes and complex surrounding rock properties.

The shear strength reduction method provides an effective tool of numerical analysis for landslides reliability analysis. However, it ignores the failure probability of the secondary failure surfaces and requires huge computational cost. To avoid these common criticisms, an intelligent multiple response surfaces method for system reliability using multiple response-surface method (MRSM) and least-squares support vector machine (LSSVM) is presented to evaluate the stability of complex multistage historic landslides with multiple sliding surfaces. Deterministic analysis of each sliding surface is first performed using the finite element method of sliding surface stress analysis, which is applied to obtain the safety factors of different sliding surfaces from the stress fields generated by finite element simulations. The LSSVM model with excellent nonlinear fitting ability is then employed to construct the multiple response-surface method (MRSM) of the sliding surfaces and a genetic algorithm (GA) is adopted to optimize the LSSVM. This proposed methodology is finally applied to investigate the probability of system failure of the Zhenggang landslide in southwestern China. The results indicate that the proposed approach can reduce the computational cost of finite element analysis in direct Monte Carlo simulation (MCS) by proper training using a limited of samples, and the calculation accuracy meets the engineering requirements of complex multistage historic landslides.

A good residential courtyard space not only brings people a psychological feeling of emotional pleasure but also attracts people to actively engage in more physical activities, which is of great significance to improving people's physical and mental health. Green vegetation and fitness facilities as the most preferred landscape elements in residential courtyard spaces and their effects on people's emotional health have not been further investigated. In this research, a virtual experiment was constructed in a residential courtyard space in Chengdu City, China, and electrodermal sensors were used to measure the real-time emotional changes of people in different virtual scenarios to analyze the effects of two landscape elements, green vegetation and fitness facilities, on people's emotional health, and the differences of such effects among different genders and ages. The results confirm that the combination of virtual reality technology and wearable physiological sensor measurement technology could effectively identify health-promoting landscape elements in urban environments; In residential courtyard spaces, green vegetation is more emotionally healthy than fitness facilities, and fitness facilities have better emotional health benefits for men and people over 30 years of age. The results of the study provide a quantitative basis for the healthier design and transformation of residential courtyard spaces for both green vegetation and fitness facilities.

Abstract Aims Senescence‐associated pathological cardiac hypertrophy (SA‐PCH) is associated with upregulation of foetal genes, fibrosis, senescence‐associated secretory phenotype (SASP), cardiac dysfunction and increased morbidity and mortality. Therefore, we conducted experiments to investigate whether GATA4 accumulation induces SA‐PCH, and whether Bmi‐1‐RING1B promotes GATA4 ubiquitination and its selective autophagic degradation to prevent SA‐PCH. Methods and results Bmi‐1‐deficient (Bmi‐1−/−), transgenic Bmi‐1 overexpressing (Bmi‐1Tg) and wild‐type (WT) mice were infused with angiotensin II (Ang II) to stimulate the development of SA‐PCH. Through bioinformatics analysis with RNA sequencing data from cardiac tissues, we found that Bmi‐1‐RING1B and autophagy are negatively related to SA‐PCH. Bmi‐1 deficiency promoted GATA4‐dependent SA‐PCH by increasing GATA4 protein and hypertrophy‐related molecules transcribed by GATA4 such as ANP and BNP. Bmi‐1 deficiency stimulated NF‐κB‐p65‐dependent SASP, leading to cardiac dysfunction, cardiomyocyte hypertrophy and senescence. Bmi‐1 overexpression repressed GATA4‐dependent SA‐PCH. GATA4 degraded by Bmi‐1 was mainly dependent on autophagy rather than proteasome. In human myocardium, p16 positively correlated with ANP and GATA4 and negatively correlated with LC3B, Bmi‐1 and RING1B; GATA4 positively correlated with p62 and negatively correlated with Bmi‐1 and LC3B. With increased p16 protein levels, ANP‐, BNP‐ and GATA4‐positive cells or areas increased; however, LC3B‐positive cells or areas decreased in human myocardium. GATA4 is ubiquitinated after combining with Bmi‐1‐RING1B, which is then recognised by p62, is translocated to autophagosomes to form autophagolysosomes and degraded. Downregulated GATA4 ameliorated SA‐PCH and cardiac dysfunction by reducing GATA4‐dependent hypertrophy and SASP‐related molecules. Bmi‐1 combined with RING1B (residues 1–179) and C‐terminus of GATA4 (residues 206–443 including zinc finger domains) through residues 1–95, including a RING‐HC‐finger. RING1B combined with C‐terminus of GATA4 through the C‐terminus (residues 180–336). Adeno‐associated viral vector serotype 9 (AAV9)‐cytomegalovirus (CMV)‐Bmi‐1‐RING1B treatment significantly attenuated GATA4‐dependent SA‐PCH through promoting GATA4 autophagic degradation. Conclusions Bmi‐1‐RING1B maintained cardiac function and prevented SA‐PCH by promoting selective autophagy for degrading GATA4. Translational perspective AAV9‐CMV‐Bmi‐1‐RING1B could be used for translational gene therapy to ubiquitinate GATA4 and prevent GATA4‐dependent SA‐PCH. Also, the combined domains between Bmi‐1‐RING1B and GATA4 in aging cardiomyocytes could be therapeutic targets for identifying stapled peptides in clinical applications to promote the combination of Bmi‐1‐RING1B with GATA4 and the ubiquitination of GATA4 to prevent SA‐PCH and heart failure. We found that degradation of cardiac GATA4 by Bmi‐1 was mainly dependent on autophagy rather than proteasome, and autophagy agonists metformin and rapamycin could ameliorate the SA‐PCH, suggesting that activation of autophagy with metformin or rapamycin could also be a promising method to prevent SA‐PCH.

The COVID-19 pandemic has been a major public health event since 2020. Multiple variant strains of SARS-CoV-2, the causative agent of COVID-19, were detected based on the mutation sites in their sequences. These sequence mutations may lead to changes in the protein structures and affect the binding states of SARS-CoV-2 and human proteins. Experimental research on SARS-CoV-2 has accumulated a large amount of structural data and protein-protein interactions (PPIs), but the studies on the SARS-CoV-2–human PPI networks lack integration of physical associations with possible protein docking information. In addition, the docking structures of variant viral proteins with human receptor proteins are still insufficient. This study constructed SARS-CoV-2–human protein–protein interaction network with data integration methods. Crystal structures were collected to map the interaction pairs. The pairs of direct interactions and physical associations were selected and analyzed for variant docking calculations. The study examined the structures of spike (S) glycoprotein of variants Delta B.1.617.2, Omicron BA.1, and Omicron BA.2. The calculated docking structures of S proteins and potential human receptors were obtained. The study integrated binary protein interactions with 3D docking structures to fulfill an extended view of SARS-CoV-2 proteins from a macro- to micro-scale.

Small and medium-sized enterprises (SMEs) play an increasingly important role in global economic development, and they have encountered many unique problems (such as resources and strategic choice). Strategic management accounting (SMA) techniques can help SMEs allocate limited resources rationally and integrate internal and external information to help managers make strategic decisions. However, how and what is the SMA applied in the reality of SMEs, especially in developing countries today. This paper aims to explore the extent to which SMEs of developing countries use SMA. This article used the qualitative research method and the data were collected by interviewing five managers and two employees in M company. The findings indicated that: (1) The senior managers of SMEs do not have an understanding of accounting nor pay enough attention to it, and the role of SMA is even worse; (2) Although the chief financial officers obtain the knowledge of SMA, they cannot fully involve it in their strategic decision making. (3) SMEs have realized that enterprise culture is very important for a company to achieve strategic goals, but it is far from enough to attach importance to and create it. (4) The general managers of SMEs believe that the operating department is the core of the company and all resources should be prioritized to meet their needs.

Sedum plumbizincicola is a cadmium (Cd) and zinc hyperaccumulator that can activate Cd by rhizosphere acidification. However, there is little understanding of the Cd leaching risk from polluted soil during phytoextraction process. Here, pot and column experiments were conducted to monitor soil Cd leaching characteristics under different rainfall simulation conditions during S. plumbizincicola phytoextraction. Soil Cd leaching increased significantly with increasing simulated rainfall intensity. Compared with normal rainfall (NR), weak rainfall (WR) resulted in a 34.3% decrease in Cd uptake by S. plumbizincicola and also led to a 68.7% decline in Cd leaching. In contrast, Cd leaching under heavy rainfall (HR) was 2.12 times that of NR in the presence of S. plumbizincicola. After two successive growing periods, phytoextraction resulted in a 53.5-66.4% decline in the amount of soil Cd leached compared with controls in which S. plumbizincicola was absent. Even compared with maize cropping as a control, S. plumbizincicola did not instigate a significant increase in Cd leaching. The contribution of Cd leaching loss to the decline in soil total Cd concentration was negligible after phytoextraction in the pot experiment. Overall, the results contribute to our understanding of soil Cd leaching risk by phytoextraction with S. plumbizincicola. [ABSTRACT FROM AUTHOR]

Physiologically aged lungs are prone to senescence-associated pulmonary diseases (SAPD). This study aimed to determine the mechanism and subtype of aged T cells affecting alveolar type II epithelial (AT2) cells, which promote the pathogenesis of senescence-associated pulmonary fibrosis (SAPF). Cell proportions, the relationship between SAPD and T cells, and the aging- and senescence-associated secretory phenotype (SASP) of T cells between young and aged mice were analyzed using lung single-cell transcriptomics. SAPD was monitored by markers of AT2 cells and found to be induced by T cells. Furthermore, IFNγ signaling pathways were activated and cell senescence, SASP, and T cell activation were shown in aged lungs. Physiological aging led to pulmonary dysfunction and TGF-ß1/IL-11/MEK/ERK (TIME) signaling-mediated SAPF, which was induced by senescence and SASP of aged T cells. Especially, IFNγ was produced by the accumulated CD4+ effector memory T (TEM) cells in the aged lung. This study also found that physiological aging increased pulmonary CD4+ TEM cells, IFNγ was produced mainly by CD4+ TEM cells, and pulmonary cells had increased responsiveness to IFNγ signaling. Specific regulon activity was increased in T cell subclusters. IFNγ transcriptionally regulated by IRF1 in CD4+ TEM cells promoted the epithelial-to-mesenchymal transition by activating TIME signaling and cell senescence of AT2 cells with aging. Accumulated IRF1+CD4+ TEM produced IFNγ in lung with aging and anti-IRF1 primary antibody treatment inhibited the expression of IFNγ. Aging might drive T cell differentiation toward helper T cells with developmental trajectories and enhance cell interactions of pulmonary T cells with other surrounding cells. Thus, IFNγ transcribed by IRF1 in CD4+ effector memory T cells promotes SAPF. IFNγ produced by CD4+ TEM cells in physiologically aged lungs could be a therapeutic target for preventing SAPF. [ABSTRACT FROM AUTHOR]

RNA N6-methyladenosine (m6A) modification is involved in diverse biological processes. However, its role in spinal cord injury (SCI) is poorly understood. The m6A level increases in injured spinal cord, and METTL3, which is the core subunit of methyltransferase complex, is upregulated in reactive astrocytes and further stabilized by the USP1/UAF1 complex after SCI. The USP1/UAF1 complex specifically binds to and subsequently removes K48-linked ubiquitination of the METTL3 protein to maintain its stability after SCI. Moreover, conditional knockout of astrocytic METTL3 in both sexes of mice significantly suppressed reactive astrogliosis after SCI, thus resulting in widespread infiltration of inflammatory cells, aggravated neuronal loss, hampered axonal regeneration, and impaired functional recovery. Mechanistically, the YAP1 transcript was identified as a potential target of METTL3 in astrocytes. METTL3 could selectively methylate the 3′-UTR region of the YAP1 transcript, which subsequently maintains its stability in an IGF2BP2-dependent manner. In vivo, YAP1 overexpression by adeno-associated virus injection remarkably contributed to reactive astrogliosis and partly reversed the detrimental effects of METTL3 knockout on functional recovery after SCI. Furthermore, we found that the methyltransferase activity of METTL3 plays an essential role in reactive astrogliosis and motor repair, whereas METTL3 mutant without methyltransferase function failed to promote functional recovery after SCI. Our study reveals the previously unreported role of METTL3-mediated m6A modification in SCI and might provide a potential therapy for SCI. [ABSTRACT FROM AUTHOR]