ENO1 regulates IL-1ß-induced chondrocyte inflammation, apoptosis and matrix degradation possibly through the potential binding to CRLF1.

In this study, we aim to investigate the role of enolase 1 (ENO1) in osteoarthritis (OA) pathogenic process and to uncover the underlying mechanism. To this end, we used IL-1ß to induce an in vitro OA­like chondrocyte model in human immortalized chondrocyte C-28/I2 cells. We manipulated the expression of ENO1 and cytokine receptor-like factor 1 (CRLF1) in IL-1ß-induced C-28/I2 cells using siRNA and/or overexpression and tested their effects on IL-1ß-induced pathologies including cell viability, apoptosis and inflammatory cytokine levels (IL-6 and TNF-α), and the expression of extracellular matrix-related enzymes and major mediators in the NF-κB signaling pathway (p-p65, p65, p-IκBα and IκBα). We used co-immunoprecipitation and immunofluorescence imaging to study a possible binding between ENO1 and CRLF1. Our data showed that IL-1ß induction elevated ENO1 and CRLF1 expression in C-28/I2 cells. Silencing ENO1 or CRLF1 inhibited the IL-1ß-induced cell viability damage, apoptosis, inflammation, and extracellular matrix degradation. The inhibitory effect of silencing ENO1 was reversed by CRLF1 overexpression, suggesting a functional connection between ENO1 and CRLF1, which could be attributed to a binding between these two partners. Our study could help validate the role of ENO1 in OA pathogenies and identify novel therapeutic targets for OA treatment.

Ternary Passivation for Enhanced Carrier Transport and Recombination Suppression in Highly Efficient Sn-Based Perovskite Solar Cells.

The exploration of nontoxic Sn-based perovskites as a viable alternative to their toxic Pb-based counterparts has garnered increased attention. However, the power conversion efficiency of Sn-based perovskite solar cells lags significantly behind their Pb-based counterparts. This study presents a ternary passivation strategy aimed at enhancing device performance, employing [6,6]-phenyl-C61-butyric-acid-methyl-ester (PCBM), poly(3-hexylthiophene) (P3HT), and indene C60 bisadduct (ICBA). These components play crucial roles in managing energy levels and enhancing carrier transportation, respectively. The results reveal that the introduction of the ternary system leads to improvements in carrier collection and transportation, accompanied by a suppression of the recombination process. Ultimately, the champion device achieves a remarkable performance with an efficiency of 14.64%. Notably, the device also exhibits robust operational and long-term stored stability.

Surface Molecularly Engineered Mitochondria Conduct Immunophenotype Repolarization of Tumor-Associated Macrophages to Potentiate Cancer Immunotherapy.

Reprogramming tumor-associated macrophages (TAMs) to an inflammatory phenotype effectively increases the potential of immune checkpoint blockade (ICB) therapy. Artificial mitochondrial transplantation, an emerging and safe strategy, has made brilliant achievements in regulating the function of recipient cells in preclinic and clinic, but its performance in reprogramming the immunophenotype of TAMs has not been reported. Here, the metabolism of M2 TAMs is proposed resetting from oxidative phosphorylation (OXPHOS) to glycolysis for polarizing M1 TAMs through targeted transplantation of mannosylated mitochondria (mPEI/M1mt). Mitochondria isolated from M1 macrophages are coated with mannosylated polyethyleneimine (mPEI) through electrostatic interaction to form mPEI/M1mt, which can be targeted uptake by M2 macrophages expressed a high level of mannose receptors. Mechanistically, mPEI/M1mt accelerates phosphorylation of NF-κB p65, MAPK p38 and JNK by glycolysis-mediated elevation of intracellular ROS, thus prompting M1 macrophage polarization. In vivo, the transplantation of mPEI/M1mt excellently potentiates therapeutic effects of anti-PD-L1 by resetting an antitumor proinflammatory tumor microenvironment and stimulating CD8 and CD4 T cells dependent immune response. Altogether, this work provides a novel platform for improving cancer immunotherapy, meanwhile, broadens the scope of mitochondrial transplantation technology in clinics in the future.

Global attractive set for quaternion-valued neural networks with neutral items.

This paper investigated the global attractive set for quaternion-valued neural networks (QVNNs) with leakage delay, time-varying delay, and neutral items. Based on various basic conditions of activation function, the global attractive set and global exponential attractive set of QVNNs are given combined with novel analytical techniques and Lyapunov theory. The QVNNs are studied by a direct method, without any decomposition. The time delay can be non-differential, which makes the results more pragmatic. Restrictions on the activation function of the neutral item are relaxed. The neutral activation function can be bounded or unbounded, which makes the results more practical. Two simulation examples are given to verify the validity of the theory results.

Safety assessment of coronary arteries during left bundle branch area pacing.

BACKGROUND: This study aimed to assess the safety of left bundle branch area pacing (LBBAP) by measuring the distance from the tip of the electrode to the nearby coronary artery with a nine-partition grid method. METHODS: From January 2019 to October 2020, patients who underwent LBBAP and postoperative coronary angiography in the Second Affiliated Hospital of Nanchang University were included in the study. The patients' fluoroscopic images of LBBAP and coronary angiography were collected and analyzed. Changes in the ST­T segment in the electrocardiogram (ECG), serum troponin, and myocardial enzyme profiles were observed before and after the LBBAP procedure. RESULTS: A total of 50 patients were included in this study, of whom 46 patients underwent implantation with a pacemaker and 4 patients received an implantable cardioverter defibrillator (ICD). The pacing electrodes were confined to the posterior-middle (PM), median (M), Posterior inferior (PI), and middle inferior (MI) positions of the two-dimensional nine-square grid or in the junction area of the above positions, and were concentrated in the rectangle formed by the line of the center points of the four positions. The average vertical distances from the electrode tip to the left anterior descending branch artery (LAD), posterior descending branches (PD) and the left posterior ventricular branches (PL) were 19.69 ± 8.72 mm, 26.09 ± 8.02 mm, and 21.11 ± 7.86 mm, respectively; the minimum was 5.28 mm, 9.51 mm, and 8.69 mm, respectively. Coronary angiography in all patients showed no significant injury to the ventricular septal branch; however, we observed elevated serum troponin and changes in ST­T segment in ECG. CONCLUSION: The study demonstrates that pacing electrodes in LBBAP can be safely implanted over a wide range. Coronary arteries are likely to be safe when the pacing electrodes are located within the rectangle formed by the line connecting the PM, M, PI, and MI zone centroids. The left bundle branch can be quickly captured and the safety of the coronary artery can be improved by locating the electrode in the posterior-mid zone. The potential risk of injury to the LAD from the electrode is greater compared with the PD.

Influencing factors for surgical treatment in neonatal necrotizing enterocolitis: a systematic review and meta-analysis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a complex disease characterized by gastrointestinal inflammation and is one of the most common gastrointestinal emergencies in neonates. Mild to moderate cases of NEC require medical treatment, whereas severe cases necessitate surgical intervention. However, evidence for surgical indications is limited and largely dependent on the surgeon's experience, leading to variability in outcomes. The primary aim of this study is to identify the risk factors for surgical intervention in neonatal NEC, which will aid in predicting the optimal timing for surgical intervention. METHODS: A literature search was conducted in PubMed, Embase, and Web of Science databases for case-control studies exploring risk factors for NEC requiring surgical intervention. The search was completed on June 16, 2024, and data analysis was performed using R Studio 4.3.2. RESULTS: 18 studies were included, comprising 1,104 cases in the surgery group and 1,686 in the medical treatment group. The meta-analysis indicated that high C-reactive protein (CRP) levels [OR = 1.42, 95% CI (1.01, 1.99)], lower gestational age [OR = 0.52, 95% CI (0.3, 0.91)], sepsis [OR = 2.94, 95% CI (1.87, 4.60)], coagulation disorder [OR = 3.45, 95% CI (1.81, 6.58)], lack of enteral feeding [OR = 3.18, 95% CI (1.37, 7.35)], and hyponatremia [OR = 1.22, 95% CI (1.07, 1.39)] are significant risk factors for surgical treatment in neonatal NEC. CONCLUSIONS: High CRP levels, coagulation disorders, sepsis, lower gestational age, lack of enteral feeding, and hyponatremia are significant risk factors for surgical intervention in neonatal NEC. These findings have potential clinical significance for predicting surgical risk.

CD36 restricts lipid-associated macrophages accumulation in white adipose tissues during atherogenesis.

Visceral white adipose tissues (WAT) regulate systemic lipid metabolism and inflammation. Dysfunctional WAT drive chronic inflammation and facilitate atherosclerosis. Adipose tissue-associated macrophages (ATM) are the predominant immune cells in WAT, but their heterogeneity and phenotypes are poorly defined during atherogenesis. The scavenger receptor CD36 mediates ATM crosstalk with other adipose tissue cells, driving chronic inflammation. Here, we combined the single-cell RNA sequencing technique with cell metabolic and functional assays on major WAT ATM subpopulations using a diet-induced atherosclerosis mouse model (Apoe-null). We also examined the role of CD36 using Apoe/Cd36 double-null mice. Based on transcriptomics data and differential gene expression analysis, we identified a previously undefined group of ATM displaying low viability and high lipid metabolism and labeled them as "unhealthy macrophages". Their phenotypes suggest a subpopulation of ATM under lipid stress. We also identified lipid-associated macrophages (LAM), which were previously described in obesity. Interestingly, LAM increased 8.4-fold in Apoe/Cd36 double-null mice on an atherogenic diet, but not in Apoe-null mice. The increase in LAM was accompanied by more ATM lipid uptake, reduced adipocyte hypertrophy, and less inflammation. In conclusion, CD36 mediates a delicate balance between lipid metabolism and inflammation in visceral adipose tissues. Under atherogenic conditions, CD36 deficiency reduces inflammation and increases lipid metabolism in WAT by promoting LAM accumulation.

Biodegradation of four polyolefin plastics in superworms (Larvae of Zophobas atratus) and effects on the gut microbiome.

Recent studies have demonstrated superworms (larvae of Zophobas atratus) ability to degrade polyethylene (PE), polystyrene (PS), polyvinyl chloride (PVC), and polypropylene (PP) within their digestive system. This study aimed to compare the ability of superworms to degrade the above four polyolefin plastics over a duration of 30 days. In this study, the degradation rate of PE was the highest, and the final average weight of superworms, as well as the final plastic mass loss consumed by them, significantly increased (73.38 % and 52.33 %, respectively) when PE was fed with wheat bran (1:1 [w/w]). FTIR and TGA indicated the occurrence of oxidation and biodegradation processes in the four polyolefin plastics when exposed to superworms. In addition, the molecular weights (Mw and Mn) of excreted polymer residues decreased by 3.1 % and 2.87 % in PE-fed superworms, suggesting that the depolymerization of PE was not entirely dependent on the gut microbial community. The analysis of the gut microbial communities revealed that the dominant microbial community were different for each type of plastic. The results indicate that the gut microbiome of superworms exhibited remarkable adaptability in degrading various types of plastics, and the intake preferences and efficiency of different plastics are associated with different dominant microbial community species.

Study on the sensitizing effect of SM-1 combined with irradiation on head and neck squamous cell carcinoma.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is globally prevalent with high recurrence, low survival rate, and poor quality of life for patients. Derived from PAC-1, SM-1 can activate procaspase-3 and induce apoptosis in cancer cells to exert anti-tumor effects. However, the inhibitory effect of SM-1 on HNSCC after combination with radiation are unclear. This study aims to investigate the radiosensitizing effect of SM-1 on HNSCC in vitro and in vivo. METHODS: MTT method was used to detect the effect of SM-1 on the viability of HNSCC cell lines (HONE1, HSC-2, and CAL27). The effects of SM-1 combined with radiation on the survival index of HONE1, HSC-2, and CAL27 cell lines were determined by colony formation assay. Flow cytometry was used to investigate the effects of SM-1 and radiation combination on cell apoptosis and cell cycle, and western blot experiments were performed to detect the expression of apoptosis and cell cycle-related proteins. Finally, a xenograft tumor model of CAL27 was established to evaluate the anti-tumor effect of SM-1 combined with radiation in vivo. RESULTS: In vitro, SM-1 effectively inhibited the activity of HNSCC cell lines HONE1, HSC-2, and CAL27 cells, and synergistically showed anti-proliferation activity during combined irradiation. Meanwhile, anti-tumor effect of SM-1 on HNSCC was higher than that of Debio1143, and the radiosensitivity of cells was greatly increased. Flow cytometry and western blot analysis showed that SM-1 induced G2/M phase arrest of head and neck squamous cell carcinoma cells via inhibiting the expression of CyclinB1 and CDC2. Moreover, SM-1 activated caspase-3 activity and up-regulated the cleaved form of PARP1 to induce cell apoptosis. In vivo, SM-1 combined irradiation showed a good anti-tumor effect. CONCLUSION: SM-1 enhances HNSCC cell radiation sensitivity in vitro and in vivo, supporting its potential as a radiosensitizer for clinical trials in combination with radiotherapy.

Triphase Enzyme Electrode Based on ZIF-8 with Enhanced Oxidase Catalytic Kinetics and Bioassay Performance.

Oxidase enzyme-based electrochemical bioassays have garnered considerable interest due to their specificity and high efficiency. However, in traditional solid-liquid diphase enzyme electrode systems, the low solubility of oxygen and its slow mass transfer rate limit the oxidase catalytic reaction kinetics, thereby affecting the bioassay performance, including the detection accuracy, sensitivity, and linear dynamic range. ZIF-8 nanoparticles (NPs) possess hydrophobic and high-porosity characteristics, enabling them to serve as oxygen nanocarriers. In this work, we constructed a solid-liquid-air triphase enzyme electrode by encapsulating ZIF-8 NPs within an oxidase network. Hydrophobic ZIF-8 NPs can provide a rapid and sufficient supply of oxygen for the oxidase-catalyzed reactions, which enhances and stabilizes the kinetics of oxidase-catalyzed reactions. This approach eliminates the issue of "oxygen deficiency" at the traditional solid-liquid diphase interface. Consequently, the triphase enzyme electrode exhibits a 12-fold higher linear detection range than the diphase system and possesses good detection accuracy in electrolytes even with fluctuating oxygen levels. This work proposes a novel approach to construct triphase reaction systems for addressing the gas deficiency problem in heterogeneous catalysis.

Fluorescent hydrogen-bonded organic framework act as a multifunctional platform for Fe3+ and F- sensing, and for information encryption.

Due to their exceptional optical properties and adjustable functional characteristics, hydrogen-bonded organic frameworks (HOFs) demonstrate significant potential in applications such as sensing, information encryption. However, studies on the synthesis of HOFs designed to construct multifunctional platforms are scant. In this work, we report the synthesis of a new fluorescent HOF by assembling melem and isophthalic acid (IPA), designated as HOF-IPA. HOF-IPA exhibited good selectivity and sensitivity towards Fe3+, making it suitable as a fluorescent sensor for Fe3+ detection. The sensor achieved satisfactory recoveries ranging from 97.79 % to106.42 % for Fe3+ sensing, with a low relative standard deviation (RSD) of less than 3.33 %, indicating significant application potential for HOF-IPA. Due to the ability of F- to mask the electrostatic action on the surface of Fe3+ and inhibit the photoelectron transfer (PET) of HOF-IPA, the HOF-IPA - Fe3+ system can be utilized as a fluorescent "off-on" sensor for F- detection. Additionally, owing to the colorless, transparent property of HOF-IPA in aqueous solution under sunlight and its blue fluorescence property under UV light (color) or microplate reader (fluorescence intensity), HOF-IPA based ink can be used for various types of information encryption, and all yielding favorable outcomes.

Genetic characterization and phylogenetic analysis of the S genes of porcine epidemic diarrhea virus isolates from China from 2020 to 2023.

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that has been the main cause of diarrhea in piglets since 2010 in China. The aim of this study was to investigate sequence variation and recombination events in the spike (S) gene of PEDV isolates from China. Thirty complete S gene sequences were obtained from PEDV-positive samples collected in six provinces in China from 2020 to 2023. Phylogenetic analysis showed that 10% (3/30) belonged to subtype GII-a, 6.67% (2/30) were categorized as subtype GII-b, 66.67% (20/30) were categorized as subtype GII-c, and 16.66% (5/30) were clustered with the S-INDEL strains. Amino acid sequence alignments showed that, when compared to strains of other subtypes, the GII-c strains had two characteristic amino acid substitutions (N139D and I289M). Five S-INDEL subtype strains had a single amino acid deletion (139N) and four amino acid substitutions (N118G, T137S, A138S, and D141G). Recombination analysis allowed six putative recombination events to be identified, one involving recombination between GII-c strains, two involving GII-c and GII-b strains, two involving GII-c and GI-a strains, and one involving GII-a and GI-b strains. These results suggest that recombination between PEDV strains has been common and complex in recent years and is one of the main reasons for the continuous variation of PEDV strains.

CX-5461 ameliorates disease in lupus-prone mice by triggering B-cell ferroptosis via p53-SLC7A11-ALOX12 pathway.

CX-5461, a first-in-class compound, is widely recognized as a selective inhibitor of RNA polymerase I. Recently, it has been reported to possess novel immunosuppressive properties with significant therapeutic effects in transplantation immune rejection. However, the potential use of CX-5461 for Systemic Lupus Erythematosus (SLE) treatment remains unknown. In this study, we elucidated the mechanism underlying the therapeutic efficacy of CX-5461 in lupus. Our findings demonstrated that CX-5461 selectively targets B cells and effectively reduces the proportions of B cells, germinal center B cells, and plasma cells in MRL/MPJ-Faslpr and Resiquimod (R848)-induced lupus mice. Molecular studies revealed that CX-5461 modulates CD36-Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4)-mediated glycerolipid metabolism in B cells, triggering ferroptosis through the p53- Solute Carrier Family 7 Member 11 (SLC7A11)- Arachidonate 12-Lipoxygenase (ALOX12) pathway, thereby decreasing IgG and Anti-Double-Stranded Deoxyribonucleic Acid (dsDNA) antibody levels and attenuating lupus. Collectively, these results suggest that CX-5461 holds promise as an effective candidate for targeted therapy against lupus.

Adipocytes promote metastasis of breast cancer by attenuating the FOXO1 effects and regulating copper homeostasis.

BACKGROUND: Obesity and the forkhead box O1(FOXO1) affect the survival of breast cancer patients, but the underlying mechanism remains unclear. We aimed to investigate the role of FOXO1 in obesity-associated-breast cancer. METHODS: We screened 383 breast disease patients from the first affiliated hospital with Nanjing Medical University in 2020. We performed wound healing, transwell, matrigel assays to assess the metastatic ability of cancer cells. We adopted mRNAs sequencing to select the differentially expressed transcripts in breast cancer. We applied immunohistochemistry, western blot, tissue microarrays to assess the level of FOXO1 and epithelial-mesenchymal transition (EMT) pathways. We conducted bioinformatic analysis to investigate interactions between FOXO1 and miR-135b. We used fluorescence in situ hybridization, RT-qPCR to confirm the characteristics of circCNIH4. We conducted luciferase reporter assay, rescue experiments to investigate interactions between circCNIH4 and miR-135b. RESULTS: Obesity was positively correlated with the incidence and progression of breast cancer. Adipocytes enhanced the migration of breast cancer and attenuated the effects of FOXO1. MiR-135b was a binding gene of FOXO1 and was regulated by circCNIH4. CircCNIH4 exhibited antitumor activity in vitro and in vivo. CONCLUSION: Adipocytes might accelerate the progression of breast cancer by modulating FOXO1/miR-135b/ circCNIH4 /EMT axis and regulating copper homeostasis.

Genome-wide variation study and inter-tissue communication analysis unveil regulatory mechanisms of egg-laying performance in chickens.

Egg-laying performance is of great economic importance in poultry, but the underlying genetic mechanisms are still elusive. In this work, we conduct a multi-omics and multi-tissue integrative study in hens with distinct egg production, to detect the hub candidate genes and construct hub molecular networks contributing to egg-laying phenotypic differences. We identifiy three hub candidate genes as egg-laying facilitators: TFPI2, which promotes the GnRH secretion in hypothalamic neuron cells; CAMK2D, which promotes the FSHß and LHß secretion in pituitary cells; and OSTN, which promotes granulosa cell proliferation and the synthesis of sex steroid hormones. We reveal key endocrine factors involving egg production by inter-tissue crosstalk analysis, and demonstrate that both a hepatokine, APOA4, and an adipokine, ANGPTL2, could increase egg production by inter-tissue communication with hypothalamic-pituitary-ovarian axis. Together, These results reveal the molecular mechanisms of multi-tissue coordinative regulation of chicken egg-laying performance and provide key insights to avian reproductive regulation.

Dynamic alternations of three-dimensional chromatin architecture contribute to phenotypic characteristics of breast muscle in chicken.

Breast muscle growth rate and intramuscular fat (IMF) content show apparent differences between fast-growing broilers and slow-growing indigenous chickens. However, the underlying genetic basis of these phenotypic characteristics remains elusive. In this study, we investigate the dynamic alterations of three-dimensional genome architecture and chromatin accessibility in breast muscle across four key developmental stages from embryo to starter chick in Arbor Acres (AA) broilers and Yufen (YF) indigenous chickens. The limited breed-specifically up-regulated genes (Bup-DEGs) are embedded in breed-specific A compartment, while a majority of the Bup-DEGs involving myogenesis and adipogenesis are regulated by the breed-specific TAD reprogramming. Chromatin loops allow distal accessible regions to interact with myogenic genes, and those loops share an extremely low similarity between chicken with different growth rate. Moreover, AA-specific loop interactions promote the expression of 40 Bup-DEGs, such as IGF1, which contributes to myofiber hypertrophy. YF-specific loop interactions or distal accessible regions lead to increased expression of 5 Bup-DEGs, including PIGO, PEMT, DHCR7, TMEM38B, and DHDH, which contribute to IMF deposition. These results help elucidate the regulation of breast muscle growth and IMF deposition in chickens.

MicroRNA-19b exacerbates systemic sclerosis through promoting Th9 cells.

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and multiple vital organs, but the immunological pathogenesis of SSc remains unclear. We show here that miR-19b promotes Th9 cells that exacerbate SSc. Specifically, miR-19b and interleukin (IL)-9 increase in CD4+ T cells in experimental SSc in mice induced with bleomycin. Inhibiting miR-19b reduces Th9 cells and ameliorates the disease. Mechanistically, transforming growth factor beta (TGF-ß) plus IL-4 activates pSmad3-Ser213 and TRAF6-K63 ubiquitination by suppressing NLRC3. Activated TRAF6 sequentially promotes TGF-ß-activated kinase 1 (TAK1) and nuclear factor κB (NF-κB) p65 phosphorylation, leading to the upregulation of miR-19b. Notably, miR-19b activated Il9 gene expression by directly suppressing atypical E2F family member E2f8. In patients with SSc, higher levels of IL9 and MIR-19B correlate with worse disease progression. Our findings reveal miR-19b as a key factor in Th9 cell-mediated SSc pathogenesis and should have clinical implications for patients with SSc.

Intervention control of aerobic exercise in maintaining quality of life and pulmonary hypertension in hemodialysis patients.

BACKGROUND: Pulmonary hypertension is a serious complication in the treatment of maintenance hemodialysis patients, which seriously affects the quality of life of patients and threatens their life safety. Prevention, treatment and improvement of pulmonary hypertension are of great significance to improve the quality of life of patients. AIM: To investigate the intervention and control of pedal-powered bicycle in maintaining quality of life and pulmonary hypertension in hemodialysis patients. METHODS: 73 patients with maintenance hemadialysis combined with pulmonary arterial hypertension at a hemodialysis center in a certain hospital from May 2021 to May 2022 are selected. Patients are divided into two groups, 37 cases in the control group (group C) and 36 cases in the intervention group (group I). Patients are divided into two groups, group C is treated with oral administration of betaglandin sodium combined with routine nursing care. Based on group C, group I conducts power cycling exercises. RESULTS: After treatment, group I patients had higher muscle strength, 36-Item Short Form Health Survey scores, and Kidney Disease Targets Areas scores; The 6-minute walk distance test index level was higher and the Borg score was lower; The group I had lower systolic blood pressure, greater vital capacity, higher positive emotion, lower systolic pulmonary artery pressure index level, higher arterial partial oxygen pressure level, lower pulmonary vascular resistance index level, and higher blood oxygen saturation level [158.91 ± 11.89 vs 152.56 ± 12.81, 1795.01 ± 603.18 vs 1907.20 ± 574.15, 24.00 (22.00, 29.00) vs 24.00 (22.00, 28.00), P < 0.001]. CONCLUSION: Aerobic exercise combined with Western medicine treatment can effectively improve patients' pulmonary hypertension, alleviate their negative emotions, and enable them to achieve a higher level of quality of life.

Celastrol alleviates atopic dermatitis by regulating Ezrin-mediated mitochondrial fission and fusion.

Celastrol, a bioactive molecule extracted from the plant Tripterygium wilfordii Hook F., possesses anti-inflammatory, anti-obesity and anti-tumour properties. Despite its efficacy in improving erythema and scaling in psoriatic mice, the specific therapeutic mechanism of celastrol in atopic dermatitis (AD) remains unknown. This study aims to examine the role and mechanism of celastrol in AD using TNF-α-stimulated HaCaT cells and DNCB-induced Balb/c mice as in vitro and in vivo AD models, respectively. Celastrol was found to inhibit the increased epidermal thickness, reduce spleen and lymph node weights, attenuate inflammatory cell infiltration and mast cell degranulation and decrease thymic stromal lymphopoietin (TSLP) as well as various inflammatory factors (IL-4, IL-13, TNF-α, IL-5, IL-31, IL-33, IgE, TSLP, IL-17, IL-23, IL-1ß, CCL11 and CCL17) in AD mice. Additionally, celastrol inhibited Ezrin phosphorylation at Thr567, restored mitochondrial network structure, promoted translocation of Drp1 to the cytoplasm and reduced TNF-α-induced cellular reactive oxygen species (ROS), mitochondrial ROS (mtROS) and mitochondrial membrane potential (MMP) production. Interestingly, Mdivi-1 (a mitochondrial fission inhibitor) and Ezrin-specific siRNAs lowered inflammatory factor levels and restored mitochondrial reticular formation, as well as ROS, mtROS and MMP production. Co-immunoprecipitation revealed that Ezrin interacted with Drp1. Knocking down Ezrin reduced mitochondrial fission protein Drp1 phosphorylation and Fis1 expression while increasing the expression of fusion proteins Mfn1 and Mfn2. The regulation of mitochondrial fission and fusion by Ezrin was confirmed. Overall, celastrol may alleviate AD by regulating Ezrin-mediated mitochondrial fission and fusion, which may become a novel therapeutic reagent for alleviating AD.