Multifunctional theranostic nanoplatforms enabling precise targeting and controlled deep tissue therapy are vital. Herein, we present a self-assembled, defect-engineered, biomimetic nanoplatform (CDMBBTO), in which piezoelectric material and downconversion nanoparticles (DCNPs) are co-assembled within a polymer matrix, preventing interactions between both components, thereby allowing each to retain its intrinsic properties while collectively enabling dual second near infrared fluorescence (NIR-II FL)/magnetic resonance (MR) imaging and synergistic piezo/chemodynamic therapy (PZDT/CDT). Mn/Bi codoped piezoelectric BaTiO3 (MBBTO) NPs exhibit a significantly enhanced piezoelectric coefficient ( 5 fold higher than pristine BTO) owing to bandgap modulation induced by defect engineering. The incorporated Mn2+ not only catalyzes Fenton like reactions for sustained tumor suppression but also provides strong T2 weighted MR contrast. Self-assembled NIR-II emissive DCNPs enable deep tissue optical imaging, forming an integrated theranostic system. Cloaking of U87 glioma cell membranes imparts homologous tumor targeting capability. In vivo dual modal imaging reveals efficient tumor accumulation, with peak NIR-II FL and MR signal intensities observed 6 h post-injection. Upon ultrasound activation, CDMBBTO elicits potent tumor ablation through synergistic reactive oxygen species generation and immune modulation, characterized by macrophage polarization (M2 → M1) and upregulation of proinflammatory cytokines (TNF-α and IL-6). This work establishes CDMBBTO as a powerful nanoplatform for dual modal imaging-guided, immune potentiated PZDT/CDT toward effective glioblastoma treatment.

Doxorubicin-induced cardiotoxicity represents a significant clinical adverse effect associated with cancer chemotherapy treatment. Inspired by cancer drug resistance mechanisms, we propose a novel strategy termed transient overexpression of p-glycoprotein for cardiac reprogramming to induce cardiac drug resistance as a treatment for cardiotoxicity. This approach involves reprogramming cardiomyocytes by delivering lipid nanoparticles-based mRNA therapeutics to induce temporary p-glycoprotein overexpression, which in turn reduces intracellular doxorubicin levels and suppresses cytotoxic effects. This strategy results in promoted p-glycoprotein overexpression in cardiomyocytes, improved survival rates, restored cardiac function, and reduced myocardial fibrosis and structural cardiac alterations in a mouse model with doxorubicin-induced cardiotoxicity. Furthermore, studies in large animals show that intrapericardial injection of lipid nanoparticles with p-glycoprotein mRNAs effectively mitigates adverse effects and restores cardiac function in male pig models of doxorubicin-induced cardiotoxicity. The significant cardioprotective effects achieved through cardiac drug resistance highlight the safety, efficacy, and clinical potential of this strategy for alleviating doxorubicin-induced cardiotoxicity.

In this study, a novel Immunoglobulin G (IgG) binding, Programmed Cell Death-Ligand 1 (PD-L1) targeting affibody, IgBD-ZPD-L1, was constructed by genetically fusing the PD-L1-specific affibody ZM1 with the IgG-binding domain (IgBD). IgBD-ZPD-L1 could simultaneously bind to IgG, PD-L1 receptor protein, and PD-L1-positive tumor cells. Furthermore, the fusion of IgBD significantly prolonged the in vivo circulation half-life of IgBD-ZPD-L1 by binding to endogenous IgG, enhancing tumor accumulation and immunotherapeutic effects. Subsequently, anti-angiogenic/immunotherapeutic and dual-targeted combination immunotherapy strategies based on IgBD-ZPD-L1 significantly improved tumor immunotherapy efficacy. Finally, IgBD-ZPD-L1 was conjugated with Indocyanine green (ICG) to construct a novel tumor-targeting photosensitizer, ICG-IgBD-ZPD-L1. In vivo, ICG-IgBD-ZPD-L1 enabled clear fluorescence imaging of tumors for diagnosis and displayed excellent photothermal properties for tumor thermal ablation, demonstrating potent antitumor effects. More importantly, ICG-IgBD-ZPD-L1-mediated photothermal/immunotherapy exerted significant therapeutic effects on primary tumors and upregulated antitumor immune responses, synergistically enhancing the efficacy of immunotherapy and inhibiting tumor metastasis. As a result, this photothermal/immunotherapy strategy ultimately achieved a synergistic therapeutic effect greater than the sum of individual treatments. In conclusion, these results suggested that IgBD-ZPD-L1 could be developed as a multifunctional IgG-delivery platform for combination tumor immunotherapy, providing a promising theoretical basis for clinical development and translation of tumor immunotherapeutic strategies.

Photodynamic therapy (PDT) generally employs cytotoxic reactive oxygen species (ROS) for eliminating tumors. However, most photosensitizers rely on oxygen to sensitize ROS production, which conflicts with the pathological hypoxia environment in solid tumors. Thus, developing oxygen‐independent therapeutic strategies for the combat of tumors is in urgent need. In this work, we report the usage of novel photoinduced reactive nitrogen radical cations for oxygen‐independent PDT. Three triarylamine derivatives (PNA‐1/2/9) are facilely constructed through a highly efficient one‐step reaction from common commercially available reagents, and demonstrate outstanding photoinduced oxidative capabilities, which are confirmed as triarylamine radical cations (PNA •+ ). The generation of PNA •+ does not require oxygen, and its stability surpasses that of ROS, leading to a more effective PDT outcome. Detailed studies reveal the excellent lipid‐droplet targeting of PNA and high in vitro PDT efficacy even in hypoxic environments. Remarkably, these triarylamines demonstrate excellent two‐photon absorbance with high cross‐sections of up to 700 GM. Furthermore, effectively inhibition of tumor growth is observed in mouse model under two‐photon excitation (808 nm). To the best of the knowledge, this work is the first case to use triarylamine radical cations for oxygen‐independent PDT, opening a new avenue for the effective treatment of hypoxic tumors.

Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC EVs) have gained significant attention in biomedical and therapeutic applications. Nevertheless, their translation in clinical practice remains limited due to the lack of scalable manufacturing techniques and the prevailing safety concerns. Cell-derived extruded nanovesicles (eNVs) with high production efficiency are regarded as promising substitutes of EVs. However, like MSC EVs, their potential for tumorigenicity has yet to be exhaustively investigated. In this work, we investigated the tumorigenicity of umbilical cord mesenchymal stem cell-derived eNVs (UMSC eNVs). A549 cancer cell-derived eNVs (A549 eNVs) with potential tumorigenicity were also prepared for comparative analysis. Our characterization findings revealed that, although UMSC eNVs and A549 eNVs exhibited similar morphologies, they differed in their molecular composition. Subsequent animal experiments demonstrated the low tumorigenicity risk of UMSC eNVs in inducing tumor pathogenesis and development. Furthermore, microRNAs (miRNAs) profiling analyses suggested that the reduced tumorigenicity of UMSC eNVs might be due to the downregulation of hsa-miR-21-5p_R+1 and hsa-miR-192-5p, and upregulation of hsa-miR-143-3p and hsa-miR-146a-5p compared to A549 eNVs. The present study provided direct experimental confirmation and underlying miRNA profiling evidence of the biosafety of UMSC eNVs in terms of tumorigenicity, which will promote the future advancement and translation of UMSC eNVs.

The management of type 2 diabetes not only requires effective medications to regulate blood glucose levels, but also needs to consider the economic implications. Liraglutide, dulaglutide, and semaglutide, three widely-used glucagon-like peptide-1 receptor agonists, have shown significant efficacy in diabetes treatment. This review aimed to systematically assess the cost-effectiveness of liraglutide in comparison to dulaglutide or oral semaglutide for treating type 2 diabetes. A comprehensive literature search was performed in PubMed, Web of Science, Scopus, Embase, and Cochrane. Studies published up to December 31, 2024 were retrieved. Two independent reviewers carefully screened the titles, abstracts, and full-text articles, and any disagreements were resolved with the involvement of a third reviewer. Data extraction was carried out following a pre-designed form. 12 studies were included, evaluating liraglutide vs. dulaglutide (n = 8) and liraglutide vs. oral semaglutide (n = 6). The minimum consolidated health economic evaluation reporting standards score for the studies was 0.75. The included studies exhibited similar results in cost-effective. Oral semaglutide would be more effective and cost-saving in the US, Netherlands, Spain, and the UK. According to the available studies, liraglutide vs. dulaglutide or oral semaglutide for the treatment of type 2 diabetes is considered not to be cost-effective. Cost-effectiveness also plays a vital role in the inclusion of these drugs in healthcare reimbursement policies. The literature suggested that dulaglutide or oral semaglutide may be more cost-effective than liraglutide.

Chimeric antigen receptor (CAR)-T cell therapy represents a promising strategy for cancer treatment. However, the diversity of solid tumor antigens and the poor infiltration of CAR-T cells significantly hinder the efficacy of CAR-T therapies against tumors. Here, a spatially distributed microneedle system (SDMNS) is developed that leverages bioorthogonal reactions to activate and guide endogenous T cells to tumors for effective destruction. The SDMNS consists of two dissolving microneedles, each loaded with complementary bioorthogonal groups and applied separately to lymph nodes and tumor sites. One microneedle loaded with two dibenzocyclooctyne (DBCO)-modified antibodies activates T cells and labels them with bioorthogonal groups in lymph nodes. The other microneedle, containing N-azidoacetylmannosamine-tetraacylated (Ac4ManNAz) for glycometabolic labeling of tumor cells, and the T cell chemotactic factor IP10, is applied directly to the tumor site. The in vivo studies demonstrate that SDMNS effectively directs the migration and infiltration of endogenous activated T cells into the tumors. Through a bioorthogonal click reaction, DBCO-modified T cells conjugate with azide (N3)-modified tumor cells, eliciting robust antitumor immune responses and durable immune memory. The SDMNS offers a novel strategy to overcomes tumor heterogeneity by facilitating the directed migration of endogenous T cells.

Accurate in-situ intracellular O2 measurements are highly desired for the study of O2-related physiology and pathology. Calibratable, ratiometric luminescent O2-responsive probes, which are self-referenced, are ideal for such applications. The common strategy for designing such probes involves the conjugation of a fluorophore and a phosphorophore. However, this dual-chromophore approach often results in a large molecular size and high photobleaching susceptibility. Here we report a single-chromophore-based dual-emission Pt(II) complex named PtQTAC for O2 sensing. PtQTAC has a simple structure and can be prepared with ease. Upon single excitation, PtQTAC simultaneously emits both fluorescence and phosphorescence, with well-separated spectra and balanced emission intensities. It shows a ratiometric response to O2 levels, which fits the Stern-Volmer equation. When incorporated into nanoparticles, PtQTAC retains its O2 sensitivity and could be readily taken up by cells. By detecting the signal from PtQTAC under a confocal microscope, intracellular O2 concentrations can be precisely mapped and quantified after calibration. To the best of our knowledge, this is the first demonstration of intracellular O2 concentration quantification using a single-chromophore-based luminescent probe.

Plant‐derived extracellular vesicles (pEVs) are nanosized vesicles that have comparable structure and properties to EVs derived from mammalian cells. Prior studies have confirmed that pEVs have remarkable efficacy in the treatment of human diseases, such as cancer. As critical regulators of gene expression, microRNAs (miRNAs) are abundant in pEVs. However, their potential functional roles and regulatory mechanisms in mediating crosskingdom regulation of mammalian cells by pEVs remain undefined. In particular, the similarities and differences in the miRNA profiles of various pEVs in gene regulation remain elusive. Herein, pEVs are isolated from grapefruit, ginger, lemon, and grape, and small RNA (sRNA) libraries are constructed to perform sRNA sequencing. Only 15 consistently expressed miRNAs are identified in these pEVs. Furthermore, the top 20 miRNAs of each pEV are highly expressed among total miRNAs, accounting for 79.93–87.12%. Through functional annotation analysis of the miRNA target genes, these miRNAs are found to be involved in regulating the progression of human cancer and viral infection. Taken together, this study demonstrates that the miRNAs contained in the pEVs play a critical role in mediating the potential crosskingdom regulatory effects against human genes and highlights their significant potential therapeutic applications in human diseases.

BACKGROUND:Adverse events (AE) in dupilumab-induced ocular surface diseases (DIOSD) have raised concerns regarding its safety. The objective of this study was to evaluate DIOSD by employing database analysis and clinical case review, along with mechanism analysis. RESEARCH DESIGN AND METHODS:Database AE data were extracted from FAERS from 2017 Quarter 1 (Q1) to 2023 Q1. Disproportionality analyses were performed to identify the risk signals associated with DIOSD. Case reports/case series reported on DIOSD from March 2017 to June 2023 were collected for a literature review. The mechanisms of DIOSD were investigated through disease-gene interaction network analysis. RESULTS:A total of 85 signals related to DIOSD were detected from FAERS. The most reported AE was 'dry eye' (n = 3503, ROR 20.32, 95% CI: 19.53-21.14). There were 36 articles, including 201 cases showing the evidence of DIOSD, with an average age of 43 years. About 64.18% patients suffered from severe atopic dermatitis, and 48.26% were reported with a previous ocular history. The mechanisms study suggested that tumor necrosis factor plays an important role in DIOSD. CONCLUSIONS:Our findings support that dupilumab use is associated with exacerbation or new-onset OSD. Particular attention should be focused on eye symptoms during dupilumab use.

Chemotherapy proves to be a successful method in treating primary breast cancer. Ironically, some commonly used chemotherapeutics may promote lung metastasis by increasing the activity of activating transcription factor 3 (ATF3). Thus, it is necessary to inhibit tumor metastasis while improving the anti-tumor effect of anti-cancer drugs. Herein, using curcumol (CUR) that possesses both anti-tumor and anti-metastasis activities as a model drug, we designed the nanogels based on temperature-responsive self-assembly and glutathione-triggered disassembly to address the abovementioned conflicts. Briefly, the copolymers (H-SS-P) were synthesized by coupling poly(N-isopropylacrylamide) onto hyaluronic acid (HA) via a disulfide bond-containing linker cystamine dihydrochloride. Copolymers could self-assemble into regular spherical nanogels at 37 °C with a 40-nm particle size for PNIPAAm's thermosensitivity. Hydrophobic CUR could be automatically entrapped into the core of nanogels. The H-SS-P@CUR nanogels could release drugs quickly upon exposure to the reductive tumor microenvironment. The superior efficacy of H-SS-P@CUR on inhibiting tumor growth was validated through assays both in vivo and in vitro. Moreover, nanogels may better down-regulate the expression of ATF3 protein by enhancing the cell uptake and tumor targeting of CUR, thereby significantly improving the anti-metastasis effect of CUR. This work not only proposed a novel strategy to simplify the preparation process of nanogels but also achieved effective drug delivery with enhanced anti-cancer and anti-metastasis effects.

Triple-negative breast cancer (TNBC) remains a significant challenge in terms of treatment, with limited efficacy of chemotherapy due to side effects and acquired drug resistance. In this study, a threose nucleic acid (TNA)-mediated antisense approach is employed to target therapeutic Akt genes for TNBC therapy. Specifically, two new TNA strands (anti-Akt2 and anti-Akt3) are designed and synthesized that specifically target Akt2 and Akt3 mRNAs. These TNAs exhibit exceptional enzymatic resistance, high specificity, enhance binding affinity with their target RNA molecules, and improve cellular uptake efficiency compared to natural nucleic acids. In both 2D and 3D TNBC cell models, the TNAs effectively inhibit the expression of their target mRNA and protein, surpassing the effects of scrambled TNAs. Moreover, when administered to TNBC-bearing animals in combination with lipid nanoparticles, the targeted anti-Akt TNAs lead to reduced tumor sizes and decreased target protein expression compared to control groups. Silencing the corresponding Akt genes also promotes apoptotic responses in TNBC and suppresses tumor cell proliferation in vivo. This study introduces a novel approach to TNBC therapy utilizing TNA polymers as antisense materials. Compared to conventional miRNA- and siRNA-based treatments, the TNA system holds promise as a cost-effective and scalable platform for TNBC treatment, owing to its remarkable enzymatic resistance, inexpensive synthetic reagents, and simple production procedures. It is anticipated that this TNA-based polymeric system, which targets anti-apoptotic proteins involved in breast tumor development and progression, can represent a significant advancement in the clinical development of effective antisense materials for TNBC, a cancer type that lacks effective targeted therapy. A TNA-mediated antisense approach selectively targets and suppresses Akt2 and Akt3 genes, providing a promising therapeutic strategy for TNBC. The designed TNAs convincingly inhibit tumor growth. The TNA system shows great potential as a cost-effective and scalable platform for TNBC treatment due to its remarkable resistance to enzymatic degradation, use of inexpensive synthetic reagents, and simple production procedures. image

This feature article delves into the realm of alpha-l-threose nucleic acid (TNA), an artificial nucleic acid analog characterized by a backbone comprising an unconventional four-carbon sugar, alpha-l-threose, with phosphodiester linkages connecting at the 2 ' and 3 ' vicinal positions of the sugar ring. Within this article, we encapsulate the potential, progress, current state of the art, and persisting challenges within TNA research. Kicking off with a historical overview of xeno nucleic acids (XNAs), the discussion transitions to the compelling attributes and structure-property relationships of TNAs as advanced tools when contrasted with natural nucleic acids. Noteworthy aspects such as their advantageous spatial arrangements of functional groups around the sugar ring, stable Watson-Crick base pairing, high binding affinity, biostability, biocompatibility, and in vivo bio-safety are highlighted. Moreover, the narrative unfolds the latest advancements in chemical and biological methodologies for TNA synthesis, spanning from monomer and oligomer synthesis to polymerization, alongside cutting-edge developments in enzyme engineering aimed at bolstering large-scale TNA synthesis for in vitro selection initiatives. The article sheds light on the evolution of TNA aptamers over time, expounding on the tools and selection techniques engineered to unearth superior binding aptamers and TNA catalysts. Furthermore, the article accentuates the recent applications of TNAs across diverse domains such as molecular detection, immunotherapy, gene therapy, synthetic biology, and molecular computing. In conclusion, we summarize the key aspects of recent TNA research, address persisting gaps and challenges, and provide crucial insights and future perspectives in the dynamic domain of TNA research. This feature article summarizes the key aspects of recent TNA research, addresses persisting gaps and challenges, and provides crucial insights and future perspectives in the dynamic domain of TNA research.

Background Sepsis is a critical condition in which organ dysfunction occurs because of aberrant response to infection, resulting in a life-threatening situation. The lung, which is the most vulnerable target organ, often experiences severe damage. IL-22, which is secreted by various immunocytes, can mitigate inflammation associated with pulmonary fibrosis and lung injury. Nevertheless, its precise function in SALI is still unclear. The current investigation was undertaken to delve into the effect of IL-22 in sepsis. Methods: In this study, a mouse CLP model of sepsis was used to detect the expression of IL-22 and investigate the effect of rIL-22 treatment, following which the survival rate and lung tissue injury and apoptosis was determined. LPS induced bronchial epithelial cells ( BEAS-2B) apoptosis model with or without rIL-22 in vitro to further evaluate the effect and mechanism of IL-22. Results The level of IL-22 in serum and lung tissue was increased after CLP. rIL-22 administration increased the survival rates of septic mice and suppressed the secretion of proinflammatory cytokines, and alleviated SALI. IL-22 also alleviated apoptosis in lung tissue and decreased the level of cleaved caspase-3/7.Furthermore, rIL-22 alleviated LPS induced BEAS-2Bs apoptosis which was associated with an increase in the phosphorylation of STAT3. Conclusions The results of this study suggest that IL-22 alleviates lung epithelial cell apoptosis and protects mice against SALI via the STAT3 signalling pathway,emphasizing its potential therapeutic value for sepsis.

Self-assembly processes commonly occur in various biological contexts to form functional biological structures. However, the self-assembly of nanofibers within cells by heterologous molecules showing a biological function is rare. In this work, we reported the intracellular formation of fluorescent nanofibers by a natural small molecule, lycobetaine (LBT), which facilitated the direct physical connection between mitochondria and synchronized their membrane potential oscillations. The luminescent properties of LBT enabled the real-time observation of nanofiber formation, while the semiconductive nature of the LBT nanofiber facilitated electrical signal transduction among the connected mitochondria. This study introduces an approach to modulate mitochondrial connectivity within cells using "nano-cables" which facilitate studies on synchronized mitochondrial operations and the underlying mechanisms of drug action.

Microwave absorption structures have significant application potential in electromagnetic compatibility, stealth technology, and radar applications.However, practical usage is constrained by limitations such as increased thickness, narrow absorption bandwidth, and high manufacturing costs, which impede their widespread adoption. In this paper, inspired by bionics and based on the distribution characteristics of helical arrangement of sunflower fruit, a novel sunflower-inspired composite metastructure is proposed. Combined with the advantages of composite metamaterial CB-CIP/PLA, the gradient characteristic impedance increment of the composite metastructure is precisely controlled to optimize its structural parameters. The experimental results show that the effective absorption broadband with an absorption rate of more than 90% (RL≦−10 dB) can reach 12.13GHz, including C, X and Ku bands, and the manufacturing cost is low. These results show that the study in this paper can provide useful reference for other applications of bioheuristic structure design in the field of microwave absorption.

The human genome's nucleotide sequence variation, such as single nucleotide mutations, can cause numerous genetic diseases. However, detecting nucleic acids accurately and rapidly in complex biological samples remains a major challenge. While natural deoxyribonucleic acid (DNA) has been used as biorecognition probes, it has limitations like poor specificity, reproducibility, nuclease-induced enzymatic degradation, and reduced bioactivity on solid surfaces. To address these issues, we introduce a stable and reliable biosensor called graphene oxide (GO)- threose nucleic acid (TNA). It comprises chemically modified TNA capture probes on GO for detecting and imaging target nucleic acids in vitro and in vivo, distinguishing single nucleobase mismatches, and monitoring dynamic changes in target microRNA (miRNA). By loading TNA capture probes onto the GO substrate, the GO-TNA sensing platform for nucleic acid detection demonstrates a significant 88-fold improvement in the detection limit compared to TNA probes alone. This platform offers a straightforward preparation method without the need for costly and labor-intensive isolation procedures or complex chemical reactions, enabling real-time analysis. The stable TNA-based GO sensing nanoplatform holds promise for disease diagnosis, enabling rapid and accurate detection and imaging of various disease-related nucleic acid molecules at the in vivo level. STATEMENT OF SIGNIFICANCE: The study's significance lies in the development of the GO-TNA biosensor, which addresses limitations in nucleic acid detection. By utilizing chemically modified nucleic acid analogues, the biosensor offers improved reliability and specificity, distinguishing single nucleobase mismatches and avoiding false signals. Additionally, its ability to detect and image target nucleic acids in vivo facilitates studying disease mechanisms. The simplified preparation process enhances practicality and accessibility, enabling real-time analysis. The biosensor's potential applications extend beyond healthcare, contributing to environmental analysis and food safety. Overall, this study's findings have substantial implications for disease diagnosis, biomedical research, and diverse applications, advancing nucleic acid detection and its impact on various fields.

Recent findings have indicated that the deficiency of inhibitory programmed cell death ligand 1 (PD-L1) and galectin-9 (Gal-9) in pancreatic β-cells is associated with the progression of type 1 diabetes (T1D). This suggests that exogenous PD-L1 and Gal-9 may have promising potential as therapeutics for the treatment of T1D. In light of these reports, a recent work investigated the potential of artificial extracellular vesicles (aEVs) with the presentation of PD-L1 and Gal-9 ligands (PD-L1-Gal-9 aEVs) as a treatment for T1D, with the findings published in Diabetes. Notably, the PD-L1-Gal-9 aEVs demonstrated the capacity to induce apoptosis of T cells and the formation of regulatory T (Treg) cells, thereby maintaining immune tolerance. Furthermore, the in vivo administration of PD-L1-Gal-9 aEVs resulted in a reduction in T cell infiltration in the pancreas, an increase in β-cell integrity protection, a significant decrease in blood glucose levels, and a delay in the progression of T1D. In conclusion, this study proposed an innovative approach to the treatment of T1D progression through the use of immunosuppressive EVs. This highlight provides a comprehensive analysis and discussion of the pivotal findings of this study.

The cardiotoxicity induced by immune checkpoint inhibitors (ICIs) is associated with high mortality rates. T cells play an important role in ICI-induced cardiac injury. The inhibition of local T-cell activity is considered an effective strategy for alleviating ICI-related cardiotoxicity. Tumor-derived extracellular vesicles (EVs) contribute to immunosuppression via PD-L1 overexpression. In this study, a bioorthogonal metabolic engineering-driven EV redirecting (Biomeder) strategy for in situ engineered EVs with myocardial-targeting peptides is developed. Accumulated tumor-derived EV (TuEVs) reverses the immune environment in the heart by increasing PD-L1 levels in cardiomyocytes and/or by directly inhibiting T-cell activity. More importantly, it is found that the redirection of TuEVs further disrupts immunosuppression in tumors, which facilitates anti-tumor activity. Thus, redirecting TuEVs to the heart simultaneously enhances the antitumor efficacy and safety of ICI-based therapy. Furthermore, the Biomeder strategy is successfully expanded to prevent ICI-induced type 1 diabetes. This Biomeder technique is a universal method for the treatment of various ICI-related adverse events.

Monitoring and regulating the formation of toxic byproducts in advanced oxidation processes (AOPs) is of great significance for their practical application in water treatment. In this work, we found that dichloroacetonitrile (DCAN), a common N-containing byproduct in chloramination disinfection, can be formed with the co-presence of g-C3N4 and chloride in a peroxymonosulfate (PMS) system. The measured value was 12.01 μM within 12 h under the given conditions. Structure analysis of raw and used g-C3N4 demonstrated that g-C3N4 decomposition indeed occurred, and C=N bonds acted as primary active sites, releasing N resources for subsequent DCAN formation. Additionally, multiple parameters, including the reactant (i.e., g-C3N4, PMS, Cl-, phenol) dose and solution pH, were observed to remarkably affect the yield of DCAN. Phenol was identified as the organic precursor of DCAN and may cooperate with inorganic chloramine to promote DCAN formation via the decarboxylation pathway. This study highlights the generation of DCAN in N-involved catalyst-based AOPs and improves understanding of the DCAN formation mechanism.