In-situ activation of biomimetic single-site bioorthogonal nanozyme for tumor-specific combination therapy.

Copper-catalyzed click chemistry offers creative strategies for activation of therapeutics without disrupting biological processes. Despite tremendous efforts, current copper catalysts face fundamental challenges in achieving high efficiency, atom economy, and tissue-specific selectivity. Herein, we develop a facile "mix-and-match synthetic strategy" to fabricate a biomimetic single-site copper-bipyridine-based cerium metal-organic framework (Cu/Ce-MOF@M) for efficient and tumor cell-specific bioorthogonal catalysis. This elegant methodology achieves isolated single-Cu-site within the MOF architecture, resulting in exceptionally high catalytic performance. Cu/Ce-MOF@M favors a 32.1-fold higher catalytic activity than the widely used MOF-supported copper nanoparticles at single-particle level, as first evidenced by single-molecule fluorescence microscopy. Furthermore, with cancer cell-membrane camouflage, Cu/Ce-MOF@M demonstrates preferential tropism for its parent cells. Simultaneously, the single-site CuII species within Cu/Ce-MOF@M are reduced by upregulated glutathione in cancerous cells to CuI for catalyzing the click reaction, enabling homotypic cancer cell-activated in situ drug synthesis. Additionally, Cu/Ce-MOF@M exhibits oxidase and peroxidase mimicking activities, further enhancing catalytic cancer therapy. This study guides the reasonable design of highly active heterogeneous transition-metal catalysts for targeted bioorthogonal reactions.

Crosstalk between macrophages and immunometabolism and their potential roles in tissue repair and regeneration.

Immune metabolism is a result of many specific metabolic reactions, such as glycolysis, the tricarboxylic acid (TCA) pathway, the pentose phosphate pathway (PPP), mitochondrial oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), fatty acid biosynthesis (FAs) and amino acid pathways, which promote cell proliferation and maintenance with structural and pathological energy to regulate cellular signaling. The metabolism of macrophages produces many metabolic intermediates that play important regulatory roles in tissue repair and regeneration. The metabolic activity of proinflammatory macrophages (M1) mainly depends on glycolysis and the TCA cycle system, but anti-inflammatory macrophages (M2) have intact functions of the TCA cycle, which enhances FAO and is dependent on OXPHOS. However, the metabolic mechanisms of macrophages in tissue repair and regeneration have not been well investigated. Thus, we review how three main metabolic mechanisms of macrophages, glucose metabolism, lipid metabolism, and amino acid metabolism, regulate tissue repair and regeneration.

Electrochemical response mechanism of DNA damaged cells: DNA damage repair and purine metabolism activation.

In modern society, due to the sharp increase in pollutants that cause DNA damage, there is a growing demand for innovative detection techniques and biomarkers. In this paper, the electrochemical behavior of HepG2 cells exposed to CdCl2 was investigated, and the electrochemical response mechanism of DNA damage was identified by exploring the correlation between the DNA damage response and purine metabolism. Western blot analysis revealed that the expression levels of ATM and Ku70 increased at 0.3 µM CdCl2, indicating a DNA damage response and activation of DNA repair processes. Simultaneously, elevated expression levels of PRPP aminotransferase, HPRT, and XOD were observed, leading to an increase in intracellular purine levels and electrochemical signals. The expression of Ku70 peaked at 0.5 µM CdCl2, indicating the highest DNA repair activity. The expression profiles of these purine metabolism proteins mirrored those of Ku70, suggesting a strong correlation between the activation of purine metabolism and DNA damage repair. Consistently, intracellular purine levels exhibited a similar trend, leading to corresponding changes in electrochemical signals. In summary, electrochemical using intracellular purines as biomarkers has the potential to emerge as a novel method for detecting early DNA damage.

N-Methyl-d-Aspartate Receptor Antibody and Sensory Gating Deficits in Non-smoking, Minimal Antipsychotic Medication Exposure, and First-Episode Patients With Schizophrenia.

BACKGROUND AND HYPOTHESIS: Sensory gating deficit is considered a pathophysiological feature of schizophrenia, which has been linked to N-methyl-d-aspartate receptor (NMDAR) hypofunction as one of the potential underlying mechanisms. Here, we hypothesize that higher levels of NMDAR antibody (Ab) may contribute to the sensory gating deficits in schizophrenia. STUDY DESIGN: We enrolled 72 non-smoking inpatients with first-episode schizophrenia (FES), most of them with only a relatively short duration of exposure to antipsychotic medications, and 51 non-smoking healthy controls (HC). Sensory gating was measured by P50 evoked potentials ratio and the difference between the two stimuli in an auditory paired-stimuli paradigm and serum NMDAR Ab levels were quantified by enzyme-linked immunosorbent assay. STUDY RESULTS: The FES group showed higher serum NMDAR Ab levels [(9.23 ±â€…4.15) ng/mL vs. (7.08 ±â€…2.83) ng/mL; P = .002], higher P50 ratio (P = .002), and less P50 difference (P = .001) than HC. In partial correlation analysis, serum NMDAR Ab levels were positively correlated with the P50 ratio (r = 0.36, P = .003) and negatively with the P50 difference (r = -0.39, P = .001) in the FES group. The NMDAR Ab levels mediated the diagnosis of schizophrenia and P50 sensory gating deficits (P50 ratio and P50 difference). CONCLUSIONS: Autoimmunity targeting NMDAR is a crucial intermediate mechanism in impaired sensory gating in patients with schizophrenia. The findings support early intervention targeting NMDAR for patients with schizophrenia.

Correction: Zhao et al. Research on the Formation Conditions and Preventive Measures of Uranium Precipitates during the Service Process of Medical Isotope Production Reactors. Materials 2024, 17, 945.

There were two errors in the original publication [...].

Ruxolitinib plus steroids for acute graft versus host disease: a multicenter, randomized, phase 3 trial.

Newly diagnosed patients with high-risk acute graft-versus-host disease (aGVHD) often experience poor clinical outcomes and low complete remission rates. Ruxolitinib with corticosteroids showed promising efficacy in improving response and failure free survival in our phase I study. This study (ClinicalTrials.gov: NCT04061876) sought to evaluate the safety and effectiveness of combining ruxolitinib (RUX, 5 mg/day) with corticosteroids (1 mg/kg/day methylprednisolone, RUX/steroids combined group) versus using methylprednisolone alone (2 mg/kg/day, steroids-only group). Newly diagnosed patients with intermediate- or high-risk aGVHD were included, with risk levels classified by either the Minnesota aGVHD Risk Score or biomarker assessment. Patients were randomized in a ratio of 1:1 into 2 groups: 99 patients received RUX combined with methylprednisolone, while the other 99 received methylprednisolone alone as the initial treatment. The RUX/steroids group showed a significantly higher overall response rate (ORR) on day 28 (92.9%) compared to the steroids-only group (70.7%, Odds Ratio [OR] = 5.8; 95% Confidence Interval [CI], 2.4-14.0; P < 0.001). Similarly, the ORR on day 56 was higher in the RUX/steroids group (85.9% vs. 46.5%; OR = 7.07; 95% CI, 3.36-15.75; P < 0.001). Additionally, the 18-month failure-free survival was significantly better in the RUX/steroids group (57.2%) compared to the steroids-only group (33.3%; Hazard Ratio = 0.46; 95% CI, 0.31-0.68; P < 0.001). Adverse events (AEs) frequencies were comparable between both groups, with the exception of fewer grade 4 AEs in the RUX/steroids group (26.3% vs. 50.5% P = 0.005). To our knowledge, this study is the first prospective, randomized controlled trial to demonstrate that adding ruxolitinib to the standard methylprednisolone regimen provides an effective and safe first-line treatment for newly diagnosed high-risk acute GVHD.

Pancreatic ß-Cells, Diabetes and Autophagy.

PURPOSE: Pancreatic ß-cells play a critical role in regulating plasma insulin levels and glucose metabolism balance, with their dysfunction being a key factor in the progression of diabetes. This review aims to explore the role of autophagy, a vital cellular self-maintenance process, in preserving pancreatic ß-cell functionality and its implications in diabetes pathogenesis. METHODS: We examine the current literature on the role of autophagy in ß-cells, highlighting its function in maintaining cell structure, quantity, and function. The review also discusses the effects of both excessive and insufficient autophagy on ß-cell dysfunction and glucose metabolism imbalance. Furthermore, we discuss potential therapeutic agents that modulate the autophagy pathway to influence ß-cell function, providing insights into therapeutic strategies for diabetes management. RESULTS: Autophagy acts as a self-protective mechanism within pancreatic ß-cells, clearing damaged organelles and proteins to maintain cellular stability. Abnormal autophagy activity, either overactive or deficient, can disrupt ß-cell function and glucose regulation, contributing to diabetes progression. CONCLUSION: Autophagy plays a pivotal role in maintaining pancreatic ß-cell function, and its dysregulation is implicated in the development of diabetes. Targeting the autophagy pathway offers potential therapeutic strategies for diabetes management, with agents that modulate autophagy showing promise in preserving ß-cell function.

Facile and scale-up syntheses of high-performance enzyme@meso-HOF biocatalysts.

Facile immobilization is essential for the wide application of enzymes in large-scale catalytic processes. However, exploration of suitable enzyme supports poses an unmet challenge, particularly in the context of scale-up biocatalyst fabrication. In this study, we present facile and scale-up syntheses of high-performance enzyme biocatalysts via in situ encapsulation of cytochrome c (Cyt-c) as mono-enzyme and glucose oxidase (GOx)-horseradish peroxidase (HRP) as dual-enzyme cascade (GOx&HRP) systems, respectively, into a stable mesoporous hydrogen-bonded organic framework (meso-HOF) matrix. In situ encapsulation reactions occur under ambient conditions, and facilitate scale up (∼3 g per reaction) of enzyme@meso-HOF within a very short period (5-10 min). The resultant biocatalysts not only exhibit high enzyme loading (37.9 wt% for mono-enzyme and 22.8 wt% for dual-enzyme) with minimal leaching, but also demonstrate high catalytic activity, superior reusability, and durability. This study represents an example of scale-up fabrication of enzyme@meso-HOF biocatalysts on the gram level and highlights superior meso-HOFs as suitable host matrices for biomolecular entities.

[5]Helicene Based π-Conjugated Macrocycles with Persistent Figure-Eight and Möbius Shapes: Efficient Synthesis, Chiral Resolution and Bright Circularly Polarized Luminescence.

π-Conjugated chiral shape-persistent molecular nanocarbons hold great potential as chiroptical materials, though their synthesis remains a considerable challenge. Here, we present a simple approach using Suzuki coupling of a [5]helicene building block with various aromatic units, enabling the one-pot synthesis of a series of chiral macrocycles with persistent figure-eight and Möbius shapes. Single-crystal structures of 7 compounds were solved, and 22 enantiomers were separated by preparative chiral HPLC. A notable pyrene-bridged figure-eight macrocycle, with its rigid, fully π-conjugated and overcrowded structure, exhibited pure excimer emission and outstanding circularly polarized luminescence (CPL) properties, including a large dissymmetric factor (|glum| = 3.8 × 10-2) and significant CPL brightness (BCPL = 710.5 M-1cm-1). This method provides a versatile synthetic platform for producing various chiral D2-symmetric figure-eight macrocycles and singly or triply twisted Möbius macrocycles with C2 and D3 symmetry, offering tunable chiroptical properties for CPL applications.

Priming of cancer-immunity cycle by alleviating hypoxia-induced ferroptosis resistance and immunosuppression.

Stimulating a robust cancer-immunity cycle (CIC) holds promising potential for eliciting potent and enduring immune responses for cancer immunotherapy. However, designing a therapeutic nanomaterial capable of both enhancing tumor immunogenicity and mitigating immunosuppression is challenging and often associated with complicated design paradigms and immune-related adverse effects. Herein, a multienzyme-mimetic alloy nanosheet incorporating palladium (Pd) and iron (Fe) is developed, which can prime effective CIC by overcoming ferroptosis resistance for enhancing tumor immunogenicity and reprograming the tumor microenvironment for enhanced second near-infrared (NIR-II) photoimmunotherapy. The nanosheets accumulate in tumors when administered intravenously and counteract hypoxia through catalase-like oxygen production and subsequent reduction of hypoxia-inducible factor-1α, M2-like macrophages, regulatory T-cell, and programmed death-ligand 1 (PD-L1) expression. The surface plasmon resonance of the nanosheets enables NIR-II phototherapy and photoacoustic imaging, coupling with its ferroptosis and tumor microenvironment reprogram properties to synergize with anti-PD-L1 checkpoint blockade therapy to achieve satisfactory antitumor outcome. This study offers a strategy for localized tumor treatment and boosting the CIC through a straightforward and inexpensive nanomaterial design.

Safety and effectiveness of weighted blankets for symptom management in patients with mental disorders: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The current practice guideline regarding treatment for insomnia and sleep disturbances among children and adolescents with autism spectrum disorder (ASD) has been published and it suggests that the use of weighted blankets might not be an evidence-informed practice. However, limited guidance and evidence synthesis exist on the overall effectiveness of a weighted blanket for symptom management among patients with mental disorders, although it has been routinely recommended and prescribed for this population in many mental health care settings. OBJECTIVE: To systematically evaluate and synthesize existing data on the safety and effectiveness of weighted blankets for symptom management among patients with mental disorders. METHODS: Comprehensive retrieval of published, unpublished, or ongoing studies was carried out across a series of bibliographic databases, grey literature sources, and clinical trial registry platforms, along with manual screening of the reference lists of the included studies or relevant reviews. Randomized controlled trials (RCTs) were included if they compared a weighted blanket intervention and a control condition among patients with mental disorders. Two reviewers independently extracted the data using a pre-specified form and assessed the methodological quality of the included studies with the revised Cochrane 'Risk of Bias' (RoB 2) tool. Review Manager (RevMan) 5.3 software was used to conduct the meta-analysis when possible. Subgroup and sensitivity analyses, where appropriate, were conducted to explore the robustness of the pooled effect estimates. RESULTS: Eight studies involving a total of 426 patients were included in this review. Half of the included studies were rated as having a high risk of bias, primarily due to the failure to blind participants for participant-reported measures. No serious adverse events were reported with the application of weighted blankets. The meta-analysis of five studies revealed that the use of weighted blankets induced a small magnitude decrease (standardized mean difference within studies [SMD]= 0.40) in anxiety management. The pooled estimate of three studies reporting the effect of weighted blankets on insomnia revealed a nonsignificant difference between the two groups (mean difference [MD] = -1.92, 95 % confidence interval [CI] = -3.92-0.09, p = 0.06). However, the leave-one-out sensitivity analysis of the two remaining homogeneous studies revealed that patients who used weighted blankets had reduced insomnia severity index (ISI) scores (MD = -2.78, 95 % CI = -4.44 to -1.12, p = 0.001). Additionally, a study without available data for inclusion in the meta-analysis also reported a positive effect in reducing the ISI score. Due to the heterogeneity across studies, summary estimates for the effects of weighted blankets on fatigue and depression were not computed. However, primary studies reporting these two outcomes demonstrated that the application of weighted blankets had a positive effect. CONCLUSION: Weighted blankets may be a safe and effective add-on treatment for managing common symptoms such as anxiety, insomnia, depression, and fatigue among psychiatric patients. However, these results need to be further confirmed due to the limited number of studies included in this review, the small sample size and the significant heterogeneity across these primary studies. To gain a better understanding of the effect and mechanism of weight blankets, future trials should preferably integrate more objective measures.

Maternal emotion regulation abilities affect adolescent depressive symptoms by mediating their emotion regulation ability: An ERP study.

Adolescents with major depressive disorder (MDD) experience significant difficulties in emotion regulation. This study aimed to explore emotion regulation in adolescents with depression using an emotion regulation paradigm combined with event-related potentials (ERP) while investigating the relationship between maternal emotion regulation and adolescent depressive symptoms through a mediation model. Overall, 38 healthy controls (HC) and 57 adolescents with depression (MDD) rated the pictures they saw according to aversive reappraisal (reappraisal of an aversive picture or down-regulate aversive emotions), aversive watch, and neutral conditions. Adolescents with depression gave more negative ratings to aversive images, and the emotional regulation success index (ERSI) of adolescents with depression was lower than that of healthy individuals. ERP data revealed an elevation in late positive potential (LPP) amplitude during the aversive reappraisal and aversive watch conditions compared with that in the neutral condition in the MDD group. Compared with the HC group, adolescents with depression showed larger LPP amplitudes under aversive watch conditions. The aversive reappraisal condition evoked a larger LPP than that in the other conditions in the HC group in the late time windows. The ΔLPP (separating the variability in the ERP wave associated with emotion regulation) was larger in the HC group than in the MDD group. Mediation analysis revealed that maternal emotion regulation influenced adolescent depression levels through its effect on the adolescent's emotion regulation. These findings provide important insights into the emotion regulation process in adolescents with depression and offer suggestions for clinical interventions.

An "AND" logic gate-based supramolecular therapeutic nanoplatform for combatting drug-resistant non-small cell lung cancer.

Despite targeted therapies like epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), non-small cell lung cancer (NSCLC) remains a clinical challenge due to drug resistance hampering their efficacy. Here, we designed an "AND" logic gate-based supramolecular therapeutic platform (HA-BPY-GEF-NPs) for the treatment of EGFR-TKI resistant NSCLC. This system integrates both internal and external stimuli-responsive mechanisms that need to be activated in a preset sequence, enabling it to precisely control drug release behavior for enhancing therapeutic precision. By programming the system to respond to sequential near-infrared (NIR) irradiation and enzyme (cathepsin B) inputs, the release of gefitinib is effectively confined to the tumor region. Moreover, the NIR irradiation induces reactive oxygen species production, suppressing tumor growth and inhibiting bypass signaling pathways. The designed drug delivery system offers a highly controlled and targeted therapeutic approach, effectively inhibiting tumor growth, suppressing bypass signaling pathways, and overcoming EGFR-TKI resistance, thus offering a potential solution for maximizing therapeutic benefits.

NIR-Activable Charge Transfer Agents for Synergistic Photoimmunotherapy.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has become an attractive tumor treatment modality, yet the facile design of photoimmunotheranostic agents with efficient near infrared (NIR) light-absorbing and immune- activating capabilities remains a tremendous challenge. Herein, we developed a NIR-activable organic charge transfer complex (CTC), with perylene (PER) as the electron donor and 4,5,9,10-tetrabromoisochromeno [6,5,4-def]isochromene-1,3,6,8-tetraone (Br4NDI) as the electron acceptor. Through further supramolecular assembly, the PER-Br4NDI nanoparticle (PBND NP) for spatiotemporally controlled photoimmunotherapy was constructed. The PBND NP exhibits superb NIR absorption, robust intermolecular charge transfer, and enhanced intersystem crossing. Upon NIR photoirradiation, the PBND NP effectively exerts photothermal and photodynamic effects with a remarkable photothermal conversion efficiency of 63.5% and a high reactive oxygen species generation capability, which not only directly ablates primary tumors, but also dramatically suppresses distant tumor growth via promoted immunogenic cell death. Moreover, programmed cell death protein 1 antibody acts synergistically to block immune evasion and ultimately enhances cancer treatment efficacy. This work therefore sheds light on the design of organic CTCs for synergistic photoimmunotherapy.

Investigating the molecular mechanisms between type 1 diabetes and mild cognitive impairment using bioinformatics analysis, with a focus on immune response.

The immune system is involved in the development and progression of several diseases. Type 1 diabetes mellitus (T1DM), an autoimmune disorder, influences the progression of several other conditions; however, the link between T1DM and mild cognitive impairment (MCI) remains unclear. This study investigated the underlying immune response mechanisms that contribute to the development and progression of T1DM and MCI. Microarray datasets for MCI (GSE63060) and T1DM (GSE30208) were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using the limma package. To explore the functional implications of these DEGs, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted using ClusterProfiler. Protein-protein interaction networks for the DEGs were constructed using the STRING database and visualized using Cytoscape. The Molecular Complex Detection algorithm was used to analyze DEGs. Immune cell infiltration in patients with T1DM and MCI was analyzed using the xCell method. Gene set enrichment analysis was used to gain in-depth insights into the functional characteristics of T1DM and MCI. Immune-related genes were obtained from the GeneCards and ImmPort databases. Machine learning algorithms were used to identify potential hub genes associated with immunity for T1DM and MCI diagnosis, and the diagnostic value was assessed using the receiver operating characteristic curve. The identified genes were validated using quantitative polymerase chain reaction. In the T1DM and MCI datasets, 610 DEGs showed consistent trends, of which 232 and 378 were upregulated and downregulated, respectively. Immune response analysis revealed significant changes in the immune cells associated with MCI and T1DM. Using immune-related genes, DEGs, and machine learning techniques, we identified CD3D in the MCI and T1DM groups. We observed a gradual decline in the cognitive function of mice with T1DM as the disease progressed. CD3D expression increased with increasing disease severity; CD3D primarily affected CD4+ T cells. This study revealed a complex interaction between T1DM and MCI, providing novel insights into the intricate relationship between immune dysregulation and cognitive impairment and expanding our understanding of these two interconnected disorders. These findings will facilitate the development of therapeutic interventions and identification of potential therapeutic targets.

A Wurster-Type Covalent Organic Framework with Internal Electron Transfer-Enhanced Catalytic Capacity for Tumor Therapy.

The low immunogenicity of tumors, along with the abnormal structural and biochemical barriers of tumor-associated vasculature, impedes the infiltration and function of effector T cells at the tumor site, severely inhibiting the efficacy of antitumor immunotherapy. In this study, a cobaloxime catalyst and STING agonist (MSA-2)-coloaded Wurster-type covalent organic framework (Co-TB COF-M) with internal electron transfer-enhanced catalytic capacity was developed as a COF-based immune activator. The covalently anchored cobaloxime adjusts the energy band structure of TB COF and provides it with good substrate adsorption sites, enabling it to act as an electron transmission bridge between the COF and substrate in proton reduction catalytic reactions. This property significantly enhances the sonodynamic catalytic performance. Under sono-irradiation, Co-TB COF-M can produce a substantial amount of reactive oxygen species (ROS) to induce Gasdermin D-mediated pro-inflammatory pyroptosis, thereby effectively enhancing the immunogenicity of tumors. Furthermore, MSA-2 is specifically released in response to ROS at the tumor site, minimizing the off-target side effects. More importantly, Co-TB COF-induced STING activation normalizes tumor vasculature and increases the expression of endothelial T cell adhesion molecules, which greatly enhance the infiltration and function of effector T cells. Thus, Co-TB COF-M as an immune activator could remold the tumor microenvironment, leading to increased infiltration and an improved function of T cells for immunotherapy.

Regulating Conformational Locking in Covalent Organic Framework for Selective and Recyclable Photocatalytic Transformation.

The exploration of new properties and functionality of covalent organic frameworks (COFs) rely mostly on the covalent modification of the starting building blocks or linkages. Noncovalent forces that guide the assembly and adhesion of layers to develop two-dimensional (2D) COFs and improve their bulk properties and functionalities, however, are rarely explored. Herein, the "conformational lock" (CL) effect in 2D hydrazine-linked COFs with intralayer F-H interaction is discovered and regulated to stabilize interlayer adhesion and develop a facile strategy to increase their stability, promote selectivity and efficiency in reactive singlet oxygen (1O2)-triggered photocatalytic transformation when acting as photocatalysts. The CL strategy endows the fluorinated COFs with an efficient intersystem crossing process for 1O2 generation and strong interlayer π-π stacking interaction. The 4F-COF with the strongest F-H noncovalent interaction exhibits the highest photocatalytic conversion and selectivity (exceeding 98%) in typical 1O2-dependent transformations, even over 7 continuous photocatalytic cycles. This work demonstrates that promoting intralayer noncovalent interaction in 2D-COFs can impart high photocatalytic activity and stability, and would vigorously inspire their developments in heterogeneous catalysis.

Bimetal-Biligand Frameworks for Spatiotemporal Nitric Oxide-Enhanced Sono-Immunotherapy.

Sonodynamic therapy can trigger immunogenic cell death to augment immunotherapy, benefiting from its superior spatiotemporal selectivity and non-invasiveness. However, the practical applications of sonosensitizers are hindered by their low efficacy in killing cancer cells and activating immune responses. Here, two US Food and Drug Administration-approved drug ligands (ferricyanide and nitroprusside) and two types of metals (copper/iron) are selected to construct a bimetal-biligand framework (Cu[PBA-NO]). Through elaborate regulation of multiple metal/ligand coordination, the systemically administered Cu[PBA-NO] nanoagent shows sono-catalytic and NO release ability under ultrasound irradiation, which can be used for effective sono-immunotherapy. Moreover, Cu[PBA-NO] can downregulate intracellular glutathione levels that would destroy intracellular redox homeostasis and facilitate reactive oxygen species accumulation. The released tumor-associated antigens subsequently facilitate dendritic cell maturation within the tumor-draining lymph node, effectively initiating a T cell-mediated immune response and thereby bolstering the capacity to identify and combat cancer cells. This study paves a new avenue for the efficient cancer sono-immunotherapy.

Polyphenol-Based Self-Assembled Nanomedicine for a Three-Pronged Approach to Reversing Tumor Immunosuppression.

The challenges of multi-pathway immune resistance and systemic toxicity caused by the direct injection of immune checkpoint inhibitors are critical factors that compromise the effectiveness of clinical immune checkpoint blockade therapy. In this context, natural polyphenols have been employed as the primary component to construct a targeted and acid-responsive PD-L1 antibody (αPD-L1) delivery nanoplatform. This platform incorporates garcinol, an inhibitor of the Nuclear Factor Kappa-B (NF-κB) signaling pathway, to regulate pro-tumor immune escape cytokines and regulatory T cells. Additionally, the nanoplatform has been verified to induce immunogenic cell death (ICD), which promotes the maturation of dendritic cells and enhances the activity of cytotoxic T lymphocytes. In vivo and in vitro experimental results demonstrated that the nanoplatform can boost the immune response through a PD-L1 and NF-κB blocking/ICD inducing three-pronged strategy, thereby effectively combating tumor growth and metastasis.

Clinical study on the characteristics and related influencing factors of deliberate drug ingestion in adolescents.

Objective: To analyze the characteristics of deliberate drug ingestion in adolescents and its related influencing factors. Method: This was a retrospective study. A total of 158 cases of deliberate drug ingestion as observation group and 160 cases of other diseases in adolescents as control group were treated in the Emergency Department of Baoding Hospital of Beijing Children's Hospital Affiliated to Capital Medical University from January 2020 to December 2022. The clinical characteristics of adolescents who engaged in deliberate drug ingestion were analyzed, and various factors that could potentially influence deliberate drug ingestion in adolescents were subjected to both univariate and multivariate analysis. Result: There was a progressive increase in the number of patients presenting with mental health issues year by year. Univariate analysis showed that family type, guardian's education level, place of residence, whether they were only children, parents' knowledge of medication, awareness of medication safety, depression/anxiety, negative life events, and social support were risk factors for deliberate drug ingestion in adolescents (all p<0.05). Logistic regression analysis showed that family type, parents' knowledge of medication, awareness of medication safety, whether they were depressed/anxious, negative life events, and social support were independent risk factors for deliberate drug ingestion in adolescents (p<0.05). Conclusion: The incidence of deliberate drug ingestion in adolescents is increasing year by year, and their behavior is influenced by multiple factors. Interventions should be targeted at controllable influencing factors to prevent or reduce deliberate drug ingestion in adolescents.