[18F]AlF-ND-bisFAPI PET imaging of fibroblast activation protein as a biomarker to monitor the progression of liver fibrosis.

BACKGROUND: Hepatic fibrosis is a progressive disease, which is reversible in the early stages. The current monitoring methods have notable limitations that pose a challenge to early detection. In this study, we evaluated the utility of [18F]AlF-ND-bisFAPI positron emission tomography imaging of fibroblast activation protein (FAP) to monitor the progression of liver fibrosis. METHODS: Two mouse models of liver fibrosis were established by bile duct ligation and carbon tetrachloride administration, respectively. Positron emission tomography imaging was performed with the FAP-specific radiotracer [18F]AlF-ND-bisFAPI for the evaluation of rat HSCs and mouse models of fibrosis and combined with histopathology, immunohistochemical staining, and immunoblotting to elucidate the relationships among radioactivity uptake, FAP levels, and liver fibrosis progression. Furthermore, [18F]AlF-ND-bisFAPI autoradiography was performed to assess tracer binding in liver sections from patients with varying degrees of liver fibrosis. RESULTS: Cell experiments demonstrated that [18F]AlF-ND-bisFAPI uptake was specific in activated HSCs. Compared with control mice, [18F]AlF-ND-bisFAPI uptake in livers increased in the early stages of fibrosis and increased significantly further with disease progression. Immunohistochemistry and western blot analyses demonstrated that FAP expression increased with fibrosis severity. In accordance with the findings in animal models, ex vivo autoradiography on human fibrotic liver sections showed that radioactivity increased as fibrosis progressed from mild to severe. CONCLUSIONS: [18F]AlF-ND-bisFAPI positron emission tomography imaging is a promising noninvasive method for monitoring the progression of liver fibrosis.

Targeted Proteomics Reveals Functional Targets for Early Diabetes Susceptibility in Young Adults.

BACKGROUND: The circulating proteome may encode early pathways of diabetes susceptibility in young adults for surveillance and intervention. Here, we define proteomic correlates of tissue phenotypes and diabetes in young adults. METHODS: We used penalized models and principal components analysis to generate parsimonious proteomic signatures of diabetes susceptibility based on phenotypes and on diabetes diagnosis across 184 proteins in >2000 young adults in the CARDIA (Coronary Artery Risk Development in Young Adults study; mean age, 32 years; 44% women; 43% Black; mean body mass index, 25.6±4.9 kg/m2), with validation against diabetes in >1800 individuals in the FHS (Framingham Heart Study) and WHI (Women's Health Initiative). RESULTS: In 184 proteins in >2000 young adults in CARDIA, we identified 2 proteotypes of diabetes susceptibility-a proinflammatory fat proteotype (visceral fat, liver fat, inflammatory biomarkers) and a muscularity proteotype (muscle mass), linked to diabetes in CARDIA and WHI/FHS. These proteotypes specified broad mechanisms of early diabetes pathogenesis, including transorgan communication, hepatic and skeletal muscle stress responses, vascular inflammation and hemostasis, fibrosis, and renal injury. Using human adipose tissue single cell/nuclear RNA-seq, we demonstrate expression at transcriptional level for implicated proteins across adipocytes and nonadipocyte cell types (eg, fibroadipogenic precursors, immune and vascular cells). Using functional assays in human adipose tissue, we demonstrate the association of expression of genes encoding these implicated proteins with adipose tissue metabolism, inflammation, and insulin resistance. CONCLUSIONS: A multifaceted discovery effort uniting proteomics, underlying clinical susceptibility phenotypes, and tissue expression patterns may uncover potentially novel functional biomarkers of early diabetes susceptibility in young adults for future mechanistic evaluation.

Preclinical study and first-in-human imaging of [18F]FAP-2286, and comparison with 2-[18F]FDG PET/CT in various cancer patients.

PURPOSE: Fibroblast-activated protein (FAP) is highly expressed in cancer-associated fibroblasts (CAFs) of many solid cancers, but low or absent in normal tissues. Our study aimed to develop a novel FAP-specific tracer, namely [18F]FAP-2286, and evaluated its performance in comparison with well-established agents such as [18F]FAPI-42 and [68Ga]Ga-FAP-2286 in preclinical research, as well as 2-[18F]FDG in pilot clinical study. METHODS: [18F]FAP-2286 was manually synthesized in accordance with Good Manufacturing Practice (GMP). Subsequent investigations encompassed cell uptake, competitive binding affinity, internalization and efflux assays using HT-1080hFAP cell lines. PET imaging and biodistribution studies were conducted in HEK-293ThFAP, A549hFAP, HT-1080hFAP tumor-bearing mice as well as HEK-293T, A549 and HT-1080 control groups. Furthermore, clinical evaluation of [18F]FAP-2286 was performed in fifteen patients with various cancers compared to 2-[18F]FDG PET. RESULTS: The radiolabeling yield of [18F]FAP-2286 was 30.53 ± 5.20%, with a radiochemical purity exceeding 97%. In cell assays, [18F]FAP-2286 showed specific uptake, high internalization fraction and low cellular efflux. Rapid tumor uptake and satisfactory tumor retention was observed on micro-PET imaging and cancer patients. Meanwhile, the clinical research demonstrated that [18F]FAP-2286 may represent an alternative for low glucose-metabolism malignant tumors PET imaging such as gastric cancers. CONCLUSION: [18F]FAP-2286 showed superior imaging quality including rapid and high target uptake and satisfactory retention in both tumor-bearing mice and cancer patients. It may emerge as a promising candidate for early or delayed phase imaging and 2-[18F]FDG non-avid cancers PET scan.

Radiofrequency ablation using the ThermoCool SmartTouch Catheter guided by ablation index versus antiarrhythmic drugs in atrial fibrillation treatment in China: a cost-consequence analysis.

Aim: To evaluate the costs and consequences of two front-line atrial fibrillation (AF) treatments from Chinese healthcare system perspective: radiofrequency catheter ablation (RFCA) using ThermoCool SmartTouch Catheter guided by Ablation Index (STAI), in comparison to antiarrhythmic drugs (AADs). Patients & methods: We simulated clinical and economic consequences for AF patients initially receiving STAI or AADs using a short-term decision tree model leading to a 10-year long-term Markov model. The model projected both clinical consequences and costs associated with, among others, AF, heart failure (HF), strokes, and deaths due to AF or AF related complications. Data informing the models included combination of a local real-world study and published clinical studies. Results: STAI was advantageous versus AADs on all 4 main clinical outcomes evaluated; AF: 25.83% lower (12.84% vs 38.67%), HF: 2.22% lower (1.33% vs 3.55%), stroke or post stroke: 1.82% lower (10.00% vs 11.82%) and deaths due to AF or AF related complications: 0.64% lower (4.11% vs 4.75%). The average total cost per patient in STAI group was ¥16,682 lower (¥123,124 vs ¥139,806). The one-way sensitivity analysis indicated that the difference in total cost was most sensitive to annual AF recurrence probability in AADs-treated patients. Probabilistic sensitivity analysis indicated a 98.5% probability that RFCA treatment would result in cost savings by the end of the 10th year. Conclusion: Radiofrequency catheter ablation using SmartTouch catheter guided by Ablation Index was superior to AADs as the first-line AF treatment in Chinese setting with better clinical outcomes and at lower costs over a 10-year time horizon.

In-situ Construction of Poly(tetraisopentyl acrylate) based Gel Polymer Electrolytes with Lix La2-x TiO3 for High Energy Density Lithium-Metal Batteries.

As promising alternatives to liquid electrolytes, polymer electrolytes attract much research interest recently, but their widespread use is limited by the low ionic conductivity. In this study, we use electrostatic spinning to introduce particles of an ionic conductor into polyacrylonitrile (PAN) fibers to prepare a porous membrane as the host of gel polymer electrolytes (GPEs). The relevant in-situ produced GPE performs a high ionic conductivity of 6.0×10-3  S cm-1 , and a high lithium transfer number (tLi + ) of 0.85 at 30 °C, respectively. A symmetrical Li cell with this GPE can cycle stably for 550 h at a current density of 0.5 mA cm-2 . While the capacity retention of the NCM|GPE|Li cell is 79.84 % after 500 cycles at 2 C. Even with an increased cut-off voltage of 4.5 V, the 1st coulomb efficiency reaches 91.58 % with a specific discharge capacity of 213.4 mAh g-1 . This study provides a viable route for the practical application of high energy density lithium metal batteries.

Synthesis and preclinical evaluation of novel 18F-labeled fibroblast activation protein tracers for positron emission tomography imaging of cancer-associated fibroblasts.

Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts in more than 90% of epithelial tumors. Several radiotracers targeting FAPs have been used in clinical settings in recent years. However, the number of 18F-labeled FAP tracers is still limited. Herein, we aimed to develop 18F-labeled FAP tracers with optimized pharmacokinetics. Labeling precursors (NOTA-DD-FAPI and NOTA-PD-FAPI) were synthesized and labeled with fluorine-18. The precursors NOTA-DD-FAPI (IC50 = 0.21 ± 0.06 nM) and NOTA -PD-FAPI (IC50 = 0.13 ± 0.07 nM) showed a higher affinity for FAP compared to NOTA-FAPI-42 (IC50 = 0.66 ± 0.19 nM). Novel 18F-labeled FAP tracers showed a specific uptake, high internalized fraction, and low cellular efflux in vitro. Compared to the clinically used tracer [18F]AlF-FAPI-42, both the novel 18F-labeled FAP tracers, and especially the [18F]AlF-PD-FAPI tracer with a higher tumor-to-background ratio demonstrated rapid renal excretion and higher tumor uptake during preclinical evaluation, resulting in images with higher contrast. Thus, [18F]AlF-PD-FAPI shows promise for use as a FAP-targeting tracer for clinical translation.

A worldwide bibliometric analysis of the research trends and hotspots of bruxism in adults during 1991-2021.

BACKGROUND AND OBJECTIVES: With the increasing attention to bruxism, the research on bruxism is increasing rapidly. However, there is still a lack of systematic bibliometric analysis in the field of bruxism in adults. This study aimed to comprehensively explore and visualize the global trends and research hotspots in the field of bruxism in adults during 1991-2021. METHODS: The study searched the literature published during 1991-2021 in the Web of Science Core Collection database without language restrictions. VOSviewer, CiteSpace and Microsoft Excel were applied to analyse the authors, institutions, journals, countries, cited references, keywords and other information of the included publications, and construct visualized cooperation networks. RESULTS: A total of 878 articles were finally included. The top two most productive authors in the past 30 years were Lobbezoo F and Manfredini D. ACTA-Amsterdam, Univ Sao Paulo, Univ Helsinki, Univ Padua, Univ Montreal, et al. were prominent institutions in this field. Journal of Oral Rehabilitation made outstanding contributions in this field. The United States produced the most documents in this field, followed by Brazil. Both countries and authors cooperated closely around the world. The two most cited articles focused on the definition, assessment and classification of bruxism. In recent years, diagnostic criteria and stress have begun to receive a lot of attention. CONCLUSION: From 1991 to 2021, the attention to bruxism in adults continued to increase. Diagnostic criteria and stress may be potential research hotspots in this field. This study references relevant scholars on development trends and research hotspots.

Prediction model of no-response before the first transarterial chemoembolization for hepatocellular carcinoma: TACF score.

Previous clinic models for patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE) mainly focused on the overall survival, whereas a simple-to-use tool for predicting the response to the first TACE and the management of risk classification before TACE are lacking. Our aim was to develop a scoring system calculated manually for these patients. A total of 437 patients with hepatocellular carcinoma (HCC) who underwent TACE treatment were carefully selected for analysis. They were then randomly divided into two groups: a training group comprising 350 patients and a validation group comprising 77 patients. Furthermore, 45 HCC patients who had recently undergone TACE treatment been included in the study to validate the model's efficacy and applicability. The factors selected for the predictive model were comprehensively based on the results of the LASSO, univariate and multivariate logistic regression analyses. The discrimination, calibration ability and clinic utility of models were evaluated in both the training and validation groups. A prediction model incorporated 3 objective imaging characteristics and 2 indicators of liver function. The model showed good discrimination, with AUROCs of 0.735, 0.706 and 0.884 and in the training group and validation groups, and good calibration. The model classified the patients into three groups based on the calculated score, including low risk, median risk and high-risk groups, with rates of no response to TACE of 26.3%, 40.2% and 76.8%, respectively. We derived and validated a model for predicting the response of patients with HCC before receiving the first TACE that had adequate performance and utility. This model may be a useful and layered management tool for patients with HCC undergoing TACE.

Bibliometric Analysis of Research on Temporomandibular Joint and Occlusion from 2000 to 2022.

Purpose: This study conducted a bibliometric analysis that comprehensively described publications on temporomandibular joint and occlusion from 1 January 2000 to 31 October 2022, aiming to reveal hotspots and predict future research trends. Methods: A total of 2985 articles and reviews were retrieved from Web of Science Core Collection (WoSCC). Excel 2019, VOSviewer and CiteSpace software were used for visualizing analysis of research trends, authors, journals, institutions, countries, keywords and cited references. Results: Both the annual publication counts and citation times increased significantly. Wang MQ was the most active author. Moreover, Manfredini D and Okeson JP were the most influential two. Journal of Oral Rehabilitation was the core journal. University of Sao Paulo was the most productive institutions. "Temporomandibular disorders" (TMDs), "temporomandibular joint" and "occlusion" were the top 3 keywords with the most frequencies. Keywords and references with burst showed that the causes of TMDs, diagnosis and treatments for TMDs as well as bruxism may be hotspots currently and in the future. Conclusion: In this study, the research trends, the most productive and influential authors, journals, institutions, countries, in addition to keywords and cited references with burst in the field of temporomandibular joint and occlusion were revealed by a bibliometric analysis, which could help scholars to understand recent hotspots and future trends.

Imaging study on the relationship between anterior and posterior occlusal planes and temporomandibular osteoarthrosis.

OBJECTIVES: The aim of this study was to compare the anterior and posterior occlusal plane characteristics of patients with different temporomandibular joint osseous statuses. METHODS: A total of 306 patients with initial cone beam CT (CBCT) and cephalograms were included. They were divided into three groups on the basis of their temporomandibular joint osseous status: bilateral normal (BN) group, indeterminate for osteoarthrosis (I) group, and osteoarthrosis (OA) group. The anterior and posterior occlusal planes (AOP and POP) of the different groups were compared. Then, the regression equation was established after adjusting for confounding factors, and a correlation analysis between the occlusion planes and other parameters was performed. RESULTS: SNA, SNB, FMA, SN-MP, Ar-Go, and S-Go were correlated with the occlusal planes. Relative to the BN and I groups, the FH-OP of the OA group increased by 1.67° on the average, FH-POP increased by 1.42° on the average, and FH-AOP increased by 2.05° on the average. CONCLUSIONS: The occlusal planes were steeper in the patients with temporomandibular osteoarthrosis than in the patients without it, and the mandible rotated downward and backward. The height of the mandibular ramus, the mandibular body length, and the posterior face height were small. In clinical practice, attention should be given to the potential risk of temporomandibular joint osteoarthrosis in such patients. In addition, SNB, FMA, SN-MP, Ar-Go, S-Go, and occlusal planes had moderate correlations.

ALDH2 rs671 and MTHFR rs1801133 polymorphisms are risk factors for arteriosclerosis in multiple arteries.

BACKGROUND: Arteriosclerosis in multiple arteries has long been associated with heightened cardiovascular risk. Acetaldehyde dehydrogenase 2 (ALDH2) and methylenetetrahydrofolate reductase (MTHFR) play an important role in the pathogenesis of arteriosclerosis by participating in the oxidation and reduction reactions in vascular endothelial cells. The purpose was to investigate the relationship of ALDH2 and MTHFR gene polymorphisms with arteriosclerosis in multiple arteries. METHODS: 410 patients with arteriosclerosis in single artery and 472 patients with arteriosclerosis in multiple arteries were included. The relationship between ALDH2 rs671 and MTHFR rs1801133 polymorphisms and arteriosclerosis in single artery and arteriosclerosis in multiple arteries was analyzed. RESULTS: The proportion of ALDH2 rs671 A allele (35.6% vs. 30.9%, P = 0.038) and MTHFR rs1801133 T allele (32.6% vs. 27.1%, P = 0.012) in patients with arteriosclerosis in multiple arteries was significantly higher than that in arteriosclerosis in single artery, respectively. The proportion of history of alcohol consumption in patients with ALDH2 rs671 G/G genotype was higher than those in ALDH2 rs671 G/A genotype and A/A genotype (P < 0.001). The results of logistic regression analysis indicated that ALDH2 rs671 A/A genotype (A/A vs. G/G: OR 1.996, 95% CI: 1.258-3.166, P = 0.003) and MTHFR rs1801133 T/T genotype (T/T vs. C/C: OR 1.943, 95% CI: 1.179-3.203, P = 0.009) may be independent risk factors for arteriosclerosis in multiple arteries (adjusted for age, sex, smoking, drinking, hypertension, and diabetes). CONCLUSIONS: ALDH2 rs671 A/A and MTHFR rs1801133 T/T genotypes may be independent risk factors for arteriosclerosis in multiple arteries.

The relationship between perfectionism, self-perception of orofacial appearance, and mental health in college students.

Background: In dental clinical practice, self-perception of orofacial appearance is highly correlated with treatment satisfaction. Therefore, it is important to explore factors correlated with self-perception of orofacial appearance. Perfectionism may be one such factor. This study investigated the role of perfectionism in self-perception of orofacial appearance. Methods: Participants completed an online questionnaire that included demographic data, a measure of perfectionism, a measure of self-perception of orofacial appearance (including body image, smile appearance concern, and self-esteem), and a measure of anxiety and depression. Results: High perfectionism scores significantly predicted greater age, body image, smile appearance concern, and mental health scores and lower self-esteem scores (p < 0.005). After adjusting for possible confounding variables, smile appearance concern largely disappeared. Mental health acted as a mediator in the relationships between perfectionism and three orofacial appearance characteristics. Conclusion: High perfectionism predicted higher self-perception of body image, and lower mental health and self-esteem in college students. Mental health could mediate the relationships between perfectionism and self-perception of orofacial appearance.

The single-cell landscape of alternative transcription start sites of diabetic retina.

More than half of mammalian protein-coding genes have multiple transcription start sites. Alternative transcription start site (TSS) modulate mRNA stability, localization, and translation efficiency on post-transcription level, and even generate novel protein isoforms. However, differential TSS usage among cell types in healthy and diabetic retina remains poorly characterized. In this study, by using 5'-tag-based single-cell RNA sequencing, we identified cell type-specific alternative TSS events and key transcription factors for each of retinal cell types. We observed that lengthening of 5'- UTRs in retinal cell types are enriched for multiple RNA binding protein binding sites, including splicing regulators Rbfox1/2/3 and Nova1. Furthermore, by comparing TSS expression between healthy and diabetic retina, we identified elevated apoptosis signal in Müller glia and microglia, which can be served as a putative early sign of diabetic retinopathy. By measuring 5'UTR isoforms in retinal single-cell dataset, our work provides a comprehensive panorama of alternative TSS and its potential consequence related to post-transcriptional regulation. We anticipate our assay can not only provide insights into cellular heterogeneity driven by transcriptional initiation, but also open up the perspectives for identification of novel diagnostic indexes for diabetic retinopathy.

CYP2C19 loss-of-function is associated with increased risk of hypertension in a Hakka population: a case-control study.

BACKGROUND: Genetic factors have a certain proportion in the risk factors of hypertension. The purpose was to investigate the relationship of cytochrome P450 2C19 (CYP2C19) polymorphisms with hypertension in Hakka population. METHODS: The study included 1,872 hypertensive patients and 1,110 controls. The genotypes of CYP2C19 rs4244285 and rs4986893 of all individuals were detected and analyzed. RESULTS: The genotype and allele distributions of CYP2C19 rs4244285 were significantly different between hypertension group and control group. The CYP2C19 *1/*1 genotype was the most predominant among the subjects (40.8%), followed by the CYP2C19 *1/*2 genotype (40.5%). The percentage of CYP2C19*1, *2, and *3 allele was 64.2%, 30.8%, and 5.0%, respectively. The proportion of intermediate metabolizers (IM) (49.3% vs. 42.9%), poor metabolizers (PM) (14.3% vs. 8.9%) (P < 0.001), and CYP2C19*2 allele (33.8% vs. 25.7%, P < 0.001) in hypertension group was significantly higher than that in control group. Multivariate logistic regression (adjusted for gender, age, smoking, and drinking) indicated that CYP2C19 *1/*2, *1/*3, and *2/*2 genotypes may increase susceptibility to hypertension. And the CYP2C19 IM genotype (IM vs. EM: OR 1.514, 95% CI: 1.291-1.775, P < 0.001), PM genotype (PM vs. EM: OR 2.120, 95% CI: 1.638-2.743, P < 0.001), IM + PM genotypes (IM + PM vs. EM: OR 1.617, 95% CI: 1.390-1.882, P < 0.001) may increase risk of hypertension. CONCLUSIONS: CYP2C19 loss-of-function (IM, PM genotypes) is independent risk factor for hypertension susceptibility. Specifically, the risk genotypes include CYP2C19 *1/*2, *1/*3, and *2/*2.

Synthesis and preclinical evaluation of a heterodimeric radioligand targeting fibroblast activation protein and integrin-αvß3.

Tumor progression is accompanied by intrinsic heterogeneity and different phenotypes, which implies a different expression of cell surface receptors. Fibroblast activation protein (FAP) and integrin αvß3 are highly expressed in the cell surface of cancer-associated cells or cancer cells compared with normal cells. Therefore, a FAP/integrin αvß3 bispecific heterodimer was developed for positron emission tomography (PET) diagnostic imaging and radiotherapy. The heterodimer DOTA-FAPI-RGD was labeled with the diagnostic radionuclide gallium-68 or the therapeutic radionuclide lutetium-177, with yields >80%, and high stability. The competitive displacement binding assay showed an IC50 = 6.8 ± 0.6 nM for DOTA-FAPI-RGD towards FAP and IC50 = 2.1 ± 0.4 nM towards integrin αvß3. Radionuclide labeled DOTA-FAPI-RGD showed high specificity and rapid internalization into U87MG cells (FAP/αvß3-positive) in vitro. Micro-PET and biodistribution studies of [68Ga]Ga-DOTA-FAPI-RGD in tumor-bearing mice demonstrated that a high and specific tumor uptake of the tracer and a fast body clearance, resulting in high contrast images. In addition to the imaging applications demonstrated in this study, the labeling of the heterodimeric ligand with the radionuclide lutetium-177 used in cancer treatment might allow the therapeutic application of this ligand.

An integrated single cell and spatial transcriptomic map of human white adipose tissue.

To date, single-cell studies of human white adipose tissue (WAT) have been based on small cohort sizes and no cellular consensus nomenclature exists. Herein, we performed a comprehensive meta-analysis of publicly available and newly generated single-cell, single-nucleus, and spatial transcriptomic results from human subcutaneous, omental, and perivascular WAT. Our high-resolution map is built on data from ten studies and allowed us to robustly identify >60 subpopulations of adipocytes, fibroblast and adipogenic progenitors, vascular, and immune cells. Using these results, we deconvolved spatial and bulk transcriptomic data from nine additional cohorts to provide spatial and clinical dimensions to the map. This identified cell-cell interactions as well as relationships between specific cell subtypes and insulin resistance, dyslipidemia, adipocyte volume, and lipolysis upon long-term weight changes. Altogether, our meta-map provides a rich resource defining the cellular and microarchitectural landscape of human WAT and describes the associations between specific cell types and metabolic states.

Visceral adipose tissue and risk of COVID-19 susceptibility, hospitalization, and severity: A Mendelian randomization study.

Background: Coronavirus Disease 2019 (COVID-19) has rapidly evolved as a global pandemic. Observational studies found that visceral adipose tissue (VAT) increased the likelihood of worse clinical outcomes in COVID-19 patients. Whereas, whether VAT is causally associated with the susceptibility, hospitalization, or severity of COVID-19 remains unconfirmed. We aimed to investigate the causal associations between VAT and susceptibility, hospitalization, and severity of COVID-19. Methods: We applied a two-sample Mendelian randomization (MR) study to infer causal associations between VAT and COVID-19 outcomes. Single-nucleotide polymorphisms significantly associated with VAT were derived from a large-scale genome-wide association study. The random-effects inverse-variance weighted method was used as the main MR approach, complemented by three other MR methods. Additional sensitivity analyses were also performed. Results: Genetically predicted higher VAT mass was causally associated with higher risks of COVID-19 susceptibility [odds ratios (ORs) = 1.13; 95% confidence interval (CI), 1.09-1.17; P = 4.37 × 10-12], hospitalization (OR = 1.51; 95% CI = 1.38-1.65; P = 4.14 × 10-20), and severity (OR = 1.58; 95% CI = 1.38-1.82; P = 7.34 × 10-11). Conclusion: This study provided genetic evidence that higher VAT mass was causally associated with higher risks of susceptibility, hospitalization, and severity of COVID-19. VAT can be a useful tool for risk assessment in the general population and COVID-19 patients, as well as an important prevention target.

Using Hyperbaric Oxygen to Improve the Radiosensitivity of Human U251 Glioma Cells.

The aim of this study was to explore the use of hyperbaric oxygen to enhance the radiosensitivity of human glioma cells. Sub-cultured U251 human glioma cells were randomly divided into four groups: an untreated control group, cells treated with hyperbaric oxygen (HBO) only, cells treated with X-ray irradiation (X-ray) only, and cells treated with both HBO and X-ray. Cell morphology, cell proliferation activity, cell cycle distribution, and apoptosis were observed in these groups to evaluate the role of HBO in improving the radiosensitivity of glioma cells. With the increase in X-ray doses (0 Gy, 2 Gy, 4 Gy, 6 Gy, 8 Gy), the survival fraction (SF) of glioma cells gradually decreased. Significantly lower SF was observed for the cells treated with the HBO and X-ray together than in the X-ray group for each dose (all P < 0.05). The proliferation inhibition was significantly higher in the HBO combined with X-ray group than in the X-ray group for each dose (all P < 0.05) for the U251 cell line. The percentage of G2/M phase cells was significantly higher in the HBO combined with X-ray (2 Gy) group (26.70% ± 2.46%) and the HBO group (22.36% ± 0.91%) than in the control group (11.56% ± 2.01%) and X-ray (2 Gy) group (10.35% ± 2.69%) (all P < 0.05). U251 cell apoptosis was significantly higher in the HBO combined with X-ray (2 Gy) group than in the HBO group, the X-ray (2 Gy) group, and the control group (all P < 0.05). We conclude that HBO can enhance the proliferation inhibition and apoptosis of glioma U251 cells by blocking glioma cells in the G2/M phase and improve the radiosensitivity of U251 glioma cells.

The impact of Internet use on the subjective well-being of Chinese residents: From a multi-dimensional perspective.

As cyberspace has become an important factor in modern-day life, the impact of the Internet on residents has also attracted more attention. Based on the data of China Family Panel Studies (CFPS), this study empirically examines the impact of Internet use on Chinese residents' subjective well-being (SWB) from a multi-dimensional perspective. The research found that Internet use had a significant impact on residents' SWB, which was mainly reflected in job satisfaction, happiness, social ties, and future confidence. The impacts of the Internet's different application fields are not consistent. Applying its use more in studying, working, socialize and commercial activities has a stronger effect, but has no significant impact on entertainment. Further heterogeneity tests also found that the marginal effect of Internet use increases with age, male and low-income groups can obtain greater benefit from the Internet, and there is almost no difference between urban and rural areas. This research provides micro evidence of the social effects of Internet use and provides enlightenment for how to further promote the quality of Internet use to better benefit people.

Polyacrylonitrile Porous Membrane-Based Gel Polymer Electrolyte by In Situ Free-Radical Polymerization for Stable Li Metal Batteries.

Because of their high ionic conductivity, utilizing gel polymer electrolytes (GPEs) is thought to be an effective way to accomplish high-energy-density batteries. Nevertheless, most GPEs have poor adaptability to Ni-rich cathodes to alleviate the problem of inevitable rapid capacity decay during cycling. Therefore, to match LiNi0.8Co0.1Mn0.1O2 (NCM811), we applied pentaerythritol tetraacrylate (PETEA) monomers to polymerize in situ in a polyacrylonitrile (PAN) membrane to obtain GPEs (PETEA-TCGG-PAN). The impedance variations and key groups during the in situ polymerization of PETEA-TCGG-PAN are investigated in detail. PETEA-TCGG-PAN with a high lithium-ion transference number (0.77) exhibits an electrochemical decomposition voltage of 5.15 V. Noticeably, the NCM811|PETEA-TCGG-PAN|Li battery can cycle at 2C for 120 cycles with a capacity retention rate of 89%. Even at 6C, the discharge specific capacity is able to reach 101.47 mAh g-1. The combination of LiF and Li2CO3 at the CEI interface is the reason for the improved rate performance. Moreover, when commercialized LFP is used as the cathode, the battery can also cycle stably for 150 cycles at 0.5C. PETEA and PAN can together foster the transportation of Li+ with the construction of a fast ion transport channel, making a contribution to stable charge-discharge of the above batteries. This study provides an innovative design philosophy for designing in situ GPEs in high-energy-density lithium metal batteries.