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Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP‐43 aggregates. Recent evidence has been indicated that phosphorylated TDP‐43 (pTDP‐43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP‐43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP‐43 detectable in routine biopsied muscles? (ii) Can detection of pTDP‐43 aggregation discriminate between ALS and non‐ALS patients? (iii) Can pTDP‐43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non‐ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP‐43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP‐43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non‐ALS controls (16/54; p < 0.001). The pTDP‐43 aggregates were mainly close to the sarcolemma. Using a semi‐quantified pTDP‐43 aggregates score, we applied a cut‐off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP‐43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof‐of‐concept for the detection of pTDP‐43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS. To explore whether testing pTDP‐43 aggregation in muscle tissue would assist in the diagnosis of ALS, we conducted a diagnostic study in 18 ALS patients and 54 randomly matched controls from ALS and muscular disease cohorts. Our results indicated that pTDP‐43 was more prone to accumulation in ALS patients, enabling differentiation between ALS and non‐ALS patients with high sensitivity and specificity. Moreover, we observed that accumulation of pTDP‐43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions.

A better understanding of the mechanisms underlying PD‐L1 aberrant expression in head and neck squamous cell carcinoma (HNSCC) will help reveal predictive biomarkers and overcome resistance to treatment. In this study, the prognostic significance of PD‐L1 in forty‐five HNSCC archival samples was determined by qRT‐PCR. The biological function associated with malignant behaviour was assessed by PD‐L1 depletion, miR‐382‐3p re‐expression and regulation of circ_0000052. The interactions of PD‐L1‐miRNA and miRNA‐circRNA were determined by qRT‐PCR, Western blot analysis, dual‐luciferase reporter assays and RNA immunoprecipitation assays. PD‐L1 was highly expressed in patient samples and cancer cell lines. Higher levels of PD‐L1 were associated with patient recurrences and play a pivotal role in regulating cell proliferation, migration, invasion, clonogenicity and apoptosis. In addition to demonstrating that the IFN‐γ/JAK2/STAT1 signalling pathway can induce PD‐L1 overexpression in HNSCC, a novel mechanism by which upregulated circ_0000052 mediates PD‐L1 overexpression was also demonstrated. To do this, circ_0000052 competitively binds to miR‐382‐3p and alleviates its repression of PD‐L1. This leads to overexpression of PD‐L1, causing the aggressiveness of the cells. Our data demonstrate that circ_0000052 is oncogenic, and the circ_0000052/miR‐382‐3p/PD‐L1 axis is critical in HNSCC progression. The manipulation of circRNAs/miRNAs in combination with anti‐PD‐L1 therapy may improve personalized disease management.

Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide and has a very poor prognosis. Its occurrence has been on the increase in recent years. Surgical resection and liver transplantation are the primary methods of treatment for HCC patients, but can only be applied to 15% of patients. The median survival time of unresectable or metastasizing HCC patients is only a few months. Existing systemic treatment methods are not effective for advanced HCC patients and a new method of treatment is needed for these patients. It has been established that the HCC occurs in multiple stages, however, the pathogenesis at a molecular level is not clear and many key factors are yet to be determined. In the past 30 years, it has become evident that the Ras/Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathway plays a significant role in the occurrence and development of HCC. This review focused on the association between the Ras/Raf/MEK/ERK signaling pathway and HCC.

The microbial terroir is an indispensable part of the terroir panorama, and can improve wine quality with special characteristics. In this study, eight autochthonous yeasts (Saccharomyces cerevisiae), selected in Huailai country, China, were trailed in small-scale and pilot fermentations for both white (Riesling and Sémillon) and red (Cabernet Sauvignon and Syrah) wines and evaluated by GC-MS analysis and the rate-all-that-apply (RATA) method. Compared to commercial yeast strains, the indigenous yeasts were able to produce higher concentrations of ethyl esters and fatty acid ethyl esters, and higher alcohol, resulting in higher odor activity values of fruity, floral attributes. Marked varietal effects were observed in the pilot fermentation, but yeast strains exerted a noticeable impact in modulating wine aroma and sensory profile. Overall, indigenous yeast could produce more preferred aroma compounds and sensory characteristics for both white and red wines, demonstrating the potential for improving wine quality and regional characteristics.

Eleutheroside B (EB) is the main active constituent derived from the Chinese herb Acanthopanax senticosus (AS) that has been reported to possess cardioprotective effects. In this study we investigated the effects of EB on cardiac electrophysiology and its suppression on atrial fibrillation (AF). Whole-cell recording was conducted in isolated rabbit atrial myocytes. The intracellular calcium ([Ca 2+ ] i ) concentration was measured using calcium indicator Fura-2/AM fluorescence. Monophasic action potential (MAP) and electrocardiogram (ECG) synchronous recordings were conducted in Langendorff-perfused rabbit hearts using ECG signal sampling and analysis system. We showed that EB dose-dependently inhibited late sodium current ( I NaL ), transient sodium current ( I NaT ), and sea anemone toxin II (ATX II)-increased I NaL with IC 50 values of 167, 1582, and 181 μM, respectively. On the other hand, EB (800 μM) did not affect L-type calcium current ( I CaL ), inward rectifier potassium channel current ( I K ), and action potential duration (APD). Furthermore, EB (300 μM) markedly decreased ATX II-prolonged the APD at 90% repolarization (APD 90 ) and eliminated ATX II-induced early afterdepolarizations (EADs), delayed afterdepolarizations (DADs), and triggered activities (TAs). Moreover, EB (200 μM) significantly suppressed ATX II-induced Na + -dependent [Ca 2+ ] i overload in atrial myocytes. In the Langendorff-perfused rabbit hearts, application of EB (200 μM) or TTX (2 μM) substantially decreased ATX II-induced incidences of atrial fibrillation (AF), ventricular fibrillation (VF), and heart death. These results suggest that augmented I NaL alone is sufficient to induce AF, and EB exerts anti-AF actions mainly via blocking I NaL , which put forward the basis of pharmacology for new clinical application of EB.

Background: Lung cancer has the highest lethality rate among malignancies worldwide. Immunotherapy is one of the common treatments for lung cancer patients. There are two main types of immunotherapies: one targets programmed cell death 1 (PD-1), and the other targets programmed cell death ligand 1 (PD-L1). These two belong to the class of immune checkpoint inhibitors (ICIs). However, immune-related adverse reactions (irAEs) were the main reasons affecting its clinical therapeutic effect. Methods: This retrospective cohort study analyzed red blood cell count (RBC), hematocrit (HCT), erythrocyte mean corpuscular volume (MCV) and immunotherapy outcomes in 920 lung cancer patients receiving immunotherapy from April 2019 to May 2023. Results: We found that high levels of RBC (>4.105 × 109, p = 0.007, OR = 0.467, 95%CI: 0.268~0.812) and MCV (>86.35, p = 0.017, OR = 0.0.441, 95%CI: 0.224~0.865) were significantly related to the better response of ICIs immunotherapy in patients. Patients with high levels of HCT (>39.75%, p = 0.035, OR = 0.737, 95%CI: 0.555~0.979) may have a lower rate of irAEs occurrence. Meanwhile, patients with a low level of RBCs (≤4.635 × 109, p < 0.001, OR = 1.636, 95%CI: 1.365~1.960) may have a longer period of PFS (progression-free survival), and patients with RBC (≤4.43 × 109, p = 0.033, OR = 0.480, 95%CI: 0.244~0.941) may have a longer time of OS (overall survival). Conclusions: The findings indicate that the levels of RBC, MCV and HCT were significantly associated with the response and irAEs of ICIs in lung cancer patients. The levels of RBC might act as a possible biomarker for predicting the survival of lung cancer patients who are receiving ICI therapy.

Background Coordination between osteo-/angiogenesis and the osteoimmune microenvironment is essential for effective bone repair with biomaterials. As a highly personalized and precise biomaterial suitable for repairing complex bone defects in clinical practice, it is essential to endow 3D-printed scaffold the above key capabilities. Results Herein, by introducing xonotlite nanofiber (Ca 6 (Si 6 O 17 ) (OH) 2 , CS) into the 3D-printed silk fibroin/gelatin basal scaffold, a novel bone repair system named SGC was fabricated. It was noted that the incorporation of CS could greatly enhance the chemical and mechanical properties of the scaffold to match the needs of bone regeneration. Besides, benefiting from the addition of CS, SGC scaffolds could accelerate osteo-/angiogenic differentiation of bone mesenchymal stem cells (BMSCs) and meanwhile reprogram macrophages to establish a favorable osteoimmune microenvironment. In vivo experiments further demonstrated that SGC scaffolds could efficiently stimulate bone repair and create a regeneration-friendly osteoimmune microenvironment. Mechanistically, we discovered that SGC scaffolds may achieve immune reprogramming in macrophages through a decrease in the expression of Smad6 and Smad7, both of which participate in the transforming growth factor-β (TGF-β) signaling pathway. Conclusion Overall, this study demonstrated the clinical potential of the SGC scaffold due to its favorable pro-osteo-/angiogenic and osteoimmunomodulatory properties. In addition, it is a promising strategy to develop novel bone repair biomaterials by taking osteoinduction and osteoimmune microenvironment remodeling functions into account. Graphical Abstract

● A protocol is proposed for simultaneous oil/water separation and electricity generation. ● Oil/water separation efficiency achieves > 99% only out of solar energy. ● A derived extra electricity power of ~0.1 W/m 2 is obtained under solar radiation. ● The protocol offers a prospect of solar-driven water treatment and resource recovery. Oily wastewater from ocean oil spills endangers marine ecosystems and human health. Therefore, developing an effective and sustainable solution for separating oil-water mixtures is urgent. Interfacial solar photothermal evaporation is a promising approach for the complete separation of two-phase mixtures using only solar energy. Herein, we report a carbonized wood-based absorber with Janus structure of comprising a hydrophobic top-layer and an oleophobic bottom-layer for simultaneous solar-driven oil-water separation and electricity generation. Under sunlight irradiation, the rapid evaporation of seawater will induce a separation of oil-water mixtures, and cause a high salt concentration region underlying the interface, while the bottom “bulk water” maintains in a low salt concentration, thus forming a salinity gradient. Electricity can be generated by salinity gradient power. Therefore, oil-water separation efficiency of > 99% and derived extra electricity power of ~0.1 W/m 2 is achieved under solar radiation, demonstrating the feasibility of oil-water separation and electricity production synchronously directly using solar energy. This work provides a green and cost-effective path for the separation of oil-water mixtures.

This review proposes an innovative closed-loop rehabilitation strategy that integrates multiple subdomains of stroke science to address the global challenge of upper-limb dyskinesia post-stroke. Despite advancements in neural remodeling and rehabilitation research, the compartmentalization of subdomains has limited the effectiveness of current rehabilitation strategies. Our approach unites key areas—including the post-stroke brain, upper-limb rehabilitation robotics, motion sensing, metrics, neural microfluidics, and neuroelectronics—into a cohesive framework designed to enhance upper-limb motion rehabilitation outcomes. By leveraging cutting-edge technologies such as lightweight rehabilitation robotics, advanced motion sensing, and neural microfluidic models, this strategy enables real-time monitoring, adaptive interventions, and personalized rehabilitation plans. Furthermore, we explore the potential of closed-loop systems to drive neural plasticity and functional recovery, offering a transformative perspective on stroke rehabilitation. Finally, we discuss future directions, emphasizing the integration of emerging technologies and interdisciplinary collaboration to advance the field. This review highlights the promise of closed-loop strategies in achieving unprecedented integration of subdomains and improving post-stroke upper-limb rehabilitation outcomes.

Background Limb-girdle muscular dystrophies (LGMDs) are a group of heterogeneous inherited diseases predominantly characterized by limb-girdle muscle weakness and dystrophic changes on histological analysis. The frequency of LGMD subtypes varies among regions in China and ethnic populations worldwide. Here, we analyzed the prevalence of LGMD subtypes, their corresponding clinical manifestations, and molecular data in a cohort of LGMD patients in Southeast China. Methods A total of 81 consecutive patients with clinically suspected LGMDs from 62 unrelated families across Southeast China were recruited for targeted next-generation sequencing and whole-exome sequencing from July 2017 to February 2020. Results Among 50 patients (41 families) with LGMDs, the most common subtypes were LGMD-R2/LGMD2B (36.6%) and LGMD-R1/LGMD2A (29.3%). Dystroglycanopathies (including LGMD-R9/LGMD2I, LGMD-R11/LGMD2K, LGMD-R14/LGMD2N and LGMD-R20/LGMD2U) were the most common childhood-onset subtypes and were found in 12.2% of the families. A total of 14.6% of the families had the LGMD-R7/LGMD2G subtype, and the mutation c.26_33dupAGGTGTCG in TCAP was the most frequent (83.3%). The only patient with the rare subtype LGMD-R18/LGMD2S had TRAPPC11 mutations; had a later onset than those previously reported, and presented with proximal‒distal muscle weakness, walking aid dependency, fatty liver disease and diabetes at 33 years of age. A total of 22.0% of the patients had cardiac abnormalities, and one patient with LMNA -related muscular dystrophy/LGMD1B experienced sudden cardiac death at 37 years of age. A total of 15.4% of the patients had restrictive respiratory insufficiency. Muscle imaging in patients with LGMD-R1/LGMD2A and LGMD-R2/LGMD2B showed subtle differences, including more severe fatty infiltration of the posterior thigh muscles in those with LGMD-R1/LGMD2A and edema in the lower leg muscles in those with LGMD-R2/LGMD2B. Conclusion We determined the prevalence of different LGMD subtypes in Southeast China, described the detailed clinical manifestations and distinct muscle MRI patterns of these LGMD subtypes and reported the frequent mutations and the cardiorespiratory involvement frequency in our cohort, all of which might facilitate the differential diagnosis of LGMDs, allowing more timely treatment and guiding future clinical trials.