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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.

Increasing evidence indicates that lymphocyte cytosolic protein 1 (LCP1) overexpression contributes to tumor progression; however, its role in osteosarcoma (OS) remains unclear. We aimed to investigate the potential effect of LCP1 in OS and the underlying mechanisms. We first demonstrated that LCP1 is upregulated in OS cell lines and tissues. Then, we found that aberrant expression of LCP1 could induce the proliferation and metastasis of OS cells in vitro and in vivo by destabilizing neuregulin receptor degradation protein-1 (Nrdp1) and subsequently activating the JAK2/STAT3 signaling pathway. When coculturing OS cells with bone marrow-derived mesenchymal stem cells (BMSCs) in vitro, we validated that oncogenic LCP1 in OS was transferred from BMSCs via exosomes. Moreover, microRNA (miR)-135a-5p, a tumor suppressor, was found to interact upstream of LCP1 to counteract the pro-tumorigenesis effects of LCP1 in OS. In conclusion, BMSC-derived exosomal LCP1 promotes OS proliferation and metastasis via the JAK2/STAT3 pathway. Targeting the miR-135a-5p/LCP1 axis may have potential in treating OS.

Haynaldia villosa is a wild relative of wheat and a valuable gene resource for wheat improvement. Owing to the limited number of probes available for fluorescence in situ hybridization (FISH), the resolution at which the karyotype of H. villosa can be characterized is poor, hampering accurate characterization of small segmental alien introgressions. We designed ten oligonucleotide probes using tandem repeats in DNA sequences derived from the short arm of H. villosa chromosome 6V (6VS). FISH with seven of them resulted in clear signals on H. villosa chromosomes. Using these, we constructed FISH karyotypes for H. villosa using oligo-6VS-1 and oligo-6VS-35 oligonucleotides and characterized the distribution of the two probes in five different H. villosa accessions. The new FISH probes can efficiently characterize H. villosa introgressions into wheat.

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.

Summary: Efficient activation of CD8+ T cells is critical for bacterial resistance and eradicating malignancy in the body. Here, we present a step-by-step protocol to use Listeria monocytogenes expressing OVA (LmOVA) to stimulate endogenous CD8+ T cells. We describe the steps for adoptive transfer of OT-I CD8+ T cells to CD45.1 mice and then detail the steps for detection of the antigen-specific CD8+ T cells in response to LmOVA.For complete details on the use and execution of this protocol, please refer to Wu et al. (2021).

This study aimed to determine whether Bmi-1 deficiency leads to intestinal epithelial barrier destruction and microbiota dysfunction, which members of the microbial community alter barrier function with age, and whether p16INK4a deletion could reverse the damage of intestinal epithelial barrier and microbial dysbiosis. Intestines from Bmi-1–deficient (Bmi-1–/–), Bmi-1 and p16INK4a double-knockout (Bmi-1–/–p16INK4a–/–), and wild-type mice were observed for aging and inflammation. Duolink Proximity Ligation Assay, immunoprecipitation, and construction of p16INK4a overexpressed adenovirus and the overexpressed plasmids of full-length, mutant, or truncated fragments for occludin were used for analyzing the interaction between p16INK4a and occludin. High-throughput sequencing of V4 region amplicon of 16S ribosomal RNA was conducted using intestinal microbiota. We found Bmi-1 deficiency destructed barrier structure, barrier function, and tight junction (TJ) in intestinal epithelium; decreased the TJ proteins; increased tumor necrosis factor α (TNF-α)–dependent barrier permeability; and up-regulated proinflammatory level of macrophages induced by intestinal microbial dysbiosis. The transplantation of fecal microbiota from wild-type mice ameliorated TJ in intestinal epithelium of Bmi-1–/– and Bmi-1–/–p16INK4a–/– mice. Harmful bacteria including Desulfovibrio, Helicobacter, and Oscillibacter were at a higher level in Bmi-1–/– mice. More harmful bacteria Desulfovibrio entered the epithelium and promoted macrophages-secreted TNF-α and caused TNF-α–dependent barrier permeability and aging. Accumulated p16INK4a combined with occludin at the 1st–160th residue in cytoplasm of intestinal epithelium cells from Bmi-1–/– mice, which blocked formation of TJ and the repair of intestinal epithelium barrier. P16INK4a deletion could maintain barrier function and microbiota balance in Bmi-1–/– mice through strengthening formation of TJ and decreasing macrophages-secreted TNF-α induced by Desulfovibrio entering the intestinal epithelium. Thus, Bmi-1 maintained intestinal TJ, epithelial barrier function, and microbiota balance through preventing senescence characterized by p16INK4a accumulation. The clearance of p16INK4a-positive cells in aging intestinal epithelium would be a new method for maintaining barrier function and microbiota balance. The residues 1–160 of occludin could be a novel therapeutic target for identifying small molecular antagonistic peptides to prevent the combination of p16INK4a with occludin for protecting TJ.

Abstract To study whether TGF-β1/IL-11/MEK/ERK (TIME) signaling mediates senescence-associated pulmonary fibrosis (SAPF) in Bmi-1-deficient (Bmi-1−/−) mice and determines the major downstream mediator of Bmi-1 and crosstalk between p16INK4a and reactive oxygen species that regulates SAPF, phenotypes were compared among 7-week-old p16INK4a and Bmi-1 double-knockout, N-acetylcysteine (NAC)-treated Bmi-1−/−, Bmi-1−/−, and wild-type mice. Pulmonary fibroblasts and alveolar type II epithelial (AT2) cells were used for experiments. Human pulmonary tissues were tested for type Ι collagen, α-smooth muscle actin (α-SMA), p16INK4a, p53, p21, and TIME signaling by using enzyme-linked immunosorbent assay (ELISA). Our results demonstrated that Bmi-1 deficiency resulted in a shortened lifespan, ventilatory resistance, poor ventilatory compliance, and SAPF, including cell senescence, DNA damage, a senescence-associated secretory phenotype and collagen overdeposition that was mediated by the upregulation of TIME signaling. The signaling stimulated cell senescence, senescence-related secretion of TGF-β1 and IL-11 and production of collagen 1 by pulmonary fibroblasts and the epithelial-to-mesenchymal transition of AT2 cells. These processes were inhibited by anti-IL-11 or the MEK inhibitor PD98059. NAC treatment prolonged the lifespan and ameliorated pulmonary dysfunction and SAPF by downregulating TIME signaling more than p16INK4a deletion by inhibiting oxidative stress and DNA damage and promoting ubiquitin-proteasome degradation of p16INK4a and p53. Cytoplasmic p16INK4a accumulation upregulated MEK/ERK signaling by inhibiting the translocation of pERK1/2 (Thr202/Tyr204) from the cytoplasm to the nucleus in senescent fibroblasts. The accumulation of collagen 1 and α-SMA in human lungs accompanied by cell senescence may be mediated by TIME signaling. Thus, this signaling in aging fibroblasts or AT2 cells could be a therapeutic target for preventing SAPF.

In recent years, landslide lake disasters occur frequently in southwest mountainous areas of China. Considering the influence of dam size and discharge channel location, three large-scale field tests were carried out in a natural river to study the failure process and mechanism of non-cohesive soil landslide dam, and the process and mechanism of non-cohesive landslide dam breach were analyzed. The results show that the dam size and discharge channel location have a significant influence on the breach mechanism of the landslide dam. The dam failure process can be divided into three stages: the initiation stage, the development stage and the failure stage. When the discharge channel is located close to the bank, the width of the breach is smaller, and the volume of the residual dam body is larger. The more stable the dam body is, the longer the breach process time is, and the smaller the peak discharge is. This study can provide a scientific reference for the emergency disposal and risk assessment of landslide dam.

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.

Seismicity sequence following a main earthquake usually contains much meaningful information for unveiling the focal mechanism and predicting the reoccurrence interval of large earthquakes. The spatiotemporal evolution of earthquakes before and after the 2008 Wenchuan earthquake (Ms 8.0) is analysed comprehensively in this study. The frequency-magnitude relation of the 3493 earthquake events retrieved from the database of the International Seismological Centre indicates that the adopted catalogue is complete for magnitudes ≥Ms 3.4. The seismicity during the 10 years before the Wenchuan earthquake remained stable, including the magnitudes and focal depths. However, seismicity attenuated sharply in the year following the Wenchuan earthquake, and the magnitude of earthquakes before the Wenchuan earthquake decreased gradually. The area of the seismogenic zone of the 2008 Wenchuan earthquake was smaller than the earthquake stricken area. The earthquakes that occurred in the Longmenshan fault area and adjacent area in the study period were mainly shallow earthquakes. The focal depths of earthquakes in the study area became stable gradually after the Wenchuan earthquake, mainly within the range from 10 to 16 km. The earthquakes in the study area were mainly distributed with an along-dip distance of 0–20 km, and the seismicity was distributed uniformly along the fault strike.

The representation of particles of complex shapes is one of the key challenges of numerical simulations based on the discrete element method (DEM). A novel algorithm has been developed by the authors to accurately represent 2D arbitrary particles for DEM modelling. In this paper, the algorithm is extended from 2D to 3D to model convex polyhedral particles based on multisphere methods, which includes three steps: the placement of spheres at the corners, along the edges, and on the facets in sequence. To give a good representation of a polyhedral particle, the spheres are placed tangent to the particle surface in each step. All spheres placed in the three steps are clumped together into a clump in DEM. In addition, the mass properties of the clump are determined based on the corresponding polyhedral particle to obtain accurate simulation results. Finally, an example is used to validate the robust and automatic performance of the algorithm in generating a sphere clump model for an assembly of polyhedral particles. A current FORTRAN version of the algorithm is available by contacting the authors.

This study proposes a new real-time diagnosis method for an in-wheel motor (IWM) of an electric vehicle (EV) based on dynamic Bayesian networks (DBNs). Since the electrical signal of the vehicle power supply is unstable because of the interference resulting from the EV's frequent acceleration and deceleration, the IWM's vibration signal is focused. Symptom parameters (SPs) in the time and frequency domains are used to represent different features of the vibration signals in the actual operating conditions of the EV. To select highly sensitive SPs, stable average discrimination rate (SADR) is proposed, which consists of the average discrimination rate (ADR) and the stability coefficient of the group (SCG). Moreover, DBNs are employed to establish a model for the real-time diagnosis of the IWM's mechanical faults, in which the parameter of road-speed-time slice (RSTS) is used to solve the problem that the state transition probability distribution between two continuous time slices cannot be obtained. Finally, the effectiveness of the proposed methods is verified by experiments using the IWM test bench.

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.

Since China’s reform and opening up, the country’s rapid marketization process has been accompanied by the rapid growth of inequality, which has been significant for all classes of society. In terms of its impact, housing inequality is particularly noticeable. In this paper, we discuss the influence of real-estate purchase time, organization, human capital, and political capital on the value of real estate and the appreciation of real estate in China by using a conditional mean model and a quantile regression model. The differences in the degree of influence of these factors on different quantile levels are also investigated. We found that, after adding the time factor, the prior possession of resources in the early stage of market transformation will benefit the long-term marketization process. Organizations that can penetrate “market-redistribution” and professions that directly participate in the distribution of real-estate resources also have significant advantages in this regard.

This study aims to develop an oxygen regeneration layer sandwiched between multiple porous polyurethanes (PU) to improve the performance of implantable glucose sensors. Sensors were prepared by coating electrodes with platinum nanoparticles, Nafion, glucose oxidase and sandwich hierarchically porous membrane with an oxygen supplement function (SHPM-OS). The SHPM-OS consisted of a hierarchically porous structure synthesized by polyethylene glycol and PU and a catalase (Cat) layer that was coated between hierarchical membranes and used to balance the sensitivity and linearity of glucose sensors, as well as reduce the influence of oxygen deficiency during monitoring. Compared with the sensitivity and linearity of traditional non-porous (NO-P) sensors (35.95 nA/mM, 0.9987, respectively) and single porous (SGL-P) sensors (45.3 nA /mM, 0.9610, respectively), the sensitivity and linearity of the SHPM-OS sensor was 98.45 nA/mM and 0.9989, respectively, which was more sensitive with higher linearity. The sensor showed a response speed of five seconds and a relative sensitivity of 90% in the first 10 days and remained 78% on day 20. This sensor coated with SHPM-OS achieved rapid responses to changes of glucose concentration while maintaining high linearity for long monitoring times. Thus, it may reduce the difficulty of back-end hardware module development and assist with effective glucose self-management for people with diabetes.

A complete picture of the deformation characteristics (distribution and evolution) of the geotechnical infrastructures serves as superior information for understanding their potential instability mechanism. How to monitor more completely and accurately the deformation of these infrastructures (either artificial or natural) in the field expediently and roundly remains a scientific topic. The conventional deformation monitoring methods are mostly carried out at a limited number of discrete points and cannot acquire the deformation data of the whole structure. In this paper, a new monitoring methodology of dam deformation and associated results interpretation is presented by taking the advantages of the terrestrial laser scanning (TLS), which, in contrast with most of the conventional methods, is capable of capturing the geometric information at a huge amount of points over an object in a relatively fast manner. By employing the non-uniform rational B-splines (NURBS) technology, the high spatial resolution models of the monitored geotechnical objects can be created with sufficient accuracy based on these point cloud data obtained from application of the TLS. Finally, the characteristics of deformation, to which the geotechnical infrastructures have been subjected, are interpreted more completely according to the models created based on a series of consecutive monitoring exercises at different times. The present methodology is applied to the Changheba earth-rock dam, which allows the visualization of deformation over the entire dam during different periods. Results from analysis of the surface deformation distribution show that the surface deformations in the middle are generally larger than those on both sides near the bank, and the deformations increase with the increase of the elevations. The results from the present application highlight that the adhibition of the TLS and NURBS technology permits a better understanding of deformation behavior of geotechnical objects of large size in the field.

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]