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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.

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.

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.

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.