Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Background Arsenic exposure is a common and important environmental and occupational hazardous factor in China, and arsenic-induced insulin resistance (IR) has attracted widespread attention as a negative health outcome to the population. Objective To explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ (PPARγ)/ glucose transporter 4 (GLUT4) pathway, and to investigate potential effects of Ginkgo biloba extract (GBE) on hepatic IR induced by arsenic exposure and associated mechanism of action. Methods The target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments. In vivo experiments: 48 SPF C57BL/6J male mice were divided into 4 groups, including control group, 50 mg·L⁻¹ NaAsO₂ model group (NaAsO₂), 50 mg·L⁻¹ NaAsO₂+10 mg·kg⁻¹ GBE intervene group (NaAsO₂+GBE), and 10 mg·kg⁻¹ GBE group (GBE), 12 mice in each group. The animals were given free access to purified water containing 50 mg·L⁻¹ NaAsO₂, or given intraperitoneal injection of normal saline containing 10 mg·kg⁻¹ GBE once per week. After 6 months of exposure, blood glucose detection, intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were performed. Serum and liver tissues were collected after the mice were neutralized, liver histopathological sections were obtained, serum insulin levels, liver tissue glycogen content, glucose content were detected by enzyme linked immunosorbent assay (ELISA), and the expression of PPARγ and GLUT4 proteins was detected by Western blot (WB). In vitro experiments: HepG2 cells were divided into 4 groups, including control group, 8 μmol·L⁻¹ NaAsO₂ group (NaAsO₂), 8 μmol·L⁻¹ NaAsO₂ + 200 mg·L⁻¹ GBE intervene group (NaAsO₂+GBE), and 200 mg·L⁻¹ GBE group (GBE). The levels of glycogen and glucose were detected by ELISA, and the expression of PPARγ and GLUT4 proteins was detected by WB. Results A strong binding effect between GBE and PPARγ was revealed by network pharmacology. In in vivo experiments, the NaAsO₂ group exhibited an elevated blood glucose compared to the control group, and the NaAsO₂+GBE group showed a decreased blood glucose compared to the NaAsO₂ group (P<0.01). The histopathological sections indicated severe liver structural damage in the arsenic exposure groups (NaAsO₂ group and NaAsO₂+GBE group), with varying staining intensity, partial liver cell necrosis, and diffuse red blood cell appearance. Both results of in vitro and in vivo experiments showed a decrease in glycogen synthesis and glucose uptake in the NaAsO₂ groups compared to the control groups, which was alleviated in the NaAsO₂+GBE group (P<0.01). The results of WB revealed inhibited PPARγ expression and reduced GLUT4 levels on the cell membrane, and all these changes were alleviated in the NaAsO₂+GBE group (P<0.01). Conclusion This study findings suggest that GBE antagonizes arsenic exposure-induced hepatic IR by regulating the PPARγ/GLUT4 pathway, indicating that GBE has a protective effect on arsenic exposure-induced hepatic IR, and PPARγ may be a potential therapeutic target for arsenic exposure-induced hepatic IR.

Objective:To investigate the current status of scientific fitness literacy (SFL) and its influencing factors among Chinese adults aged 20-59 years.Methods:Totally 63 338 adults aged 20-59 years in the status of national fitness activities in 2020 from 1 January to 31 March 2020 were selected as the subjects, and they were divided into four age groups, namely, the 20-29 age group, the 30-39 age group, the 40-49 age group and the 50-59 age group. Data were analyzed by SPSS 29.0.Comparative analyses for age, gender, urban-rural difference were carried out by applying non-parametric tests, and multiple regression models were applied to find the influencing factors of SFL.Results:The SFL score of Chinese adults aged 20-59 years was 53.40 (41.67, 63.73), and the scores of cognition, attitude, ability and skills, behavior and habits sub-dimensions were 86.11 (72.22, 100.00), 62.96 (50.62, 75.31), 27.78 (11.11, 44.44) and 33.33 (11.11, 55.56), respectively. The SFL and the four sub-dimensions were demonstrated to have higher scores for males than females, and higher scores for adults in urban area than those in rural area(all P<0.01). The multiple regression results showed that regular exercise at a fitness facility (20-29 age group: β=0.321, t=5.940, P<0.01; 30-39 age group: β=0.187, t=2.937, P<0.01; 40-49 age group: β=0.230, t=3.988, P<0.01; 50-59 age group: β=0.415, t=5.671, P<0.01) was the Chinese adults' common influence factor on SFL.Motivation, evaluation by those around them, experience from exercising, and convenience and atmosphere of exercising were the main influence factors in the 20-29 and 30-39 age groups(all P<0.05).Comfort level of fitness venue, convenience, safety, and support of fitness place were the main influence factors in adults aged 40-59 years(all P<0.05). Conclusions:Chinese adults aged 20-59 years old have high SFL awareness scores, but low overall SFL scores. Surrounding people's evaluation, experience in exercise, comfort level of fitness place, convenience, safety and fitness policy support are the influential factors of scientific fitness literacy.

Heme/metabolism* ; Cryoelectron Microscopy ; Membrane Transport Proteins ; Escherichia coli Proteins/metabolism*

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

By combing out the historical development logic of sports and health integration and the current development achievement, the underlying logic of sports and health integration is described systematically in multiple dimensions, and the prominent dilemmas in development are analyzed as follows: lack of residents' health literacy, excessive dependence on medical treatment, low bridging of talent team construction, lack of the guidance of funds centralization, insufficient financial support, imperfect management system and mechanism, and unspecific departmental collaboration.The strategies for solving the problems are as follows: strengthening the integration of sports science and clinical medicine, consolidating the technical integration of sports prescription and clinical standardization process, further improving the business integration of exercise intervention and clinical treatment, and enhancing the industrial integration of sports products and medical treatment.

Objective:To discusses the formation mechanism and influencing factors of sports fitness behavior interruption.Methods:From January 1st to April 30th in 2015, the adults aged 20 and above in the national survey of fitness activities were selected as the research objects to analyze the reasons for the interruption of fitness behavior of Chinese residents, including 32 877 people with fitness habits and 5 152 people with interrupted fitness habits.SPSS 19.0 and AMOS 17.0 software were used to process the data.The chi-square test was used to analyze the characteristics and changing trend of people who interrupted physical fitness behavior.Correlation analysis and factor analysis were used to categorize public factors of residents' physical fitness behavior characteristics.Validating factor analysis and path analysis were used to analyze the main reasons affecting the disruption of residents' physical fitness behaviors.Results:The fitness interruption behavior among Chinese residents were statistically significant different in terms of age, gender, and habitation( χ2=2.791, 199.435, 12.402, all P<0.05). The highest percentage of fitness interruptions was observed among residents aged 20-39 (19.1%) in China, women (16.2%) were higher than men (15.5%), and urban (16.4%) were higher than rural (14.9%). Factor classification and model analysis showed that the occurrence of disruptions in physical fitness behavior among Chinese residents was influenced by a combination of health factors( β=0.52), social environment( β=0.57), psychological factors( β=0.42), and fitness behavior environment( β=0.22). Conclusion:The occurrence of disruption of physical fitness behavior of our residents is mainly influenced by the combination of health factors, psychological factors, social environment, and fitness behavior environment.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall, this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.

Objective:To study the efficacy, feasibility and safety of transjugular intrahepatic portosystemic shunt (TIPS) in treatment of recurrent portal hypertension after splenectomy and devascularization in patients presenting with upper gastrointestinal bleeding.Methods:Cirrhotic patients with recurrent portal hypertension after splenectomy and devascularization and presenting with upper gastrointestinal bleeding from August 2015 to December 2020 were studied. Thirty-nine patients were included in this study. There were 24 males and 15 females, with age of (51.56±9.08) years old. These patients were treated with TIPS by using the Viabahn stent. Intraoperative portal vein pressure, success operative rate, hemostasis rate after surgery, changes in hematological indicators and postoperative efficacy and complication rate were studied.Results:Thirty-eight of 39 patients successfully underwent TIPS shunt and 1 patient failed because of portal vein spongiosis. The success rate was 97.44%(38/39). Thirty-three patients underwent TIPS and variceal vein embolization, while 5 patients were treated with TIPS alone. Thirty-nine Viabahn stents with a diameter of 8 mm were implanted in 38 patients, of which 5 patients had the stent expanded to its nominal diameter of 8 mm. The remaining 33 patients (86.84%) had a shunt with a diameter of 6 mm. The hemostasis rate of postoperative gastrointestinal bleeding was 97.37% (37/38). The portal vein pressure and portal venous pressure gradient decreased from (31.28±6.24), (20.61±5.14) mmHg (1 mmHg=0.133 kPa) to (19.58±4.69), (9.24±3.07) mmHg respectively, the differences were significant (all P<0.001). All patients were followed-up for 3 to 36 months, with a median follow-up of 12 months. The postoperative rebleeding rate was 6.90% (2/29). The incidence of hepatic encephalopathy was 13.79% (4/29), and the incidence of shunt disorder was 13.79% (4/29). Conclusion:TIPS was safe, effective and feasible in treating patients with recurrent portal hypertension after splenectomy and devascularization presenting with upper gastrointestinal bleeding. Most patients obtained good clinical outcomes with a 6 mm diameter shunt.