SODB facilitates comprehensive exploration of spatial omics data.

Spatial omics technologies generate wealthy but highly complex datasets. Here we present Spatial Omics DataBase (SODB), a web-based platform providing both rich data resources and a suite of interactive data analytical modules. SODB currently maintains >2,400 experiments from >25 spatial omics technologies, which are freely accessible as a unified data format compatible with various computational packages. SODB also provides multiple interactive data analytical modules, especially a unique module, Spatial Omics View (SOView). We conduct comprehensive statistical analyses and illustrate the utility of both basic and advanced analytical modules using multiple spatial omics datasets. We demonstrate SOView utility with brain spatial transcriptomics data and recover known anatomical structures. We further delineate functional tissue domains with associated marker genes that were obscured when analyzed using previous methods. We finally show how SODB may efficiently facilitate computational method development. The SODB website is https://gene.ai.tencent.com/SpatialOmics/ . The command-line package is available at https://pysodb.readthedocs.io/en/latest/ .

SC-AIR-BERT: a pre-trained single-cell model for predicting the antigen-binding specificity of the adaptive immune receptor.

Accurately predicting the antigen-binding specificity of adaptive immune receptors (AIRs), such as T-cell receptors (TCRs) and B-cell receptors (BCRs), is essential for discovering new immune therapies. However, the diversity of AIR chain sequences limits the accuracy of current prediction methods. This study introduces SC-AIR-BERT, a pre-trained model that learns comprehensive sequence representations of paired AIR chains to improve binding specificity prediction. SC-AIR-BERT first learns the 'language' of AIR sequences through self-supervised pre-training on a large cohort of paired AIR chains from multiple single-cell resources. The model is then fine-tuned with a multilayer perceptron head for binding specificity prediction, employing the K-mer strategy to enhance sequence representation learning. Extensive experiments demonstrate the superior AUC performance of SC-AIR-BERT compared with current methods for TCR- and BCR-binding specificity prediction.

Interpretable artificial intelligence model for accurate identification of medical conditions using immune repertoire.

Underlying medical conditions, such as cancer, kidney disease and heart failure, are associated with a higher risk for severe COVID-19. Accurate classification of COVID-19 patients with underlying medical conditions is critical for personalized treatment decision and prognosis estimation. In this study, we propose an interpretable artificial intelligence model termed VDJMiner to mine the underlying medical conditions and predict the prognosis of COVID-19 patients according to their immune repertoires. In a cohort of more than 1400 COVID-19 patients, VDJMiner accurately identifies multiple underlying medical conditions, including cancers, chronic kidney disease, autoimmune disease, diabetes, congestive heart failure, coronary artery disease, asthma and chronic obstructive pulmonary disease, with an average area under the receiver operating characteristic curve (AUC) of 0.961. Meanwhile, in this same cohort, VDJMiner achieves an AUC of 0.922 in predicting severe COVID-19. Moreover, VDJMiner achieves an accuracy of 0.857 in predicting the response of COVID-19 patients to tocilizumab treatment on the leave-one-out test. Additionally, VDJMiner interpretively mines and scores V(D)J gene segments of the T-cell receptors that are associated with the disease. The identified associations between single-cell V(D)J gene segments and COVID-19 are highly consistent with previous studies. The source code of VDJMiner is publicly accessible at https://github.com/TencentAILabHealthcare/VDJMiner. The web server of VDJMiner is available at https://gene.ai.tencent.com/VDJMiner/.

Mitochondrial pyruvate carrier 1 regulates fatty acid synthase lactylation and mediates treatment of nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: NAFLD has become a major metabolic disease worldwide. A few studies have reported the potential relationship between mitochondrial pyruvate carrier 1 (MPC1) and inflammation, fibrosis, and insulin sensitivity in obese or NASH mouse models. However, the impact of MPC1 on NAFLD-related liver lipid metabolism and its role in the NAFLD progression require further investigation. APPROACH AND RESULTS: MPC1 expression was measured in liver tissues from normal controls and patients with NAFLD. We characterized the metabolic phenotypes and expression of genes involved in hepatic lipid accumulation in MPC1 systemic heterozygous knockout (MPC1 +/- ) mice. Hepatic protein lactylation was detected using Tandem Mass Tags proteomics and verified by the overexpression of lactylation mutants in cells. Finally, the effect of MPC1 inhibition on liver inflammation was examined in mice and AML-12 cells. Here, we found that MPC1 expression was positively correlated to liver lipid deposition in patients with NAFLD. MPC1 +/- mice fed with high-fat diet had reduced hepatic lipid accumulation but no change in the expression of lipid synthesis-related genes. MPC1 knockout affected the lactylation of several proteins, especially fatty acid synthase, through the regulation of lactate levels in hepatocytes. Lactylation at the K673 site of fatty acid synthase inhibited fatty acid synthase activity, which mediated the downregulation of liver lipid accumulation by MPC1. Moreover, although MPC1 knockout caused lactate accumulation, inflammation level was controlled because of mitochondrial protection and macrophage polarization. CONCLUSIONS: In NAFLD, MPC1 levels are positively correlated with hepatic lipid deposition; the enhanced lactylation at fatty acid synthase K673 site may be a downstream mechanism.

High Microeukaryotic Diversity in the Cold-Seep Sediment.

Microeukaryotic diversity, community structure, and their regulating mechanisms remain largely unclear in chemosynthetic ecosystems. Here, using high-throughput sequencing data of 18S rRNA genes, we explored microeukaryotic communities from the Haima cold seep in the northern South China Sea. We compared three distinct habitats: active, less active, and non-seep regions, with vertical layers (0-25 cm) from sediment cores. The results showed that seep regions harbored more abundant and diverse parasitic microeukaryotes (e.g., Apicomplexa and Syndiniales) as indicator species, compared to nearby non-seep region. Microeukaryotic community heterogeneity was larger between habitats than within habitat, and greatly increased when considering molecular phylogeny, suggesting the local diversification in cold-seep sediments. Microeukaryotic α-diversity at cold seeps was positively increased by metazoan richness and dispersal rate of microeukaryotes, while its ß-diversity was promoted by heterogeneous selection mainly from metazoan communities (as potential hosts). Their combined effects led to the significant higher γ-diversity (i.e., total diversity in a region) at cold seeps than non-seep regions, suggesting cold-seep sediment as a hotspot for microeukaryotic diversity. Our study highlights the importance of microeukaryotic parasitism in cold-seep sediment and has implications for the roles of cold seep in maintaining and promoting marine biodiversity.

Genomic and transcriptomic evidence for the diverse adaptations of Synechococcus subclusters 5.2 and 5.3 to mesoscale eddies.

Mesoscale eddies are ubiquitous oceanographic features that influence the metabolism and community structure of Synechococcus. However, the metabolic adaptations of this genus to eddy-associated environmental changes have rarely been studied. We recovered two high-quality Synechococcus metagenome-assembled genomes (MAGs) from eddies in the South China Sea and compared their metabolic variations using metatranscriptomic samples obtained at the same time. The two MAGs (syn-bin1 and syn-bin2) are affiliated with marine Synechococcus subclusters 5.2 (S5.2) and 5.3 (S5.3), respectively. The former exhibited a higher abundance at the surface layer, whereas the latter was more abundant in the deep euphotic layer. Further analysis indicated that syn-bin1 had a strong ability to utilize organic nutrients, which could help it to thrive in the nutrient-deprived surface water. By contrast, syn-bin2 had the genetic potential to perform chromatic acclimation, which could allow it to capture green or blue light at different depths. Additionally, transcriptomic analysis showed that syn-bin2 upregulated genes involved in the synthesis of C4 acids, photosystem II proteins, and HCO3- transporters in the deep euphotic layer, which might contribute to its predominance in low-light environments. Overall, this study expands our understanding of oceanic S5.2 and S5.3 Synechococcus by revealing their metabolic adaptations to mesoscale eddies.

Nutrient-imbalanced conditions shift the interplay between zooplankton and gut microbiota.

BACKGROUND: Nutrient stoichiometry of phytoplankton frequently changes with aquatic ambient nutrient concentrations, which is mainly influenced by anthropogenic water treatment and the ecosystem dynamics. Consequently, the stoichiometry of phytoplankton can markedly alter the metabolism and growth of zooplankton. However, the effects of nutrient-imbalanced prey on the interplay between zooplankton and their gut microbiota remain unknown. Using metatranscriptome, a 16 s rRNA amplicon-based neutral community model (NCM) and experimental validation, we investigated the interactions between Daphnia magna and its gut microbiota in a nutrient-imbalanced algal diet. RESULTS: Our results showed that in nutrient-depleted water, the nutrient-enriched zooplankton gut stimulated the accumulation of microbial polyphosphate in fecal pellets under phosphorus limitation and the microbial assimilation of ammonia under nitrogen limitation. Compared with the nutrient replete group, both N and P limitation markedly promoted the gene expression of the gut microbiome for organic matter degradation but repressed that for anaerobic metabolisms. In the nutrient limited diet, the gut microbial community exhibited a higher fit to NCM (R2 = 0.624 and 0.781, for N- and P-limitation, respectively) when compared with the Control group (R2 = 0.542), suggesting increased ambient-gut exchange process favored by compensatory feeding. Further, an additional axenic grazing experiment revealed that the growth of D. magna can still benefit from gut microbiota under a nutrient-imbalanced diet. CONCLUSIONS: Together, these results demonstrated that under a nutrient-imbalanced diet, the microbes not only benefit themselves by absorbing excess nutrients inside the zooplankton gut but also help zooplankton to survive during nutrient limitation.

An Angle Recognition Algorithm for Tracking Moving Targets Using WiFi Signals with Adaptive Spatiotemporal Clustering.

An angle estimation algorithm for tracking indoor moving targets with WiFi is proposed. First, phase calibration and static path elimination are proposed and performed on the collected channel state information signals from different antennas. Then, the angle of arrival information is obtained with the joint estimation algorithm of the angle of arrival (AOA) and time of flight (TOF). To deal with the multipath effects, we adopt the DBscan spatiotemporal clustering algorithm with adaptive parameters. In addition, the time-continuous angle of arrival information is obtained by interpolating and supplementing points to extract the dynamic signal paths better. Finally, the least-squares method is used for linear fitting to obtain the final angle information of a moving target. Experiments are conducted with the tracking data set presented with Tsinghua's Widar 2.0. The results show that the average angle estimation error with the proposed algorithm is smaller than Widar2.0. The average angle error is about 7.18° in the classroom environment, 3.62° in the corridor environment, and 12.16° in the office environment; they are smaller than the errors of the existing system.

A People-Counting and Speed-Estimation System Using Wi-Fi Signals.

Counting the number of people and estimating their walking speeds are essential in crowd control and flow. In this work, we propose a system that uses prevalent Wi-Fi signals to identify the number of people entering and leaving a room through a door. It selects the best subcarrier of Wi-Fi signals and applies the Hampel filter to remove outlier information first. Then, it employs a double threshold method to determine the start and end times of entering or leaving. Afterward, it compares the detected signals with the precollected database using the dynamic time-warping algorithm and determines the number of people. It uses a variance threshold method to identify the states of entering or leaving. It also employs a nonlinear fitting approach to calculate the walking speeds. The experiments show that, in a large empty laboratory, the accuracy rates in determining the number of people are 100% for one person, 81% for two persons, and 95% for three persons. In a small office, the accuracy rates for detecting the number of people are 98% for one or two persons, 82% for three persons, 93% for four, and 75% for five persons. For the walking speed estimation, the accuracy rate for a speed error of less than 0.2410 m/s is 75% for a single person.

[Advances in research on cardiomyocyte pyroptosis mediated by NLRP3 inflammasome and traditional Chinese medicine intervention].

Pyroptosis is a pro-inflammatory programmed cell death, and its role in cardiac inflammatory response has become a hot topic. The activation of nucleotide binding oligomerization domain like receptor protein 3(NLRP3) inflammasome is an important mechanism for pyroptosis induced by cysteinyl aspartate specific proteinase 1(caspase-1). The existing studies have shown that cardiomyocyte pyroptosis participates in the pathogenesis of different cardiovascular diseases and the NLRP3 inflammasome-mediated cardiomyocyte pyroptosis has been most widely studied. Also, the intervention in NLRP3 inflammasome activation and cardiomyocyte pyroptosis contributes to ameliorating myocardial injury, which may be the main mechanism of many traditional Chinese medicines in exerting the cardio-protective effects. Therefore, this paper reviewed the studies on cardiomyocyte pyroptosis mediated by NLRP3 inflammasome and put forward the importance of exploring traditional Chinese medicine intervention in the activation of NLRP3 inflammasome.

HIV-related stigma and quality of life in people living with HIV and depressive symptoms: indirect effects of positive coping and perceived stress.

Despite a strong evidence on the negative association between HIV-related stigma and quality of life (QoL), few studies have examined the indirect effects of this relationship. This study aimed to examine the association between HIV-related stigma and QoL and the indirect effects of positive coping and perceived stress in people living with HIV and depressive symptoms (PLWHD). This study used baseline date from a randomized controlled trial. Structural equation model was used to examine the association between HIV-related stigma and QoL as well as the indirect effects of positive coping and perceived stress. Perceived and internalized stigma had negative direct (ß = -0.14, p < 0.05) effect on QoL. Moreover, perceived and internalized stigma had indirect effects on QoL through decreased positive coping and increased perceived stress (ß = -0.23, p < 0.001). Multilevel interventions to reduce perceived and internalized stigma and perceived stress as well as programs to enhance positive coping may improve QoL of PLWHD. Integrated interventions that both enhance positive coping and reduce perceived stress and stigma are potentially more effective in improving QoL than programs that focus on only one aspect of stigma reduction among PLWHD.

Gender differences in the relationship of sexual partnership characteristics and inconsistent condom use among people living with HIV in China.

Few studies have examined the relationship between inconsistent condom use and sexual partnership characteristics among people living with HIV (PLWH). The current study focused on such association and its gender differences. The study was conducted in a large hospital in South China in 2013. A total of 320 dyads (PLWH indexes and their sexual partners) were recruited from an outpatient clinic using convenience sampling. The proportion of inconsistent condom use in the last six months among female indexes was higher than that among male indexes (52.4% vs. 43.6%). Of sexual partnership characteristics, HIV seropositive status was a risk factor for inconsistent condom use for both male and female indexes (aOR = 2.32, 95%CI = 1.15∼4.66, aOR = 3.09, 95%CI = 1.10∼8.67, respectively). For male indexes, lower educational level was also a risk factor (aOR = 2.39, 95%CI = 1.23∼4.67); while having had emotionally intimate relationships was a protective factor (aOR = 0.40, 95%CI = 0.21∼0.77). For female indexes, receiving material support was a risk factor (aOR = 10.17, 95%CI = 2.13∼48.61) and receiving health-related advice was a protective factor (aOR = 0.11, 95%CI = 0.02∼0.55). Future HIV interventions for PLWH need to be gender-sensitive and include their sexual partners.

Systemic In Silico Screening in Drug Discovery for Coronavirus Disease (COVID-19) with an Online Interactive Web Server.

The emergence of the new coronavirus (nCoV-19) has impacted human health on a global scale, while the interaction between the virus and the host is the foundation of the disease. The viral genome codes a cluster of proteins, each with a unique function in the event of host invasion or viral development. Under the current adverse situation, we employ virtual screening tools in searching for drugs and natural products which have been already deposited in DrugBank in an attempt to accelerate the drug discovery process. This study provides an initial evaluation of current drug candidates from various reports using our systemic in silico drug screening based on structures of viral proteins and human ACE2 receptor. Additionally, we have built an interactive online platform (https://shennongproject.ai/) for browsing these results with the visual display of a small molecule docked on its potential target protein, without installing any specialized structural software. With continuous maintenance and incorporation of data from laboratory work, it may serve not only as the assessment tool for the new drug discovery but also an educational web site for the public.

Effect of a WeChat-Based Intervention (Run4Love) on Depressive Symptoms Among People Living With HIV in China: A Randomized Controlled Trial.

BACKGROUND: People living with HIV (PLWH) have high rates of depressive symptoms. However, only a few effective mental health interventions exist for this vulnerable population. OBJECTIVE: The aim of this study was to assess the efficacy of a WeChat-based intervention, Run4Love, with a randomized controlled trial among 300 people living with HIV and depression (PLWHD) in China. METHODS: We recruited PLWH from the HIV outpatient clinic in South China. Participants were screened based on the Center for Epidemiologic Studies-Depression (CES-D) scale. Those who scored 16 or higher were eligible to participate. A total of 300 eligible patients were enrolled. After obtaining informed consent from the participants, completion of a baseline survey, and collection of participants' hair samples for measuring cortisol, the participants were randomly assigned to an intervention or a control group in a 1:1 ratio. The intervention group received the Run4Love program, delivered via the popular social media app WeChat. Cognitive behavioral stress management courses and weekly reminders of exercise were delivered in a multimedia format. Participants' progress was monitored with timely and tailored feedback. The control group received usual care and a brochure on nutrition for PLWH. Data were collected at 3, 6, and 9 months. The primary outcome was depression, which was measured by a validated instrument. RESULTS: Participants in the intervention and control groups were comparable at baseline; about 91.3% (139/150), 88.3% (132/150), and 86.7% (130/150) participants completed the 3-, 6-, and 9-month follow-ups, respectively. At the 3-month follow-up, a significant reduction in CES-D score was observed in the intervention group (from 23.9 to 17.7 vs from 24.3 to 23.8; mean difference=-5.77, 95% CI -7.82 to -3.71; P<.001; standard effect size d=0.66). The mean changes in CES-D score from baseline to the 6- and 9-month follow-ups between the two groups remained statistically significant. No adverse events were reported. CONCLUSIONS: The WeChat-based mobile health (mHealth) intervention Run4Love significantly reduced depressive symptoms among PLWHD, and the effect was sustained. An app-based mHealth intervention could provide a feasible therapeutic option for many PLWHD in resource-limited settings. Further research is needed to assess generalizability and cost-effectiveness of this intervention. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-17012606; http://www.chictr.org.cn/showproj.aspx?proj=21019 (Archived by WebCite at https://www.webcitation.org/78Bw2vouF).

Ginsenoside Rg1 protects H9c2 cells against nutritional stress-induced injury via aldolase /AMPK/PINK1 signalling.

Insufficient nutrients supply will greatly affect the function of cardiac myocytes. The adaptive responses of cardiac myocytes to nutritional stress are not fully known. Ginsenoside Rg1 is one of the most pharmacologically active components in Panax Ginseng and possesses protective effects on cardiomyocyte. Here, we investigate the effects of ginsenoside Rg1 on H9c2 cells which were subjected to nutritional stress. Nutritional stress-induced by glucose deprivation strongly induced cell death and this response was inhibited by ginsenoside Rg1. Importantly, glucose deprivation decreased intracellular ATP levels and mitochondrial membrane potential. Ginsenoside Rg1 rescued ATP levels and mitochondrial membrane potential in nutrient-starved cells. For molecular mechanisms, ginsenoside Rg1 increased the expressions of PTEN-induced kinase 1 (PINK1) and p-AMPK in glucose deprivation treated H9c2 cells. Reducing the expression of aldolase in H9c2 cells inhibited ginsenoside Rg1's actions on PINK1 and p-AMPK. Further, the nutritional stress mice were used to verify the mechanisms obtained in vitro. Ginsenoside Rg1 increased the expressions of aldolase, p-AMPK, and PINK1 in starved mice heart. Taken together, our results reveal that ginsenoside Rg1 limits nutritional stress-induced H9c2 cells injury by regulating the aldolase /AMP-activated protein kinase/PINK1 pathway.

Differential effects of unemployment on depression in people living with HIV/AIDS: a quantile regression approach.

Unemployment is associated with depression in people living with HIV (PLWH). However, few studies have examined the effects of unemployment on PLWH with different levels of depression. The current study explores the plausible differential effects of unemployment on the different percentiles of depression in PLWH employing a quantile regression (QR) approach, based on a recent survey of 411 PLWH in China. Among participants, 47.7% had elevated depressive symptoms, and 23.8% were unemployed. The effects of unemployment on depression were statistically significant with a trend of initial increase followed by a decline at the quantile levels of 0.51-0.90 of depression. The maximum effect of unemployment status on depression was statistically significant at the 70th and 75th percentiles of depression (coefficient = 7.0, p < .01). Tailored strategies and interventions should be implemented to address the differential needs of PLWH with various levels of depressive symptoms.

Mechanisms and Effects of a WeChat-Based Intervention on Suicide Among People Living With HIV and Depression: Path Model Analysis of a Randomized Controlled Trial.

BACKGROUND: People living with HIV and depression have high rates of suicide. Studies of mobile health (mHealth) interventions have shown feasibility, acceptability, and efficacy in improving mental health in people living with HIV and depression. However, few studies have examined the mechanisms and effects of mHealth interventions on suicide. OBJECTIVE: This study was designed to examine the mechanisms and effects of a WeChat-based intervention, Run4Love, on suicide among people living with HIV and depression in China, while considering perceived stress and depressive symptoms as mediators. METHODS: A sample of 300 People living with HIV and depression was recruited from the outpatient clinic of a large HIV or AIDS treatment hospital and was randomized to the Run4Love group or a control group. Data were collected at baseline, 3-, 6-, and 9-month follow-ups. Path analysis modeling, with longitudinal data, was used in data analyses. RESULTS: The Run4Love mHealth intervention had a direct effect on reducing suicide rate at the 6-month follow-up (beta=-.18, P=.02) and indirect effect through reducing perceived stress and depressive symptoms at the 3-month follow-up (beta=-.09, P=.001). A partial mediating effect between perceived stress and depressive symptoms accounted for 33% (-0.09/-0.27) of the total effect. CONCLUSIONS: Through path analyses, we understood the mechanisms and effects of an mHealth intervention on suicide prevention. The findings underscored the importance of stress reduction and depression treatment in such a program. We call for more effective suicide prevention, especially mHealth interventions targeting the vulnerable population of people living with HIV and depression. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-17012606; http://www.chictr.org.cn/showprojen.aspx?proj=21019.

[Advances in research on hypolipidemic mechanism of phytosterols].

Hyperlipidemia,as one of the severe risk factors of cardiovascular disease,could easily trigger atherosclerosis,coronary heart disease,peripheral vascular disease,pancreatitis,etc.,and could also increase the incidence of type 2 diabetes and fatty liver disease. Improving dyslipidemia could slow down the progression of atherosclerosis and reduce the risk of coronary heart disease. This is of great importance for prevention and treatment of cardiovascular disease. Phytosterols are natural active ingredients in plants. Many researches have shown that phytosterols have significant lipid-lowering activity,which could effectively lower blood cholesterol and triglyceride levels. Foods containing phytosterols have been widely used as therapeutic diets for improving dyslipidemia. In the early years,it was believed that the lipid-lowering effect of phytosterols was achieved by competitively inhibiting the absorption of dietary cholesterol in the intestine since phytosterols had similar chemical structures with cholesterol. In further researches in recent years,more progress has been made in the lipid-lowering mechanisms of phytosterols. In this paper,PubMed and Web of Science were used to review the cholesterol-lowering and triglyceride-lowering mechanisms of phytosterols according to the available data published,so as to use phytosterols more rationally in clinical application to improve hyperlipidemia and other induced diseases.

Run4Love, a mHealth (WeChat-based) intervention to improve mental health of people living with HIV: a randomized controlled trial protocol.

BACKGROUND: People living with HIV (PLWH) suffer from high rates of mental illness; but targeted effective interventions are limited, especially in developing countries. High penetration of smartphone usage and widespread acceptance of social media applications provide an unprecedented opportunity for mobile-based health interventions (mHealth interventions) in resource-limited settings like China. The current report describes the design and sample characteristics of the Run4Love randomized controlled trial (RCT) aimed at improving mental health in PLWH in China. METHODS: A total of 300 PLWH with elevated depressive symptoms were recruited and randomized into either the intervention or control group. Participants in the intervention group received an adapted cognitive-behavioral stress management (CBSM) course delivered by the enhanced WeChat platform (for 3 months) and were motivated to engage in physical activities. Progress of the participants was automatically tracked and monitored with timely feedback and rewards. The control group received a brochure on nutrition for PLWH in addition to standard care. The outcome assessments are conducted at baseline, 3, 6, and 9 months using tablets. The primary outcome is depressive symptoms measured by the scale of the Center for Epidemiology Studies Depression (CES-D). Secondary outcomes include quality of life, chronic stress measured with biomarker of hair cortisol, and other measures of stress and depression, self-efficacy, coping, HIV-related stigma, physical activity, and patient satisfaction. Mixed effects model with repeated measures (MMRM) will be used to analyze the intervention effects. DISCUSSION: The Run4Love study is among the first efforts to develop and evaluate a multicomponent and integrated mHealth intervention to improve the mental health and quality of life of PLWH. Once proven effective, Run4Love could be scaled up and potentially integrated into the routine case management of PLWH and adapted to other populations with chronic diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry - ChiCTR-IPR-17012606 , registered on 07 September 2017.