Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Interferon stimulating factor STING, a transmembrane protein residing in the endoplasmic reticulum, is extensively involved in the sensing and transduction of intracellular signals and serves as a crucial component of the innate immune system. STING is capable of directly or indirectly responding to abnormal DNA originating from diverse sources within the cytoplasm, thereby fulfilling its classical antiviral and antitumor functions. Structurally, STING is composed of 4 transmembrane helices, a cytoplasmic ligand binding domain (LBD), and a C terminal tail structure (CTT). The transmembrane domain (TM), which is formed by the transmembrane helical structures, anchors STING to the endoplasmic reticulum, while the LBD is in charge of binding to cyclic dinucleotides (CDNs). The classical second messenger, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), represents a key upstream molecule for STING activation. Once cGAMP binds to LBD, STING experiences conformational alterations, which subsequently lead to the recruitment of Tank-binding kinase 1 (TBK1) via the CTT domain. This, in turn, mediates interferon secretion and promotes the activation and migration of dendritic cells, T cells, and natural killer cells. Additionally, STING is able to activate nuclear factor-κB (NF-κB), thereby initiating the synthesis and release of inflammatory factors and augmenting the body’s immune response. In recent years, an increasing number of studies have disclosed the non-classical functions of STING. It has been found that STING plays a significant role in organelle regulation. STING is not only implicated in the quality control systems of organelles such as mitochondria and endoplasmic reticulum but also modulates the functions of these organelles. For instance, STING can influence key aspects of organelle quality control, including mitochondrial fission and fusion, mitophagy, and endoplasmic reticulum stress. This regulatory effect is not unidirectional; rather, it is subject to organelle feedback regulation, thereby forming a complex interaction network. STING also exerts a monitoring function on the nucleus and ribosomes, which further enhances the role of the cGAS-STING pathway in infection-related immunity. The interaction mechanism between STING and organelles is highly intricate, which, within a certain range, enhances the cells’ capacity to respond to external stimuli and survival pressure. However, once the balance of this interaction is disrupted, it may result in the occurrence and development of inflammatory diseases, such as aseptic inflammation and autoimmune diseases. Excessive activation or malfunction of STING may trigger an over-exuberant inflammatory response, which subsequently leads to tissue damage and pathological states. This review recapitulates the recent interactions between STING and diverse organelles, encompassing its multifarious functions in antiviral, antitumor, organelle regulation, and immune regulation. These investigations not only deepen the comprehension of molecular mechanisms underlying STING but also offer novel concepts for the exploration of human disease pathogenesis and the development of potential treatment strategies. In the future, with further probing into STING function and its regulatory mechanisms, it is anticipated to pioneer new approaches for the treatment of complex diseases such as inflammatory diseases and tumors.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Purpose: This study evaluated a school-based mental health program within a psychiatry clerkship to enhance medical students’ competencies in mental health literacy, empathy, communication, and adaptability. The program aimed to bridge theoretical knowledge with practical skills through experiential learning in a real-world, community-based setting. Methods: The study utilized convenience sampling to select 32 medical students from the 2023–2024 psychiatry clerkship cohort. Four focus group discussions, each lasting 60–90 minutes, provided qualitative data, which were analyzed using reflexive thematic analysis in Atlas.ti (ATLAS.ti GmbH, Germany) to identify themes related to professional development. Results: Five key themes emerged, highlighting significant gains in context-sensitive communication, empathy, and mental health literacy specific to adolescent issues. The students reported increased clinical confidence, enhanced resilience through psychological techniques such mindfulness and motivational interviewing, and benefited from sustained engagement and peer support, fostering collaboration and stress management. Conclusion The school-based mental health program enhanced essential competencies in mental health literacy, empathy, communication, and practical skills for medical students. By integrating experiential learning into medical education, the program addressed training gaps, equipping future healthcare providers with the skills necessary for holistic and patient-centered mental healthcare across diverse clinical settings. The approach showed potential for broader applications in medical education to prepare students for comprehensive mental health support skills.

Purpose: This study evaluated a school-based mental health program within a psychiatry clerkship to enhance medical students’ competencies in mental health literacy, empathy, communication, and adaptability. The program aimed to bridge theoretical knowledge with practical skills through experiential learning in a real-world, community-based setting. Methods: The study utilized convenience sampling to select 32 medical students from the 2023–2024 psychiatry clerkship cohort. Four focus group discussions, each lasting 60–90 minutes, provided qualitative data, which were analyzed using reflexive thematic analysis in Atlas.ti (ATLAS.ti GmbH, Germany) to identify themes related to professional development. Results: Five key themes emerged, highlighting significant gains in context-sensitive communication, empathy, and mental health literacy specific to adolescent issues. The students reported increased clinical confidence, enhanced resilience through psychological techniques such mindfulness and motivational interviewing, and benefited from sustained engagement and peer support, fostering collaboration and stress management. Conclusion The school-based mental health program enhanced essential competencies in mental health literacy, empathy, communication, and practical skills for medical students. By integrating experiential learning into medical education, the program addressed training gaps, equipping future healthcare providers with the skills necessary for holistic and patient-centered mental healthcare across diverse clinical settings. The approach showed potential for broader applications in medical education to prepare students for comprehensive mental health support skills.

Purpose: This study evaluated a school-based mental health program within a psychiatry clerkship to enhance medical students’ competencies in mental health literacy, empathy, communication, and adaptability. The program aimed to bridge theoretical knowledge with practical skills through experiential learning in a real-world, community-based setting. Methods: The study utilized convenience sampling to select 32 medical students from the 2023–2024 psychiatry clerkship cohort. Four focus group discussions, each lasting 60–90 minutes, provided qualitative data, which were analyzed using reflexive thematic analysis in Atlas.ti (ATLAS.ti GmbH, Germany) to identify themes related to professional development. Results: Five key themes emerged, highlighting significant gains in context-sensitive communication, empathy, and mental health literacy specific to adolescent issues. The students reported increased clinical confidence, enhanced resilience through psychological techniques such mindfulness and motivational interviewing, and benefited from sustained engagement and peer support, fostering collaboration and stress management. Conclusion The school-based mental health program enhanced essential competencies in mental health literacy, empathy, communication, and practical skills for medical students. By integrating experiential learning into medical education, the program addressed training gaps, equipping future healthcare providers with the skills necessary for holistic and patient-centered mental healthcare across diverse clinical settings. The approach showed potential for broader applications in medical education to prepare students for comprehensive mental health support skills.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Purpose: This study evaluated a school-based mental health program within a psychiatry clerkship to enhance medical students’ competencies in mental health literacy, empathy, communication, and adaptability. The program aimed to bridge theoretical knowledge with practical skills through experiential learning in a real-world, community-based setting. Methods: The study utilized convenience sampling to select 32 medical students from the 2023–2024 psychiatry clerkship cohort. Four focus group discussions, each lasting 60–90 minutes, provided qualitative data, which were analyzed using reflexive thematic analysis in Atlas.ti (ATLAS.ti GmbH, Germany) to identify themes related to professional development. Results: Five key themes emerged, highlighting significant gains in context-sensitive communication, empathy, and mental health literacy specific to adolescent issues. The students reported increased clinical confidence, enhanced resilience through psychological techniques such mindfulness and motivational interviewing, and benefited from sustained engagement and peer support, fostering collaboration and stress management. Conclusion The school-based mental health program enhanced essential competencies in mental health literacy, empathy, communication, and practical skills for medical students. By integrating experiential learning into medical education, the program addressed training gaps, equipping future healthcare providers with the skills necessary for holistic and patient-centered mental healthcare across diverse clinical settings. The approach showed potential for broader applications in medical education to prepare students for comprehensive mental health support skills.

Objective To investigate the peripheral blood cytokine levels in patients with acute myocardial infarction(AMI),and to analyze its correlation with Killip classification,N-terminal brain natriuretic peptide precursor(NT-proBNP),cardiac troponin I(cTnI),creatine kinase isoenzymes(CK-MB),and to provide a theoretical basis for assessing the severity and prognosis of the disease.Methods A total of 312 patients with AMI admitted to Minhang Hospital,Fudan University from Jul 2021 to Oct 2023 were enrolled as the case group,and 201 patients with unstable angina pectoris were selected as the control group.General clinical data of the subjects were collected,and the concentrations of cytokines(IL-5,IFN-α,IFN-γ,IL-10,IL-12p70,IL-17,IL-1β,IL-2,IL-4,IL-6,IL-8,and TNF-α)in peripheral blood were detected by multiplex bead-based flow cytometry.NT-proBNP,cTnI and CK-MB were measured by chemiluminescence methods.The levels of cytokines between the two groups were compared,and their correlations with Killip classification,NT-proBNP,cTnI and CK-MB were analyzed.The predictive efficacy of cytokines for AMI was evaluated by receiver operating characteristic(ROC)curves.Results There were no significant differences in baseline data between the AMI group and the control group(P>0.05),with the exception of age.The levels of IL-6,IL-8 and TNF-α in the AMI group were higher than those in the control group(all P<0.01).The correlation analyses showed that IL-6 was positively correlated with Killip classification,NT-proBNP,cTnI and CK-MB(all P<0.01).ROC analyses showed that IL-6 levels had good predictive efficacy for AMI(AUC=0.882 9,P<0.01).Conclusion The expression of IL-6 was significantly increased in patients with AMI,and it was positively correlated with Killip classification,NT-proBNP,cTnI and CK-MB,suggesting that IL-6 may serve as a potential biomarker for assessing the severity of AMI.