In-Situ Electrolyte for Electrosynthesis: Scalable Anodically-Enabled One-Pot Sequence from Aldehyde to Isoxazol(in)es.

Electrochemical transformations are considered a green alternative to classical redox chemistry as it eliminates the necessity for toxic and waste producing redox reagents. Typical electrochemical reactions require the addition of a so-called supporting electrolyte - a salt bridge - and other additives, such as hexafluorisopropanol, to enhance conductivity and reaction outcomes, respectively. However, this is often accompanied by an increase in the amount of produced waste. Here, we report an "in-situ electrolyte" concept for facile, transition-metal-free, additive-free one-pot electrochemical preparation of isoxazol(in)es, important scaffolds for biologically active natural and synthetic molecules, from the respective aldehydes. The protocol utilizes no halogenated solvents and no external oxidants, while salt side-products provide the ionic conductivity necessary for the electrosynthesis. The electrolysis is performed in an undivided cell, using the state-of-the-art electrodes for the chlor-alkali industry dimensionally stable and scalable mixed metal oxide anode and platinized titanium anode of high durability. The cascade transformation comprises the condensation of aldehyde to oxime followed by its anodic oxidation and subsequent intra- and/or intermolecular [3+2] cycloadditions with an appropriate dipolarophile. Chemical yields up to 97%, and good Faradaic efficiency, scalability, and stability are observed for most substrates in a broad scope.

Aerobic exercise suppresses CCN2 secretion from senescent muscle stem cells and boosts muscle regeneration in aged mice.

BACKGROUND: Aging negatively impacts tissue repair, particularly in skeletal muscle, where the regenerative capacity of muscle stem cells (MuSCs) diminishes with age. Although aerobic exercise is known to attenuate skeletal muscle atrophy, its specific impact on the regenerative and repair capacity of MuSCs remains unclear. METHODS: Mice underwent moderate-intensity continuous training (MICT) from 9 months (aged + Ex-9M) or 20 months (aged + Ex-20M) to 25 months, with age-matched (aged) and adult controls. Histological examinations and MuSC transplantation assays assessed aerobic exercise effects on MuSC function and muscle regeneration. CCN2/connective tissue growth factor modulation (overexpression and knockdown) in MuSCs and AICAR supplementation effects were explored. RESULTS: Aged mice displayed significantly reduced running duration (65.33 ± 4.32 vs. 161.9 ± 1.29 min, mean ± SD, P < 0.001) and distance (659.17 ± 103.64 vs. 3058.28 ± 46.26 m, P < 0.001) compared with adults. This reduction was accompanied by skeletal muscle weight loss and decreased myofiber cross-sectional area (CSA). However, MICT initiated at 9 or 20 months led to a marked increase in running duration (142.75 ± 3.14 and 133.86 ± 20.47 min, respectively, P < 0.001 compared with aged mice) and distance (2347.58 ± 145.11 and 2263 ± 643.87 m, respectively, P < 0.001). Additionally, MICT resulted in increased skeletal muscle weight and enhanced CSA. In a muscle injury model, aged mice exhibited fewer central nuclear fibres (CNFs; 266.35 ± 68.66/mm2), while adult, aged + Ex-9M and aged + Ex-20M groups showed significantly higher CNF counts (610.82 ± 46.76, 513.42 ± 47.19 and 548.29 ± 71.82/mm2, respectively; P < 0.001 compared with aged mice). MuSCs isolated from aged mice displayed increased CCN2 expression, which was effectively suppressed by MICT. Transplantation of MuSCs overexpressing CCN2 (Lenti-CCN2, Lenti-CON as control) into injured tibialis anterior muscle compromised regeneration capacity, resulting in significantly fewer CNFs in the Lenti-CCN2 group compared with Lenti-CON (488.07 ± 27.63 vs. 173.99 ± 14.28/mm2, P < 0.001) at 7 days post-injury (dpi). Conversely, knockdown of CCN2 (Lenti-CCN2shR, Lenti-NegsiR as control) in aged MuSCs improved regeneration capacity, significantly increasing the CNF count from 254.5 ± 26.36 to 560.39 ± 48.71/mm2. Lenti-CCN2 MuSCs also increased fibroblast proliferation and exacerbated skeletal muscle fibrosis, while knockdown of CCN2 in aged MuSCs mitigated this pattern. AICAR supplementation, mimicking exercise, replicated the beneficial effects of aerobic exercise by mitigating muscle weight decline, enhancing satellite cell activity and reducing fibrosis. CONCLUSIONS: Aerobic exercise effectively reverses the decline in endurance capacity and mitigates muscle atrophy in aged mice. It inhibits CCN2 secretion from senescent MuSCs, thereby enhancing skeletal muscle regeneration and preventing fibrosis in aged mice. AICAR supplementation mimics the beneficial effects of aerobic exercise.

Expression Level and Clinical Significance of AK021443 in Non-Small-Cell Lung Carcinoma.

To explore the prognostic potential of AK021443 in non-small-cell lung carcinoma (NSCLC), AK021443 levels in NSCLC specimens were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between the AK021443 level and pathological factors in NSCLC patients was analyzed. Kaplan-Meier curves were plotted for assessing the prognostic value of AK021443 in NSCLC patients. Potential factors influencing NSCLC prognosis were analyzed by multivariable Cox regression test. AK021443 was upregulated in NSCLC specimens than normal ones. Its level was correlated to histological type, tumor differentiation, TNM staging, and lymphatic metastasis in NSCLC patients. AK021443 was the independent risk factor for the overall survival of NSCLC. AK021443 is highly expressed in NSCLC specimens, which is correlated to histological type, tumor differentiation, TNM staging, and lymphatic metastasis in NSCLC patients. It is the independent prognostic factor for NSCLC.

The benefits of exercise for outcome improvement following traumatic brain injury: Evidence, pitfalls and future perspectives.

Traumatic brain injury (TBI), also known as a silent epidemic, is currently a substantial public health problem worldwide. Given the increased energy demands following brain injury, relevant guidelines tend to recommend absolute physical and cognitive rest for patients post-TBI. Nevertheless, recent evidence suggests that strict rest does not provide additional benefits to patients' recovery. By contrast, as a cost-effective non-pharmacological therapy, exercise has shown promise for enhancing functional outcomes after injury. This article summarizes the most recent evidence supporting the beneficial effects of exercise on TBI outcomes, focusing on the efficacy of exercise for cognitive recovery after injury and its potential mechanisms. Available evidence demonstrates the potential of exercise in improving cognitive impairment, mood disorders, and post-concussion syndrome following TBI. However, the clinical application for exercise rehabilitation in TBI remains challenging, particularly due to the inadequacy of the existing clinical evaluation system. Also, a better understanding of the underlying mechanisms whereby exercise promotes its most beneficial effects post-TBI will aid in the development of new clinical strategies to best benefit of these patients.

Strengths and weaknesses of immunotherapy for advanced non-small-cell lung cancer: a meta-analysis of 12 randomized controlled trials.

BACKGROUND: Lung cancer is one of the leading causes of cancer death worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Immunotherapy has yielded no consistent benefit to date for those patients. Assessing the objective efficacy and safety of immunotherapy for advanced NSCLC patients will help to instruct the future development of immunotherapeutic drugs. METHODOLOGY AND PRINCIPAL FINDINGS: We performed a meta-analysis of 12 randomized controlled trials including 3134 patients (1570 patients in the immunotherapy group and 1564 patients in the control group) with histologically confirmed stage IIIA, IIIB, or IV NSCLC. The analysis was executed with efficacy end points regarding overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), and total effective rate. Overall unstratified OS, PFS, PR, and total effective rate were significantly improved in advanced NSCLC patients in the immunotherapy group (P = 0.0007, 0.0004, 0.002, 0.003, respectively), whereas CR was not improved (P = 0.97). Subgroup analysis showed that monoclonal antibody (mAb) immunotherapy significantly improved the PFS, PR, and total effective rate and showed a trend of improving OS of advanced NSCLC patients compared with the control group, with one kind of adverse event being significantly dominant. Compared with the control group, the vaccine subgroup showed no significant difference with regard to serious adverse events, whereas cytokine immunotherapy significantly induced three kinds of serious adverse events. CONCLUSIONS: Immunotherapy works efficiently on advanced NSCLC patients. Of several immunotherapies, mAb therapy may be a potential immunotherapy for advanced NSCLC patients, and become a standard complementary therapeutic approach in the future if the issues concerning toxicity and allergenicity of mAbs have been overcome.