Effect of ultrashort-acting ß-blockers on 28-day mortality in patients with sepsis with persistent tachycardia despite initial resuscitation: a meta-analysis of randomized controlled trials and trial sequential analysis.

Purpose: This meta-analysis aims to identify whether patients with sepsis who have persistent tachycardia despite initial resuscitation can benefit from ultrashort-acting ß-blockers. Materials and methods: Relevant studies from MEDLINE, the Cochrane Library, and Embase were searched by two independent investigators. RevMan version 5.3 (Cochrane Collaboration) was used for statistical analysis. Results: A total of 10 studies were identified and incorporated into the meta-analysis. The results showed that the administration of ultrashort-acting ß-blockers (esmolol/landiolol) in patients with sepsis with persistent tachycardia despite initial resuscitation was significantly associated with a lower 28-day mortality rate (risk ratio [RR], 0.73; 95% confidence interval [CI], 0.57-0.93; and p˂0.01). Subgroup analysis showed that the administration of esmolol in patients with sepsis was significantly associated with a lower 28-day mortality rate (RR, 0.68; 95% CI, 0.55-0.84; and p˂0.001), while there was no significant difference between the landiolol and control groups (RR, 0.98; 95% CI, 0.41-2.34; and p = 0.96). No significant differences between the two groups were found in 90-day mortality, mean arterial pressure (MAP), lactate (Lac) level, cardiac index (CI), and troponin I (TnI) at 24 h after enrollment. Conclusion: The meta-analysis indicated that the use of esmolol in patients with persistent tachycardia, despite initial resuscitation, was linked to a notable reduction in 28-day mortality rates. Therefore, this study advocates for the consideration of esmolol in the treatment of sepsis in cases where tachycardia persists despite initial resuscitation.

Review of the therapeutic effects of traditional Chinese medicine in sepsis-associated encephalopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis-associated encephalopathy (SAE) is a common and serious complication during the acute phase of and after recovery from sepsis that seriously affects the quality of life of patients. Traditional Chinese medicine (TCM) has been widely used in modern medicine for neurological anomalies and has become a therapeutic tool for the treatment of SAE due to its multitargeting effects and low toxicity and side effects. AIMS OF THE STUDY: This review provides insights into the pathogenesis and treatments of SAE, focusing on the clinical and experimental impacts of TCM formulations and their single components. METHODS: Several known databases such as PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI), and others were extensively explored with keywords and phrases such as "sepsis-associated encephalopathy", "traditional Chinese medicine", "herbs", "SAE", "sepsis", "cerebral" or other relevant terms to obtain literature between 2018 and 2024. RESULTS: Extensive evidence indicated that TCM could decrease mortality and normalize neurological function in patients with sepsis; these effects might be associated with factors such as reduced oxidative stress and downregulated expression of inflammatory factors. CONCLUSIONS: TCM shows notable efficacy in treating SAE, warranting deeper mechanistic studies to optimize its clinical application.

Cadherin 17 Nanobody-Mediated Near-Infrared-II Fluorescence Imaging-Guided Surgery and Immunotoxin Delivery for Colorectal Cancer.

Surgery and targeted therapy are of equal importance for colorectal cancer (CRC) treatment. However, complete CRC tumor resection remains challenging, and new targeted agents are also needed for efficient CRC treatment. Cadherin 17 (CDH17) is a membrane protein that is highly expressed in CRC and, therefore, is an ideal target for imaging-guided surgery and therapeutics. This study utilizes CDH17 nanobody (E8-Nb) with the near-infrared (NIR) fluorescent dye IRDye800CW to construct a NIR-II fluorescent probe, E8-Nb-IR800CW, and a Pseudomonas exotoxin (PE)-based immunotoxin, E8-Nb-PE38, to evaluate their performance for CRC imaging, imaging-guided precise tumor excision, and antitumor effects. Our results show that E8-Nb-IR800CW efficiently recognizes CDH17 in CRC cells and tumor tissues, produces high-quality NIR-II images for CRC tumors, and enables precise tumor removal guided by NIR-II imaging. Additionally, fluorescent imaging confirms the targeting ability and specificity of the immunotoxin toward CDH17-positive tumors, providing the direct visible evidence for immunotoxin therapy. E8-Nb-PE38 immunotoxin markedly delays the growth of CRC through the induction of apoptosis and immunogenic cell death (ICD) in multiple CRC tumor models. Furthermore, E8-Nb-PE38 combined with 5-FU exerts synergistically antitumor effects and extends survival. This study highlights CDH17 as a promising target for CRC imaging, imaging-guided surgery, and drug delivery. Nanobodies targeting CDH17 hold great potential to construct NIR-II fluorescent probes for surgery navigation, and PE-based toxins fused with CDH17 nanobodies represent a novel therapeutic strategy for CRC treatment. Further investigation is warranted to validate these findings for potential clinical translation.

Manipulation of Moiré Superlattice in Twisted Monolayer-multilayer Graphene by Moving Nanobubbles.

In the heterostructure of two-dimensional (2D) materials, many novel physics phenomena are strongly dependent on the Moiré superlattice. How to achieve the continuous manipulation of the Moiré superlattice in the same sample is very important to study the evolution of various physical properties. Here, in minimally twisted monolayer-multilayer graphene, we found that bubble-induced strain has a huge impact on the Moiré superlattice. By employing the AFM tip to dynamically and continuously move the nanobubble, we realized the modulation of the Moiré superlattice, like the evolution of regular triangular domains into long strip domain structures with single or double domain walls. We also achieved controllable modulation of the Moiré superlattice by moving multiple nanobubbles and establishing the coupling of nanobubbles. Our work presents a flexible method for continuous and controllable manipulation of Moiré superlattices, which will be widely used to study novel physical properties in 2D heterostructures.

Circ_0008571 modulates the phenotype of vascular smooth muscle cells by targeting miR-145-5p in intracranial aneurysms.

BACKGROUND: The dysfunction of human vascular smooth cells (hVSMCs) is significantly connected to the development of intracranial aneurysms (IAs). By suppressing the activity of microRNAs (miRNAs), circular RNAs (circRNAs) participate in IA pathogenesis. Nevertheless, the role of hsa_circ_0008571 in IAs remains unclear. METHODS: circRNA sequencing was used to identify circRNAs from human IA tissues. To determine the function of circ_0008571, Transwell, wound healing, and cell proliferation assays were conducted. To identify the target of circ_0008571, the analyses of CircInteractome and TargetScan, as well as the luciferase assay were carried out. Furthermore, circ_0008571 knockdown and over-expression were performed to investigate its functions in IA development and the underlying molecular mechanisms. RESULTS: Both hsa_circ_0008571 and Integrin beta 8 (ITGB8) were downregulated, while miR-145-5p transcription was elevated in the aneurysm wall of IAs patients compared to superficial temporal artery tissues. In vitro, cell migration and growth were dramatically suppressed after hsa_circ_0008571 overexpression. Mechanistically, has_circ_0008571 could suppress miR-145-5p activity by direct sponging. Moreover, we found that ITGB8 expression and the activation of the TGF-ß-mediated signaling pathway were significantly enhanced. CONCLUSION: The hsa_circ_0008571-miR-145-5p-ITGB8 axis plays an essential role in IA progression.

Ligand-Enabled ortho-Selective C-H Olefination of Tertiary Aniline Derivatives.

A highly ortho-selective CAr-H olefination of tertiary anilines without a directing group was developed. This reaction tolerated various substituted arenes and olefin coupling partners, affording ortho-olefination products in moderate to good yields. Preliminary mechanistic studies showed that N-Ac-d-Ala, Ag2CO3, and BQ were the key factors for tuning the regioselectivity from para to ortho. Density functional theory was used to achieve a theoretical understanding of the ortho selectivity.

Nanobody-Engineered Biohybrid Bacteria Targeting Gastrointestinal Cancers Induce Robust STING-Mediated Anti-Tumor Immunity.

Bacteria can be utilized for cancer therapy owing to their preferential colonization at tumor sites. However, unmodified non-pathogenic bacteria carry potential risks due to their non-specific targeting effects, and their anti-tumor activity is limited when used as monotherapy. In this study, a biohybrid-engineered bacterial system comprising non-pathogenic MG1655 bacteria modified with CDH17 nanobodies on their surface and conjugated with photosensitizer croconium (CR) molecules is developed. The resultant biohybrid bacteria can efficiently home to CDH17-positive tumors, including gastric, pancreatic, and colorectal cancers, and significantly suppress tumor growth upon irradiation. More importantly, biohybrid bacteria-mediated photothermal therapy (PTT) induced abundant macrophage infiltration in a syngeneic murine colorectal model. Further, that the STING pathway is activated in tumor macrophages by the released bacterial nucleic acid after PTT is revealed, leading to the production of type I interferons. The addition of CD47 nanobody but not PD-1 antibody to the PTT regimen can eradicate the tumors and extend survival. This results indicate that bacteria endowed with tumor-specific selectivity and coupled with photothermal payloads can serve as an innovative strategy for low-immunogenicity cancers. This strategy can potentially reprogram the tumor microenvironment by inducing macrophage infiltration and enhancing the efficacy of immunotherapy targeting macrophages.

Prognostic marker VPS72 could promote the malignant progression of prostate cancer.

BACKGROUND: This paper attempted to clarify the role and mechanism of vacuolar protein sorting-associated protein 72 homolog (VPS72) in the progression of prostate cancer (PCa). METHODS: Clinical information and gene expression profiles of patients with prostate cancer were obtained from The Cancer Genome Atlas (TCGA). VPS72 expression in PCa and the potential mechanism by which VPS72 affects PCa progression was investigated. Next, we performed COX regression analysis to identify the independent prognostic factors of PCa, and constructed a nomogram. The sensitivity of chemotherapeutic medications was anticipated using "pRRophetic". Subsequently, in vitro assays to validate the effect of VPS72 on PCa cell proliferation, migration and susceptibility to anti-androgen therapy. RESULTS: The expression of VPS72 was considerably higher in PCa tissues compared to normal tissues. Significant correlations were found between high VPS72 expression and a poor prognosis and adverse clinicopathological factors. The nomogram model constructed based on VPS72 expression has good predictive performance. According to GSEA, VPS72-related genes were enriched in the NF-kB pathways, cytokine-cytokine receptor interaction and chemokine signaling pathway in PCa. Although PCa with low VPS72 expression was more adaptable to chemotherapeutic medications, our in vitro experiment showed that VPS72 knockdown significantly decreased the PCa cell migration, proliferation, and resistance to anti-androgen therapy. CONCLUSIONS: In summary our findings suggests that VPS72 could play a crucial role in the malignant progression of PCa, and its expression level can be employed as a possible biomarker of PCa prognosis.

Unravelling the metabolic landscape of cutaneous melanoma: Insights from single-cell sequencing analysis and machine learning for prognostic assessment of lactate metabolism.

This manuscript presents a comprehensive investigation into the role of lactate metabolism-related genes as potential prognostic markers in skin cutaneous melanoma (SKCM). Bulk-transcriptome data from The Cancer Genome Atlas (TCGA) and GSE19234, GSE22153, and GSE65904 cohorts from GEO database were processed and harmonized to mitigate batch effects. Lactate metabolism scores were assigned to individual cells using the 'AUCell' package. Weighted Co-expression Network Analysis (WGCNA) was employed to identify gene modules correlated with lactate metabolism. Machine learning algorithms were applied to construct a prognostic model, and its performance was evaluated in multiple cohorts. Immune correlation, mutation analysis, and enrichment analysis were conducted to further characterize the prognostic model's biological implications. Finally, the function of key gene NDUFS7 was verified by cell experiments. Machine learning resulted in an optimal prognostic model, demonstrating significant prognostic value across various cohorts. In the different cohorts, the high-risk group showed a poor prognosis. Immune analysis indicated differences in immune cell infiltration and checkpoint gene expression between risk groups. Mutation analysis identified genes with high mutation loads in SKCM. Enrichment analysis unveiled enriched pathways and biological processes in high-risk SKCM patients. NDUFS7 was found to be a hub gene in the protein-protein interaction network. After the expression of NDUFS7 was reduced by siRNA knockdown, CCK-8, colony formation, transwell and wound healing tests showed that the activity, proliferation and migration of A375 and WM115 cell lines were significantly decreased. This study offers insights into the prognostic significance of lactate metabolism-related genes in SKCM.

Single-Cell Sensitive Colorimetric pH Detection Based on Microscope Ratiometric Grayscale.

Rapid and accurate identification of the intracellular pH is critical in the field of biomedicine. In this work, we effectively identified and quantified the intracellular pH and its distribution at the single-cell level using an image sensor based on an ordinary bright-field optical microscope that divided the cell staining images into their red (R) and blue (B) channels. The grayscale of the R and B channels was subjected to a ratiometric operation to generate ratiometric grayscale cell images of the microscope. A standard curve of pH against ratiometric grayscale curve was then obtained by incubating HeLa cells at pH 6.00-7.60 in a high concentration K+ ion buffer solution containing nigericin for obtaining certain intracellular pH values. A good correlation was evidenced between pH and the ratiometric grayscale of the R and B channels in the pH range of 6.00-7.60. Subsequently, the intracellular pH value of the A549 cells under the experimental conditions was measured to be 7.22 ± 0.01 by the method. Furthermore, the changes in the intracellular pH of HeLa cells stimulated with hydrogen peroxide were sensitively monitored, which demonstrated the applicability of the method. Due to its ease of use, the developed colorimetric microscopy pH detection and monitoring method provide prospects for pH-related single-cell studies.

Effect of Chinese Medicine in Patients with COVID-19: A Multi-center Retrospective Cohort Study.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION: This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).

Fe-Co Co-Doped 1D@2D Carbon-Based Composite as an Efficient Catalyst for Zn-Air Batteries.

A Fe-Co dual-metal co-doped N containing the carbon composite (FeCo-HNC) was prepared by adjusting the ratio of iron to cobalt as well as the pyrolysis temperature with the assistance of functionalized silica template. Fe1Co-HNC, which was formed with 1D carbon nanotubes and 2D carbon nanosheets including a rich mesoporous structure, exhibited outstanding oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalytic activities. The ORR half-wave potential is 0.86 V (vs. reversible hydrogen electrode, RHE), and the OER overpotential is 0.76 V at 10 mA cm-2 with the Fe1Co-HNC catalyst. It also displayed superior performance in zinc-air batteries. This method provides a promising strategy for the fabrication of efficient transition metal-based carbon catalysts.

Enhancing Electrocatalytic Kinetics via Synergy of Co Nanoparticles and Co/Ni-N4-C- and N-Doped Porous Carbon.

Transition-metal species embedded in carbon have sparked intense interest in the fields of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). However, improvement of the electrocatalytic kinetics remains a challenge caused by the synergistic assembly. Here, we propose a biochemical strategy to fabricate the Co nanoparticles (NPs) and Co/Ni-N4-C co-embedded N-doped porous carbon (CoNPs&Co/Ni-N4-C@NC) catalysts via constructing the zeolitic imidazolate framework (ZIF)@yeast precursor. The rich amino groups provide the possibility for the anchorage of Co2+/Ni2+ ions as well as the construction of Co/Ni-ZIF@yeast through the yeast cell biomineralization effect. The functional design induces the formation of CoNPs and Co/Ni-N4-C sites in N-doped carbon as well as regulates the porosity for exposing such sites. Synergy of CoNPs, Co/Ni-N4-C, and porous N-doped carbon delivered excellent electrocatalytic kinetics (the ORR Tafel slope of 76.3 mV dec-1 and the OER Tafel slope of 80.4 mV dec-1) and a high voltage of 1.15 V at 10 mA cm-2 for the discharge process in zinc air batteries. It provides an effective strategy to fabricate high-performance catalysts.

Effects of nonsynonymous single nucleotide polymorphisms of the KIAA1217, SNTA1 and LTBP1 genes on the growth traits of Ujumqin sheep.

Sheep body size can directly reflect the growth rates and fattening rates of sheep and is also an important index for measuring the growth performance of meat sheep. In this study, high-resolution resequencing data from four sheep breeds (Dorper sheep, Suffolk sheep, Ouessant sheep, and Shetland sheep) were analyzed. The nonsynonymous single nucleotide polymorphisms of three candidate genes (KIAA1217, SNTA1, and LTBP1) were also genotyped in 642 healthy Ujumqin sheep using MALDI-TOFMS and the genotyping results were associated with growth traits. The results showed that different genotypes of the KIAA1217 g.24429511T>C locus had significant effects on the chest circumferences of Ujumqin sheep. The SNTA1 g.62222626C>A locus had different effects on the chest depths, shoulder widths and rump widths of Ujumqin sheep. This study showed that these two sites can be used for marker-assisted selection, which will be beneficial for future precision molecular breeding.

Development of Recombinant High-Density Lipoprotein Platform with Innate Adipose Tissue-Targeting Abilities for Regional Fat Reduction.

As an escalating public health issue, obesity and overweight conditions are predispositions to various diseases and are exacerbated by concurrent chronic inflammation. Nonetheless, extant antiobesity pharmaceuticals (quercetin, capsaicin, catecholamine, etc.) manifest constrained efficacy alongside systemic toxic effects. Effective therapeutic approaches that selectively target adipose tissue, thereby enhancing local energy expenditure, surmounting the limitations of prevailing antiobesity modalities are highly expected. In this context, we developed a temperature-sensitive hydrogel loaded with recombinant high-density lipoprotein (rHDL) to achieve targeted delivery of resveratrol, an adipose browning activator, to adipose tissue. rHDL exhibits self-regulation on fat cell metabolism and demonstrates natural targeting toward scavenger receptor class B type I (SR-BI), which is highly expressed by fat cells, thereby achieving a synergistic effect for the treatment of obesity. Additionally, the dispersion of rHDL@Res in temperature-sensitive hydrogels, coupled with the regulation of their degradation and drug release rate, facilitated sustainable drug release at local adipose tissues over an extended period. Following 24 days' treatment regimen, obese mice exhibited improved metabolic status, resulting in a reduction of 68.2% of their inguinal white adipose tissue (ingWAT). Specifically, rHDL@Res/gel facilitated the conversion of fatty acids to phospholipids (PA, PC), expediting fat mobilization, mitigating triglyceride accumulation, and therefore facilitating adipose tissue reduction. Furthermore, rHDL@Res/gel demonstrated efficacy in attenuating obesity-induced inflammation and fostering angiogenesis in ingWAT. Collectively, this engineered local fat reduction platform demonstrated heightened effectiveness and safety through simultaneously targeting adipocytes, promoting WAT browning, regulating lipid metabolism, and controlling inflammation, showing promise for adipose-targeted therapy.

Quality Control of L-Ascorbic Acid 2-Phosphate Magnesium Using Reversed-Phase Liquid Chromatography.

L-Ascorbic acid 2-phosphate magnesium (AP-Mg) salt is a Vitamin C derivative frequently used as a raw material in cell culture media for research purposes as well as for Good Manufacturing Practice (GMP)-manufacturing of cell and tissue advanced therapy medicinal products. A selective reversed-phase HPLC (RP-LC) method was developed and validated. Commercially available AP-Mg products from different suppliers were analyzed. Various new impurities were found using this newly developed RP-LC method. Using quantitative nuclear magnetic resonance spectroscopy, a mass balance of roughly 99.9% was obtained; the total numbers of impurities detected in both methods are also identical. The values of the relative ultraviolet (UV) response factors at λ = 210 nm of the impurities in this RP-LC method were discussed. When equaling the overall mean relative response factor of the impurities to 0.6 (estimated central value), the mass balance in the RP-LC method was nearly 100%. The structures of the new impurities are proposed as ethylation derivatives of open-ring AP-Mg products as well as phosphorylated derivatives of ascorbic acid.

Deep insight into regulation mechanism of band distribution in phase junction CdS for enhanced photocatalytic H2 production.

An in-depth understanding of structure-activity relationship between the phase constitution and solar-to-hydrogen (STH) conversion efficiency is conducive to guiding the optimization route of targeted photocatalyst candidates, further establishing advanced photocatalytic systems. Herein, based on the concept of phase engineering, we encompassed the crystalline phase of CdS and achieved precise regulation of phase proportion as well as phase boundary width in the phase junction for the first time. The above cooperative effect not only modifies energy band distribution for sufficient redox potentials, but also guarantees the reverse migration orientation of photogenerated carriers in phase junction, thereby endowing photocarriers with a prolonged lifetime. Compared to pure cubic or hexagonal phase (72.6 or 101.1 µmol h-1 g-1), this CdS system with optimized phase junction demonstrates an improved photocatalytic hydrogen evolution activity of 1.04 mmol h-1 g-1 and favorable stability without cocatalyst assistance, which mainly stems from an efficient protons reduction process interacting with long-lived photogenerated electrons. This research explores the mechanism behind phase regulation and its relationship with junction capability, providing a powerful strategy to manipulate crystal phase distribution and paving a feasible avenue for other phase-dependent photocatalysts towards rational design of heterostructures based on different phases in solar energy conversion field.

Nanoproteases: Alternatives to Natural Protease for Biotechnological Applications.

Some nanomaterials with intrinsic protease-like activity have the advantages of good stability, biosafety, low price, large-scale preparation and unique property of nanomaterials, which are promising alternatives for natural proteases in various applications. An especial term, "nanoprotease", has been coined to stress the intrinsic proteolytic property of these nanomaterials. As a new generation of artificial proteases, they have become a burgeoning field, attracting many researchers to design and synthesize high performance nanoproteases. In this review, we summarize recent progress on all types of nanoproteases with regard of their activity, mechanism and application and introduce a new and effective strategy for engineering high-performance nanoproteases. In addition, we discuss the challenges and opportunities of nanoprotease research in the future.

An ultrasound-activated nanoplatform remodels tumor microenvironment through diverse cell death induction for improved immunotherapy.

Although nanomaterial-based nanomedicine provides many powerful tools to treat cancer, most focus on the "immunosilent" apoptosis process. In contrast, ferroptosis and immunogenic cell death, two non-apoptotic forms of programmed cell death (PCD), have been shown to enhance or alter the activity of the immune system. Therefore, there is a need to design and develop nanoplatforms that can induce multiple modes of cell death other than apoptosis to stimulate antitumor immunity and remodel the immunosuppressive tumor microenvironment for cancer therapy. In this study, a new type of multifunctional nanocomposite mainly consisting of HMME, Fe3+ and Tannic acid, denoted HFT NPs, was designed and synthesized to induce multiple modes of cell death and prime the tumor microenvironment (TME). The HFT NPs consolidate two functions into one nano-system: HMME as a sonosensitizer for the generation of reactive oxygen species (ROS) 1O2 upon ultrasound irradiation, and Fe3+ as a GSH scavenger for the induction of ferroptosis and the production of ROS ·OH through inorganic catalytic reactions. The administration of HFT NPs and subsequent ultrasound treatment caused cell death through the consumption of GSH, the generation of ROS, ultimately inducing apoptosis, ferroptosis, and immunogenic cell death (ICD). More importantly, the combination of HFT NPs and ultrasound irradiation could reshape the TME and recruit more T cell infiltration, and its combination with immune checkpoint blockade anti-PD-1 antibody could eradicate tumors with low immunogenicity and a cold TME. This new nano-system integrates sonodynamic and chemodynamic properties to achieve outstanding therapeutic outcomes when combined with immunotherapy. Collectively, this study demonstrates that it is possible to potentiate cancer immunotherapy through the rational and innovative design of relatively simple materials.