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Aim: Choosing the initial treatment for type 2 diabetes (T2D) is pivotal, requiring consideration of solid clinical evidence and patient characteristics. Despite metformin's historical preference, its efficacy in preventing cerebrovascular events lacked empirical validation. This study aimed to evaluate the associations between first‐line monotherapy (metformin or non‐metformin antidiabetic medications) and cerebrovascular complications in patients with T2D without diabetic complications. Methods: We analysed 9090 patients with T2D without complications who were prescribed either metformin or non‐metformin medications as initial therapy. Propensity score matching ensured group comparability. Cox regression analyses, stratified by initial metformin use, assessed cerebrovascular disease risk, adjusting for multiple covariates and using competing risk analysis. Metformin exposure was measured using cumulative defined daily doses. Results: Metformin users had a significantly lower crude incidence of cerebrovascular diseases compared with non‐users (p <.0001). Adjusted hazard ratios (aHRs) consistently showed an association between metformin use and a lower risk of overall cerebrovascular diseases (aHRs: 0.67‐0.69) and severe events (aHRs: 0.67‐0.69). The association with reduced risk of mild cerebrovascular diseases was significant across all models (aHRs: 0.73‐0.74). Higher cumulative defined daily doses of metformin correlated with reduced cerebrovascular risk (incidence rate ratio: 0.62‐0.94, p <.0001), indicating a dose‐dependent effect. Conclusion: Metformin monotherapy is associated with a reduced risk of cerebrovascular diseases in early‐stage T2D, highlighting its dose‐dependent efficacy. However, the observed benefits might also be influenced by baseline differences and the increased risks associated with other medications, such as sulphonylureas. These findings emphasize the need for personalized diabetes management, particularly in mitigating cerebrovascular risk in early T2D stages. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) is one of the most widely abused synthetic drugs in the world. The users generally present hyperthermia (HT) and psychiatric symptoms. However, the mechanisms involved in METH/HT-induced neurotoxicity remain elusive. Here, we investigated the role of heat shock protein 90 alpha (HSP90α) in METH/HT (39.5°C)-induced necroptosis in rat striatal neurons and an in vivo rat model. METH treatment increased core body temperature and up-regulated LDH activity and the molecular expression of canonical necroptotic factors in the striatum of rats. METH and HT can induce necroptosis in primary cultures of striatal neurons. The expression of HSP90α increased following METH/HT injuries. The specific inhibitor of HSP90α, geldanamycin (GA), and HSP90α shRNA attenuated the METH/HT-induced upregulation of receptor-interacting protein 3 (RIP3), phosphorylated RIP3, mixed lineage kinase domain-like protein (MLKL), and phosphorylated MLKL. The inhibition of HSP90α protected the primary cultures of striatal neurons from METH/HT-induced necroptosis. In conclusion, HSP90α plays an important role in METH/HT-induced neuronal necroptosis and the HSP90α-RIP3 pathway is a promising therapeutic target for METH/HT-induced neurotoxicity in the striatum.

Small-pore zeolites catalyze the methanol-to-olefins (MTO) reaction via a dual-cycle mechanism, encompassing both olefin- and aromatic-based cycles. Zeolite topology is crucial in determining both the catalytic pathway and the product selectivity of the MTO reaction. Herein, we investigate the mechanistic influence of MCM-35 zeolite on the MTO process. The structural properties of the as-synthesized MCM-35 catalyst, including its confined cages (6.19 Å), were characterized, confirming them as the catalytic centers. Then, the MTO reactions were systematically performed and investigated over a MCM-35 catalyst. Feeding pure methanol to the reactor yielded minimal MTO activity despite the formation of some aromatic species within the zeolite. The results suggest that the aromatic-based cycle is entirely suppressed in MCM-35, preventing the simultaneous occurrence of the olefin-based cycle. However, cofeeding a small amount of propene in methanol can obviously enhance the methanol conversion under the same studied reaction conditions. Thus, the exclusive operation of the olefin-based cycle in the MTO reaction, independent of the aromatic-based cycle, was demonstrated in MCM-35 zeolite. [ABSTRACT FROM AUTHOR]

Over the past few years, the field of regulated cell death continues to expand and novel mechanisms that orchestrate multiple regulated cell death pathways are being unveiled. Meanwhile, researchers are focused on targeting these regulated pathways which are closely associated with various diseases for diagnosis, treatment, and prognosis. However, the complexity of the mechanisms and the difficulties of distinguishing among various regulated types of cell death make it harder to carry out the work and delay its progression. Here, we provide a systematic guideline for the fundamental detection and distinction of the major regulated cell death pathways following morphological, biochemical, and functional perspectives. Moreover, a comprehensive evaluation of different assay methods is critically reviewed, helping researchers to make a reliable selection from among the cell death assays. Also, we highlight the recent events that have demonstrated some novel regulated cell death processes, including newly reported biomarkers (e.g., non-coding RNA, exosomes, and proteins) and detection techniques.

Tunable materials have been extensively studied due to their potential applications in many electrical devices. High tunability has been practically achieved in a number of ferroelectric materials such as perovskite phases under usually high DC electric field of 10–100 kV/cm. In this work, single phased M-type barium ferrite ceramics with colossal permittivity accompanied by defect pair dipoles and giant tunability under super low DC bias were successfully prepared by the sol-gel method. Results show that Zr4+ ions substituted for Fe3+ in the spinel phase of ferrites. The concentration of Fe2+ increased from 37.23% to 43.22% and subsequently decreased to 36.72% with increasing Zr4+ ions from 0 to 0.1 and then continuously to 0.3, respectively. The highest content of Fe2+ was ∼43.22% and thus the maximum concentration of Fe2+/Fe3+ pair dipoles formed between Fe2+ generated and Fe3+ nearby appeared in the ferrites with Zr4+ doping of 0.1. Not only in Zr4+ doped ferrites but also in the ferrites with doping other high valent ions, Fe2+/Fe3+ pair dipoles formed and controlled permittivity. Giant permittivity of above 30 k appeared in the ferrites with Zr4+ content of 0.1–0.3 and was controlled by external bias to form tunability. The activation energy of modulation of defect pair dipoles was only ∼0.182 eV, which is 85% lower than 1.2 eV of traditional perovskite BaTiO3. High dielectric tunability of more than 65% with only a low DC electric field of <25 V/cm was obtained in BaFe11.9Zr0.1O19 ferrites, which was in high contrast to conventional ferroelectrics where a high DC bias of dozens of kV/cm was required. Similarly, dielectric tunability of ∼40% with a low electric field of <40 V/cm was exhibited in Nb5+ or Ti4+ doped barium ferrites. Such a high tunability controlled by an extremely low bias field in barium ferrite ceramics doped by the target ions might be promised for novel applications in tunable devices. [ABSTRACT FROM AUTHOR]