Apoptotic Body-Mediated Intracellular Delivery Strategy for Enhanced STING Activation and Improved Tumor Immunogenicity.

Agonists of stimulators of interferon genes (STING) are a promising class of immunotherapeutics that trigger potent innate immunity. However, the therapeutic efficacy of conventional STING agonists, such as 2',3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), is severely restricted to poor cytosolic delivery and lacks the capacity to promote the recognition of tumor-specific antigens. Here, we tackle these challenges through a nanovaccine platform based on Fenton-reactive and STING-activating nanoparticles, synergistically contributing to the generation of tumor-cell-derived apoptotic bodies (ABs). ABs loaded with exogenous cGAMP are readily phagocytosed by antigen-presenting cells (APCs), as a Trojan horse for rendering tumor cells with high immunogenicity instead of a noninflammatory response. This leads to enhanced STING activation and an improved tumor-specific antigen presentation ability, boosting the adaptive immunity in collaboration with innate immune. The strategy of exploiting a metal-based nanovaccine platform possesses great potential to be clinically translated into a trinitarian system of diagnosis, treatment, and prognosis.

Synthesis and biological evaluation of resveratrol derivatives with anti-breast cancer activity.

Resveratrol is a natural phytoestrogen produced by plants to protect themselves from injury, UV irradiation, and fungal attack. The main active structure is E-resveratrol, which has many pharmacological activities. As the structure of resveratrol is similar to the natural estrogen 17ß-estradiol and the synthetic estrogen E-diethylstilbestrol, resveratrol is used in reducing the incidence of breast cancer. However, the therapeutic application of resveratrol is limited due to its low bioavailability. To improve its bioavailability and pharmacological activity, some resveratrol derivatives have been designed and synthesized by substitutions of methoxy, hydroxyl, and other functional groups or heterocyclic esterification either on the "A" or "B" ring, and double bonds were replaced by imine bonds and isometric heterocycles such as naphthyl and imidazole, or synthetic resveratrol oligomers. The structures, synthetic routes, and evaluation of the biological activities of these compounds are discussed. These are aimed at providing some references for the study of resveratrol derivatives in anti-breast cancer treatment.

Chinese undergraduates' mental health help-seeking behavior: the health belief model.

The detection rate of mental health problems among undergraduates has recently risen significantly. However, undergraduates underutilize mental health services; approximately a third only of undergraduates in need of treatment use school counseling resources. Based on a social psychological theoretical framework, the health belief model, factors of undergraduates' willingness to seek help when dealing with psychological problems were investigated. A cross-sectional online questionnaire and a snowball sampling method with 446 undergraduates investigated perceived susceptibility, perceived severity, perceived behavioral benefits, perceived barriers, self-efficacy, and cues to action to understand how students' mental health-seeking behaviors are affected. We found that perceived susceptibility (p < 0.01), perceived severity (p < 0.01), perceived benefits (p < 0.01), perceived barriers (p < 0.01), self-efficacy (p < 0.01), and cues to action (p < 0.01) significantly correlated with behavioral intention. Encouragement or counseling from others would be more likely to motivate undergraduates to seek mental health help. In addition, we used a bias-corrected Bootstrap approach to test the significance of the mediating effect, the mediation effect of cues to action between undergraduates' perceived susceptibility and mental health help-seeking behavior was utterly significant [mediation effect value of 0.077, with an SE value of 0.027 and a 95% CI (0.028, 0.133)]. It demonstrated that those who perceived themselves to be at high risk of developing a mental illness and who had received encouragement or counseling to seek mental health help were more likely to be motivated to seek mental health help. Multiple regression analyses indicated that self-efficacy (Z = 5.425, p < 0.01) and cues to action (Z = 6.673, p < 0.01) independently influenced behavioral intentions. Encouragement or counseling from others would be more likely to motivate undergraduates to seek mental health help.

Advances in new targets for immunotherapy of small cell lung cancer.

Small cell lung cancer (SCLC) is one of the highly aggressive malignancies characterized by rapid growth and early metastasis, but treatment options are limited. For SCLC, carboplatin or cisplatin in combination with etoposide chemotherapy has been considered the only standard of care, but the standard first-line treatment only results in 10-month survival. The majority of patients relapse within a few weeks to months after treatment, despite the relatively sensitive response to chemotherapy. Over the past decade, immunotherapy has made significant progress in the treatment of SCLC patients. However, there have been limited improvements in survival rates for SCLC patients with the current immune checkpoint inhibitors PD-1/PD-L1 and CTLA-4. In the face of high recurrence rates, small beneficiary populations, and low survival benefits, the exploration of new targets for key molecules and signals in SCLC and the development of drugs with novel mechanisms may provide fresh hope for immunotherapy in SCLC. Therefore, the aim of this review was to explore four new targets, DLL3, TIGIT, LAG-3, and GD2, which may play a role in the immunotherapy of SCLC to find useful clues and strategies to improve the outcome for SCLC patients.

Efficacy and safety of immunotherapy combined with chemotherapy in patients with ES-SCLC: A systematic review and network meta-analysis of RCTs and RWSs.

OBJECTIVES: To evaluate the efficacy and safety of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors in the treatment of extensive-stage small-cell lung cancer (ES-SCLC), we conducted a systematic review and meta-analysis that included randomized controlled trials (RCTs) and real-world studies (RWS). METHODS: By scanning PubMed, Web of science, Embase, and other relevant clinical information public databases, nine RCTs and eight RWSs involving 5205 patients were included in the study. We directly compared the differences between chemotherapy and PD-1/PD-L1 inhibitors plus chemotherapy, and determined the optimal treatment strategy through network meta-analysis (NMA). RESULTS: Compared to chemotherapy, the addition of PD-1/PD-L1 inhibitors significantly improves the overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) in SCLC patients. Regarding safety, both RCTs and RWSs indicated no significant difference in grade 3-4 adverse events between chemotherapy and chemoimmunotherapy. NMA showed serplulimab plus chemotherapy (Serp_Chemo) appears to provide the best OS, PFS, and ORR benefit, while nivolumab plus chemotherapy shows higher toxicity than other regimens. In subgroup analysis, for elderly patients (age ≥65) and non-elderly (age <65) patients, the most promising quality regimens for achieving better OS extension are atezolizumab plus chemotherapy (Atez_Chemo) and Serp_Chemo, respectively. For patients with PD-L1 ≥ 1% and lactate dehydrogenase (LDH) > upper limit of normal (ULN), there is no apparent OS benefit from immune therapy. CONCLUSIONS: In ES-SCLC treatment, adding PD-1/PD-L1 inhibitors to standard chemotherapy improves OS, PFS, and ORR, with Serp_Chemo shows the most promise. Atez_Chemo and Serp_Chemo provided better survival for elderly and non-elderly patients, respectively.

Modulating Smart Mechanoluminescent Phosphors for Multistimuli Responsive Optical Wood.

Mechanoluminescence is a smart light-emitting phenomenon in which applied mechanical energy is directly converted into photon emissions. In particular, mechanoluminescent materials have shown considerable potential for applications in the fields of energy and sensing. This study thoroughly investigates the mechanoluminescence and long afterglow properties of singly doped and codoped Sr2 MgSi2 O7 (SMSO) with varying concentrations of Eu2+ and Dy3+ ions. Subsequently, a comprehensive analysis of its multimode luminescence properties, including photoluminescence, mechanoluminescence, long afterglow, and X-ray-induced luminescence, is conducted. In addition, the density of states mapping is acquired through first-principles calculations, confirming that the enhanced mechanoluminescence properties of SMSO primarily stem from the deep trap introduced by Dy3+ . In contrast to traditional mixing with Polydimethylsiloxane, in this study, the powders are incorporated into optically transparent wood to produce a multiresponse with mechanoluminescence, long afterglow, and X-ray-excited luminescence. This structure is achieved by pretreating natural wood, eliminating lignin, and subsequently modifying the wood to overall modification using various smart phosphors and epoxy resin composites. After natural drying, a multifunctional composite wood structure with diverse luminescence properties is obtained. Owing to its environmental friendliness, sustainability, self-power, and cost-effectiveness, this smart mechanoluminescence wood is anticipated to find extensive applications in construction materials and energy-efficient displays.

A Review on the Mechanism and Structure-activity Relationship of Resveratrol Heteroaryl Analogues.

Resveratrol is one of the most interesting naturally-occurring nonflavonoid phenolic compounds with various biological activities, such as anticancer, neuroprotection, antibacterial, and anti-inflammatory. However, there is no clinical usage of resveratrol due to either its poor activity or poor pharmacokinetic properties. Heteroarenes-modified resveratrol is one pathway to improve its biological activities and bioavailability, and form more modification sites. In this review, we present the progress of heteroaryl analogues of resveratrol with promising biological activities in the latest five years, ranging from the synthesis to the structure-activity relationship and mechanism of actions. Finally, introducing heteroarenes into resveratrol is an effective strategy, which focuses on the selectivity of structure-activity relationship in vivo.

Immunization against Zika by entrapping live virus in a subcutaneous self-adjuvanting hydrogel.

The threat of new viral outbreaks has heightened the need for ready-to-use vaccines that are safe and effective. Here we show that a subcutaneous vaccine consisting of live Zika virus electrostatically entrapped in a self-adjuvanting hydrogel recruited immune cells at the injection site and provided mice with effective protection against a lethal viral challenge. The hydrogel prevented the escape of the viral particles and upregulated pattern recognition receptors that activated innate antiviral immunity. The local inflammatory niche facilitated the engulfment of the virus by immune cells infiltrating the hydrogel, the processing and cross-presentation of antigens and the expansion of germinal centre B cells and induced robust antigen-specific adaptive responses and immune memory. Inflammatory immune niches entrapping live viruses may facilitate the rapid development of safe and efficacious vaccines.

RBBP4 plays a vital role in the malignant progression of triple-negative breast cancer by regulating epithelial-mesenchymal transition.

BACKGROUND: Mounting findings have revealed the increasingly appreciated functional importance of Retinoblastoma binding protein (RBBP) family members in tumorigenesis. However, the biological function of RBBP4 in breast cancer, especially in the most malignant and aggressive subtype, i.e., triple-negative breast cancer (TNBC), remains to be elucidated. OBJECTIVE: The present study was aimed at elucidating the role of RBBP4 in TNBC pathogenesis. METHODS: The expression of RBBP4 in TNBC tissues and cell lines was examined and its oncogenic-related functions were verified by performing a series of in vitro and in vivo experiments. RESULTS: At the cellular and tissue level, a marked increase in the RBBP4 expression was observed. Functionally, RBBP4 knockdown dramatically inhibited the proliferation, invasion, and migration of TNBC cells in vitro. Further, mechanistically, RBBP4 downregulation regulated the inactivation of epithelial-mesenchymal transition (EMT) of TNBC cells. In vivo xenograft model in nude mice also validated these results. CONCLUSION: Collectively, our results showed that the inhibition of RBBP4 suppresses the malignant progression of TNBC cells by regulating EMT. Thus, RBBP4 could serve as a novel biomarker and target for TNBC diagnosis and treatment.

19F MRI-fluorescence imaging dual-modal cell tracking with partially fluorinated nanoemulsions.

As a noninvasive "hot-spot" imaging technology, fluorine-19 magnetic resonance imaging (19F MRI) has been extensively used in cell tracking. However, the peculiar physicochemical properties of perfluorocarbons (PFCs), the most commonly used 19F MRI agents, sometimes cause low sensitivity, poor cell uptake, and misleading results. In this study, a partially fluorinated agent, perfluoro-tert-butyl benzyl ether, was used to formulate a 19F MRI-fluorescence imaging (FLI) dual-modal nanoemulsion for cell tracking. Compared with PFCs, the partially fluorinated agent showed considerably improved physicochemical properties, such as lower density, shorter longitudinal relaxation times, and higher solubility to fluorophores, while maintaining high 19F MRI sensitivity. After being formulated into stable, monodisperse, and paramagnetic Fe3+-promoted nanoemulsions, the partially fluorinated agent was used in 19F MRI-FLI dual imaging tracking of lung cancer A549 cells and macrophages in an inflammation mouse model.