Tumor microenvironment (TME)‐triggered phototheranostic platform offers a feasible strategy to improve cancer diagnosis accuracy and minimize treatment side effects. Developing a stable and biocompatible molecular phototheranostic platform for TME‐activated second near‐infrared (NIR‐II) fluorescence imaging‐guided multimodal cascade therapy is a promising strategy for creating desirable anticancer agents. Herein, a new NIR‐II fluorescence imaging‐guided activatable molecular phototheranostic platform (IR‐FEP‐RGD‐S‐S‐S‐Fc) is presented for actively targeted tumor imaging and hydrogen sulfide (H₂S) gas‐enhanced chemodynamic‐hypothermal photothermal combined therapy (CDT/HPTT). It is revealed for the first time that the coupling distance between IR‐FE and ferrocene is proportional to the photoinduced electron transfer (PET), and the aqueous environment is favorable for PET generation. The part of Cyclic‐RGDfK (cRGDfk) peptides can target the tumor and benefit the endocytosis of nanoparticles. The high‐concentration glutathione (GSH) in the TME will separate the fluorescence molecule and ferrocene by the GSH‐sensitive trisulfide bond, realizing light‐up NIR‐II fluorescence imaging and a cascade of trimodal synergistic CDT/HPTT/gas therapy (GT). In addition, the accumulation of hydroxyl radicals (•OH) and down‐regulation of glutathione peroxidase 4 (GPX4) can produce excessive harmful lipid hydroperoxides, ultimately leading to ferroptosis.

Mitochondria are not only the power plant for intracellular oxidative phosphorylation and ATP synthesis, but also involved in cell proliferation, differentiation, signaling and apoptosis. Recent studies have shown that mitochondria play an important role in other pathophysiological functions in addition to cellular energy metabolism. Mitochondria release mitochondrial DNA (mtDNA) as a damage-associated molecular pattern (DAMP) to activate Toll-like receptor 9 (TLR9), NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) innate immune signaling pathways against foreign pathogenic microorganisms. The innate immune response not only promotes antimicrobial immune defense and regulates antiviral signaling, but their overactivation also induces the onset and progression of inflammatory diseases. In this paper, we review the role of mtDNA in the activation of innate immune signaling pathways and the crosstalk among innate immune signaling pathways activated by mtDNA, providing clues for the study of inflammatory diseases caused by mtDNA cytoplasmic translocation.

Malignant tumors have been a serious threat to human health with their increasing incidence. Difficulties with conventional treatments are toxicity, drug resistance, and recurrence. For this reason, non-invasive treatment modalities such as photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), and others have received much attention. Among them, Ferrocene (Fc)-based nanomedicines for enhanced Chemodynamic Therapy (ECDT) is a new therapeutic strategy based on the Fenton reaction. Based on ferrocene's good biocompatibility, potentiation in medicinal chemistry, and good stability of divalent iron ions, scientists are increasingly using it as a Fenton's iron donor for tumor therapy. Such ferrocene-based ECDT nanoplatforms have shown remarkable promise for clinical applications and have significantly increased the efficacy of CDT treatment. Ferrocene-based nanomedicines exhibit exceptional consistency owing to their low toxicity, high stability, enhanced bioavailability, and a multitude of advantages over conventional approaches to cancer treatment. As a consequence, a number of tactics have been investigated in recent years to raise the effectiveness of ferrocene-based ECDT. In this review, we detail the different forms and strategies used to enhance Ferrocene-based ECDT efficiency.

Sarcopenia refers to the decline in skeletal muscle mass and function. Due to its increased mortality rate and severe disability, the clinical importance of sarcopenia is becoming increasingly prominent. Although the exact cause of sarcopenia is not fully understood, the gut microbiota (GM) plays a crucial role in the pathogenesis of sarcopenia, and increasing evidence suggests that gut dysbiosis may be associated with disease development. In the past few decades, the use of probiotics has surged, few studies have explored their impact on sarcopenia prevention and treatment. Lactobacillus probiotics are commonly used for gut health and immune support, but their mechanism in sarcopenia via the gut-muscle axis remains uncertain. This review highlights the treatment challenges, GM’s role in sarcopenia, and the potential of Lactobacillus as an adjunct therapy. In addition, we also discuss the possible mechanisms by which Lactobacillus affect muscle function, such as alleviating inflammatory states, clearing excessive reactive oxygen species (ROS), improving skeletal muscle metabolism, enhancing intestinal barrier function and modulating the gut microbiota and its metabolites. These mechanisms may collectively contribute to the preservation of muscle mass and function, offering a promising avenue for advancing microbial therapies for sarcopenia.

T cell receptors (TCRs) that recognize cancer neoantigens are important for anticancer immune responses and immunotherapy. Understanding the structural basis of TCR recognition of neoantigens provides insights into their exquisite specificity and can enable design of optimized TCRs. We determined crystal structures of a human TCR in complex with NRAS Q61K and Q61R neoantigen peptides and HLA-A1 major histocompatibility complex (MHC), revealing the molecular underpinnings for dual recognition and specificity versus wild-type NRAS peptide. We then used multiple versions of AlphaFold to model the corresponding complex structures, given the challenge of immune recognition for such methods. One implementation of AlphaFold2 (TCRmodel2) with additional sampling was able to generate accurate models of the complexes, while AlphaFold3 also showed strong performance, although success was lower for other complexes. This study provides insights into TCR recognition of a shared cancer neoantigen as well as the utility and practical considerations for using AlphaFold to model TCR-peptide-MHC complexes.

Background: In China, condomless sex among men who have sex with men (MSM) is the primary route of HIV infection in young people. Chengdu is a hotspot for reported HIV cases among young people nationwide. Extensive use of geosocial networking (GSN) smartphone apps has dramatically changed the pattern of sexual behavior among young MSM (YMSM). However, data on HIV incidence and the risk behavior of YMSM using the GSN app are still obscure. Objective: This study aims to analyze and understand the HIV incidence and its risk factors among YMSM using GSN apps in Chengdu, China. Methods: An open cohort study was conducted among YMSM aged 18-24 years through a gay GSN smartphone app in Chengdu, China, from July 2018 to December 2020. Every participant completed a web-based questionnaire on sociodemographic characteristics, sexual behaviors, and other related statuses; made a reservation for a web-based HIV testing; and then voluntarily got tested at the designated testing site. At least one additional HIV test was taken via the app during the study period, and participants were evaluated at the end of the study or at the time of HIV seroconversion. By dividing the sum of the observed HIV seroconversions by the observed person-years, HIV incidence was calculated and compared between the student and nonstudent MSM. Univariate and multivariate (Cox proportional hazards regression) analyses were used to discuss the risk factors for new HIV infections. Results: In the study cohort, 24 seroconversions occurred among 625 YMSM who took at least two HIV tests through the app during the study period, contributing to 505 observed person-years. The HIV incidence rate per 100 person-years was 4.75 (95% CI 2.89-6.61) among all MSM, 3.60 (95% CI 1.27-5.93) among student MSM, and 5.88 (95% CI 2.97-8.79) among nonstudent MSM. In addition, the HIV incidence per 100 person-years was 11.11 (95% CI 4.49-17.73) among those who had resided in the area for 6 months or less and 7.14 (95% CI 1.52-12.77) among those with senior high school or less education. Two or more sexual partners (adjusted hazards ratio [HR] 3.63, 95% CI 1.08-12.23) in the preceding 6 months was a risk factor for new HIV infections. Consistent condom use for anal sex (adjusted HR 0.38, 95% CI 0.16-0.88) and insertive anal sex only (adjusted HR 0.10, 95% CI 0.01-0.75) in the preceding 6 months were protective factors for new HIV infections. Conclusions: The rate of new HIV infections among YMSM who actively used GSN smartphone apps was high, especially among migrant nonstudent MSM. Targeted interventions on GSN smartphone apps should be implemented to provide demand-adapted prevention and services to reduce the threat of HIV.