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Distinct multi-omics signatures of clinical subgroups of type 2 diabetes define heterogeneous responses to an insulin sensitizer

Nat Commun. 2026 Aug 29;17(1):10311. doi: 10.1038/s41467-026-77187-8.

ABSTRACT

Type 2 diabetes (T2D) subgroups defined by clinical variables differ in disease progression and treatment response. To uncover potential molecular drivers of this heterogeneity, we performed a multi-omics analysis of 826 drug-naïve T2D patients from two phase 3 trials of the insulin sensitizer chiglitazar. Here we show that severe insulin-resistant diabetes (SIRD) is characterized by distinct miRNA profiles (e.g., miR-122-5p) correlated with liver injury, and metabolic shifts in amino acids and primary bile acids. Mild obesity-related diabetes (MOD) showed the lowest level of phenylacetylglutamine, a metabolite known to promote cardiovascular disease. Severe insulin-deficient diabetes (SIDD) exhibited high pancreas-specific miR-7-5p, while mild age-related diabetes (MARD) presented the mildest abnormalities. Finally, integrating these multi-omics signatures into machine learning models enhanced prediction of insulin sensitizer efficacy over clinical data alone. Our findings define the distinct molecular signatures of T2D subgroups, facilitating the prediction of heterogeneous treatment responses and supporting personalized clinical management.

PMID:42805981 | PMC:PMC13620142 | DOI:10.1038/s41467-026-77187-8

Digitally Adapting LGBTQ-Affirmative Cognitive Behavioral Therapy for Chinese Men Who Have Sex With Men Living With HIV: User-Centered Design Approach

Background: Chinese men who have sex with men living with HIV (MSMLWH) experience substantial psychological distress driven by minority stress and HIV-related challenges. However, culturally tailored digital mental health interventions that address HIV-specific maladaptive cognitive schemas and culturally specific psychosocial stressors remain scarce in China. Objective: This study aimed to systematically adapt an evidence-based cognitive behavioral therapy (CBT) intervention Effective Skills to Empower Effective Men (ESTEEM) into a WeChat (Tencent) Mini-Program–based intervention (iESTEEM) specifically for Chinese MSMLWH and to evaluate its preliminary feasibility and usability. Methods: We used a three-phase user-centered design approach guided by the Assessment, Decision, Adaptation, Production, Topical Experts, Integration, Training, and Testing (ADAPT-ITT) framework. The study proceeded in three phases: (1) a qualitative needs assessment using semistructured interviews with 20 MSMLWH (mean age 23.25, SD 3.08 years); (2) systematic intervention adaptation and platform development, including theater testing (n=5); and (3) a 2-week pilot study involving 10 MSMLWH and five counselors to evaluate feasibility, usability, and acceptability through focus groups and objective platform analytics. Results: Phase 1 identified 3 major themes of psychological distress: persistent health anxiety fueled by catastrophizing, intersectional stigma internalization, the disclosure dilemma, and intimacy barriers rooted in defectiveness and shame schemas. Participants also prioritized anonymity and bite-sized learning. Guided by these findings, iESTEEM was developed as a counselor-assisted, privacy-preserving WeChat Mini-Program incorporating HIV-specific scenarios, multimodal learning modules, and a back-end risk-alert system. During the 2-week pilot, participants logged into the platform 14.1 (SD 6.7) times per person and completed 134.3 (SD 103.1) minutes of learning activities; all participants accessed module 1, and 90% (9/10) accessed modules 2‐5. Anxiety scores decreased from 8.9 (SD 2.3) to 7.2 (SD 3.0), whereas depression scores remained stable. All participants expressed a willingness to continue using the program and to recommend it to peers. Participants and counselors endorsed its contextual relevance, privacy protections, and clinical utility. Conclusions: This study provides a theory- and evidence-informed model for culturally adapting digital mental health interventions for highly stigmatized populations. By integrating lesbian, gay, bisexual, transgender, and queer (LGBTQ)-affirmative CBT principles, HIV-specific adaptations, and a privacy-preserving, counselor-assisted WeChat Mini-Program, iESTEEM demonstrated promising preliminary feasibility, acceptability, and engagement among Chinese MSMLWH. These findings support the potential of culturally tailored digital interventions to expand access to psychological support for this stigmatized population in resource-constrained settings. Ongoing randomized controlled trials will further evaluate its efficacy, implementation outcomes, and mechanism of action. Trial Registration: Chinese Clinical Trial Registry ChiCTR2400080263; https://www.chictr.org.cn/showproj.html?proj=216926

LINC-AC092535.5 regulates MICAL2 mRNA level to inhibit p53-mediated ferroptosis in nasopharyngeal carcinoma

Oncogene, Published online: 14 March 2026; doi:10.1038/s41388-026-03714-y

LINC-AC092535.5 regulates MICAL2 mRNA level to inhibit p53-mediated ferroptosis in nasopharyngeal carcinoma
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