Roles of STAT3 in the pathogenesis and treatment of glioblastoma

Glioblastoma (GBM) is the most malignant of astrocytomas mainly involving the cerebral hemispheres and the cerebral cortex. It is one of the fatal and refractory solid tumors, with a 5-year survival rate of merely 5% among the adults. IL6/JAK/STAT3 is an important signaling pathway involved in the pathogenesis and progression of GBM. The expression of STAT3 in GBM tissues is substantially higher than that of normal brain cells. The abnormal activation of STAT3 renders the tumor microenvironment of GBM immunosuppression. Besides, blocking the STAT3 pathway can effectively inhibit the growth and metastasis of GBM. On this basis, inhibition of STAT3 may be a new therapeutic approach for GBM, and the combination of STAT3 targeted therapy and conventional therapies may improve the current status of GBM treatment. This review summarized the roles of STAT3 in the pathogenesis of GBM and the feasibility of STAT3 for GBM target therapy

The Role of Alfalfa and Forage Resources in Crop-Livestock Systems in a Rain-Fed Region of North-Western China

Western China has been facing the challenges of both environmental sustainability and economic development. Current government policies and interventions support the development of integrated crop-livestock production systems for enhancing food security and environment sustainability. Compared with traditional grain-based faming systems, integrated systems have better resource utilisation, however annual forage supply deficits estimated at 1.37 t DM forage/farm are experienced in the region, especially in late winter and early spring. Accordingly, optimising the use of available forage resources is a priority for regional researchers and extension officers, with research seeking pathways for better fodder conservation and greater and more effective use of fodder sources to close the spring feed gap. This paper presents relevant research activities relating to alfalfa (Medicago sativa L.) and winter wheat (Triticum aestivum L.) management in integrated crop-livestock production systems. As the planting of alfalfa is strongly encouraged in northern China, alfalfa species selection and optimised harvesting management are essential to ensure the full benefits of alfalfa are available for livestock intensification. The capacity for a prevalent grain crop, winter wheat to be managed as a dual-purpose fodder and grain source shows potential as a means to alleviate deficits of animal feed supply. The present information expands our understanding of integrated forage-livestock production in rain-fed areas, exploring options that can improve productivity in small-farm households leading to income generation

Influence of lifestyle on suboptimal health: Insights from a national cross-sectional survey in China

Background: Suboptimal health status (SHS) is a non-clinical or pre-disease state between optimal/ideal health and disease. While its etiology remains unclear, lifestyle is considered one of the most important risk factors. We aimed to examine the effects of lifestyles on SHS through a nationwide survey in China. Methods: We conducted a cross-sectional survey in 148 cities across China between 20 June and 31 August 2022, on 30 505 participants from rural and urban communities gathered through stratified quota sampling. We measured SHS with the Short-Form Suboptimal Health Status Questionnaire (SHSQ-SF). We gathered information on participants\u27 lifestyles (ie, smoking, alcohol consumption, breakfast habits, weekly food delivery frequency, intermittent fasting, sleep duration and physical activities) through face-to-face interview. We determined the relationship between lifestyle and SHS logistic regression analysis by based on odds ratios (ORs) and 95% confidence intervals (CIs). Results: We included 22 897 participants (female: 13 056, male: 9841), 12 108 (52.88%) of whom reported exposure to SHS. After adjusting for demographic characteristics, individuals who currently smoked (OR = 1.165; 95% CI = 1.058-1.283) and those who drank alcohol (OR = 1.483; 95% CI = 1.377.1.596) were at a higher risk of SHS than those who have never done either. In a dose-response way, takeaway food consumption was associated with a higher risk of SHS, while increased frequency of breakfast and mild-intensity exercise conversely reduced said risk. Individuals with shorter sleep duration had a higher risk of SHS when compared to those who slept for more than seven hours per day. Conclusions: We observed a relatively high prevalence of SHS across China, highlighting the importance of lifestyle in health promotion. Specifically, adopting healthy dietary habits, engaging in regular physical activity, and ensuring high-quality sleep are key in preventing SHS. Registration: Chinese Clinical Trial Registry (ChiCTR2200061046)

Serum Cytokines Th1, Th2, and Th17 Expression Profiling in Active Lupus Nephritis-IV: From a Southern Chinese Han Population

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant T cell immune response. Diffuse proliferative lupus nephritis (LN-IV) is the most common, severe, and active form of lupus nephritis. In this study, we investigated the production of Th1, Th2, and Th17 cytokines in prediction of active form of LN-IV. ProcartaPlex multiplex immunoassays panels were used for detection of serum Th1, Th2, and Th17 cytokines profiling. Th1 and Th17 cytokines (IL-18, IFN-γ, IL-12p70, IL-6, and IL-17A) were considerably expressed in the serum of lupus nephritis IV patients in comparison to the healthy control. However, only IL18 and IL6 were higher in class IV versus class III lupus nephritis. Importantly, the ratios of Th1/Th2 (IL-18/IL-4) and Th17/Th2 (IL-17A/IL-4) were significantly elevated in LN-IV when compared with LN-III, LN-V, and healthy controls. Consistently, the serum cytokines IL-18, IL-17A, and IFN-γ were markedly expressed in LN-IV patient glomeruli and interstitial tissue compared to other classes of LN by IHC. ROC further suggests that IL-18 was a potential marker for LN-IV. The data from our study suggests that the early detection and quantification of these cytokines may help in prediction of active form of LN-IV

Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208): A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial

Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multi-regional phase 2 study, RATIONALE-208, examined single-agent tislelizumab (200 mg intravenously every three weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab. Results: Between April 9, 2018 and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9–18), including five complete and 27 partial responses. Number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8–20]; two or more prior lines, 13% [95% CI, 7–20]). Median duration of response was not reached. Disease control rate was 53% and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment. Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC

Solid polymer electrolytes: Ion conduction mechanisms and enhancement strategies

Solid polymer electrolytes (SPEs) possess comprehensive advantages such as high flexibility, low interfacial resistance with the electrodes, excellent film-forming ability, and low price, however, their applications in solid-state batteries are mainly hindered by the insufficient ionic conductivity especially below the melting temperatures, etc. To improve the ion conduction capability and other properties, a variety of modification strategies have been exploited. In this review article, we scrutinize the structure characteristics and the ion transfer behaviors of the SPEs (and their composites) and then disclose the ion conduction mechanisms. The ion transport involves the ion hopping and the polymer segmental motion, and the improvement in the ionic conductivity is mainly attributed to the increase of the concentration and mobility of the charge carriers and the construction of fast-ion pathways. Furthermore, the recent advances on the modification strategies of the SPEs to enhance the ion conduction from copolymer structure design to lithium salt exploitation, additive engineering, and electrolyte micromorphology adjustion are summarized. This article intends to give a comprehensive, systemic, and profound understanding of the ion conduction and enhancement mechanisms of the SPEs for their viable applications in solid-state batteries with high safety and energy density