IL-2 promotes expansion and intratumoral accumulation of tumor infiltrating dendritic cells in pancreatic cancer.

This study aims to investigate the diagnostic potential of IL-2 for PDAC and develop a method to improve the dendritic cell (DC) based vaccine against PDAC. The gene expression data and clinical characteristics information for 178 patients with PDAC were obtained from The Cancer Genome Atlas (TCGA). DCs were isolated from Human peripheral blood mononuclear cells (PBMCs) and were cultured in 4 different conditions. DCs were pulsed by tumor cell lysates or KRAS G12D1 - 23 peptide, and then used to activate T cells. The mixture of DCs and T cells were administered to xenograft mouse model through the tail vein. The infiltration of DCs and T cells were detected by immunohistochemistry. The generation of KRAS G12D mutation specific cytotoxic T cells was determined by in vitro killing assay. We observed that PDAC patients with higher IL-2 mRNA levels exhibited improved overall survival and increased infiltration of CD8 + T cells, NK cells, naïve B cells, and resting myeloid DCs in the tumor microenvironment. IL-2 alone did not enhance DC proliferation, antigen uptake, or apoptosis inhibition unless co-cultured with PBMCs. DCs co-cultured with PBMCs in IL-2-containing medium demonstrated the strongest tumor repression effect in vitro and in vivo. Compared to DCs obtained through the traditional method (cultured in medium containing GM-CSF and IL-4), DCs cultured with PBMCs, and IL-2 exhibited increased tumor infiltration capacity, potentially facilitating sustained T cell immunity. DCs cultured in the PBMCs-IL-2 condition could promote the generation of cytotoxic T cells targeting tumor cells carrying KRAS G12D mutation.

The Gap Between Self-Rated Health Information Literacy and Internet Health Information-Seeking Ability for Patients With Chronic Diseases in Rural Communities: Cross-sectional Study.

BACKGROUND: The internet has become one of the most important channels for residents to seek health information, particularly in remote rural areas in China. OBJECTIVE: In this study, we aimed to explore the gap between self-rated health information literacy and internet health information seeking ability for patients with chronic diseases in rural communities and to preliminarily evaluate their barriers when seeking health information via the internet. METHODS: Residents from rural communities near Bengbu City and with chronic diseases were included in this study. A self-rated questionnaire was used to evaluate their health information literacy, 3 behavioral competency tasks were designed to preliminarily evaluate their ability to seek health information on the internet and semistructured interviews were used to investigate their barriers to obtaining health information via the internet. A small audiorecorder was used to record the interview content, and screen-recording software was used to record the participants' behavior during the web-based operational tasks. RESULTS: A total of 70 respondents completed the self-rated health information literacy questionnaire and the behavioral competence test, and 56 respondents participated in the semistructured interviews. Self-rated health information literacy (score out of 70: mean 46.21, SD 4.90) of the 70 respondents were moderate. Although 91% (64/70) of the respondents could find health websites, and 93% (65/70) of the respondents could find information on treatment that they thought was the best, 35% (23/65) of respondents did not know how to save the results they had found. The operational tasks indicated that most articles selected by the respondents came from websites with encyclopedic knowledge or answers from people based on their own experiences rather than authoritative health information websites. After combining the results of the semistructured interviews with the DISCERN scale test results, we found that most interviewees had difficulty obtaining high-quality health information via the internet. CONCLUSIONS: Although the health information literacy level of patients with rural chronic disease was moderate, they lack the ability to access high-quality health information via the internet. The vast majority of respondents recognized the importance of accessing health information but were not very proactive in accessing such information.

Transcriptome-wide association study identifies multiple genes associated with childhood body mass index.

BACKGROUND: Childhood obesity is one of the most common and costly nutritional problems with high heritability. The genetic mechanism of childhood obesity remains unclear. Here, we conducted a transcriptome-wide association study (TWAS) to identify novel genes for childhood obesity. METHODS: By integrating the GWAS summary of childhood body mass index (BMI), we conducted TWAS analyses with pre-computed gene expression weights in 39 obesity priority tissues. The GWAS summary statistics of childhood BMI were derived from the early growth genetics consortium with 35,668 children from 20 studies. RESULTS: We identified 15 candidate genes for childhood BMI after Bonferroni corrections. The most significant gene, ADCY3, was identified in 13 tissues, including adipose, brain, and blood. Interestingly, eight genes were only identified in the specific tissue, such as FAIM2 in the brain (P = 2.04 × 10-7) and fat mass and obesity-associated gene (FTO) in the muscle (P = 1.93 × 10-8). Compared with the TWAS results of adult BMI, we found that one gene TUBA1B with predominant influence only on childhood BMI in the muscle (P = 1.12 × 10-7). We evaluated the candidate genes by querying public databases and identified 12 genes functionally related to obesity phenotypes, including nine differentially expressed genes during the differentiation of human preadipocyte cells. The remaining genes (FAM150B, KNOP1, and LMBR1L) were regarded as novel candidate genes for childhood BMI. CONCLUSIONS: Our study identified multiple candidate genes for childhood BMI, providing novel clues for understanding the genetic mechanism of childhood obesity.

Characterization of an agmatine N-acetyltransferase from Bactrocera dorsalis that modulates ovary development.

Agmatine N-acetyltransferase (AgmNAT), which catalyzes the formation of N-acetylagmatine from acetyl-CoA and agmatine, is a member of the GCN5-related N-acetyltransferase family. So far, knowledge of the physiological roles of AgmNAT in insects is limited. Here, we identified one gene encoding protein homologous to that of Drosophila AgmNAT using sequence information from an activity-verified Drosophila AgmNAT in a BLAST search of the Bactrocera dorsalis genome. We expressed and purified B. dorsalis AgmNAT in Escherichia coli and used the purified enzyme to define the substrate specificity for acyl-CoA and amine substrates. Our application of the screening strategy to BdorAgmNAT led to the identification of agmatine as the best amine substrate for this enzyme, with the highest kcat/Km value. We successfully obtained a BdorAgmNAT knockout strain based on a wild-type strain (WT) using the CRISPR/Cas9 technique. The ovary development of the BdorAgmNAT knockout mutants was delayed for 10 days compared with the WT specimens. Moreover, mutants had a much smaller mature ovary size and laid far fewer eggs than WT. Loss of function of BdorAgmNAT caused by RNAi with mature WT females did not affect their fecundity. These findings indicate that BdorAgmNAT is critical for oogenesis. Our data provide the first evidence for AgmNAT in regulating ovary development.

Effect of WeChat-based continuous care intervention on the somatic function, depression, anxiety, social function and cognitive function for cancer patients: Meta-analysis of 18 RCTs.

AIM: This meta-analysis systematically reviewed and identified the effects of WeChat-based continuous care (WCC) interventions on various outcomes in cancer patients. DESIGN: Systematic review and meta-analysis. METHODS: In this study, outcome measures included somatic function, anxiety, depression, social function, and cognitive function. The standardized mean differences and 95% CIs of pooled effect sizes were calculated using fixed- and random-effects models. NFail-safe and Begg's tests were performed to evaluate publication bias, and sensitivity analysis was performed to evaluate the robustness of the meta-analysis results. RESULTS: The meta-analysis included 18 RCTs of moderate quality. WCC interventions significantly improved somatic function, depression, anxiety, social function, and cognitive function in cancer patients. There was no significant publication bias, and the sensitivity analysis indicated robust results. PATIENT OR PUBLIC CONTRIBUTION: WCC interventions improved depression, anxiety, social function, and cognitive function in cancer patients.

Aminoacyl-tRNA Synthetase-based Prognosis Model and Exploration of Potential Mechanisms in Hepatocellular Carcinoma.

Background and Aims: Aminoacyl-tRNA synthetases (ARSs) participate in tumor initiation and progression but their involvement in hepatocellular carcinoma (HCC) is not clear. This study aimed to investigate the prognostic value and underlying mechanisms of ARS in HCC. Methods: Data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium, Gene Expression Omnibus and Human Protein Atlas databases. The prognostic model was constructed with the use of Cox regression and least absolute shrinkage and selection operator regression. Kaplan-Meier survival analysis, enrichment analysis, single sample gene set enrichment analysis and tumor mutation burden calculation were performed with R to evaluate the model and explore the underlying mechanism. Wilcoxon tests were used for comparisons between groups. Results: Aspartyl-tRNA synthetase 2 (DARS2), tyrosyl-tRNA synthetase 1 (YARS1) and cysteinyl-tRNA synthetase 2 (CARS2) were identified as prognostic biomarkers and enrolled in model construction. The area under receiver operating characteristic curve of the model was 0.775. The model was used to assign patients from TCGA into low- and high-risk groups. Those in the high-risk group had a worse prognosis (p<0.001). The clinical significance of the model was tested in different clinical subgroups. Genetic mutation analysis had a higher TP53 mutation frequency in high-risk group. Enrichment analysis and study of immune-related cells and molecules found that the high-risk group was characterized by immune-cell infiltration and immunosuppression states. Conclusions: A novel ARS family-based model of HCC prognosis was constructed. TP53 mutation frequency and immune-suppressive status accounted for a worse prognosis in patients included in the high-risk group.

The function and quality of individual epidemic prevention and control apps during the COVID-19 pandemic: A systematic review of Chinese apps.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a global pandemic that has driven the widespread use of applications (apps) for outbreak management in China, but the characteristics and quality of these apps are currently unknown. OBJECTIVE: The first objective of this study was to investigate the functional characteristics of individual epidemic prevention and control apps in China, and the second objective was to evaluate the quality of these apps. METHODS: We searched the QimaiTM mobile application data analysis platform and the AladdinTM WeChat applet data analysis platform with keywords and quantified the search results based on the search index, relevance, and the Aladdin index to identify apps with high public popularity. The quality of the apps was rated by 2 independent raters using the Mobile App Rating Scale (MARS). The intraclass correlation coefficient (ICC) between raters was used as a measure of interrater reliability. RESULTS: All 20 of the included apps had acceptable quality. Functionality had the highest score, followed by information quality, aesthetics, and engagement. There were no significant differences between the independent apps and WeChat applets in app quality (t = 1.907, p = 0.073) and subjective quality (t = 0.899, p = 0.381). These apps were related to COVID-19 individual prevention and control, and the functional features that contributed to the quality of the apps were grouped into six categories, i.e., health self-checking and reporting, news about COVID-19, scientific publicity and education, telemedicine services, personal travel inquiries, and digital contact tracing. CONCLUSIONS: Individual COVID-19 prevention and control apps in China were developed by adding epidemic prevention and control functions to existing social apps rather than independently developing apps. The overall quality of such apps was acceptable, but scores in the engagement section were generally low, especially for WeChat applets.

Up-Regulated MISP Is Associated With Poor Prognosis and Immune Infiltration in Pancreatic Ductal Adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a poor prognosis. More effective biomarkers and treatment options remain to be discovered. Mitotic Spindle Positioning (MISP), also called C19orf21, has been reported to be upregulated in several malignancies. However, the effects of MISP on PDAC have yet to be investigated. Materials and Methods: The differential expression of MISP at the mRNA and protein levels were evaluated using Gene Expression Profiling Interactive Analysis 2 (GEPIA 2), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA) databases, and was further verified by quantitative real-time PCR and western blotting in PDAC cell lines. Correlations between MISP expression and clinical characteristics were explored using Kaplan-Meier Plotter Database and clinical data from The Cancer Genome Atlas (TCGA). CCK-8 assays, Transwell assays, and immunoblotting were used to determine the role of MISP in PDAC proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were executed by the R package 'clusterProfiler'. Correlations between MISP expression and immune cell infiltration, immune checkpoints, immunophenoscore (IPS) and the tumor mutational burden (TMB) in PDAC were explored using the R package 'CIBERSORT', the Tumor Immune Estimation Resource 2.0 (TIMER2.0), and The Cancer Immunome Atlas (TCIA) database based on TCGA data. Result: MISP expression was significantly higher in pancreatic cancer tissues compared to normal pancreas tissues, which was associated with a poor prognosis. Increased expression of MISP was related to the proliferation, migration and invasion of PDAC cell lines. GO and KEGG pathway analyses determined that MISP is involved in the Ras signaling pathway and immune regulation. Higher expression of MISP was associated with decreased infiltration levels of activated CD4+ memory T cells, CD8+ T cells, M2 macrophages and neutrophils. Furthermore, increased MISP was associated with lower expression of immune checkpoint molecules, higher gene mutation burden and IPS. Conclusions: This study reveals that MISP, which is associated with the progression and prognosis of PDAC, may exert a potential regulatory effect on immune infiltration and predict the response to immunotherapy in PDAC.

Arylalkylamine N-acetyltransferase 1 gene (AANAT1) regulates cuticle pigmentation and ovary development of the adult oriental fruit fly, Bactrocera dorsalis.

The arylalkylamine N-acetyltransferase (AANAT) enzymes catalyze the acetyl-CoA-dependent acetylation of an amine or arylalkylamine, which is involved in important biological processes of insects. Here, we carried out the molecular and biochemical identification of an arylalkylamine N-acetyltransferase (AANAT) from the oriental fruit fly, Bactrocera dorsalis. Using a bacterial expression system, we expressed and purified the encoded recombinant BdorAANAT1-V3 protein. The purified recombinant protein acts on a wide range of substrates, including dopamine, tyramine, octopamine, serotonin, methoxytryptamine, and tryptamine, and shows similar substrate affinity (i.e., Km values: 0.16-0.26 mM) except for serotonin (Km = 0.74 mM) and dopamine (Km = 0.84 mM). Transcriptional profile analysis of BdorAANAT1 revealed that this gene is most prevalent in adults and abundant in the adult brain, gut, and ovary. Using the CRISPR/Cas9 technique, we successfully obtained a BdorAANAT1 knockout strain based on a wild-type strain (WT). Compared with the WT, the cuticle color of larvae and pupae is normal; however, in adult mutants, the yellow region of their thorax is darkly pigmented, and two black spots were evident at the abdomen's end. Moreover, the female BdorAANAT1 knockout mutant had a smaller ovary than the WT, and laid far fewer eggs. Loss of function of BdorAANAT1 caused by RNAi with mature adult females in which the reproductive system is fully developed had no effect on their fecundity. Altogether, these results indicate that BdorAANAT1 regulates ovary development. Our findings provide evidence for the insect AANAT1 modulating adult cuticle pigmentation and female fecundity.

Gaps in the Utilization of Community Health Services for the Elderly Population in Rural Areas of Mainland China: A Systematic Review Based on Cross-Sectional Investigations.

Background: While the community health service system was initially established in rural areas of mainland China, the utilization of community health service resources by the rural elderly population is not clear. Methods: Cross-sectional studies on the utilization of community health services by the rural elderly population in mainland China published within the last 10 years were retrieved from the China National Knowledge Infrastructure (CNKI), Wan Fang, Medline and Web of Science (WOS) databases. The quality of the article was evaluated by the Critical Appraisal Skills Programme (CASP), and obstacles to the utilization of community health services by the rural elderly population were analyzed based on the Andersen model. Results: Twenty-four studies were analyzed, and 3 gaps were found. (i) The cognition of rural elderly residents does not match the current health security system. (ii) There is a gap between the supply of health service resources in rural communities and the health needs of the elderly residents in these areas. (iii) The health services provided by rural primary health service institutions are not targeted. Conclusions: In mainland China, the provision of community health services to the rural elderly population has improved significantly. However, several factors from the individual level to the system level lead to low levels of access and utilization. This finding means that under the leadership of the government, it is necessary to integrate the strength of multiple departments to cooperate in improving the welfare system, policy publicity, health education, financial support, system guarantees and resource exchange and sharing for the elderly population in rural areas and to jointly promote community health services for the elderly population in rural areas.

Evaluating the Quality of Health-Related WeChat Public Accounts: Cross-Sectional Study.

BACKGROUND: As representatives of health information communication platforms accessed through mobile phones and mobile terminals, health-related WeChat public accounts (HWPAs) have a large consumer base in the Chinese-speaking world. However, there is still a lack of general understanding of the status quo of HWPAs and the quality of the articles they release. OBJECTIVE: The aims of this study were to assess the conformity of HWPAs to the Health on the Net Foundation Code of Conduct (HONcode) and to evaluate the suitability of articles disseminated by HWPAs. METHODS: The survey was conducted from April 23 to May 5, 2019. Based on the monthly (March 1-31, 2019) WeChat Index provided by Qingbo Big Data, the top 100 HWPAs were examined to evaluate their HONcode compliance. The first four articles published by each HWPA on the survey dates were selected as samples to evaluate their suitability. All materials were assessed by three raters. The materials were assessed using the HONcode checklist and the Suitability Assessment of Materials (SAM) score sheet. Data analysis was performed with SPSS version 17.0 (SPSS Inc, Chicago, IL, USA) and Excel version 2013 (Microsoft Inc, Washington DC, USA). RESULTS: A total of 93 HWPAs and 210 of their released articles were included in this study. For six of the eight principles, the 93 HWPAs nearly consistently did not meet the requirements of the HONcode. The HWPAs certified by Tencent Corporation (66/93, 71%) were generally slightly superior to those without such certification (27/93, 29%) in terms of compliance with HONcode principles. The mean SAM score for the 210 articles was 67.72 (SD 10.930), which indicated "adequate" suitability. There was no significant difference between the SAM scores of the articles published by certified and uncertified HWPAs (P=.07), except in the literacy requirements dimension (tdf=97=-2.418, P=.02). CONCLUSIONS: The HWPAs had low HONcode conformity. Although the suitability of health information released by HWPAs was at a moderate level, there were still problems identified, such as difficulty in tracing information sources, excessive implicit advertisements, and irregular usage of charts. In addition, the low approval requirements of HWPAs were not conducive to improvement of their service quality.