IL-13 facilitates ferroptotic death in asthmatic epithelial cells via SOCS1-mediated ubiquitinated degradation of SLC7A11.

Th2-high asthma is characterized by elevated levels of type 2 cytokines, such as interleukin 13 (IL-13), and its prevalence has been increasing worldwide. Ferroptosis, a recently discovered type of programmed cell death, is involved in the pathological process of Th2-high asthma; however, the underlying mechanisms remain incompletely understood. In this study, we demonstrated that the serum level of malondialdehyde (MDA), an index of lipid peroxidation, positively correlated with IL-13 level and negatively correlated with the predicted forced expiratory volume in 1 s (FEV1%) in asthmatics. Furthermore, we showed that IL-13 facilitates ferroptosis by upregulating of suppressor of cytokine signaling 1 (SOCS1) through analyzing immortalized airway epithelial cells, human airway organoids, and the ovalbumin (OVA)-challenged asthma model. We identified that signal transducer and activator of transcription 6 (STAT6) promotes the transcription of SOCS1 upon IL-13 stimulation. Moreover, SOCS1, an E3 ubiquitin ligase, was found to bind to solute carrier family 7 member 11 (SLC7A11) and catalyze its ubiquitinated degradation, thereby promoting ferroptosis in airway epithelial cells. Last, we found that inhibiting SOCS1 can decrease ferroptosis in airway epithelial cells and alleviate airway hyperresponsiveness (AHR) in OVA-challenged wide-type mice, while SOCS1 overexpression exacerbated the above in OVA-challenged IL-13-knockout mice. Our findings reveal that the IL-13/STAT6/SOCS1/SLC7A11 pathway is a novel molecular mechanism for ferroptosis in Th2-high asthma, confirming that targeting ferroptosis in airway epithelial cells is a potential therapeutic strategy for Th2-high asthma.

O-POSSUM and P-POSSUM as predictors of morbidity and mortality in older patients after hip fracture surgery: a meta-analysis.

BACKGROUND: The POSSUM model has been widely used to predict morbidity and mortality after general surgery. Modified versions known as O-POSSUM and P-POSSUM have been used extensively in orthopedic surgery, but their accuracy is unclear. This systematic review evaluated the predictive value of these models in older patients with hip fractures. METHODS: This study was performed and reported based on the "Preferred reporting items for systematic reviews and meta-analyses" guidelines. PubMed, Cochrane, EMBASE, and Web of Science were comprehensively searched for relevant studies, whose methodological quality was evaluated according to the "Methodological index for non-randomized studies" scale. Revman 5 was used to calculate weighted ratios of observed to expected morbidity or mortality. RESULTS: The meta-analysis included 10 studies, of which nine (2549 patients) assessed the ability of O-POSSUM to predict postoperative morbidity, nine (3649 patients) assessed the ability of O-POSSUM to predict postoperative mortality, and four (1794 patients) assessed the ability of P-POSSUM to predict postoperative mortality. The corresponding weighted ratios of observed to expected morbidity or mortality were 0.84 (95% CI 0.70-1.00), 0.68 (95% CI 0.49-0.95), and 0.61 (95% CI 0.16-2.38). CONCLUSIONS: While O-POSSUM shows reasonable accuracy in predicting postoperative morbidity in older patients with hip fractures, both P-POSSUM and O-POSSUM substantially overestimate postoperative mortality. The POSSUM model should be optimized further for this patient population.

Mesenchymal stem cell-derived extracellular vesicles, osteoimmunology and orthopedic diseases.

Mesenchymal stem cells (MSCs) play an important role in tissue healing and regenerative medicine due to their self-renewal and multi-directional differentiation properties. MSCs exert their therapeutic effects mainly via the paracrine pathway, which involves the secretion of extracellular vesicles (EVs). EVs have a high drug loading capacity and can transport various molecules, such as proteins, nucleic acids, and lipids, that can modify the course of diverse diseases. Due to their ability to maintain the therapeutic effects of their parent cells, MSC-derived EVs have emerged as a promising, safe cell-free treatment approach for tissue regeneration. With advances in inflammation research and emergence of the field of osteoimmunology, evidence has accumulated pointing to the role of inflammatory and osteoimmunological processes in the occurrence and progression of orthopedic diseases. Several studies have shown that MSC-derived EVs participate in bone regeneration and the pathophysiology of orthopedic diseases by regulating the inflammatory environment, enhancing angiogenesis, and promoting the differentiation and proliferation of osteoblasts and osteoclasts. In this review, we summarize recent advances in the application and functions of MSC-derived EVs as potential therapies against orthopedic diseases, including osteoarthritis, intervertebral disc degeneration, osteoporosis and osteonecrosis.

Associations between smoking and clinical outcomes after total hip and knee arthroplasty: A systematic review and meta-analysis.

Background: Smoking increases risk of several complications after total hip or knee arthroplasty (THA/TKA), so we systematically reviewed and meta-analyzed the literature to take into account all relevant evidence, particularly studies published since 2010. Methods: The PubMed, Ovid Embase, Web of Science, and EBSCOHost databases were searched and studies were selected and analyzed according to MOOSE recommendations. Methodological quality of included studies was assessed using the Newcastle-Ottawa Scale. Data were qualitatively synthesized or meta-analyzed using a random-effects model. Results: A total of 40 studies involving 3,037,683 cases were included. Qualitative analysis suggested that smoking is associated with worse patient-reported outcomes within one year after surgery, and meta-analysis showed that smoking significantly increased risk of the following outcomes: total complications (OR 1.41, 95% CI 1.01-1.98), wound complications (OR 1.77, 95% CI 1.50-2.10), prosthetic joint infection (OR 1.84, 95% CI 1.52-2.24), aseptic loosening (OR 1.62, 95% CI 1.12-2.34), revision (OR 2.12, 95% CI 1.46-3.08), cardiac arrest (OR 4.90, 95% CI 2.26-10.60), cerebrovascular accident (OR 2.22, 95% CI 1.01-4.85), pneumonia (OR 2.35, 95% CI 1.17-4.74), acute renal insufficiency (OR 2.01, 95% CI 1.48-2.73), sepsis (OR 4.35, 95% CI 1.35-14.00), inpatient mortality (OR 12.37, 95% CI 4.46-34.28), and persistent opioid consumption (OR 1.64, 95% CI 1.39-1.92). Conclusion: Smoking patients undergoing THA and TKA are at increased risk of numerous complications, inpatient mortality, persistent opioid consumption, and worse 1-year patient-reported outcomes. Pre-surgical protocols for these outcomes should give special consideration to smoking patients.

Three-Dimensional Bi-Continuous Nanoporous Gold/Nickel Foam Supported MnO2 for High Performance Supercapacitors.

A three-dimensional bi-continuous nanoporous gold (NPG)/nickel foam is developed though the electrodeposition of a gold-tin alloy on Ni foam and subsequent chemical dealloying of tin. The newly-designed 3D metal structure is used to anchor MnO2 nanosheets for high-performance supercapacitors. The formed ternary composite electrodes exhibit significantly-enhanced capacitance performance, rate capability, and excellent cycling stability. A specific capacitance of 442 Fg-1 is achieved at a scan rate of 5 mV s-1 and a relatively high mass loading of 865 µg cm-2. After 2500 cycles, only a 1% decay is found at a scan rate of 50 mV s-1. A high power density of 3513 W kg-1 and an energy density of 25.73 Wh kg-1 are realized for potential energy storage devices. The results demonstrate that the NPG/nickel foam hybrid structure significantly improves the dispersibility of MnO2 and makes it promising for practical energy storage applications.