LncReader: identification of dual functional long noncoding RNAs using a multi-head self-attention mechanism.

Long noncoding ribonucleic acids (RNAs; LncRNAs) endowed with both protein-coding and noncoding functions are referred to as 'dual functional lncRNAs'. Recently, dual functional lncRNAs have been intensively studied and identified as involved in various fundamental cellular processes. However, apart from time-consuming and cell-type-specific experiments, there is virtually no in silico method for predicting the identity of dual functional lncRNAs. Here, we developed a deep-learning model with a multi-head self-attention mechanism, LncReader, to identify dual functional lncRNAs. Our data demonstrated that LncReader showed multiple advantages compared to various classical machine learning methods using benchmark datasets from our previously reported cncRNAdb project. Moreover, to obtain independent in-house datasets for robust testing, mass spectrometry proteomics combined with RNA-seq and Ribo-seq were applied in four leukaemia cell lines, which further confirmed that LncReader achieved the best performance compared to other tools. Therefore, LncReader provides an accurate and practical tool that enables fast dual functional lncRNA identification.

DELFMUT: duplex sequencing-oriented depth estimation model for stable detection of low-frequency mutations.

Duplex sequencing technology has been widely used in the detection of low-frequency mutations in circulating tumor deoxyribonucleic acid (DNA), but how to determine the sequencing depth and other experimental parameters to ensure the stable detection of low-frequency mutations is still an urgent problem to be solved. The mutation detection rules of duplex sequencing constrain not only the number of mutated templates but also the number of mutation-supportive reads corresponding to each forward and reverse strand of the mutated templates. To tackle this problem, we proposed a Depth Estimation model for stable detection of Low-Frequency MUTations in duplex sequencing (DELFMUT), which models the identity correspondence and quantitative relationships between templates and reads using the zero-truncated negative binomial distribution without considering the sequences composed of bases. The results of DELFMUT were verified by real duplex sequencing data. In the case of known mutation frequency and mutation detection rule, DELFMUT can recommend the combinations of DNA input and sequencing depth to guarantee the stable detection of mutations, and it has a great application value in guiding the experimental parameter setting of duplex sequencing technology.

RNALocate v2.0: an updated resource for RNA subcellular localization with increased coverage and annotation.

Resolving the spatial distribution of the transcriptome at a subcellular level can increase our understanding of biology and diseases. To facilitate studies of biological functions and molecular mechanisms in the transcriptome, we updated RNALocate, a resource for RNA subcellular localization analysis that is freely accessible at http://www.rnalocate.org/ or http://www.rna-society.org/rnalocate/. Compared to RNALocate v1.0, the new features in version 2.0 include (i) expansion of the data sources and the coverage of species; (ii) incorporation and integration of RNA-seq datasets containing information about subcellular localization; (iii) addition and reorganization of RNA information (RNA subcellular localization conditions and descriptive figures for method, RNA homology information, RNA interaction and ncRNA disease information) and (iv) three additional prediction tools: DM3Loc, iLoc-lncRNA and iLoc-mRNA. Overall, RNALocate v2.0 provides a comprehensive RNA subcellular localization resource for researchers to deconvolute the highly complex architecture of the cell.

ViRBase v3.0: a virus and host ncRNA-associated interaction repository with increased coverage and annotation.

As a means to aid in the investigation of viral infection mechanisms and identification of more effective antivirus targets, the availability of a source which continually collects and updates information on the virus and host ncRNA-associated interaction resources is essential. Here, we update the ViRBase database to version 3.0 (http://www.virbase.org/ or http://www.rna-society.org/virbase/). This update represents a major revision: (i) the total number of interaction entries is now greater than 820,000, an approximately 70-fold increment, involving 116 virus and 36 host organisms, (ii) it supplements and provides more details on RNA annotations (including RNA editing, RNA localization and RNA modification), ncRNA SNP and ncRNA-drug related information and (iii) it provides two additional tools for predicting binding sites (IntaRNA and PRIdictor), a visual plug-in to display interactions and a website which is optimized for more practical and user-friendly operation. Overall, ViRBase v3.0 provides a more comprehensive resource for virus and host ncRNA-associated interactions enabling researchers a more effective means for investigation of viral infections.

RNAInter v4.0: RNA interactome repository with redefined confidence scoring system and improved accessibility.

Establishing an RNA-associated interaction repository facilitates the system-level understanding of RNA functions. However, as these interactions are distributed throughout various resources, an essential prerequisite for effectively applying these data requires that they are deposited together and annotated with confidence scores. Hence, we have updated the RNA-associated interaction database RNAInter (RNA Interactome Database) to version 4.0, which is freely accessible at http://www.rnainter.org or http://www.rna-society.org/rnainter/. Compared with previous versions, the current RNAInter not only contains an enlarged data set, but also an updated confidence scoring system. The merits of this 4.0 version can be summarized in the following points: (i) a redefined confidence scoring system as achieved by integrating the trust of experimental evidence, the trust of the scientific community and the types of tissues/cells, (ii) a redesigned fully functional database that enables for a more rapid retrieval and browsing of interactions via an upgraded user-friendly interface and (iii) an update of entries to >47 million by manually mining the literature and integrating six database resources with evidence from experimental and computational sources. Overall, RNAInter will provide a more comprehensive and readily accessible RNA interactome platform to investigate the regulatory landscape of cellular RNAs.

RNAPhaSep: a resource of RNAs undergoing phase separation.

Liquid-liquid phase separation (LLPS) partitions cellular contents, underlies the formation of membraneless organelles and plays essential biological roles. To date, most of the research on LLPS has focused on proteins, especially RNA-binding proteins. However, accumulating evidence has demonstrated that RNAs can also function as 'scaffolds' and play essential roles in seeding or nucleating the formation of granules. To better utilize the knowledge dispersed in published literature, we here introduce RNAPhaSep (http://www.rnaphasep.cn), a manually curated database of RNAs undergoing LLPS. It contains 1113 entries with experimentally validated RNA self-assembly or RNA and protein co-involved phase separation events. RNAPhaSep contains various types of information, including RNA information, protein information, phase separation experiment information and integrated annotation from multiple databases. RNAPhaSep provides a valuable resource for exploring the relationship between RNA properties and phase behaviour, and may further enhance our comprehensive understanding of LLPS in cellular functions and human diseases.

Angiotensin-(1-7) ameliorates intestinal barrier dysfunction by activating the Keap1/Nrf2/HO-1 signaling pathway in acute pancreatitis.

BACKGROUND: Intestinal barrier dysfunction is a serious complication associated with acute pancreatitis (AP). Angiotensin (Ang)-(1-7) plays a protective role in the intestinal barrier, but the underlying mechanism remains clear. This study investigated the impact of Ang-(1-7) on AP-induced intestinal dysfunction and its involvement in the Keap1/Nrf2/HO-1 pathway. METHODS AND RESULTS: We studied caerulein- and lipopolysaccharide (LPS)-induced AP in mice and an epithelial cell line (IEC-6) from the small intestinal crypt of rats. Ang-(1-7) was administered orally or via the tail vein. IEC-6 cells were divided into five groups: control; LPS; LPS + Ang-(1-7); LPS + Ang-(1-7) + ML385 (an Nrf2 inhibitor); and LPS + ML385. Pancreatic and intestinal histopathology scores were analyzed using the Schmidt and Chiu scores. The expression of intestinal barrier-associated proteins and Keap1/Nrf2/HO-1 pathway constituents was assessed by RT-PCR and western blotting. The peroxide and antioxidant activities in the IEC-6 cells were measured. Compared to those in AP mice, Ang-(1-7) diminished the intestinal levels of proinflammatory factors (interleukin-1ß and tumor necrosis factor α) and serum levels of intestine permeability (D-lactate). Ang-(1-7) increased the expression of barrier-associated proteins (aquaporin-1, claudin-1, and occludin) compared to those in the AP and LPS group. Moreover, Ang-(1-7) promoted the Keap/Nrf2/HO-1 pathway, which resulted in significantly reduced malondialdehyde and increased superoxide dismutase levels.. However, ML385 abolished the effects of Ang-(1-7) on barrier-associated proteins and reversed the Keap1/Nrf2/HO-1 pathway. CONCLUSIONS: Ang-(1-7) reduces AP-induced intestinal inflammation and oxidative injuries by activating the Keap1/Nrf2/HO-1 pathway.

Performance of HIV Infection Prediction Models in Men Who Have Sex with Men: A Systematic Review and Meta-Analysis.

Effective ways to identify and predict men who have sex with men (MSM) at substantial risk for HIV is a global priority. HIV risk assessment tools can improve individual risk awareness and subsequent health-seeking actions. We sought to identify and characterize the performance of HIV infection risk prediction models in MSM through systematic review and meta-analysis. PubMed, Embase, and The Cochrane Library were searched. Eighteen HIV infection risk assessment models with a total of 151,422 participants and 3643 HIV cases were identified, eight of which have been externally validated by at least one study (HIRI-MSM, Menza Score, SDET Score, Li Model, DHRS, Amsterdam Score, SexPro model, and UMRSS). The number of predictor variables in each model ranged from three to 12, age, the number of male sexual partners, unprotected receptive anal intercourse, recreational drug usage (amphetamines, poppers), and sexually transmitted infections were critical scoring variables. All eight externally validated models performed well in terms of discrimination, with the pooled area under the receiver operating characteristic curve (AUC) ranging from 0.62 (95%CI: 0.51 to 0.73, SDET Score) to 0.83 (95%CI: 0.48 to 0.99, Amsterdam Score). Calibration performance was only reported in 10 studies (35.7%, 10/28). The HIV infection risk prediction models showed moderate-to-good discrimination performance. Validation of prediction models across different geographic and ethnic environments is needed to ensure their real-world application.

MNDR v3.0: mammal ncRNA-disease repository with increased coverage and annotation.

Many studies have indicated that non-coding RNA (ncRNA) dysfunction is closely related to numerous diseases. Recently, accumulated ncRNA-disease associations have made related databases insufficient to meet the demands of biomedical research. The constant updating of ncRNA-disease resources has become essential. Here, we have updated the mammal ncRNA-disease repository (MNDR, http://www.rna-society.org/mndr/) to version 3.0, containing more than one million entries, four-fold increment in data compared to the previous version. Experimental and predicted circRNA-disease associations have been integrated, increasing the number of categories of ncRNAs to five, and the number of mammalian species to 11. Moreover, ncRNA-disease related drug annotations and associations, as well as ncRNA subcellular localizations and interactions, were added. In addition, three ncRNA-disease (miRNA/lncRNA/circRNA) prediction tools were provided, and the website was also optimized, making it more practical and user-friendly. In summary, MNDR v3.0 will be a valuable resource for the investigation of disease mechanisms and clinical treatment strategies.

CellCall: integrating paired ligand-receptor and transcription factor activities for cell-cell communication.

With the dramatic development of single-cell RNA sequencing (scRNA-seq) technologies, the systematic decoding of cell-cell communication has received great research interest. To date, several in-silico methods have been developed, but most of them lack the ability to predict the communication pathways connecting the insides and outsides of cells. Here, we developed CellCall, a toolkit to infer inter- and intracellular communication pathways by integrating paired ligand-receptor and transcription factor (TF) activity. Moreover, CellCall uses an embedded pathway activity analysis method to identify the significantly activated pathways involved in intercellular crosstalk between certain cell types. Additionally, CellCall offers a rich suite of visualization options (Circos plot, Sankey plot, bubble plot, ridge plot, etc.) to present the analysis results. Case studies on scRNA-seq datasets of human testicular cells and the tumor immune microenvironment demonstrated the reliable and unique functionality of CellCall in intercellular communication analysis and internal TF activity exploration, which were further validated experimentally. Comparative analysis of CellCall and other tools indicated that CellCall was more accurate and offered more functions. In summary, CellCall provides a sophisticated and practical tool allowing researchers to decipher intercellular communication and related internal regulatory signals based on scRNA-seq data. CellCall is freely available at https://github.com/ShellyCoder/cellcall.

cncRNAdb: a manually curated resource of experimentally supported RNAs with both protein-coding and noncoding function.

RNA endowed with both protein-coding and noncoding functions is referred to as 'dual-function RNA', 'binary functional RNA (bifunctional RNA)' or 'cncRNA (coding and noncoding RNA)'. Recently, an increasing number of cncRNAs have been identified, including both translated ncRNAs (ncRNAs with coding functions) and untranslated mRNAs (mRNAs with noncoding functions). However, an appropriate database for storing and organizing cncRNAs is still lacking. Here, we developed cncRNAdb, a manually curated database of experimentally supported cncRNAs, which aims to provide a resource for efficient manipulation, browsing and analysis of cncRNAs. The current version of cncRNAdb documents about 2600 manually curated entries of cncRNA functions with experimental evidence, involving more than 2,000 RNAs (including over 1300 translated ncRNAs and over 600 untranslated mRNAs) across over 20 species. In summary, we believe that cncRNAdb will help elucidate the functions and mechanisms of cncRNAs and develop new prediction methods. The database is available at http://www.rna-society.org/cncrnadb/.

Angiotensin-(1-7) promotes mitochondrial translocation of human telomerase reverse transcriptase in HUVECs through the TOM20 complex.

BACKGROUND: Angiotensin (Ang) (1-7) is a vasodilator peptide that ameliorates microcirculation dysfunction, increases telomerase activity in cells, and exerts vasodilatory, anti-inflammatory, antioxidative stress, and antiapoptotic effects. Mitochondrial human telomerase reverse transcriptase (hTERT) plays an important role in the processes of antiapoptosis, antioxidative stress, and immortalization. This study aimed to investigate the effect of Ang(1-7) on the mitochondrial translocation of hTERT. METHODS: An in vitro model of lipopolysaccharide (LPS)-induced inflammation was established in human umbilical vein endothelial cells (HUVECs). Ang(1-7) was added to cells 30 min before LPS stimulation. The Ang(1-7)/Mas receptor antagonist A779 plus Ang(1-7) were added to the cells 30 min before LPS stimulation. The translocase outer membrane (TOM)20-overexpression HUVECs (HUVEC-TOM20OE), TOM20-knockdown HUVECs (HUVEC-TOM20KD), and the corresponding negative control cell lines were constructed by lentiviral transfection of HUVECs. Cells subjected to LPS stimulation alone, LPS plus Ang(1-7), LPS plus Ang(1-7) and A779, vehicle and no treatment were termed the LPS group, LPS + A group, LPS + A + A779 group, Con group and Neg group, respectively. Immunofluorescence staining was used to detect the distribution of hTERT in the nuclei and mitochondria of HUVECs and to locate TOM20, TOM40, and translocase inner membrane (TIM)23 in the mitochondria. The protein expression levels of total hTERT, mitochondrial hTERT, TOM20, TOM40, and TIM23 were measured by Western blot. The mRNA expression levels of hTERT, TOM20, TOM40, and TIM23 were assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: hTERT colocalized with TOM40, TOM20 and TIM23 in the mitochondria. The mitochondrial hTERT protein level of the LPS + A group was significantly greater than that of the LPS group (P = 0.001), and the LPS group showed significantly increased expression of mitochondrial hTERT compared with that of the control group (P = 0.001). No significant difference in the level of total hTERT was observed between the LPS + A and LPS groups. The mitochondrial hTERT protein level of the LPS + A + A779 group was significantly lower than that of the LPS + A group (P = 0.021). The protein level of mitochondrial hTERT in HUVEC-TOM20KD treated with or without LPS alone or LPS + A was significantly decreased compared with the corresponding groups of control HUVECs (HUVEC-TOM20KD-Con vs. HUVEC-Con, P = 0.035; HUVEC-TOM20KD-LPS vs. HUVEC-LPS, P = 0.003; HUVEC-TOM20KD-LPS + A vs. HUVEC-LPS + A, P = 0.001), and treatment with Ang(1-7) did not restore the downregulation of mitochondrial hTERT in HUVEC-TOM20KD. HUVEC-TOM20OE showed a significantly increased level of mitochondrial hTERT (HUVEC-TOM20OE-Con vs. HUVEC-Con, P = 0.010), which was further elevated by Ang(1-7) stimulation (HUVEC-TOM20OE-LPS + A vs. HUVEC-TOM20OE-Con, P = 0.011). Lastly, the protein expression levels of TOM40 (HUVEC-TOM20KD-Con vs. HUVEC-Con, P = 0.007) and TIM23 (HUVEC-TOM20KD-Con vs. HUVEC-Con, P = 0.001) were significantly increased in HUVEC-TOM20KD in comparison to HUVECs. CONCLUSIONS: Ang(1-7) effectively promoted mitochondrial translocation of hTERT in HUVECs via TOM20, indicating that hTERT may be transported to the mitochondria through the TOM20 complex. In addition, A779 could block the effects of Ang(1-7) in HUVECs.

Dual Responsive Molecular-Arm Modified Single Enzyme Molecules for Efficient Cellulose Hydrolysis.

Immobilizing cellulase for improving its hydrolysis activity and recyclability is critical for a cost-effective and environment-friendly conversion of cellulosic biomass. However, developing a strategy for achieving a high mass-transfer rate and good separation efficiency between an insoluble cellulose substrate and cellulase remains difficult. Instead of the traditional method, a single-enzyme molecular modification method is used in this study. To modify cellulase and provide it with a temperature-pH dual responsive property, systemized poly(acrylic-acrylonitrile) (PAA-PAN) molecular arms are used. The modified cellulase can reversibly transform between liquid and solid phases. In the liquid phase, the modified cellulase can adjust its active center, increasing its hydrolysis efficiency and separation efficiency. Cellulase and glucose products can be easily separated in the solid phase, allowing the reuse of cellulase. The results show that the modified cellulase's hydrolysis efficiency is comparable to that of free cellulase and that the modified enzyme preserves more than 60% of its initial activity after 15 batches of efficient hydrolysis. Thus, the proposed modification route considerably lowers the cost of cellulose enzymatic hydrolysis.

RNAInter in 2020: RNA interactome repository with increased coverage and annotation.

Research on RNA-associated interactions has exploded in recent years, and increasing numbers of studies are not limited to RNA-RNA and RNA-protein interactions but also include RNA-DNA/compound interactions. To facilitate the development of the interactome and promote understanding of the biological functions and molecular mechanisms of RNA, we updated RAID v2.0 to RNAInter (RNA Interactome Database), a repository for RNA-associated interactions that is freely accessible at http://www.rna-society.org/rnainter/ or http://www.rna-society.org/raid/. Compared to RAID v2.0, new features in RNAInter include (i) 8-fold more interaction data and 94 additional species; (ii) more definite annotations organized, including RNA editing/localization/modification/structure and homology interaction; (iii) advanced functions including fuzzy/batch search, interaction network and RNA dynamic expression and (iv) four embedded RNA interactome tools: RIscoper, IntaRNA, PRIdictor and DeepBind. Consequently, RNAInter contains >41 million RNA-associated interaction entries, involving more than 450 thousand unique molecules, including RNA, protein, DNA and compound. Overall, RNAInter provides a comprehensive RNA interactome resource for researchers and paves the way to investigate the regulatory landscape of cellular RNAs.

Revealing spatiotemporal interaction patterns behind complex cities.

Cities are typical dynamic complex systems that connect people and facilitate interactions. Revealing general collective patterns behind spatiotemporal interactions between residents is crucial for various urban studies, of which we are still lacking a comprehensive understanding. Massive cellphone data enable us to construct interaction networks based on spatiotemporal co-occurrence of individuals. The rank-size distributions of dynamic population of locations in all unit time windows are stable, although people are almost constantly moving in cities and hot-spots that attract people are changing over time in a day. A larger city is of a stronger heterogeneity as indicated by a larger scaling exponent. After aggregating spatiotemporal interaction networks over consecutive time windows, we reveal a switching behavior of cities between two states. During the "active" state, the whole city is concentrated in fewer larger communities, while in the "inactive" state, people are scattered in smaller communities. Above discoveries are universal over three cities across continents. In addition, a city stays in an active state for a longer time when its population grows larger. Spatiotemporal interaction segregation can be well approximated by residential patterns only in smaller cities. In addition, we propose a temporal-population-weighted-opportunity model by integrating a time-dependent departure probability to make dynamic predictions on human mobility, which can reasonably well explain the observed patterns of spatiotemporal interactions in cities.

PtS2 nanosheets as a peroxidase-mimicking nanozyme for colorimetric determination of hydrogen peroxide and glucose.

Using an ultrasonication-assisted liquid exfoliation method, we have synthesized PtS2 nanosheets with good reproducibility. Herein, intrinsic peroxidase-like activity was for the first time demonstrated for PtS2 nanosheets, which can catalyze H2O2 oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to generate a colored solution. The catalytic mechanism of PtS2 nanosheets was investigated, which indicated that acceleration of the electron transfer between TMB and H2O2 was the main reason for the peroxidase-like activity of PtS2 nanosheets. Based on these observations, we exploited PtS2 nanosheets integrated into dopamine-functionalized hyaluronic acid (HA-DA) hydrogel microspheres by droplet microfluidics to construct PtS2 nanosheet- and PtS2@HA-DA microsphere-based sensors for highly sensitive determination of H2O2. When coupled with glucose oxidase, we further developed two glucose sensors based on the above two methods. Among them, the linearity of the PtS2 nanosheet-based spectrophotometry was in the range of 0.5 to 150 µM and the limit of detection as low as 0.20 µM. The linearity of the microsphere-based colorimetry was in the range 200 to 12,000 µM with a detection limit of 29.95 µM. Both of the glucose sensors can be applied to the determination of glucose in human serum with reliable results and reproducibility.

MNDR v2.0: an updated resource of ncRNA-disease associations in mammals.

Accumulating evidence suggests that diverse non-coding RNAs (ncRNAs) are involved in the progression of a wide variety of diseases. In recent years, abundant ncRNA-disease associations have been found and predicted according to experiments and prediction algorithms. Diverse ncRNA-disease associations are scattered over many resources and mammals, whereas a global view of diverse ncRNA-disease associations is not available for any mammals. Hence, we have updated the MNDR v2.0 database (www.rna-society.org/mndr/) by integrating experimental and prediction associations from manual literature curation and other resources under one common framework. The new developments in MNDR v2.0 include (i) an over 220-fold increase in ncRNA-disease associations enhancement compared with the previous version (including lncRNA, miRNA, piRNA, snoRNA and more than 1400 diseases); (ii) integrating experimental and prediction evidence from 14 resources and prediction algorithms for each ncRNA-disease association; (iii) mapping disease names to the Disease Ontology and Medical Subject Headings (MeSH); (iv) providing a confidence score for each ncRNA-disease association and (v) an increase of species coverage to six mammals. Finally, MNDR v2.0 intends to provide the scientific community with a resource for efficient browsing and extraction of the associations between diverse ncRNAs and diseases, including >260 000 ncRNA-disease associations.

PEG-PtS2 nanosheet-based fluorescence biosensor for label-free human papillomavirus genotyping.

A simple and efficient ultrasonication-assisted liquid exfoliation method is proposed to produce PtS2 nanosheets on a large scale and improve their dispersion in aqueous solution by surface polyethylene glycol modification. The interaction of polyethylene glycol-modified PtS2 (PEG-PtS2) nanosheets with fluorescent labeled DNA and the fluorescence quenching mechanism using FAM-labeled hpv16e6 gene fragment as a probe was investigated. The excitation and emission wavelengths were 468 and 517 nm, respectively. The fluorescence quenching mechanism of PEG-PtS2 nanosheets for double-stranded DNA (dsDNA) might stem from the static quenching effect. Based on the difference in fluorescence quenching capability of PEG-PtS2 nanosheets in fluorescent probe tagged single-stranded DNA (ssDNA) and dsDNA, a mix-and-detect method was proposed for determination of DNA. Without the need for probe immobilization and tedious washing steps, the genotyping of human papillomavirus (HPV) was easily achieved. The limit of detection was calculated to 0.44 nM, showing a good linear range within 0.05-10 nM. We believe this biosensor provides opportunities to develop a simple and low-cost strategy for molecular diagnostics. Graphical abstract.

RAID v2.0: an updated resource of RNA-associated interactions across organisms.

With the development of biotechnologies and computational prediction algorithms, the number of experimental and computational prediction RNA-associated interactions has grown rapidly in recent years. However, diverse RNA-associated interactions are scattered over a wide variety of resources and organisms, whereas a fully comprehensive view of diverse RNA-associated interactions is still not available for any species. Hence, we have updated the RAID database to version 2.0 (RAID v2.0, www.rna-society.org/raid/) by integrating experimental and computational prediction interactions from manually reading literature and other database resources under one common framework. The new developments in RAID v2.0 include (i) over 850-fold RNA-associated interactions, an enhancement compared to the previous version; (ii) numerous resources integrated with experimental or computational prediction evidence for each RNA-associated interaction; (iii) a reliability assessment for each RNA-associated interaction based on an integrative confidence score; and (iv) an increase of species coverage to 60. Consequently, RAID v2.0 recruits more than 5.27 million RNA-associated interactions, including more than 4 million RNA-RNA interactions and more than 1.2 million RNA-protein interactions, referring to nearly 130 000 RNA/protein symbols across 60 species.

mHealth-Based Gamification Interventions Among Men Who Have Sex With Men in the HIV Prevention and Care Continuum: Systematic Review and Meta-Analysis.

Background: In the past few years, a burgeoning interest has emerged in applying gamification to promote desired health behaviors. However, little is known about the effectiveness of such applications in the HIV prevention and care continuum among men who have sex with men (MSM). Objective: This study aims to summarize and evaluate research on the effectiveness of gamification on the HIV prevention and care continuum, including HIV-testing promotion; condomless anal sex (CAS) reduction; and uptake of and adherence to pre-exposure prophylaxis (PrEP), postexposure prophylaxis (PEP), and antiretroviral therapy (ART). Methods: We comprehensively searched PubMed, Embase, the Cochrane Library, Web of Science, Scopus, and the Journal of Medical Internet Research and its sister journals for studies published in English and Chinese from inception to January 2024. Eligible studies were included when they used gamified interventions with an active or inactive control group and assessed at least one of the following outcomes: HIV testing; CAS; and uptake of and adherence to PrEP, PEP, and ART. During the meta-analysis, a random-effects model was applied. Two reviewers independently assessed the quality and risk of bias of each included study. Results: The systematic review identified 26 studies, including 10 randomized controlled trials (RCTs). The results indicated that gamified digital interventions had been applied to various HIV outcomes, such as HIV testing, CAS, PrEP uptake and adherence, PEP uptake, and ART adherence. Most of the studies were conducted in the United States (n=19, 73%). The most frequently used game component was gaining points, followed by challenges. The meta-analysis showed gamification interventions could reduce the number of CAS acts at the 3-month follow-up (n=2 RCTs; incidence rate ratio 0.62, 95% CI 0.44-0.88). The meta-analysis also suggested an effective but nonstatistically significant effect of PrEP adherence at the 3-month follow-up (n=3 RCTs; risk ratio 1.16, 95% CI 0.96-1.38) and 6-month follow-up (n=4 RCTs; risk ratio 1.28, 95% CI 0.89-1.84). Only 1 pilot RCT was designed to evaluate the effectiveness of a gamified app in promoting HIV testing and PrEP uptake. No RCT was conducted to evaluate the effect of the gamified digital intervention on PEP uptake and adherence, and ART initiation among MSM. Conclusions: Our findings suggest the short-term effect of gamified digital interventions on lowering the number of CAS acts in MSM. Further well-powered studies are still needed to evaluate the effect of the gamified digital intervention on HIV testing, PrEP uptake, PEP initiation and adherence, and ART initiation in MSM.