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Overcoming immunosuppression in the tumor microenvironment (TME) is crucial for developing novel cancer immunotherapies. Here, we report that IL-16 administration enhances the polarization of T helper 1 (Th1) cells by inhibiting glutamine catabolism through the downregulation of glutaminase in CD4 + T cells and increases the production of Th1 effector cytokine IFN-γ, thus improving anti-tumor immune responses. Moreover, we find that establishing an IL-16-dependent, Th1-dominant TME relies on mast cell-produced histamine and results in the increased expression of the CXCR3 ligands in tumor-associated macrophages (TAM), thereby improving the therapeutic effectiveness of immune checkpoint blockade (ICB). Cancer patients exhibit impaired production of IL-16, which correlates with poorer prognosis. Additionally, low IL-16 production is associated with unresponsiveness to immunotherapy in cancer patients. Collectively, our findings provided new insights into the biological function of IL-16, emphasizing its potential clinical significance as a therapeutic approach to augment anti-tumor immunity and sensitize ICB-based cancer immunotherapy. Overcoming the suppressive tumor microenvironment (TME) is crucial to improving the efficacy of cancer therapy. Here the authors show that, in mouse cancer models, administration of exogenous IL-16 establishes a Th1-dominant TME via regulation of glutamine catabolism and triggers a Th1 cell-macrophage crosstalk, enhancing anti-tumor immune responses and the efficacy of immunotherapy.

Most patients with inflammatory bowel disease (IBD) develop anemia, which is attributed to the dysregulation of iron metabolism. Reciprocally, impaired iron homeostasis also aggravates inflammation. How this iron‐mediated, pathogenic anemia‐inflammation crosstalk is regulated in the gut remains elusive. Herein, it is for the first time revealed that anemic IBD patients exhibit impaired production of short‐chain fatty acids (SCFAs), particularly butyrate. Butyrate supplementation restores iron metabolism in multiple anemia models. Mechanistically, butyrate upregulates ferroportin (FPN) expression in macrophages by reducing the enrichment of histone deacetylase (HDAC) at the Slc40a1 promoter, thereby facilitating iron export. By preventing iron sequestration, butyrate not only mitigates colitis‐induced anemia but also reduces TNF‐α production in macrophages. Consistently, macrophage‐conditional FPN knockout mice exhibit more severe anemia and inflammation. Finally, it is revealed that macrophage iron overload impairs the therapeutic effectiveness of anti‐TNF‐α antibodies in colitis, which can be reversed by butyrate supplementation. Hence, this study uncovers the pivotal role of butyrate in preventing the pathogenic circuit between anemia and inflammation. Anemia is the most common extraintestinal complication in patients with inflammatory bowel disease (IBD). As a short‐chain fatty acid (SCFA), butyrate ameliorates inflammation‐associated anemia by facilitating ferroportin (FPN)‐mediated iron export in macrophages. By this mechanism, butyrate also reduces the production of inflammatory cytokine TNF‐α in macrophages. This study uncovers a new role of butyrate as an inhibitor of the pathological “anemia‐inflammation” cycle.

Although biologics have been revolutionizing the treatment of inflammatory bowel diseases (IBD) over the past decade, a significant number of patients still fail to benefit from these drugs. Overcoming the nonresponse to biologics is one of the top challenges in IBD treatment. In this study, we revealed that hyaluronan (HA), an extracellular matrix (ECM) component in the gut, is associated with nonresponsiveness to infliximab and vedolizumab therapy in patients with IBD. In murine colitis models, inhibition of HA synthase 2-mediated (HAS2-mediated) HA synthesis sensitized the therapeutic response to infliximab. Mechanistically, HA induced the expression of MMP3 in colonic fibroblasts by activating STAT3 signaling, thereby mediating the proteolytic cleavage of multiple IgG1 biologics. Finally, we found that macrophage-derived factors upregulated HAS2 expression in fibroblasts, thereby contributing to infliximab nonresponse. In summary, we identified a pathogenic connection between abnormal ECM remodeling and biologics nonresponse and provided insights for the precise therapy for IBD.

This meta-analysis aimed to systematically review the evidence on cancer risk of the MMP-8 rs11225395 promoter polymorphism. Relevant studies published by 12 June 2019 were identified by systematically searching PubMed, Web of Science, Cochrane Library, CNKI and Wanfang databases. R programs and STATA software were used to calculate odds ratio (OR) and 95% confidence interval (CI). In total, 7375 cancer samples and 8117 controls were included by integrating 15 case-control data sets. Pooled estimates from the statistical analysis revealed no statistical significance for the association between this polymorphism and cancer risk. All pooled estimates resulting from subgroup analyses by cancer type and sample size were not materially altered and did not draw significantly different conclusions. The stratified analyses according to geographic region showed the statistical significance for increased cancer risk of the MMP-8 rs11225395 polymorphism in non-Asian populations under the allele model (OR = 1.11, 95% CI: 1.04–1.19), homozygote model (OR = 1.22, 95% CI: 1.05–1.41), heterozygote model (OR = 1.21, 95% CI: 1.07–1.36), and dominant model (OR = 1.21, 95% CI: 1.08–1.35). However, no statistical significance was detected in Asian populations. In conclusion, these findings suggested that the MMP-8 rs11225395 polymorphism is associated with elevated susceptibility to cancer in non-Asian populations.

Purpose The purpose of this study is to investigate manufacturing industry leaders’ perspectives on the prevailing skills gap in the current Illinois workforce. The insights gained hold significant importance for the emerging generation of workers, helping them discern the essential proficiencies and plan their educational and career paths in response. Design/methodology/approach Guided by Becker’s (1962) human capital theory (HCT) framework, a qualitative study was conducted to identify the skills gap and explore the perspectives of manufacturing industry leaders. Fourteen industry leaders participated in this study, representing various occupational industries. Findings The findings underscore the prominence of the skills gap as perceived by manufacturing industry leaders, with notable aspects including limited durable skills and difficulty transitioning from content-based knowledge to practical skills. Originality/value The findings of this study can offer insights to researchers, scholars and practitioners in the field of human resource development, as well as to leaders in the manufacturing industry who aim to address the skills gap. Furthermore, this research can inform policy decisions and assist higher education institutions in preparing students for careers in the industry.

Understanding the mechanisms of drug-induced bone remodeling is critical for optimizing therapeutic interventions and minimizing adverse effects in bone health management. Bone remodeling is a highly dynamic process that involves the intricate interplay between osteoblasts, osteoclasts, and osteocytes, regulated by a complex network of signaling pathways and molecular interactions. Traditional experimental and computational approaches often fail to capture this dynamic and multi-scale nature, particularly when influenced by pharmacological agents, which can have both therapeutic and adverse effects. In this work, we present a novel deep learning-based framework for action recognition, specifically designed to analyze drug-induced bone remodeling mechanisms. Our framework leverages graph neural networks (GNNs) to model the spatial and temporal dependencies of multi-scale biological data, combined with a dynamic signal propagation model to identify key molecular interactions driving bone remodeling. A predictive pharmacological interaction model is integrated to quantify drug-target interactions, assess their systemic impacts, and simulate off-target effects. This approach also evaluates combinatorial drug effects, offering insights into the synergistic or antagonistic behaviors of multiple agents. By incorporating these features, our method provides a comprehensive view of drug-induced changes, enabling accurate prediction of their effects on bone formation and resorption pathways. Experimental results highlight the model's potential to advance precision medicine, enabling the development of more effective and safer therapeutic strategies for managing bone health.

Background On October 10, 2022, The Lancet Psychiatry launched a global campaign aimed at ending the stigma surrounding mental illness, reinforcing the need for continued efforts to combat this pervasive issue. We previously surveyed knowledge and attitudes towards mental illness in a Chinese sample population. Seven years later, we aimed to conduct a study to reassess public perceptions of mental health and the level of mental illness literacy within the community today. Methods A cross-sectional survey was designed and administered via a web-based chat application (WeChat) from March to September 2024. The survey tools were consistent with those employed in 2017. The Mental Health Knowledge Questionnaire (MHKQ) and the Perceived Devaluation and Discrimination Scale (PDDS) were used to evaluate the respondents’ mental health knowledge and attitudes towards mental illness. The study protocol was approved by the Research Ethics Committee of the Second Affiliated Hospital of Xinxiang Medical University. Results A total of 1061 respondents were involved in the study. When education was included as a covariate, the adjusted mean total scores for the PDDS and MHKQ were (36.03 ± 0.19) and (16.51 ± 2.53), respectively, significantly higher than the survey results of 2017. Females were more closely associated with positive attitudes towards mental illness than males ( t  = − 2.06, P  = 0.039). Respondents in the following groups were associated with higher MHKQ scores (all P  < 0.05): Females; those with higher education levels; those who have had experience of others with mental illness; those who have learned about mental illness through personal experiences; those under 45 years old; and urban residents. Conclusions Attitudes and knowledge levels showed positive changes between the two survey periods, suggesting potential improvements in mental health literacy among surveyed populations.More anti-stigma campaigns should be carried out for certain targeted groups, such as rural residents and middle-aged and elderly groups.

Objectives: Acute kidney injury (AKI) is a growing global health concern, and is associated with high rates of mortality and morbidity in intensive care units. Se is a trace element with antioxidant properties. This study aimed to determine whether porous Se@SiO2 nanospheres could relieve oxidative stress and inflammation in ischemia/reperfusion (I/R)-induced AKI. Methods: Male 6- to 8-week-old C57bl/6 mice were divided into four groups: sham + saline, sham + Se@SiO2, I/R + saline, and I/R + Se@SiO2. Mice in the I/R groups experienced 30 minutes of bilateral renal I/R to induce an AKI. Porous Se@SiO2 nanospheres (1 mg/kg) were intraperitoneally injected into mice in the I/R + Se@SiO2 group 2 hours before I/R, and the same dose was injected every 12 hours thereafter. Hypoxia/reoxygenation (H/R) was used to mimic I/R in vitro. PBS was used as a control treatment. Human kidney 2 cells were seeded into 12-well plates (5×105 cells/well) and divided into four groups: control + PBS group, control + Se@SiO2 group, H/R + PBS group, and H/R + Se@SiO2 group (n=3 wells). We then determined the expression levels of ROS, glutathione, inflammatory cytokines and proteins, fibrosis proteins, and carried out histological analysis upon kidney tissues. Results: In vitro, intervention with porous Se@SiO2 nanospheres significantly reduced levels of ROS (P<0.05), inflammatory cytokines (P<0.05), and inflammation-associated proteins (P<0.05). In vivo, tubular damage, cell apoptosis, and interstitial inflammation during AKI were reduced significantly following treatment with porous Se@SiO2 nanospheres. Moreover, the occurrence of fibrosis and tubular atrophy after AKI was attenuated by porous Se@SiO2 nanospheres. Conclusion: Porous Se@SiO2 nanospheres exhibited a protective effect in I/R-induced AKI by resisting oxidative stress and inflammation. This suggests that porous Se@SiO2 nanospheres may represent a new therapeutic method for AKI.

Endometrial cancer (EC) is an increasingly common malignancy among women, and associated mortality rates continue to rise. Preferred treatment options for advanced or recurrent EC patients include a combination of carboplatin and paclitaxel, with modest clinical outcomes. Chemoresistance and drug toxicity are important factors that significantly affect the clinical efficacy of carboplatin. Therefore, there is an urgent need for therapeutic strategies that enhance carboplatin sensitivity, reduce its dose while maintaining efficacy, and ensure treatment safety. This study identified the novel small-molecule inhibitor AC1Q3QWB (AQB) as a potent enhancer of carboplatin efficacy. AQB disrupts the binding of HOTAIR to EZH2 and upregulates a series of tumor suppressor genes, such as CDKN1A , ATF3 , and BBC3 , thereby epigenetically suppressing the homologous recombination repair (HRR) pathway in EC, causing cell cycle arrest and inducing apoptosis. AQB inhibits carboplatin-induced RAD51 expression via the p21-E2F1 axis. Additionally, AQB epigenetically silences BRCA1 via ATF3-HDAC1 interactions at the BRCA1 promoter. In vivo studies using subcutaneous xenografts and a stage IV EC patient-derived xenograft (PDX) model demonstrated that AQB enhanced carboplatin’s antitumor effects, reduced the required carboplatin dose, and alleviated associated toxicity. The combination of AQB with standard chemotherapy holds promise for improving outcomes in patients with advanced or recurrent EC. The schematic diagram illustrates the mechanism by which AQB enhances the sensitivity of EC cells to CBPt.