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Dynamic regulation of nanoparticles in a controllable manner has great potential in various areas. Compared to the individual nanoparticles, the assembled nanoparticles exhibit superior properties and functions, which can be applied to achieve desirable performances. Here, a pH‐responsive i‐motif DNA‐mediated strategy to tailor the programmable behaviors of erbium‐based rare‐earth nanoparticles (ErNPs) decorated copper doped metal‐organic framework (CPM) nanohybrids (ECPM) under physiological conditions is reported. Within the acidic tumor microenvironment, the i‐motif DNA strands are able to form quadruplex structures, resulting in the assembly of nanohybrids and selective tumor accumulation, which further amplify the ErNPs downconversion emission (1550 nm) signal for imaging. Meanwhile, the ECPM matrix acts as a near‐infrared (NIR) photon‐activated reactive oxygen species (ROS) amplifier through the singlet oxygen generation of the matrix in combination with its ability of intracellular glutathione depletion upon irradiation. In short, this work displays a classical example of engineering of nanoparticles, which will manifest the importance of developing nanohybrids with structural programmability in biomedical applications. “Unity makes strength,” the smart use of MOF‐based nanohybrid (ECPM) for depleting the intracellular GSH and thus increasing the delivery efficiency of the ECPM is reported. The unique acidity‐responsive assembly of ECPM enables in situ clustering of the nanohybrid in the acidic tumor microenvironment (TME), which can achieve NIR‐activated tumor‐specific cancer theranostics with negligible side effects.

Stimuli‐responsive nanomaterials offer significant potential for enhancing diagnostic accuracy, optimizing therapeutic efficacy, and advancing precision theranostics. Hydrogen sulfide (H2S) was found to be upregulated in colorectal cancer, which endows it with an ideal endogenous trigger for tumor targeting. Here, we introduce a novel class of H2S‐activated metal‐organic framework (MOF) systems specifically designed for targeted colorectal cancer imaging and synergistic copper‐induced tumor regression. The Cu‐MOF nanoplatform demonstrated a rapid response to H2S at the tumor site, producing copper sulfide with strong near infrared absorption and activated PA signals. In vivo studies demonstrated remarkable tumor inhibition in an orthotopic colon cancer model with minimal side effects. The copper‐based MOFs theranostic nanosystem effectively reduced protein lipoylation and Fe‐S cluster protein levels (FDX1), triggering cuproptosis. This study presents a novel strategy for designing multifunctional nanoparticles for synergistic PA/CDT/PTT/cuproptosis theranostics. The in situ reaction of Cu‐MOFs with endogenous H2S enabled PA imaging and facilitated combined PTT/chemotherapy for colorectal cancer therapy.

Gene therapy has attracted much attention because of its unique mechanism of action, non-toxicity, and good tolerance, which can kill cancer cells without damaging healthy tissues. siRNA-based gene therapy can downregulate, enhance, or correct gene expression by introducing some nucleic acid into patient tissues. Routine treatment of hemophilia requires frequent intravenous injections of missing clotting protein. The high cost of combined therapy causes most patients to lack the best treatment resources. siRNA therapy has the potential of lasting treatment and even curing diseases. Compared with traditional surgery and chemotherapy, siRNA has fewer side effects and less damage to normal cells. The available therapies for degenerative diseases can only alleviate the symptoms of patients, while siRNA therapy drugs can upregulate gene expression, modify epigenetic changes, and stop the disease. In addition, siRNA also plays an important role in cardiovascular diseases, gastrointestinal diseases, and hepatitis B. However, free siRNA is easily degraded by nuclease and has a short half-life in the blood. Research has found that siRNA can be delivered to specific cells through appropriate vector selection and design to improve the therapeutic effect. The application of viral vectors is limited because of their high immunogenicity and low capacity, while non-viral vectors are widely used because of their low immunogenicity, low production cost, and high safety. This paper reviews the common non-viral vectors in recent years and introduces their advantages and disadvantages, as well as the latest application examples.

BackgroundInternet addiction poses serious harm to the physical and mental health of college students. Insecure attachment is one of the key factors of internet addiction， while self-compassion and psychological resilience serve as crucial psychological factors closely related to it. However， the chain mediating role of self-compassion and psychological resilience between insecure attachment and college students' internet addiction remains unclear.ObjectiveTo explore the mediating role of self-compassion and psychological resilience in the relationship between insecure attachment and internet addiction in college students， so as to provide references for the prevention and intervention of internet addiction in this population.MethodsFrom November 2023 to February 2024， a total of 1 380 college students were recruited using a cluster sampling method from two universities in Sichuan Province. The assessment was conducted using the Chinese Internet Addiction Scale （CIAS）， the Self-Compassion Scale （SCS）， the Experiences in Close Relationships Scale （ECR）， and the Resilience Scale for Chinese Adolescents （RSCA）. Pearson correlation analysis was conducted to examine the correlations of the scores of each scale. Model 6 in Process 4.2 was used to test the mediating roles of self-compassion and psychological resilience in the relationship between insecure attachment and internet addiction among college students.ResultsA total of 1 232 （89.28%） college students completed the valid questionnaire survey. The ECR score was positively correlated with the CIAS score （r=0.299， P<0.01）， and SCS score was positively correlated with the RSCA score （r=0.299， P<0.01）. The ECR score was negatively correlated with both SCS score and RSCA score （r=-0.122、-0.147，P<0.01）； the SCS score was negatively correlated with both RSCA score and CIAS score （r=-0.238、-0.263， P<0.01）. Self-compassion and psychological resilience were the pathways between insecure attachment and internet addiction， with effect sizes of 0.015 （95% CI： 0.007–0.023） and 0.010 （95% CI： 0.004–0.017）， respectively. Self-compassion and psychological resilience played chain mediating role between insecure attachment and internet addiction， with effect sizes of 0.003 （95% CI： 0.001–0.006）.ConclusionInsecure attachment can directly affect internet addiction in college students， and it can also influence internet addiction through independent pathway of self-compassion and psychological resilience， as well as the chain mediating pathways involving both self-compassion and psychological resilience.

BackgroundAnxiety symptoms have become a public health issue affecting the physical and mental health of the elderly population. Mental health literacy is a predictor of anxiety symptoms in the elderly. Currently， there are limited studies on the pathogenic mechanism between the two. Exploring the relationship and mechanism between mental health literacy and anxiety symptoms among the elderly is of great significance for improving the mental health level of the elderly.ObjectiveTo investigate the impact of mental health literacy on anxiety symptoms in the elderly， and to analyze the role of insomnia in this process， in order to provide references for the formulation of prevention and intervention strategies for anxiety symptoms in the elderly.MethodsFrom August 2021 to December 2022， a total of 10 650 older adults aged 60 years old and above were selected from a city in Sichuan Province using a multistage stratified sampling method. Participants completed the self-compiled demographic questionnaire， the Insomnia Severity Index （ISI）， the Generalized Anxiety Disorder Scale-7 item （GAD-7）， and the National Mental Health Literacy Questionnaire （NMHLQ）. Spearman correlation analysis was adopted to examine the correlation between the scores of the scales. Model 4 in SPSS 27.0 plugin Process 4.1 was employed to test the pathway of insomnia between mental health literacy （and its various dimensions） and anxiety symptoms.ResultsAmong the participants， 9 609 cases （90.23%） completed the valid questionnaire survey， and 1 680 cases （17.48%） were found to have anxiety symptoms. The total score of the NMHLQ for the elderly， as well as the scores of the knowledge， awareness， and skills dimensions， were negatively correlated with the GAD-7 score and the ISI score （rs=-0.506–-0.054， P<0.01）， and the ISI score was positively correlated with the GAD-7 score （rs=0.666， P<0.01）. Insomnia served as the mediating pathway between the mental health literacy and anxiety symptoms， with an indirect effect value of -0.210 （95% CI： -0.227–-0.193）， accounting for 54.97% of the total effect. Insomnia was the mediating pathway between the mental health literacy knowledge and anxiety symptoms of the elderly， with an indirect effect value of -0.161 （95% CI： -0.178–-0.144）， accounting for 52.61% of the total effect. Insomnia played a mediating role in the relationship between the awareness of mental health literacy and anxiety symptoms， with an indirect effect value of -0.323 （95% CI： -0.342–-0.302）， accounting for 76.36% of the total effect. Insomnia was the mediating pathway between the mental health literacy skills and anxiety symptoms of the elderly， with an indirect effect value of -0.172 （95% CI： -0.187–-0.159）， accounting for 53.75% of the total effect.ConclusionThe dimensions of mental health literacy， knowledge， awareness and skills of the elderly not only directly affect anxiety symptoms， but also indirectly influence anxiety symptoms through the pathway of insomnia.［Funded by Medical Research Project Plan of Sichuan Province （number， S23049）］

Support vector regression (SVR) optimized by particle swarm optimization (PSO) has low predictive accuracy and premature convergence in milling. To solve this problem, A PSO-SVR model combined with the cutting feature weight was proposed in this paper. Firstly, basing on the SVR, the feature weight was integrated with the kernel function, and added the premature judging to the PSO to improve the global searching ability. Secondly, the mathematical model composed of the cutting force, temperature and cutting vibration was built based on the datasets obtained by experiment. The covariance was calculated to get the characteristic weights of process parameters, which promoted the incremental data in turn. Finally, the predictive model of the dimensional deviation was established based on the promoted PSO-SVR and the result was compared with the general PSO-SVR. The accuracy of the predictive model reached 97.5%. And compared with the predictive model of the general PSO-SVR without feature weighting, the dimensional deviation predictive accuracy and generalization ability of the regeneration PSO-SVR predictive model with feature weighting was improved by 37.75% and 24.5%.

Although immunotherapy has demonstrated remarkable progress in cancer treatment, its clinical benefits remain restricted to a subset of patients and specific cancer types, primarily due to the immunosuppressive nature of the tumor microenvironment (TME) in solid tumors. Therefore, many strategies have focused on targeting the immunosuppressive TME to enhance immune-mediated tumor eradication. In parallel, the repositioning of old drugs represents an attractive discovery approach compared with the traditional de novo drug discovery process, which is time-consuming and costly. Thus, repurposing US Food and Drug Administration (FDA)-approved old drugs to modulate the tumor immune microenvironment represents a promising strategy to augment the effectiveness of cancer immunotherapy. Indeed, emerging evidence indicates that several approved drugs can reprogram the tumor immune landscape, thereby enhancing responses to immunotherapy. This review provides a comprehensive overview of US FDA-approved old drugs with immunomodulatory properties in the tumor context. We discuss their mechanisms in reversing immunosuppression, summarize key findings from preclinical studies and clinical trials involving their combination with immunotherapies, and outline future perspectives for their clinical translation. Collectively, this work highlights the translational potential of drug repurposing as a strategy to expand the therapeutic reach of cancer immunotherapy. [Display omitted] •Repurposed drugs reprogram the tumor microenvironment to enhance immunotherapy.•Mechanisms by which repurposed drugs reverse immunosuppression are detailed.•Preclinical and clinical data on combinations and future directions are summarized.

Stimuli‐responsive nanomaterials offer significant potential for enhancing diagnostic accuracy, optimizing therapeutic efficacy, and advancing precision theranostics. Hydrogen sulfide (H 2 S) was found to be upregulated in colorectal cancer, which endows it with an ideal endogenous trigger for tumor targeting. Here, we introduce a novel class of H 2 S‐activated metal‐organic framework (MOF) systems specifically designed for targeted colorectal cancer imaging and synergistic copper‐induced tumor regression. The Cu‐MOF nanoplatform demonstrated a rapid response to H 2 S at the tumor site, producing copper sulfide with strong near infrared absorption and activated PA signals. In vivo studies demonstrated remarkable tumor inhibition in an orthotopic colon cancer model with minimal side effects. The copper‐based MOFs theranostic nanosystem effectively reduced protein lipoylation and Fe‐S cluster protein levels (FDX1), triggering cuproptosis. This study presents a novel strategy for designing multifunctional nanoparticles for synergistic PA/CDT/PTT/cuproptosis theranostics.

BackgroundChronic insomnia disorder has become a significant public health issue， and it may be associated with dyslipidemia. Previous studies on dyslipidemia in patients with chronic insomnia disorder have mainly focused on exploring the relationship between subjective short sleep duration and dyslipidemia， while there have been limited studies on the relationship between objective short sleep duration and dyslipidemia.ObjectiveTo explore the relationship between objective short sleep duration and dyslipidemia in patients with chronic insomnia disorder， in order to provide references for the prevention and intervention of dyslipidemia in this population.MethodsA total of 103 patients who were hospitalized at The Third Hospital of Mianyang from August 2022 to November 2023 and met the diagnostic criteria for chronic insomnia disorder as defined in the International Classification of Sleep Disorder， third edition （ICSD-3） were retrospectively collected. The objective sleep duration of the patients was obtained

Background Acute spinal cord injury (SCI) could cause mainly two types of pathological sequelae, the primary mechanical injury, and the secondary injury. The macrophage in SCI are skewed toward the M1 phenotype that might cause the failure to post-SCI repair. Methods SCI model was established in Balb/c mice, and the changes in macrophage phenotypes after SCI were monitored. Bioinformatic analyses were performed to select factors that might regulate macrophage polarization after SCI. Mouse bone marrow-derived macrophages (BMDMs) were isolated, identified, and induced for M1 or M2 polarization; the effects of lncRNA guanylate binding protein-9 (lncGBP9) and suppressor of cytokine signaling 3 (SOCS3) on macrophages polarization were examined in vitro and in vivo. The predicted miR-34a binding to lncGBP9 and SOCS3 was validated; the dynamic effects of lncGBP9 and miR-34a on SOCS3, signal transducer and activator of transcription 1 (STAT1)/STAT6 signaling, and macrophage polarization were examined. Finally, we investigated whether STAT6 could bind the miR-34a promoter to activate its transcription. Results In SCI Balb/c mice, macrophage skewing toward M1 phenotypes was observed after SCI. In M1 macrophages, lncGBP9 silencing significantly decreased p-STAT1 and SOCS3 expression and protein levels, as well as the production of Interleukin (IL)-6 and IL-12; in M2 macrophages, lncGBP9 overexpression increased SOCS3 mRNA expression and protein levels while suppressed p-STAT6 levels and the production of IL-10 and transforming growth factor-beta 1 (TGF-β1), indicating that lncGBP9 overexpression promotes the M1 polarization of macrophages. In lncGBP9-silenced SCI mice, the M2 polarization was promoted on day 28 after the operation, further indicating that lncGBP9 silencing revised the predominance of M1 phenotype at the late stage of secondary injury after SCI, therefore improving the repair after SCI. IncGBP9 competed with SOCS3 for miR-34a binding to counteract miR-34a-mediated suppression on SOCS3 and then modulated STAT1/STAT6 signaling and the polarization of macrophages. STAT6 bound the promoter of miR-34a to activate its transcription. Conclusions In macrophages, lncGBP9 sponges miR-34a to rescue SOCS3 expression, therefore modulating macrophage polarization through STAT1/STAT6 signaling. STAT6 bound the promoter of miR-34a to activate its transcription, thus forming two different regulatory loops to modulate the phenotype of macrophages after SCI.