Genome-wide analysis of the ERF Family in Stephania japonica provides insights into the regulatory role in Cepharanthine biosynthesis.

Introduction: Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid (bisBIA) extracted from Stephania japonica, has received significant attention for its anti-coronavirus properties. While ethylene response factors (ERFs) have been reported to regulate the biosynthesis of various alkaloids, their role in regulating CEP biosynthesis remains unexplored. Methods: Genome-wide analysis of the ERF genes was performed with bioinformatics technology, and the expression patterns of different tissues, were analyzed by transcriptome sequencing analysis and real-time quantitative PCR verification. The nuclear-localized ERF gene cluster was shown to directly bind to the promoters of several CEP-associated genes, as demonstrated by yeast one-hybrid assays and subcellular localization assays. Results: In this work, 59 SjERF genes were identified in the S. japonica genome and further categorized into ten subfamilies. Notably, a SjERF gene cluster containing three SjERF genes was found on chromosome 2. Yeast one-hybrid assays confirmed that the SjERF gene cluster can directly bind to the promoters of several CEP-associated genes, suggesting their crucial role in CEP metabolism. The SjERFs cluster-YFP fusion proteins were observed exclusively in the nuclei of Nicotiana benthamiana leaves. Tissue expression profiling revealed that 13 SjERFs exhibit high expression levels in the root, and the qRT-PCR results of six SjERFs were consistent with the RNA-Seq data. Furthermore, a co-expression network analysis demonstrated that 24 SjERFs were highly positively correlated with the contents of various alkaloids and expression levels of CEP biosynthetic genes. Conclusion: This study provides the first systematic identification and analysis of ERF transcription factors in the S.japonica genome, laying the foundation for the future functional research of SjERFs transcription factors.

Gene regulatory mechanisms of T cell exhaustion in diffuse large B cell lymphoma based on single-cell transcriptome data.

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous and aggressive B cell malignancy that accounts for about 30 % of non-Hodgkin lymphomas. The current standard treatment for DLBCL is rituximab plus chemotherapy, but many patients are refractory or relapse, indicating the need for improved understanding of its molecular pathology. T cell exhaustion is a state of dysfunction or impairment that occurs in chronic infections or cancers, and is associated with poor prognosis in DLBCL. However, the molecular mechanisms of T cell exhaustion in DLBCL are poorly understood. In this study, we performed a comprehensive analysis of T cell exhaustion in DLBCL using public single-cell transcriptome data. We identified different subtypes of T cells and characterized their gene expression features. We found that DLBCL had a significantly higher proportion of exhausted T cells than normal tonsil, and that exhausted T cells had distinct gene expression signatures from non-exhausted T cells. These signatures included genes related to inhibitory receptors, cytokines, transcription factors and metabolic enzymes. We also found that ID3 gene was significantly upregulated in exhausted T cells in DLBCL, which may play a key role in T cell exhaustion. We constructed a protein-protein interaction network, identifying major hub proteins involved in T cell exhaustion or migration. We also performed KEGG and GO enrichment analysis for the differentially expressed genes between exhausted and non-exhausted T cells, and found important signaling pathways related to T cell exhaustion in DLBCL. Our results provide new insights into the molecular mechanisms underlying T cell exhaustion and offer novel therapeutic targets for this complex disease.

Asteraceae genome database: a comprehensive platform for Asteraceae genomics.

Asteraceae, the largest family of angiosperms, has attracted widespread attention for its exceptional medicinal, horticultural, and ornamental value. However, researches on Asteraceae plants face challenges due to their intricate genetic background. With the continuous advancement of sequencing technology, a vast number of genomes and genetic resources from Asteraceae species have been accumulated. This has spurred a demand for comprehensive genomic analysis within this diverse plant group. To meet this need, we developed the Asteraceae Genomics Database (AGD; http://cbcb.cdutcm.edu.cn/AGD/). The AGD serves as a centralized and systematic resource, empowering researchers in various fields such as gene annotation, gene family analysis, evolutionary biology, and genetic breeding. AGD not only encompasses high-quality genomic sequences, and organelle genome data, but also provides a wide range of analytical tools, including BLAST, JBrowse, SSR Finder, HmmSearch, Heatmap, Primer3, PlantiSMASH, and CRISPRCasFinder. These tools enable users to conveniently query, analyze, and compare genomic information across various Asteraceae species. The establishment of AGD holds great significance in advancing Asteraceae genomics, promoting genetic breeding, and safeguarding biodiversity by providing researchers with a comprehensive and user-friendly genomics resource platform.

Low-dose atorvastatin calcium combined with evolocumab: effect on regulatory proteins, lipid profiles, and cardiac function in coronary heart disease patients.

OBJECTIVE: To assess the effects of combining low-dose atorvastatin calcium with evolocumab on complement regulatory protein levels, lipid profiles, and cardiac function in patients with coronary heart disease (CHD). METHODS: A prospective randomized controlled study was conducted, with 180 CHD patients enrolled from Guang'anmen Hospital, China Academy of Chinese Medical Sciences, and the Second Hospital of Shanxi Medical University between February 2022 and April 2023. These patients were randomly assigned to either the control group (n = 90), receiving low-dose atorvastatin calcium, or the research group (n = 90), receiving a combination of low-dose atorvastatin calcium and evolocumab. The changes in cardiac function indices, levels of blood lipids and complement proteins, incidence of side effects, and cardiovascular events were compared between the two groups. RESULTS: After treatment, both groups exhibited reductions in blood lipid levels. However, the research group demonstrated significantly lower levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) compared to the control group (all P < 0.001). Additionally, improvements in cardiac function indices were observed in both groups, with the research group displaying greater enhancements in cardiac output (CO), stroke volume (SV), and left ventricular ejection fraction (LVEF). Furthermore, the levels of complement regulatory proteins, including CD45, CD46, CD55, and CD59, increased in both groups after treatment, with the research group exhibiting significantly higher levels (all P < 0.001). Notably, the research group also exhibited a lower incidence of cardiovascular events. CONCLUSION: The combined use of low-dose atorvastatin calcium and evolocumab effectively modulates complement regulatory protein levels, optimizes blood lipid profiles, and enhances cardiac function in patients with CHD. This combination therapy represents a promising approach for management of CHD.

Comprehensive landscape of m6A regulator-related gene patterns and tumor microenvironment infiltration characterization in gastric cancer.

The epigenetic regulation of N6-methyladenosine (m6A) has attracted considerable interest in tumor research, but the potential roles of m6A regulator-related genes, remain largely unknown within the context of gastric cancer (GC) and tumor microenvironment (TME). Here, a comprehensive strategy of data mining and computational biology utilizing multiple datasets based on 28 m6A regulators (including novel anti-readers) was employed to identify m6A regulator-related genes and patterns and elucidate their underlying mechanisms in GC. Subsequently, a scoring system was constructed to evaluate individual prognosis and immunotherapy response. Three distinct m6A regulator-related patterns were identified through the unsupervised clustering of 56 m6A regulator-related genes (all significantly associated with GC prognosis). TME characterization revealed that these patterns highly corresponded to immune-inflamed, immune-excluded, and immune-desert phenotypes, and their TME characteristics were highly consistent with different clinical outcomes and biological processes. Additionally, an m6A-related scoring system was developed to quantify the m6A modification pattern of individual samples. Low scores indicated high survival rates and high levels of immune activation, whereas high scores indicated stromal activation and tumor malignancy. Furthermore, the m6A-related scores were correlated with tumor mutation loads and various clinical traits, including molecular or histological subtypes and clinical stage or grade, and the score had predictive values across all digestive system tumors and even in all tumor types. Notably, a low score was linked to improved responses to anti-PD-1/L1 and anti-CTLA4 immunotherapy in three independent cohorts. This study has expanded the important role of m6A regulator-related genes in shaping TME diversity and clinical/biological traits of GC. The developed scoring system could help develop more effective immunotherapy strategies and personalized treatment guidance.

Erratum to: Bioinformatic analysis for potential biological processes and key targets of heart failure-related stroke.

The original version of this article (Liu et al., 2021) unfortunately contained a mistake: statement of equal contribution is missing. This correction article shows that Chiyu LIU and Sixu CHEN contributed equally to this work. The original article has been corrected.

Effects of photodynamic therapy in patients with infected skin ulcers: A meta-analysis.

The purpose of the meta-analysis was to evaluate and compare the photodynamic therapy's effectiveness in treating infected skin wounds. The results of this meta-analysis were analysed, and the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated using dichotomous or contentious random- or fixed-effect models. For the current meta-analysis, 6 examinations spanning from 2013 to 2021 were included, encompassing 154 patients with infected skin wounds were the used studies' starting point. Photodynamic therapy had a significantly lower wound ulcer size (MD, -4.42; 95% CI, -7.56--1.28, p = 0.006), better tissue repair (MD, -8.62; 95% CI, -16.76--0.48, p = 0.04) and lower microbial cell viability (OR, 0.13; 95% CI, 0.04-0.42, p < 0.001) compared with red light exposure in subjects with infected skin wounds. The examined data revealed that photodynamic therapy had a significantly lower wound ulcer size, better tissue repair and lower microbial cell viability compared with red light exposure in subjects with infected skin wounds. However, given that all examinations had a small sample size, consideration should be given to their values.

Survival time prediction in patients with high-grade serous ovarian cancer based on 18F-FDG PET/CT- derived inter-tumor heterogeneity metrics.

BACKGROUND: The presence of heterogeneity is a significant attribute within the context of ovarian cancer. This study aimed to assess the predictive accuracy of models utilizing quantitative 18F-FDG PET/CT derived inter-tumor heterogeneity metrics in determining progression-free survival (PFS) and overall survival (OS) in patients diagnosed with high-grade serous ovarian cancer (HGSOC). Additionally, the study investigated the potential correlation between model risk scores and the expression levels of p53 and Ki-67. METHODS: A total of 292 patients diagnosed with HGSOC were retrospectively enrolled at Shengjing Hospital of China Medical University (median age: 54 ± 9.4 years). Quantitative inter-tumor heterogeneity metrics were calculated based on conventional measurements and texture features of primary and metastatic lesions in 18F-FDG PET/CT. Conventional models, heterogeneity models, and integrated models were then constructed to predict PFS and OS. Spearman's correlation coefficient (ρ) was used to evaluate the correlation between immunohistochemical scores of p53 and Ki-67 and model risk scores. RESULTS: The C-indices of the integrated models were the highest for both PFS and OS models. The C-indices of the training set and testing set of the integrated PFS model were 0.898 (95% confidence interval [CI]: 0.881-0.914) and 0.891 (95% CI: 0.860-0.921), respectively. For the integrated OS model, the C-indices of the training set and testing set were 0.894 (95% CI: 0.871-0.917) and 0.905 (95% CI: 0.873-0.936), respectively. The integrated PFS model showed the strongest correlation with the expression levels of p53 (ρ = 0.859, p < 0.001) and Ki-67 (ρ = 0.829, p < 0.001). CONCLUSIONS: The models based on 18F-FDG PET/CT quantitative inter-tumor heterogeneity metrics exhibited good performance for predicting the PFS and OS of patients with HGSOC. p53 and Ki-67 expression levels were strongly correlated with the risk scores of the integrated predictive models.

A haplotype-resolved gap-free genome assembly provides novel insight into monoterpenoid diversification in Mentha suaveolens 'Variegata'.

Mentha is a commonly used spice worldwide, which possesses medicinal properties and fragrance. These characteristics are conferred, at least partially, by essential oils such as menthol. In this study, a gap-free assembly with a genome size of 414.3 Mb and 31,251 coding genes was obtained for Mentha suaveolens 'Variegata'. Based on its high heterozygosity (1.5%), two complete haplotypic assemblies were resolved, with genome sizes of 401.9 and 405.7 Mb, respectively. The telomeres and centromeres of each haplotype were almost fully annotated. In addition, we detected a total of 41,135 structural variations. Enrichment analysis demonstrated that genes involved in terpenoid biosynthesis were affected by these structural variations. Analysis of volatile metabolites showed that M. suaveolens mainly produces piperitenone oxide rather than menthol. We identified three genes in the M. suaveolens genome which encode isopiperitenone reductase (ISPR), a key rate-limiting enzyme in menthol biosynthesis. However, the transcription levels of ISPR were low. Given that other terpenoid biosynthesis genes were expressed, M. suaveolens ISPRs may account for the accumulation of piperitenone oxide in this species. The findings of this study may provide a valuable resource for improving the detection rate and accuracy of genetic variants, thereby enhancing our understanding of their impact on gene function and expression. Moreover, our haplotype-resolved gap-free genome assembly offers novel insights into molecular marker-assisted breeding of Mentha.

Cepharanthine analogs mining and genomes of Stephania accelerate anti-coronavirus drug discovery.

Cepharanthine is a secondary metabolite isolated from Stephania. It has been reported that it has anti-conronaviruses activities including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we assemble three Stephania genomes (S. japonica, S. yunnanensis, and S. cepharantha), propose the cepharanthine biosynthetic pathway, and assess the antiviral potential of compounds involved in the pathway. Among the three genomes, S. japonica has a near telomere-to-telomere assembly with one remaining gap, and S. cepharantha and S. yunnanensis have chromosome-level assemblies. Following by biosynthetic gene mining and metabolomics analysis, we identify seven cepharanthine analogs that have broad-spectrum anti-coronavirus activities, including SARS-CoV-2, Guangxi pangolin-CoV (GX_P2V), swine acute diarrhoea syndrome coronavirus (SADS-CoV), and porcine epidemic diarrhea virus (PEDV). We also show that two other genera, Nelumbo and Thalictrum, can produce cepharanthine analogs, and thus have the potential for antiviral compound discovery. Results generated from this study could accelerate broad-spectrum anti-coronavirus drug discovery.

Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial).

PURPOSE: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 µm) microspheres loaded with epirubicin. MATERIALS AND METHODS: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) µm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. RESULTS: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death. CONCLUSION: DEB-TACE using epirubicin-loaded small-sized (≤ 100 µm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. LEVEL OF EVIDENCE: 2, Prospective, Non-randomized, Single-arm, study.

Fine-Regional Role of the Claustrum in Anxiety and Higher Sensitivity to Cocaine in Adolescent Cocaine-Exposed Male Mice during Adulthood.

Adolescent cocaine exposure (ACE) induces anxiety and higher sensitivity to substances abuse during adulthood. Here, we show that the claustrum is crucial for controlling these psychiatric problems in male mice. In anxiety-like behavioral tests, the CaMKII-positive neurons in the median portion of the claustrum (MClaustrum) were triggered, and local suppression of these neurons reduced the anxiety-like behavior in ACE mice during adulthood. In contrast, the CaMKII-positive neurons in the anterior portion of the claustrum (AClaustrum) were more activated in response to subthreshold dose of cocaine induced conditioned place preference (CPP), and local suppression of these neurons blocked the acquisition of cocaine CPP in ACE mice during adulthood. Our findings for the first time identified the fine-regional role of the claustrum in regulating the anxiety and susceptibility to cocaine in ACE mice during adulthood, extending our understanding of the claustrum in substance use disorder.

Analysis on Intraoperative Electrocorticogram Characteristics for Evaluating the Risk of Postoperative Epilepsy.

Epilepsy is one of the most common complications after craniotomy, which happens suddenly and does great harm. There still lacks of effective prediction method during the operation. The main purpose of this paper is to explore the correlation between the characteristics of intraoperative electrocorticogram (ECoG) and postoperative epilepsy, and select effective features to establish a prediction model. This retrospective study uses intraoperative ECoG recordings of 144 patients with cerebrovascular diseases undergoing cerebral revascularization surgeries. The cases are divided into subtypes of ischemic and hemorrhagic. Nine types of ECoG features are designed on different frequency bands indicating clinical information, power spectrum, complexity, sequence change, and information quantity, while their changes in different surgical stages are also considered. Then statistical analysis is used to obtain features significantly related to postoperative epilepsy (p<0.05). The sparse representation method is used on these features to further screen and reduce the redundancy, and then machine learning methods are used to establish a prediction model for postoperative epilepsy. The accuracy, sensitivity and specificity of the best prediction model can achieve 0.817, 0.800 and 0.833 respectively under 5-fold cross validation.Clinical Relevance-This study explores the correlation between the characteristics of intraoperative ECoG and postoperative epilepsy, investigates the possibility to use the ECoG features and machine learning algorithms to assess the risk of postoperative epilepsy during the surgery. Further results are expected to provide reference for preventive measures to reduce the occurrence of postoperative epilepsy.

Empagliflozin alleviates atherosclerotic calcification by inhibiting osteogenic differentiation of vascular smooth muscle cells.

SGLT-2 inhibitors, such as empagliflozin, have been shown to reduce the occurrence of cardiovascular events and delay the progression of atherosclerosis. However, its role in atherosclerotic calcification remains unclear. In this research, ApoE-/- mice were fed with western diet and empagliflozin was added to the drinking water for 24 weeks. Empagliflozin treatment significantly alleviated arterial calcification assessed by alizarin red and von kossa staining in aortic roots and reduced the lipid levels, while had little effect on body weight and blood glucose levels in ApoE-/- mice. In vitro studies, empagliflozin significantly inhibits calcification of primary vascular smooth muscle cells (VSMCs) and aortic rings induced by osteogenic media (OM) or inorganic phosphorus (Pi). RNA sequencing of VSMCs cultured in OM with or without empagliflozin showed that empagliflozin negatively regulated the osteogenic differentiation of VSMCs. And further studies confirmed that empagliflozin significantly inhibited osteogenic differentiation of VSMCs via qRT-PCR. Our study demonstrates that empagliflozin alleviates atherosclerotic calcification by inhibiting osteogenic differentiation of VSMCs, which addressed a critical need for the discovery of a drug-based therapeutic approach in the treatment of atherosclerotic calcification.

Reverse genetic study reveals the molecular targets of chordotonal organ TRPV channel modulators.

Insecticides have been widely used for the control of insect pests that have a significant impact on agriculture and human health. A better understanding of insecticide targets is needed for effective insecticide design and resistance management. Pymetrozine, afidopyropen and flonicamid are reported to target on proteins that located on insect chordotonal organs, resulting in the disruption of insect coordination and the inhibition of feeding. In this study, we systematically examined the susceptibility of six Drosophila melanogaster mutants (five transient receptor potential channels and one mechanoreceptor) to three commercially used insecticides, in order to identify the receptor subunits critical to the insect's response to insecticides. Our results showed that iav1, nan36aand wtrw1 mutants exhibited significantly reduced susceptibility to pymetrozine and afidopyropen, but not to flonicamid. The number of eggs produced by the three mutant females were significantly less than that of the w1118 strain. Meanwhile, the longevity of all male mutants and females of nan36a and wtrw1 mutants was significantly shorter than that of the w1118 strain as the control. However, we observed no gravitaxis defects in wtrw1 mutants and the anti-gravitaxis of wtrw1 mutants was abolished by pymetrozine. Behavioral assays using thermogenetic tools further confirmed the bioassay results and supported the idea that Nan as a TRPV subfamily member located in Drosophila chordotonal neurons, acting as a target of pymetrozine, which interferes with Drosophila and causes motor deficits with gravitaxis defects. Taken together, this study elucidates the interactions of pymetrozine and afidopyropen with TRPV channels, Nan and Iav, and TRPA channel, Wtrw. Our research provides another evidence that pymetrozine and afidopyropen might target on nan, iav and wtrw channels and provides insights into the development of sustainable pest management strategies.

Homocysteine Combined with Apolipoprotein B as Serum Biomarkers for Predicting Carotid Atherosclerosis in the Oldest-Old.

Background: The measurement of serum biomarkers is a promising decision aid in the assessment of atherosclerosis. However, data on the levels and epidemiological distribution of serum biomarkers of carotid atherosclerosis (CAS) in the oldest-old are limited. This study aimed to investigate the characteristics of CAS serum biomarkers in the oldest-old over 80 and explore their predictive value for CAS. Methods: As part of the China Hainan Centenarian Cohort Study, a total of 1565 individuals over 80 years old were included. Atherosclerosis was assessed by carotid plaque and carotid intima-media thickness. Serum biomarker levels, demographic indicators, and physical examination indicators were detected. Prediction factors correlated to the CAS were explored by logistic regression and verified by receiver operating characteristic curve analysis. Multivariate regression models were fitted, along with subgroup analysis and robustness tests. Results: Among the oldest-old population, 83.5% (1306) had CAS. In a fully adjusted multivariate logistic regression model, systolic blood pressure (SBP), heart rhythm (HR), serum homocysteine (Hcy), and apolipoprotein B (ApoB) levels were significantly and positively associated with CAS in the oldest-old (PS < 0.001). ROC analysis indicated that the combination of serum Hcy, ApoB, SBP, and HR increased the predictive value for CAS in the oldest-old (area under the curve: 0.856, 95% CI: 0.803-0.879; sensitivity: 81.8%; specificity: 85.9%). Conclusion: SBP, HR, Hcy and ApoB are independent risk factors for CAS in the oldest-old. The specific set of biomarkers and their combination with other risk markers may be a promising strategy for assessing CAS in the elderly, especially in global aging.

The impact of liver abscess formation on prognosis of patients with malignant liver tumors after transarterial chemoembolization.

Purpose: Liver abscess is a rare and serious complication after transarterial chemoembolization (TACE) for liver cancer; however, its impact on the prognosis is unclear. This retrospective study examined the outcomes of patients with liver abscess formation following TACE for malignant liver tumors to elucidate the impact of liver abscess formation on the prognosis of these patients. Methods: From January 2017 to January 2022, 1,387 patients with malignant tumors underwent 3,341 sessions of TACE at our hospital. Clinical characteristics of patients at baseline and follow-up were examined, including treatment and outcome of liver abscess, tumor response to the TACE leading to liver abscess, and overall survival time. Results: Of 1,387 patients, 15 (1.1%) patients with liver abscess complications after TACE resulted in a total of 16 (0.5%) cases of liver abscess after 3,341 TACE sessions (including one patient with two events). After antibiotic or percutaneous catheter drainage (PCD) treatment, all the infections associated with liver abscesses were controlled. In the PCD group, eight patients died before drainage tube removal, one retained the drainage tube until the end of follow-up, and five underwent drainage tube removal; the mean drainage tube removal time was 149.17 ± 134.19 days. The efficacy of TACE leading to liver abscess was evaluated as partial response (18.75%), stable disease (37.5%), and progressive disease (43.75%). Eleven patients died during the follow-up period owing to causes unrelated to infections caused by liver abscesses. The survival rates at 3 months, 6 months, 1 year, and 5 years were 86.7%, 50.9%, 25.5%, and 17%, respectively. Conclusion: Patients with liver abscess formation following TACE for malignant liver tumors experienced prolonged drainage tube removal time after PCD; while this condition did not directly cause death, it indirectly contributed to a poor prognosis in these patients.

Enhancing Mental Health and Medication Adherence Among Men Who Have Sex With Men Recently Diagnosed With HIV With a Dialectical Behavior Therapy-Informed Intervention Incorporating mHealth, Online Skills Training, and Phone Coaching: Development Study Using Human-Centered Design Approach.

BACKGROUND: Mental health problems are common among men who have sex with men (MSM) living with HIV and may negatively affect medication adherence. Psychosocial interventions designed to address these urgent needs are scarce in China. Incorporating behavioral health theories into intervention development strengthens the effectiveness of these interventions. The absence of a robust theoretical basis for interventions may also present challenges to identify active intervention ingredients. OBJECTIVE: This study aims to systematically describe the development of a mobile health-based intervention for MSM recently diagnosed with HIV in China, including the theoretical basis for the content and the considerations for its technological delivery. METHODS: We used intervention mapping (IM) to guide overall intervention development, a behavioral intervention technology model for technological delivery design, and a human-centered design and cultural adaptation model for intervention tailoring throughout all steps of IM. RESULTS: The dialectical behavior therapy (DBT)-informed intervention, Turning to Sunshine, comprised 3 components: app-based individual skills learning, group-based skills training, and on-demand phone coaching. The theoretical basis for the intervention content is based on the DBT model of emotions, which fits our conceptualization of the intervention user's mental health needs. The intervention aims to help MSM recently diagnosed with HIV (1) survive moments of high emotional intensity and strong action urges, (2) change emotional expression to regulate emotions, and (3) reduce emotional vulnerability, as well as (4) augment community resources for mental health services. Technological delivery considerations included rationale of the medium, complexity, and esthetics of information delivery; data logs; data visualization; notifications; and passive data collection. CONCLUSIONS: This study laid out the steps for the development of a DBT-informed mobile health intervention that integrated app-based individual learning, group-based skills training, and phone coaching. This intervention, Turning to Sunshine, aims to improve mental health outcomes for MSM newly diagnosed with HIV in China. The IM framework informed by human-centered design principles and cultural adaptation considerations offered a systematic approach to develop the current intervention and tailor it to the target intervention users. The behavioral intervention technology model facilitated the translation of behavioral intervention strategies into technological delivery components. The systematic development and reporting of the current intervention can serve as a guide for similar intervention studies. The content of the current intervention could be adapted for a broader population with similar emotional struggles to improve their mental health outcomes.

Paternal methamphetamine exposure induces higher sensitivity to methamphetamine in male offspring through driving ADRB1 on CaMKII-positive neurons in mPFC.

Paternal abuse of drugs, such as methamphetamine (METH), elevates the risk of developing addiction in subsequent generations, however, its underlying molecular mechanism remains poorly understood. Male adult mice (F0) were exposed to METH for 30 days, followed by mating with naïve female mice to create the first-generation mice (F1). When growing to adulthood, F1 were subjected to conditioned place preference (CPP) test. Subthreshold dose of METH (sd-METH), insufficient to induce CPP normally, were used in F1. Selective antagonist (betaxolol) for ß1-adrenergic receptor (ADRB1) or its knocking-down virus were administrated into mPFC to regulate ADRB1 function and expression on CaMKII-positive neurons. METH-sired male F1 acquired sd-METH-induced CPP, indicating that paternal METH exposure induce higher sensitivity to METH in male F1. Compared with saline (SAL)-sired male F1, CaMKII-positive neuronal activity was normal without sd-METH, but strongly evoked after sd-METH treatment in METH-sired male F1 during adulthood. METH-sired male F1 had higher ADRB1 levels without sd-METH, which was kept at higher levels after sd-METH treatment in mPFC. Either inhibiting ADRB1 function with betaxolol, or knocking-down ADRB1 level on CaMKII-positive neurons (ADRB1CaMKII) with virus transfection efficiently suppressed sd-METH -evoked mPFC activation, and ultimately blocked sd-METH-induced CPP in METH-sired male F1. In the process, the p-ERK1/2 and ΔFosB may be potential subsequent signals of mPFC ADRB1CaMKII. The mPFC ADRB1CaMKII mediates paternal METH exposure-induced higher sensitivity to drug addiction in male offspring, raising a promising pharmacological target for predicting or treating transgenerational addiction.

A novel hybrid framework based on temporal convolution network and transformer for network traffic prediction.

BACKGROUND: Accurately predicting mobile network traffic can help mobile network operators allocate resources more rationally and can facilitate stable and fast network services to users. However, due to burstiness and uncertainty, it is difficult to accurately predict network traffic. METHODOLOGY: Considering the spatio-temporal correlation of network traffic, we proposed a deep-learning model, Convolutional Block Attention Module (CBAM) Spatio-Temporal Convolution Network-Transformer, for time-series prediction based on a CBAM attention mechanism, a Temporal Convolutional Network (TCN), and Transformer with a sparse self-attention mechanism. The model can be used to extract the spatio-temporal features of network traffic for prediction. First, we used the improved TCN for spatial information and added the CBAM attention mechanism, which we named CSTCN. This model dealt with important temporal and spatial features in network traffic. Second, Transformer was used to extract spatio-temporal features based on the sparse self-attention mechanism. The experiments in comparison with the baseline showed that the above work helped significantly to improve the prediction accuracy. We conducted experiments on a real network traffic dataset in the city of Milan. RESULTS: The results showed that CSTCN-Transformer reduced the mean square error and the mean average error of prediction results by 65.16%, 64.97%, and 60.26%, and by 51.36%, 53.10%, and 38.24%, respectively, compared to CSTCN, a Long Short-Term Memory network, and Transformer on test sets, which justified the model design in this paper.