An injectable and antifouling hydrogel prevents the development of abdominal adhesions by inhibiting the CCL2/CCR2 interaction.

Abdominal adhesion, a serious complication of abdominal surgery, often resists mitigation by current drug administration and physical barriers. To address this issue, we developed an injectable, antifouling hydrogel through the free-radical polymerization of methacrylate chondroitin sulfate (CS-GMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC) monomers, dubbed the CGM hydrogel. We systematically analyzed its physicochemical properties, including rheological strength, biocompatibility, and antifouling capabilities. A rat abdominal cecum adhesion model was constructed to assess the effectiveness of CGM hydrogel in preventing postoperative adhesion and recurrent adhesion. In addition, multi-omics analyses identified the relationship between adhesion development and CCL2/CCR2 interaction. Notably, CGM hydrogel can thwart the recruitment and aggregation of fibroblasts and macrophages by inhibiting the CCL2/CCR2 interaction. Moreover, CGM hydrogel significantly dampens the activity of fibrosis-linked cytokines (TGF-ßR1) and recalibrates extracellular matrix deposition-related cytokines (t-PA and PAI-1, Col Ⅰ and MMP-9). Cumulatively, the dual action of CGM hydrogel-as a physical barrier and cytokine regulator-highlights its promising potential in clinical application for abdominal adhesion prevention.

Norway's Battery Electric Vehicles and Public Health- Findings From the Literature.

The transportation sector is among the highest contributors to the increase in greenhouse gas emissions in European nations, with private cars emerging as the primary source. Although reducing emissions presents a formidable challenge, the emergence of battery electric vehicles (BEVs) offers a promising and sustainable avenue toward achieving zero greenhouse gases within the transportation infrastructure. Since the 1990s, the Norwegian parliament has fervently supported this transition, leveraging public awareness campaigns and a range of financial incentives for its users nationwide. The widespread utilization of BEVs promises substantial health benefits, including ensuring cleaner air for all citizens regardless of their socioeconomic status and fostering improvements in public health outcomes. This transition potentially curtails hundreds of thousands of annual deaths attributed to climate change, enhances the quality of life, bolsters civilian productivity, and fuels economic and population growth. The adoption of BEVs offers a myriad of advantages, including reduced health risks and premature mortality, as well as a quieter environment with diminished noise pollution. Nonetheless, the integration of BEVs necessitates robust road infrastructure with considerable maintenance costs, alongside limitations on driving range for users. Concerns arise regarding potential particle emissions from BEV tire wear due to the increased weight of batteries compared to conventional vehicles. Rapid acceleration capabilities may accelerate tire degradation, contributing to higher particle emissions, of which only 10% to 20% remain suspended in the air, whereas the majority settles on road surfaces, posing a threat to nearby aquatic ecosystems when washed into water bodies and soils. While BEVs hold promise for valuable benefits, successful policy creation and implementation require a detailed awareness of their limitations and challenges to ensure a comprehensive approach to sustainable mobility and public health improvement. Therefore, more research on the limitations of BEVs can help inform improved tactics for maximizing their benefits while limiting potential disadvantages.

A swift transition to electric vehicles is a good public health intervention that benefits the quality of the air and climate systems. It is expedient to know that this new technology will not solve all problems caused by transportation systems, as there will always be some unwanted and unexpected side effects as usual with new technologies. We suggest more advanced research on EVs shortcomings for better understanding and usage.

Astragalus polysaccharides driven stretchable nanofibrous membrane wound dressing for joint wound healing.

Joint wound dressings are currently significantly limited in their clinical applications due to their inferior mechanical properties and single therapeutic effect. Therefore, it is imperative to develop a versatile joint wound dressing that integrates adequate stretchability, desirable biocompatibility, and multiple biological effects into one system. We implemented the electrospinning technique in this study to fabricate a novel nanofibrous membrane (NFM) composed of gelatin (GEL) and astragalus polysaccharides (APS), termed GEL/APS NFM. The selection of GEL and APS confers excellent biocompatibility to GEL/APS NFM. Furthermore, the optimally proportioned GEL/APS NFM exhibits satisfactory stretchability and desirable wound healing efficiency. Furthermore, released APS can exert anti-inflammatory, procollagen deposition, and proangiogenic effects to accelerate epithelial tissue, enhancing joint wound healing. In summary, GEL/APS NFM offers a convenient and effective approach to promoting rapid joint wound healing, providing a novel approach to joint wound care.

Association between migration status and subsequent labour market marginalisation among individuals with posttraumatic stress disorder: a Swedish nationwide register-based cohort study.

PURPOSE: The high prevalence of posttraumatic stress disorder (PTSD) among migrants in Europe is widely reported. Our research aimed to investigate the association between migration status and subsequent labour market marginalisation (LMM) events, i.e., long-term unemployment (LTU), long-term sickness absence (LTSA), and disability pension (DP) among individuals with PTSD, and to elucidate how the sociodemographic factors and the pre-existing health conditions influence such association. METHODS: We established a cohort of 36,714 individuals born between 1960 and 1995, living in Sweden during 2004-2009, aged 19 years or above, with PTSD diagnosis during 2006-2009. Migration status, categorized as refugees, non-refugees, second-generation migrants, and Swedish-born with Swedish-born parents (reference group) was considered as exposure and LMM events as outcome. The cohort was followed from 01-Jan-2010 until LMM, death, or end of follow-up (31-Dec-2016). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox regression with a seven-year follow-up. RESULTS: Refugees (HR 2.07, 95% CI 1.86-2.30), and non-refugees (HR 1.96, 95% CI 1.85-2.07) had almost doubled relative risk of long-term unemployment, compared with the Swedish-born. The hazards of long-term sickness absence were similar across the groups. Refugees (HR 1.49, 95% CI 1.24-1.77), and non-refugees (HR 1.42, 95% CI 1.30-1.56) also had elevated relative risk of disability pension, whereas second-generation migrants had moderately increased relative risks for all three labour market marginalisation events compared with the Swedish-born. CONCLUSION: Among the individuals with PTSD, being a migrant increases the risk of LMM, refugees being the foremost among migrants. Further research may benefit from including more recent migrant population, pre-migration information and measuring PTSD clinical severity.

Engineered CAR T cells targeting mesothelin by piggyBac transposon system for the treatment of pancreatic cancer.

Patients with pancreatic cancer have a poor prognosis largely due to the poor efficacy of the available treatment modalities. In this study, we engineered mesothelin-targeting chimeric antigen receptor T cells (mesoCAR T) using the piggyBac transposon based plasmid electroporation technique for specific targeting of pancreatic cancer cells expressing mesothelin. In vitro, mesoCAR T cells exhibited rapid and robust killing effect against ASPC1 cells with high expression levels of mesothelin with high production of IFN-γ; the cytotoxic effect on PANC1 cells with low expressions of mesothelin was relatively attenuated. In the ASPC1 xenograft mice model, mesoCAR T cells significantly suppressed the tumor growth accompanied with higher-level IFN-γ secretion as compared to control T cells. Besides, more mesoCAR T cells differentiated into memory T cells after tumor remission, whilst causing minimal lesions in major organs. Our study suggests promising efficacy of piggyBac transposon-based mesoCAR T cell therapy for pancreatic cancer, which is a potential candidate for clinical translation.

Mesothelin-targeting chimeric antigen receptor-modified T cells by piggyBac transposon system suppress the growth of bile duct carcinoma.

Chimeric antigen receptor modified T cell-based immunotherapy is revolutionizing the field of cancer treatment. However, its potential in treating bile duct carcinoma has not been fully explored. Herein, we developed the second-generation mesothelin-targeting chimeric antigen receptor-modified T cells with the 4-1BB co-stimulatory module by the piggyBac transposon system. Mesothelin-targeting chimeric antigen receptor was expressed by 66.0% of mesothelin-targeting chimeric antigen receptor-modified T cells post electrophoretic transfection and stimulation with K562-meso cells; the expressions of activation markers were tested by flow cytometry assay and showed greater activation of mesothelin-targeting chimeric antigen receptor-modified T cells than control T cells (CD107α: 71.9% vs 48.6%; CD27: 92.1% vs 61.8%; CD137: 55.5% vs 8.4%; CD28: 98.0% vs 82.1%; CD134: 37.5% vs 10.4%). Furthermore, mesothelin-targeting chimeric antigen receptor-modified T cells exerted cytotoxicity toward mesothelin-expressing EH-CA1b and EH-CA1a cells in an effector-to-target ratio-dependent manner, while leaving mesothelin-negative GSC-SD and EH-GB1 cells and normal liver L02 cells almost unharmed. Mesothelin-targeting chimeric antigen receptor-modified T cells secreted cytokines at higher levels when co-cultured with mesothelin-positive EH-CA1a and EH-CA1b cells than with mesothelin-negative GSC-SD and EH-GB1 cells. Enhanced cytotoxicity and cytokine secretion of mesothelin-targeting chimeric antigen receptor-modified T cells compared to control T cells were also observed when co-cultured with 293-meso cells (interferon γ: 85.1% ± 1.47% vs 8.3% ± 2.50%, p = 0.000; tumor necrosis factor α: 90.9% ± 4.67% vs 18.5% ± 3.62%, p = 0.0004; interleukin 2: 60.8% ± 2.00% vs 15.6% ± 2.06%, p = 0.002; interleukin 6: 6.4% ± 2.95% vs 1.7% ± 0.63%, p = 0.055). In addition, mesothelin-targeting chimeric antigen receptor-modified T cells showed greater inhibitory and proliferative capability than control T cells within EH-CA1a cell xenografts. This study shows the potential of mesothelin-targeting chimeric antigen receptor-modified T cells in treating bile duct carcinoma.