Comprehensive molecular phenotyping of ARID1A-deficient gastric cancer reveals pervasive epigenomic reprogramming and therapeutic opportunities.

OBJECTIVE: Gastric cancer (GC) is a leading cause of cancer mortality, with ARID1A being the second most frequently mutated driver gene in GC. We sought to decipher ARID1A-specific GC regulatory networks and examine therapeutic vulnerabilities arising from ARID1A loss. DESIGN: Genomic profiling of GC patients including a Singapore cohort (>200 patients) was performed to derive mutational signatures of ARID1A inactivation across molecular subtypes. Single-cell transcriptomic profiles of ARID1A-mutated GCs were analysed to examine tumour microenvironmental changes arising from ARID1A loss. Genome-wide ARID1A binding and chromatin profiles (H3K27ac, H3K4me3, H3K4me1, ATAC-seq) were generated to identify gastric-specific epigenetic landscapes regulated by ARID1A. Distinct cancer hallmarks of ARID1A-mutated GCs were converged at the genomic, single-cell and epigenomic level, and targeted by pharmacological inhibition. RESULTS: We observed prevalent ARID1A inactivation across GC molecular subtypes, with distinct mutational signatures and linked to a NFKB-driven proinflammatory tumour microenvironment. ARID1A-depletion caused loss of H3K27ac activation signals at ARID1A-occupied distal enhancers, but unexpectedly gain of H3K27ac at ARID1A-occupied promoters in genes such as NFKB1 and NFKB2. Promoter activation in ARID1A-mutated GCs was associated with enhanced gene expression, increased BRD4 binding, and reduced HDAC1 and CTCF occupancy. Combined targeting of promoter activation and tumour inflammation via bromodomain and NFKB inhibitors confirmed therapeutic synergy specific to ARID1A-genomic status. CONCLUSION: Our results suggest a therapeutic strategy for ARID1A-mutated GCs targeting both tumour-intrinsic (BRD4-assocatiated promoter activation) and extrinsic (NFKB immunomodulation) cancer phenotypes.

Standardized rate of hospitalization for violent injuries among different generations in counties and cities in Taiwan from 2000 to 2015.

This study aimed to understand the distribution of the standardized rate of hospitalization for violent injuries in counties and cities in Taiwan. The ICD-9 diagnosis code N-codes 995.5 (abused child) and 995.8 (abused adult) or E-code E960-E969 (homicide and intentional injury by others) were defined as research cases. The study analyzed the standardized medical treatment rate of children and adolescents aged 0 to 17, adults aged 18 to 64, and older adults over 65 years old suffering from violence for the first time. During the 15-year period, the counties and cities with the highest rate of medical treatment for violent injuries among children (unit: per 105 people) were Pingtung County (33.1 males, 22.9 females), Lienchiang County (8.8 males, 9.8 females), and New Taipei City (8.2 males, 8.8 females). For adults, Pingtung County (73.2 males, 36.8 females), New Taipei City (26.0 males, 14.3 females), and Yunlin County (19.7 males, 7.7 females) registered the highest rates. For older adults, Pingtung County (33.6 persons), New Taipei City (12.5 persons), Yun Lin County (11.2 persons), and Taichung City (9.2 persons) registered the highest rates. The highest rates of older female adults receiving treatment were recorded in Pingtung County (15.1 persons), Yunlin County (9.0 persons), Taichung City (5.5 persons), and New Taipei City (5.1 persons). With the Poisson regression model, the relative risk ratio of seeking medical care owing to violence in Pingtung County (reference: Taipei City) was 25.1 times for children, 20.1 times for adults, and 11.7 times for older adults. The counties and cities with higher rates of violent medical treatment for adults and older adults during the 15-year period were Pingtung County, New Taipei City, and Yunlin County. For children and adolescents, Pingtung County, Lienchiang County, and New Taipei City recorded the highest rates. Pingtung County had the highest risk of sexual violence. These results may be related to the local industrial structure, demographic composition, and other characteristics explained in the text.

Should acupuncture therapy be used for acute facial paralysis? A protocol for systematic review.

BACKGROUND: Peripheral facial paralysis (PFP) results in functional disorder and social dysfunction, when it is under a severe condition at onset, long-term poor outcomes do occur. Different acupuncture methods have been reported to be potentially effective for shortening the disease course and reducing the occurrence of sequelae when they are applied at an early stage. Neuro edema is a common pathological feature in the acute phase, and many clinical studies have suggested its effect of reducing facial nerve edema. It is of value to estimate the effectiveness and safety of acupuncture treatment at the onset, and to assess the most suitable acupuncture method for the acute period. METHODS AND ANALYSIS: All the RCTs and quasi-RCTs on acupuncture therapy for patients who is during acute stage of PFP will be included. The recovery rate of facial function, the time it takes to restore facial function and the odds of sequelae occurring will be the key parts we focus on. Psychological well-being and quality of life will also be evaluated. Literature searching will be conducted until December 31th, 2022 from eight databases systematically. Two reviewers will screen the literature and extract the data independently. RevMan software will be used for data analysis, and the version 2 of the Cochrane risk-of-bias tool (RoB 2) will be used to assess the certainty of evidence. Forest plots and summary findings will be generated. If data permits, a meta-analysis will be conducted. ETHICS AND DISSEMINATION: Since this study will not involve clinical treatment of patients, ethics approval is not required. The result of this study will be submitted to a peer-reviewed journal for publication and as a proposal for clinical practice and further study on acupuncture treatment at the early stage of PFP. DISCUSSION: This review will summarize the evidence on the different type of acupuncture therapy for acute Bell's palsy and Ramsay-Hunt syndrome. We anticipate that it would be safe and effective when applied to the acute phase of PFP, and some specific suitable acupuncture methods would be found resulting from this review. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register for Systematic Reviews (PROSPERO) number CRD42020205127.

[Preparation and bone repair capability of a new plastic bone filler material].

Objective: To prepare a new plastic bone filler material with adhesive carrier and matrix particles derived from human bone, and evaluate its safety and osteoinductive ability through animal tests. Methods: The human long bones donated voluntarily were prepared into decalcified bone matrix (DBM) by crushing, cleaning, and demineralization, and then the DBM was prepared into bone matrix gelatin (BMG) by warm bath method, and the BMG and DBM were mixed to prepare the experimental group's plastic bone filler material; DBM was used as control group. Fifteen healthy male thymus-free nude mice aged 6-9 weeks were used to prepare intermuscular space between gluteus medius and gluteus maximus muscles, and all of them were implanted with experimental group materials. The animals were sacrificed at 1, 4, and 6 weeks after operation, and the ectopic osteogenic effect was evaluated by HE staining. Eight 9-month-old Japanese large-ear rabbits were selected to prepare 6-mm-diameter defects at the condyles of both hind legs, and the left and right sides were filled with the materials of the experimental group and the control group respectively. The animals were sacrificed at 12 and 26 weeks after operation, and the effect of bone defect repair were evaluated by Micro-CT and HE staining. Results: In ectopic osteogenesis experiment, HE staining showed that a large number of chondrocytes could be observed at 1 week after operation, and obvious newly formed cartilage tissue could be observed at 4 and 6 weeks after operation. For the rabbit condyle bone filling experiment, HE staining showed that at 12 weeks after operation, part of the materials were absorbed, and new cartilage could be observed in both experimental and control groups; at 26 weeks after operation, the most of the materials were absorbed, and large amount of new bone could be observed in the 2 groups, while new bone unit structure could be observed in the experimental group. Micro-CT observation showed that the bone formation rate and area of the experimental group were better than those of the control group. The measurement of bone morphometric parameters showed that the parameters at 26 weeks after operation in both groups were significantly higher than those at 12 weeks after operation ( P<0.05). At 12 weeks after operation, the bone mineral density and bone volume fraction in the experimental group were significantly higher than those in the control group ( P<0.05), and there was no significant difference between the two groups in trabecular thickness ( P>0.05). At 26 weeks after operation, the bone mineral density of the experimental group was significantly higher than that of the control group ( P<0.05). There was no significant difference in bone volume fraction and trabecular thickness between the two groups ( P>0.05). Conclusion: The new plastic bone filler material is an excellent bone filler material with good biosafety and osteoinductive activity.

Bilirubin gates the TRPM2 channel as a direct agonist to exacerbate ischemic brain damage.

Stroke prognosis is negatively associated with an elevation of serum bilirubin, but how bilirubin worsens outcomes remains mysterious. We report that post-, but not pre-, stroke bilirubin levels among inpatients scale with infarct volume. In mouse models, bilirubin increases neuronal excitability and ischemic infarct, whereas ischemic insults induce the release of endogenous bilirubin, all of which are attenuated by knockout of the TRPM2 channel or its antagonist A23. Independent of canonical TRPM2 intracellular agonists, bilirubin and its metabolic derivatives gate the channel opening, whereas A23 antagonizes it by binding to the same cavity. Knocking in a loss of binding point mutation for bilirubin, TRPM2-D1066A, effectively antagonizes ischemic neurotoxicity in mice. These findings suggest a vicious cycle of stroke injury in which initial ischemic insults trigger the release of endogenous bilirubin from injured cells, which potentially acts as a volume neurotransmitter to activate TRPM2 channels, aggravating Ca2+-dependent brain injury.

Effect of body mass index on the cumulative live birth rate over multiple complete IVF cycles in women with polycystic ovary syndrome: A retrospective study.

OBJECTIVE: The purpose of this study was to investigate the effect of body mass index (BMI) before treatment on the cumulative live birth rate (CLBR) over multiple complete in vitro fertilization (IVF) cycles in patients with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: This study is a single-center retrospective cohort study. It included 5016 patients with PCOS who started their first IVF cycle in our hospital between 2009 and 2018. Kaplan-Meier and log-rank tests were used for the comparison of CLBR across BMI groups. Univariate, multivariate models and stratification analysis were used to evaluate possible influencing factors of CLBR. Smoothing curve fitting was applied to present the correlation between BMI and CLBR. A one-line linear regression model was compared with a two-piecewise linear model using a log-likelihood ratio test. RESULTS: During the 8-year follow-up, 3604 women (71.85%) obtained at least one live birth. The study population was grouped according to BMI, with BMI ranging from [14.53-23.00) kg/m2 in the normal weight group, [23.00-27.50) kg/m2 in the overweight group, and [27.50-37.80] kg/m2 in the obese group, respectively. The CLBR of the obese group and the overweight group were significantly lower than the normal weight group. In the multivariate regression model, HR for CLBR was 0.86 [95%CI: 0.78-0.95] for the obese group, and 0.93 [0.86-1.00] for the overweight group, compared with the normal weight group as control. The curve fitting after adjustment for confounding factors and log-likelihood ratio test showed a one-line linear negative correlation between BMI and CLBR. CONCLUSION: We concluded that the BMI of PCOS patients had a negative one-line linear correlation with CLBR over multiple complete cycles.

Urea impregnation into fungus pretreated corn stover to perform pyrolysis for production of nitrogen-containing bio-oil and nitrogen-doped biochar.

Urea was introduced into the fungal pretreated corn stover and then the urea soaked materials were subjected to pyrolysis for the production of nitrogen-containing bio-oil and nitrogen-doped biochar. The urea soaking effectively realized the enrichment of nitrogen-containing compounds in the bio-oil and the maximal content of the nitrogen-containing compounds in bio-oils reached up to 66.32% under 4 wt% urea concentration. Among the nitrogen-containing compounds, amines were the most dominant component with the maximal content of 41.17%. The higher urea concentration is beneficial to make more nitrogen be fixed in the biochar. The nitrogen content of the biochar reached up to 12.86 wt% under 8 wt% urea concentration. Nitrogen on the biochar surface existed in the form of pyrrolic-N, pyridinic-N and graphite-N. In conclusion, urea simple soak on fungus pretreated biomass to perform pyrolysis is a promising approach to obtain high value-added nitrogen-containing chemicals and nitrogen-doped biochar with high nitrogen content.

Negative life events and aggression among Chinese rural left-behind adolescents: do self-esteem and resilience mediate the relationship?

BACKGROUND: Left-behind adolescents (LBAs) are adolescents aged 11-18 years who are separated from their parents and left behind in local cities by one or both parents for a period of more than 6 months. LBAs in rural areas are likely to engage in aggressive behavior, which can affect interpersonal relationships, reduce academic performance, and even lead to anxiety and depression. To our knowledge, no studies have examined the mediating effect of resilience and self-esteem on the relationship between negative life events and aggression among Chinese rural LBAs. Therefore, this study aimed to explore the relationship between negative life events and aggression among Chinese rural LBAs and how self-esteem and resilience mediate the association. METHODS: Using a stratified random sampling method, 1344 LBAs in Hunan Province of China were investigated. Information was collected by a self-designed sociodemographic questionnaire, Adolescent Self-Rating Life Events Checklist, Resilience Scale Chinese Adolescent, Rosenberg Self-Esteem Scale and Aggression Scales to assess the psychology of LBAs. Data analysis was conducted using descriptive statistics, Pearson correlation, and regression analysis to estimate direct and indirect effects using bootstrap analysis. RESULTS: Negative life events were significantly related to self-esteem (r = - 0.338), resilience (r = - 0.359), and aggression (r = 0.441). Aggression was directly affected by self-esteem (ß = - 0.44) and resilience (ß = - 0.34). Negative life events were not only directly related to aggression (ß = 0.34, 95% CI: 0.275 ~ 0.398) but also showed an indirect effect on aggression through self-esteem and resilience. The direct effect, total effect and indirect effect of negative life events on aggression through self-esteem and resilience were 0.3364, 0.4344 and 0.0980, respectively. The mediating effect of self-esteem and resilience accounted for 22.56% of the relationship between negative life events and aggression. CONCLUSIONS: We found that self-esteem and resilience mediated most negative life events on aggression. It is imperative for educators and families to improve LBAs' self-esteem and resilience to reduce the occurrence of aggression. Future intervention studies should be designed to strengthen self-esteem and resilience.

Adjusting phosphate feeding regimen according to daily rhythm increases eggshell quality via enhancing medullary bone remodeling in laying hens.

BACKGROUND: Body phosphorus metabolism exhibits a circadian rhythm over the 24-h daily cycle. The egg laying behavior makes laying hens a very special model for investigating phosphorus circadian rhythms. There is lack of information about the impact of adjusting phosphate feeding regimen according to daily rhythm on the phosphorus homeostasis and bone remodeling of laying hens. METHODS AND RESULTS: Two experiments were conducted. In Exp. 1, Hy-Line Brown laying hens (n = 45) were sampled according the oviposition cycle (at 0, 6, 12, and 18 h post-oviposition, and at the next oviposition, respectively; n = 9 at each time point). Diurnal rhythms of body calcium/phosphorus ingestions and excretions, serum calcium/phosphorus levels, oviduct uterus calcium transporter expressions, and medullary bone (MB) remodeling were illustrated. In Exp. 2, two diets with different phosphorus levels (0.32% and 0.14% non-phytate phosphorus (NPP), respectively) were alternately presented to the laying hens. Briefly, four phosphorus feeding regimens in total (each included 6 replicates of 5 hens): (1) fed 0.32% NPP at both 09:00 and 17:00; (2) fed 0.32% NPP at 09:00 and 0.14% NPP at 17:00; (3) fed 0.14% NPP at 09:00 and 0.32% NPP at 17:00; (4) fed 0.14% NPP at both 09:00 and 17:00. As a result, the regimen fed 0.14% NPP at 09:00 and 0.32% NPP at 17:00, which was designed to strengthen intrinsic phosphate circadian rhythms according to the findings in Exp. 1, enhanced (P < 0.05) MB remodeling (indicated by histological images, serum markers and bone mineralization gene expressions), elevated (P < 0.05) oviduct uterus calcium transportation (indicated by transient receptor potential vanilloid 6 protein expression), and subsequently increased (P < 0.05) eggshell thickness, eggshell strength, egg specific gravity and eggshell index in laying hens. CONCLUSIONS: These results underscore the importance of manipulating the sequence of daily phosphorus ingestion, instead of simply controlling dietary phosphate concentrations, in modifying the bone remodeling process. Body phosphorus rhythms will need to be maintained during the daily eggshell calcification cycle.

Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province, China.

Objective: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and ß-globin gene mutations in Hunan Province. Methods: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. Results: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for ß-thalassemia, and 0.12% for both α- and ß-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and ß-thalassemia was -α 3.7/αα (50.23%) and ß IVS-II-654/ß N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six ß-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. Conclusion: Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.

Lactobacillus Plantarum injection at the embryonic stage alters the early growth performance and lipid metabolism of broilers by specific genera of bacteria.

The main objective of this study was to explore the effects of broiler embryonic injection of Lactobacillus Plantarum on the growth performance, lipid metabolism of serum and liver, microbial diversity, and short-chain fatty acids of broiler intestines after hatching. On d 14 of incubation, 720 eggs of Arbor Acres were randomly divided into 4 experimental groups: no treatment control (C), Treatments injected with stroke-physiological saline solution (S), Supernatant of MRS medium culture of lactobacillus (Q) and Lactobacillus Plantarum spp. (J). The Hatch rate for each replicate was counted at 1 d of age. After hatching, each group were divided into six replicates of 10 broilers, and chicken from groups C, Q and J were reared until 14 d of age. The production performance of the three groups of chicks from 1 to 14 days was recorded and statistically analyzed separately. Serum and liver tissue were collected at 7 and 14 days of age for the detection of lipid metabolism index. 16S rDNA sequencing and Short-Chain Fatty Acids measurement of cecum contents were performed at 14 days of age. Overall, Lactobacillus injection significantly reduced feed conversion ratio (FCR) at 1-7 and 1-14 days of age, compared to the other 2 groups (P < 0.05). 16S rRNA sequencing results showed that the Roseburia and coprobacillus had a significantly positive correlation with body weight (P < 0.05). The Roseburia and lachnospira were significantly correlated with FCR (P < 0.05), and the absolute abundance of g_Anaerostipes as a biomarker in the J group was higher than in the C group (P < 0.05). The Q and J group increased the content of acetic, propionic, butyric, and total acid in the cecum contents (P < 0.05). In the jejunum, the J group increased the content of acetic, propionic, butyric, and total acids compared to the C and Q groups (P < 0.05). The J group increased the blood of total cholesterol (TC) content at 1 day of age and the triglyceride (TG) content of 7- and 14-day-old broilers (P < 0.05). and the J group raised the TG, TC, and high-density lipoprotein (HDL) level in the liver of 14-day-old broilers (P < 0.05). The J group reduced the liver's low-density lipoprotein (LDL) at 14 days of age (P < 0.05). In conclusion, the lactobacillus Plantarum injection at the embryonic stage alters lipid metabolism by short-chain fatty acids especially butyric produced by the specific bacteria of Roseburia and Anaerostipes.

General temporal ghost imaging model with detection resolution and noise.

Improving imaging quality while reducing the sampling time simultaneously is a crucial challenge that limits the practical application of temporal ghost imaging (TGI). To improve the performance of TGI, various methods have been proposed and verified. However, a work analyzing in detail the influence of intensity accuracy and detection noise of TGI is still absent. Here, we establish an evaluation model to quantify the imaging quality of TGI and differential TGI (DTGI). Our model considers the intensity detection accuracy, threshold, and noise of the test path during image reconstruction and quantifies their influences by developing general imaging formulas of (D)TGI. We also simulate the imaging of (D)TGI numerically. The evaluation demonstrates that (D)TGI is relatively not sensitive to detection accuracy and thresholds of the test path, and image quality is degraded slightly even when those parameters turn much worse. (D)TGI is relatively robust to detection noise but will be unable to reconstruct the object when noise is too strong. DTGI does not show clear advantages over TGI. Our work develops an effective model to quantify the image quality with practical parameters and is significant to real applications of (D)TGI.

A Cohort Study on Deficiency of ADA2 from China.

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

scMINER: a mutual information-based framework for identifying hidden drivers from single-cell omics data.

The sparse nature of single-cell omics data makes it challenging to dissect the wiring and rewiring of the transcriptional and signaling drivers that regulate cellular states. Many of the drivers, referred to as "hidden drivers", are difficult to identify via conventional expression analysis due to low expression and inconsistency between RNA and protein activity caused by post-translational and other modifications. To address this issue, we developed scMINER, a mutual information (MI)-based computational framework for unsupervised clustering analysis and cell-type specific inference of intracellular networks, hidden drivers and network rewiring from single-cell RNA-seq data. We designed scMINER to capture nonlinear cell-cell and gene-gene relationships and infer driver activities. Systematic benchmarking showed that scMINER outperforms popular single-cell clustering algorithms, especially in distinguishing similar cell types. With respect to network inference, scMINER does not rely on the binding motifs which are available for a limited set of transcription factors, therefore scMINER can provide quantitative activity assessment for more than 6,000 transcription and signaling drivers from a scRNA-seq experiment. As demonstrations, we used scMINER to expose hidden transcription and signaling drivers and dissect their regulon rewiring in immune cell heterogeneity, lineage differentiation, and tissue specification. Overall, activity-based scMINER is a widely applicable, highly accurate, reproducible and scalable method for inferring cellular transcriptional and signaling networks in each cell state from scRNA-seq data. The scMINER software is publicly accessible via: https://github.com/jyyulab/scMINER.

scMINER: a mutual information-based framework for identifying hidden drivers from single-cell omics data.

The sparse nature of single-cell omics data makes it challenging to dissect the wiring and rewiring of the transcriptional and signaling drivers that regulate cellular states. Many of the drivers, referred to as "hidden drivers", are difficult to identify via conventional expression analysis due to low expression and inconsistency between RNA and protein activity caused by post-translational and other modifications. To address this issue, we developed scMINER, a mutual information (MI)-based computational framework for unsupervised clustering analysis and cell-type specific inference of intracellular networks, hidden drivers and network rewiring from single-cell RNA-seq data. We designed scMINER to capture nonlinear cell-cell and gene-gene relationships and infer driver activities. Systematic benchmarking showed that scMINER outperforms popular single-cell clustering algorithms, especially in distinguishing similar cell types. With respect to network inference, scMINER does not rely on the binding motifs which are available for a limited set of transcription factors, therefore scMINER can provide quantitative activity assessment for more than 6,000 transcription and signaling drivers from a scRNA-seq experiment. As demonstrations, we used scMINER to expose hidden transcription and signaling drivers and dissect their regulon rewiring in immune cell heterogeneity, lineage differentiation, and tissue specification. Overall, activity-based scMINER is a widely applicable, highly accurate, reproducible and scalable method for inferring cellular transcriptional and signaling networks in each cell state from scRNA-seq data. The scMINER software is publicly accessible via: https://github.com/jyyulab/scMINER .

Parents' understanding and attitudes toward the use of the WeChat platform for postoperative follow-up management of children with congenital heart disease.

OBJECTIVE: This study aimed to investigate parents' understanding and attitudes toward using the WeChat platform for postoperative follow-up management of children with congenital heart disease (CHD). METHODS: A total of 196 children with CHD were followed up using the WeChat platform. A self-designed questionnaire was administered to their parents at discharge. RESULTS: Only 188 parents completed the questionnaire. One hundred nineteen parents (63.3%) confirmed that they heard about using the WeChat platform for postoperative follow-up, and 104 (87.4%) of them expressed that they were willing to accept the WeChat platform for their follow-up. A total of 42 parents (35.3%) were willing to undergo a follow-up of 1 to 3 months, and 32 (26.8%) were willing to undergo a long-term follow-up. Eighty parents (67.2%) had a positive attitude toward the effect of the WeChat platform on follow-up. Parents in rural areas and those educated at the middle school level or below were more willing to engage with the WeChat platform for postoperative follow-up management (P < 0.05). CONCLUSIONS: Although the WeChat platform is an essential tool for daily communication, its application in postoperative follow-up management is still under study. Most parents who participated in the follow-up study had a positive attitude toward the WeChat platform, especially those in rural areas and with lower education levels.

Resection of a schwannoma originating from vagus nerve in the right superior mediastinum.

BACKGROUND: Schwannoma is the most common mediastinal neurogenic tumor, while schwannoma originating from mediastinal vagus nerve is rare. CASE PRESENTATION: This article reported one case of schwannoma originating from vagus nerve in the right superior mediastinum. The mediastinal schwannoma was completely resected through a right-sided video-assisted thoracoscopic thoracotomy. Histologic examination clarified the diagnosis as schwannoma. CONCLUSION: Chest CT scan and MRI can be used to determine the location of mediastinal schwannoma and its relationship with adjacent tissue. Histologic examination showing distinctive feature of Antoni A areas and Antoni B areas can help clarify the diagnosis. Complete surgical resection is the first-line treatment option for mediastinal schwannomas.

pH-Sensitive and Biodegradable Mn3(PO4)2·3H2O Nanoparticles as an Adjuvant of Protein-Based Bivalent COVID-19 Vaccine to Induce Potent and Broad-Spectrum Immunity.

Developing a novel and potent adjuvant with great biocompatibility for immune response augmentation is of great significance to enhance vaccine efficacy. In this work, we prepared a long-term stable, pH-sensitive, and biodegradable Mn3(PO4)2·3H2O nanoparticle (nano-MnP) by simply mixing MnCl2/NaH2PO4/Na2HPO4 solution for the first time and employed it as an immune stimulant in the bivalent COVID-19 protein vaccine comprised of wild-type S1 (S1-WT) and Omicron S1 (S1-Omicron) proteins as antigens to elicit a broad-spectrum immunity. The biological experiments indicated that the nano-MnP could effectively activate antigen-presenting cells through the cGAS-STING pathway. Compared with the conventional Alum-adjuvanted group, the nano-MnP-adjuvanted bivalent vaccine elicited approximately 7- and 8-fold increases in IgG antibody titers and antigen-specific IFN-γ secreting T cells, respectively. Importantly, antisera of the nano-MnP-adjuvanted group could effectively cross-neutralize the SARS-CoV-2 and its five variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron, demonstrating that this bivalent vaccine based on S1-WT and S1-Omicron proteins is an effective vaccine design strategy to induce broad-spectrum immune responses. Collectively, this nano-MnP material may provide a novel and efficient adjuvant platform for various prophylactic and therapeutic vaccines and provide insights for the development of the next-generation manganese adjuvant.