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With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic β-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.

Alzheimer’s disease (AD) is a complex degenerative disease of the central nervous system that is clinically characterized by a progressive decline in memory and cognitive function. The pathogenesis of AD is intricate and not yet fully understood. Neuroinflammation, particularly microglial activation-mediated neuroinflammation, is believed to play a crucial role in increasing the risk, triggering the onset, and hastening the progression of AD. Modulating microglial activation and regulating microglial energy metabolic disorder are seen as promising strategies to intervene in AD. The application of anti-inflammatory drugs and the targeting of microglia for the prevention and treatment of AD has emerged as a new area of research interest. This article provides a comprehensive review of the role of neuroinflammation of microglial regulation in the development of AD, exploring the connection between microglial energy metabolic disorder, neuroinflammation, and AD development. Additionally, the advancements in anti-inflammatory and microglia-regulating therapies for AD are discussed.

A gradient-tracking generalized vertical coordinate (GT) for ocean models is proposed in the study. The movement of the grid height surfaces is based on a simple Arbitrary Lagrangian–Eulerian (ALE) method ensuring that the discrete representation of the main gradient features of ocean states is uniform and small, optimal for the resolution of gradients in the vertical profile throughout the simulation. We have successfully implemented this algorithm into the Regional Oceanic Modeling System (ROMS v3.7). The numerical experiments used to evaluate the performance of the ALE ROMS include the propagation of linear internal waves, the lock-exchange flow, the gravitational currents over steep topography, and the seamount problem. The results demonstrate that generally, a better solution with significantly less spurious numerical mixing and smaller horizontal pressure gradient force error is produced by the GT coordinate compared to the sigma and s coordinate in ROMS. Further examinations of the GT coordinate are necessary regarding its performance in more realistic scenarios of simulations.

It has been reported that 1,25 dihydroxyvitamin D [1,25(OH)2D] deficiency leads to the loss of mandibular bone, however the mechanism is unclear. We investigated whether the Sirt1/FOXO3a signaling pathway is involved in this process. Using a 1,25(OH)2D deficiency model induced by genetic deletion in mice of 25-hydroxyvitamin D-1α hydroxylase [1α(OH)ase-/- mice]. We first documented a sharp reduction of expression levels of Sirt1 in the 1α(OH)ase-/- mice in vivo. Next, we demonstrated dose-dependent upregulation of Sirt1 by treatment with exogenous 1,25(OH)2D3 in vitro. We then identified a functional VDR binding site in the Sirt1 promoter. By crossing Prx1-Sirt1 transgenic mice with 1α(OH)ase-/- mice we demonstrated that the overexpression of Sirt1 in mesenchymal stem cells (MSCs) greatly improved the 1α(OH)ase-/- mandibular bone loss phenotype by increasing osteoblastic bone formation and reducing osteoclastic bone resorption. In mechanistic studies, we showed, in 1α(OH)ase-/- mice, decreases of Sirt1 and FoxO3a, an increase in oxidative stress as reflected by a reduction of the antioxidant enzymes peroxiredoxin1 (Prdx1), SOD1 and SOD2 expression, and an increase of markers for osteocyte senescence and senescence associated secretory phenotypes (SASP), including β-galactosidase (β-gal), p16, p53 and p21. The targeted overexpression of Sirt1 in the 1α(OH)ase-/- mice restored the expression levels of these molecules. Finally, we demonstrated that a Sirt1 agonist can upregulate FOXO3a activity by increasing deacetylation and nuclear translocation. Overall, results from this study support the concept that targeted increases in Sirt1/FOXO3a signaling levels can greatly improve the bone loss caused by 1,25(OH)2D deficiency.

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.Lung fibrosis: calling TIME on disease progressionTargeting cellular signals that are increased in lung fibrosis may help halt disease progression. The build-up of scarred and thickened tissues in the lungs associated with aging and cellular deterioration is known as senescence-associated pulmonary fibrosis (SAPF). There are limited treatment options, and Jianliang Jin at Nanjing Medical University, China, and co-workers believe that targeting a complex of cellular signaling pathways called TGF-β1/IL-11/MEK/ERK (TIME) signals, the disruption of which affects tissue homeostasis, may hold the key to tackling the disease. The team conducted experiments on mouse models of SAPF, deficient in a gene called Bmi-1. The protein encoded by Bmi-1 is critical for cell division and DNA damage repair. In the Bmi-1-deficient mice, the researchers found that TIME signals were overexpressed, resulting in premature cellular deterioration, increased inflammation and accelerated collagen production.

Antimicromial and antioxidant bioactive films based on poly(lactic acid)/poly(trimenthylene carbonate) films incorporated with different concentrations of oregano essential oil (OEO) were prepared by solvent casting. The antimicrobial, antioxidant, physical, thermal, microstructural, and mechanical properties of the resulting films were examined. Scanning electron microscopy analysis revealed that the cross-section of films became rougher when OEO was incorporated into PLA/PTMC blends. Differential scanning calorimetry analysis indicated that crystallinity of PLA phase decreased by the addition of OEO, but this did not affect the thermal stability of the films. Water vapor permeability of films slightly increased with increasing concentration of OEO. However, active PLA/PTMC/OEO composite films showed adequate barrier properties for food packaging application. The antimicrobial and antioxidant capacities were significantly improved with the incorporation of OEO (p < 0.05). The results demonstrated that an optimal balance between the mechanical, barrier, thermal, antioxidant, and antimicrobial properties of the films was achieved by the incorporation of 9 wt % OEO into PLA/PTMC blends.

Osteoarthritis (OA) is the most common degenerative joint disease worldwide, characterized by synovial inflammation, cartilage loss, and reactive hyperplasia of subchondral bone, affecting the quality of life of hundreds of millions of people. However, the molecular mechanisms underlying the occurrence and progression of OA remain unclear, and there is no therapy can substantially interrupt or reverse the destructive process of OA. More insight into the pathogenesis of OA may result in innovative therapeutics. The OA microenvironment plays a pivotal role in the development and progression of OA, which encompasses chondrocytes, adipocytes, synovial fibroblasts, endothelial cells, and immune cells. Extracellular vesicles (EVs) have emerged as a novel form of intercellular communication, mediating the transfer of a range of bioactive molecules to create a specific microenvironment. Recent studies have reported that the cargos of EVs play a crucial role in the pathogenesis of OA, including noncoding RNAs (ncRNAs), proteins, and lipids. This review systematically analyzes and summarizes the biological characteristics and functionalities of EVs derived from diverse cellular sources, especially how EVs mediate communication between different cells in the OA microenvironment, with a view to providing new insights into the pathogenesis of OA.

Background Data are currently lacking regarding perioperative stroke recurrence in hip fracture patients with previous stroke. We aimed to analyze the incidence and risk factors of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery. Methods We used 2019 and 2020 data from the United States National Inpatient Sample database. We identified elderly patients with previous ischemic stroke who had undergone hip fracture surgery to analyze the incidence of stroke recurrence. A 1:4 propensity score matching was used to balance confounding factors related to demographic data and matched the control group with the stroke recurrence group. Risk factors for stroke recurrence were determined using univariate and multivariate logistic analysis. Results The incidence of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery was 5.7% (51/882). Multivariate logistic regression analysis showed that intertrochanteric fracture (odds ratio 2.24, 95% confidence interval 1.14–4.57; p  = 0.021), hypertension (odds ratio 2.49, 95% confidence interval 1.26–5.02; p  = 0.009), and postoperative pneumonia (odds ratio 4.35, 95% confidence interval 1.59–11.82; p  = 0.004) were independently associated with stroke recurrence. Conclusions The perioperative stroke recurrence rate in elderly hip fracture patients with previous stroke was 5.7%. Intertrochanteric fracture, hypertension, and postoperative pneumonia were identified as factors significantly associated with stroke recurrence in this study. Adequate systemic support post-fracture, effective blood pressure management, and proactive infection prevention may help reduce stroke recurrence, especially in patients with intertrochanteric fractures.

The contents of main components in 45 walnut kernels from 5 walnut-planting provinces in China (Yunnan, Shaanxi, Shandong, Hebei, and Sichuan) were determined using colorimetry, high-performance liquid chromatography, and gas chromatography, including flavonoids, vitamin E, trace elements, fatty acids, and amino acids. The levels of flavonoids and vitamin E were higher in walnuts from Yunnan than in walnuts from the other four provinces. The levels of zinc and iron were relatively higher in walnuts from Shandong, and the calcium content in walnuts from Yunnan was much lower. No obvious difference was found in crude fat concentration for nuts from the five provinces, but differences were observed in the crude protein content. Oleic acid was the predominant unsaturated fatty acids in all walnut species; the monounsaturated fatty acid content was the highest in walnuts from Yunnan. The data obtained here provided insight into differences in walnuts resulting from different growing environments and germplasm genetic traits.

Background A consensus regarding the optimal approach for treating femoral neck fractures is lacking. We aimed to investigate the biomechanical outcomes of Femoral Neck System (FNS) internal fixation components in the treatment of nonanatomically reduced femoral neck fractures. Method We constructed two types of femoral neck fractures of the Pauwels classification with angles of 30° and 50°, and three models of anatomic reduction, positive buttress reduction and negative buttress reduction were constructed. Subgroups of 1 to 4 mm were divided according to the distance of displacement in the positive buttress reduction and negative buttress reduction models. The von Mises stress and displacements of the femur and FNS internal fixation components were measured for each fracture group under 2100-N axial loads. Results When the Pauwels angle was 30°, the positive 1-mm and 2-mm models had lower FNS stress than the negative buttress model. The positive 3- and 4-mm models showed FNS stress similar to that of the negative buttress model. But the four positive buttress models had similar stresses on the femur as the negative buttress model. When the Pauwels angle was 50°, the four positive buttress models had higher FNS stress than the negative buttress model. Three positive buttress models (2 mm, 3 and 4 mm) resulted in lower stress of the femur than the negative buttress model, though the 1-mm model did not. When the Pauwels angle was 30°, the positive buttress model had a lower displacement of the FNS than the negative buttress model and a similar displacement of the femur with the negative buttress model. When the Pauwels angle was 50°, the positive buttress model had a higher displacement of the FNS and femur than the negative buttress model. Our study also showed that the von Mises stress and displacement of the internal fixation and the femur increased as the fracture angle increased. Conclusion From the perspective of biomechanics, when the Pauwels angle was 30°, positive buttress was more stable to negative buttress. However, when the Pauwels angle was 50°, this advantage weakens. In our opinion, the clinical efficacy of FNS internal fixation with positive buttress may be related to the fracture angle, neck-shaft angle and alignment in the lateral view. This result needs verification in further clinical studies.