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Mesenchymal stem cells (MSCs) are pluripotent stem cells with multidirectional differentiation potential and strong immunomodulatory capacity. MSCs have been widely used in the treatment of injured, inflammatory, and immune-related diseases. Resting MSCs lack differentiation and immunomodulatory ability. Instead, they rely on microenvironmental factors to: 1) stimulate and regulate their expression of specific cell growth factors, chemokines, immunomodulatory factors, or receptors; or 2) direct their differentiation into specific tissue cells, which ultimately perform tissue regeneration and repair and immunomodulatory functions. Tumor necrosis factor (TNF)-α is central to the creation of an inflammatory microenvironment. TNF-α regulates the fate and functional reprogramming of MSCs, either alone or in combination with a variety of other inflammatory factors. TNF-α can exert opposing effects on MSCs, from inducing MSC apoptosis to enhancing their anti-tumor capacity. In addition, the immunomodulation and osteogenic differentiation capacities of MSCs, as well as their exosome or microvesicle components vary significantly with TNF-α stimulating concentration, time of administration, or its use in combination with or without other factors. Therefore, this review discusses the impact of TNF-α on the fate and functional reprogramming of MSCs in the inflammatory microenvironment, to provide new directions for improving the immunomodulatory and tissue repair functions of MSCs and enhance their therapeutic potential.

The purpose of this study is to compare and analyze the changes of CPET and pulmonary function indexes in patients with mild and moderate SARS-CoV-2 before infection and in the early recovery period, and to explore the influence of SARS-CoV-2 on cardiopulmonary fitness and its pathogenesis. Clinical data of 39 cases are collected, and paired analyses of CPET and pulmonary ventilation parameters before and after infection are performed using software SPSS. Bivariate correlations are analyzed for days post-infection, VO 2peak decline rate, VO 2peak /kg after infection, AHRR decline rate, and residual symptom count. The results show that VO 2peak , VO 2peak /kg, and AT significantly decreased after infection. The VE/VCO 2 slope increased, while PetCO 2 , VE peak , and VE/VCO 2 minimum showed reductions. FVC, FEV1, and FEV1/FVC remained unchanged. OUES significantly declined, along with AHRR and HR peak , although no significant differences are observed in HR rest , HRR-1 min, and HRR-2 min. The number of residual symptoms is significantly correlated with VO 2peak /kg and its decline rate, but not with infection duration. Additionally, the decline rate of VO 2peak /kg is strongly associated with post-infection time and post-infection VO 2peak /kg. VO 2 /HR and power also decreased significantly. Moreover, after SARS-CoV-2 infection, cardiopulmonary function, including cardiac chronotropic and muscle function, is significantly impaired in mild and moderate patients. Residual symptoms are closely linked to cardiopulmonary function. Given the large proportion of mild and moderate cases, these findings offer valuable insights for developing targeted interventions to prevent further symptom progression and improve cardiopulmonary health in this population.

It is recognized that the semi-rigidity of the glass fiber reinforced polymer (GFRP) joint should be considered in the structural analysis of GFRP structures, because of the relatively small initial stiffness resulting from the intrinsic property of GFRP material. Regarding the integrally-formed GFRP T-joint in the GFRP transmission tower, the study of its semi-rigidity remains inadequate. This paper aims to develop the relevant method for approximating the initial stiffness of the integrally-formed GFRP T-joint, in which the joint connects a vertical column with circular hollow section (CHS) and a horizontal bracing beam with rectangle section (RS). The finite Element (FE) models are first established, and validated by comparing the FE analysis results with the experimental results extracted from the previous study by the authors. The parametric study is subsequently conducted by using the validated FE model to investigate the sensitivity of the initial stiffness to the joint’s main geometrical parameters, i.e., the diameter and the thickness of the column, and the width and the height of the bracing beam. The total number of the specimens numerically modeled for the parametric study is 255. The mechanical model that reveals the main physical source of the initial stiffness is proposed. Based on the parametric analysis results, the approximating formula is then concluded, which is capable of well predicting the initial stiffness of the joint. The formula is first validated by comparing the theoretical results with the FE analysis results, considering the simply-supported T-shaped structures with/without the tapered haunches. Then, the GFRP line-suspension module (GFRP-LSM) utilized in a GFRP transmission tower is employed for further experimental validation. It is found that the structural analysis results, with consideration of the semi-rigidity of the joints, agree well the continuum shell element-based FE analysis results. In terms of the top displacement, the result obtained via the structural analysis is close to the measured data, indicating an error of 9.03%. In contrast, a significant discrepancy would be found when the semi-rigidity of the joints is neglected in the analysis, and the error would increase to 21.86%. The comparison again highlights the importance of considering the semi-rigidity of the GFRP joints in the structural analysis of a GFRP structure.

The purpose of this study was to investigate whether heart rate variability (HRV), a predictor of autonomic function, is associated with arterial stiffness in hypertensive patients. A total of 1,132 essential hypertension patients were included in this retrospective study. The standard deviation of normal-to-normal intervals (SDNN), an indicator of HRV, was selected to assess autonomic function. Arterial stiffness was evaluated by measuring the brachial-ankle pulse wave velocity (baPWV). Patients were categorized into tertiles based on their SDNN values. Participants in the lowest tertile of SDNN were older and exhibited higher levels of triglycerides and fasting blood glucose compared to those in the highest tertile of SDNN. Multivariate linear regression analyses indicated that SDNN had an independent negative correlation with baPWV (β=−3.60; 95% confidence interval [CI] =−4.78 ~ −2.41) after adjusting for all covariates. Consistently, multiple logistic regression analyses revealed a negative relationship between SDNN and the elevated baPWV (>75th percentile) (odds ratio [OR]=0.97; 95% CI=0.95 ~ 0.99). Evaluations utilizing restricted cubic splines confirmed that the relationships between SDNN and baPWV displayed an L-shaped curve (non-linear, P< 0.001). Subgroup analyses indicated that more pronounced associations between SDNN and baPWV were observed in younger individuals (under 65 years) ( P for interaction< 0.05). This study demonstrated that the SDNN is independently and negatively associated with baPWV in hypertensive patients, particularly in those under 65 years of age. These findings suggest a potential relationship between arterial stiffness and autonomic nervous system function.

Progression of chronic lymphocytic leukemia (CLL) and resistance to therapy are affected by tumor microenvironmental factors. One such factor is B-cell activating factor (BAFF), a cytokine that is produced mainly by nurse-like cells (NLC) and enhances CLL cells survival and modulates response to therapy. In CLL cells, BAFF activates NF-κB signaling, but how NF-κB supports CLL survival is not entirely clear. In this study we show that BAFF induces accumulation of the signaling and autophagy adaptor p62/SQSTM1 in a manner dependent on NF-κB activation. p62 potentiates mTORC1 signaling and activates NRF2, the master regulator of the anti-oxidant response. We found that expression of NRF2 target genes, such as NAD(P)H quinone oxidoreductase 1 (NQO1), is particularly enriched in CLL cells with high ROR1 surface expression (ROR1 Hi ). ROR1 Hi CLL cells with elevated NQO1 expression exhibit resistance to drugs that induce ROS accumulation, such venetoclax. However, such cells are more sensitive to compound 29h, a pro-drug that only becomes active after being metabolized by NQO1. Accordingly, 29h sensitizes high NQO1 CLL cells to venetoclax. Collectively, our study unravels a previously unknown signaling network through which the NF-κB-p62-NRF2 axis protects ROR1-high CLL cells from ROS-inducing therapeutics.

Exploring the coordination and analysis of intangible cultural heritage (ICH) and tourism development is a key issue in advancing cultural heritage and conservation in Chinese society. This paper employs panel data from 30 Chinese provinces from 2013 to 2022, utilizing the coupled coordination degree model and the panel vector autoregression (PVAR) model. In terms of provinces and regions, the data investigates the development relationship between intangible cultural heritage and tourism. The results of the study are: 1. The degree of coupling coordination between the two has shown an increasing trend over the ten-year sample data period. In 2021 and 2022, COVID-19 will have a stronger negative impact on the coupling degree. 2. The eastern coastal provinces of China, as well as the municipal areas, have a higher level of coupling coordination. Inland provinces, such as those in central and western China, exhibit relatively lower levels of coordination. The PVAR model data reveals a positive correlation between the interactions generated by intangible cultural heritage. The development of intangible cultural heritage has a particular impact on tourism. Intangible cultural heritage, in turn, depends on its own development. We should strengthen the development of intangible cultural heritage in the future. The study's findings provide theoretical references for the coordinated development of intangible cultural heritage and tourism in China.

Visual place recognition (VPR) is crucial for enabling autonomous agents to accurately localize themselves within a known environment. While existing methods leverage neural networks to enhance performance and robustness, they often suffer from the limited representation power of local feature extractors. To address this limitation, we propose CriSALAD, a novel VPR model that integrates visual foundation models (VFMs) and cross-image information to improve feature extraction robustness. Specifically, we adapt pre-trained VFMs for VPR by incorporating a parameter-efficient adapter inspired by Xception, ensuring effective task adaptation while preserving computational efficiency. Additionally, we employ the Sinkhorn Algorithm for Locally Aggregated Descriptors (SALAD) as a global descriptor to enhance place recognition accuracy. Furthermore, we introduce a transformer-like cross-image encoder that facilitates information sharing between neighboring images, thus enhancing feature representations. We evaluate CriSALAD on multiple publicly available place recognition datasets, achieving promising performance with a recall@1 of 89.3% on the Nordland dataset, while the closest rival achieves only 76.2%. CriSALAD outperforms both baseline models and advanced VFM-based VPR approaches.

Oridonin belongs to ent-kaurane tetracyclic diterpenoid and was first isolated from Isodon species. It exhibits inhibitory activities against a variety of tumor cells, and pharmacological study shows that oridonin could inhibit cell proliferation, DNA, RNA and protein synthesis of cancer cells, induce apoptosis and exhibit an antimutagenic effect. In addition, the large amount of the commercially-available supply is also very important for the natural lead oridonin. Moreover, the good stability, suitable molecular weight and drug-like property guarantee its further generation of a natural-like compound library. Oridonin has become the hot molecule in recent years, and from the year 2010, more than 200 publications can be found. In this review, we summarize the synthetic medicinal chemistry work of oridonin from the first publication 40 years ago and share our research experience of oridonin for about 10 years, which may provide useful information to those who are interested in this research field.

Alzheimer’s disease (AD) is a complex neurodegenerative disease that can lead to the loss of cognitive function. The progression of AD is regulated by multiple signaling pathways and their associated targets. Therefore, multitarget strategies theoretically have greater potential for treating AD. In this work, a series of new hybrids were designed and synthesized by the hybridization of tacrine (4, AChE: IC50 = 0.223 μM) with pyrimidone compound 5 (GSK-3β: IC50 = 3 μM) using the cysteamine or cystamine group as the connector. The biological evaluation results demonstrated that most of the compounds exhibited moderate to good inhibitory activities against acetylcholinesterase (AChE) and glycogen synthase kinase 3β (GSK-3β). The optimal compound 18a possessed potent dual AChE/GSK-3β inhibition (AChE: IC50 = 0.047 ± 0.002 μM, GSK-3β: IC50 = 0.930 ± 0.080 μM). Further molecular docking and enzymatic kinetic studies revealed that this compound could occupy both the catalytic anionic site and the peripheral anionic site of AChE. The results also showed a lack of toxicity to SH-SY5Y neuroblastoma cells at concentrations of up to 25 μM. Collectively, this work explored the structure–activity relationships of novel tetrahydroacridin hybrids with sulfur-inserted linkers, providing a reference for the further research and development of new multitarget anti-AD drugs.

Isodon rubescens has been used as a traditional green tea for more than 1000 years and many medicinal functions of I. rubescens are also very useful, such as its well-known antitumor and antibacterial activities. Oridonin, a bioactive ent-kaurane diterpenoid, is the major ingredient of this medicinal tea. Herein, 22 novel oridonin derivatives were designed and synthesized. The antibacterial activity was evaluated for the first time. Compound 12 was the most promising one with MIC of 2.0 μg/mL against B. subtilis, which was nearly 3-fold stronger than positive control chloromycetin. The antiproliferative property was also assayed and compound 19 showed stronger activity than taxol. The apoptosis-inducing ability, cell cycle arrest effect at S phase and influence of mitochondrial membrane potential by 19 in CaEs-17 cancer cells were first disclosed. Based on the above results, the cell apoptosis induced by compound 19 in CaEs-17 cells was most probably involved in the intrinsic apoptotic pathway.