D-LMBmap: a fully automated deep-learning pipeline for whole-brain profiling of neural circuitry.

Recent proliferation and integration of tissue-clearing methods and light-sheet fluorescence microscopy has created new opportunities to achieve mesoscale three-dimensional whole-brain connectivity mapping with exceptionally high throughput. With the rapid generation of large, high-quality imaging datasets, downstream analysis is becoming the major technical bottleneck for mesoscale connectomics. Current computational solutions are labor intensive with limited applications because of the exhaustive manual annotation and heavily customized training. Meanwhile, whole-brain data analysis always requires combining multiple packages and secondary development by users. To address these challenges, we developed D-LMBmap, an end-to-end package providing an integrated workflow containing three modules based on deep-learning algorithms for whole-brain connectivity mapping: axon segmentation, brain region segmentation and whole-brain registration. D-LMBmap does not require manual annotation for axon segmentation and achieves quantitative analysis of whole-brain projectome in a single workflow with superior accuracy for multiple cell types in all of the modalities tested.

Chlamydia trachomatis T3SS Effector CT622 Induces Proinflammatory Cytokines Through TLR2/TLR4-Mediated MAPK/NF-κB Pathways in THP-1 Cells.

BACKGROUND: The pathogenesis of Chlamydia trachomatis is associated with the induction of the host inflammatory response; however, the precise underlying molecular mechanisms remain poorly understood. METHODS: CT622, a T3SS effector protein, has an important role in the pathogenesis of C trachomatis; however, whether CT622 can induce a host inflammatory response is not understood. Our findings demonstrate that CT622 induces the expression of interleukins 6 and 8 (IL-6 and IL-8). Mechanistically, these effects involve the activation of the MAPK/NF-κB signaling pathways (mitogen-activated protein kinase/nuclear factor κB). RESULTS: Interestingly, we demonstrated that the suppression of toll-like receptor 4 using small interfering RNA markedly reduced the phosphorylation of ERK, p38, JNK, and IκBα, concomitant with a significant decrease in IL-6 and IL-8 secretion. Conversely, disruption of toll-like receptor 2 abrogated the CT622-induced upregulation of IL-8 and activation of ERK, whereas IL-6 expression and p38, JNK, and IκBα phosphorylation were unaffected. CONCLUSIONS: Taken together, these results indicate that CT622 contributes to the inflammatory response through the toll-like receptor 2/4-mediated MAPK/NF-κB pathways, which provides insight into the molecular pathology of C trachomatis infection.

Design of Atomically Dispersed CoN4 Sites and Co Clusters for Synergistically Enhanced Oxygen Reduction Electrocatalysis.

Constructing dual-site catalysts consisting of atomically dispersed metal single atoms and metal atomic clusters (MACs) is a promising approach to further boost the catalytic activity for oxygen reduction reaction (ORR). Herein, a porous CoSA-AC@SNC featuring the coexistence of Co single-atom sites (CoN4) and S-coordinated Co atomic clusters (SCo6) in S, N co-doped carbon substrate is successfully synthesized by using porphyrinic metal-organic framework (Co-TPyP MOF) as the precursor. The introduction of the sulfur source creates abundant microstructural defects to anchor Co metal clusters, thus modulating the electronic structure of its surrounding carbon substrate. The synergistic effect between the two types of active sites and structural advantages, in turn, results in high ORR performance of CoSA-AC@SNC with half-wave potential (E1/2) of 0.86 V and Tafel slope of 50.17 mV dec-1. Density functional theory (DFT) calculations also support the synergistic effect between CoN4 and SCo6 by detailing the catalytic mechanism for the improved ORR performance. The as-fabricated Zn-air battery (ZAB) using CoSA-AC@SNC demonstrates impressive peak power density of 174.1 mW cm-2 and charge/discharge durability for 148 h. This work provides a facile synthesis route for dual-site catalysts and can be extended to the development of other efficient atomically dispersed metal-based electrocatalysts.

Epoxy Resins With Controllable "Thermally Conductive-Self-Healing" Synergies: a New Material to Meet the Needs of Flexible Electronic Devices.

With the popularization of 5G technology and artificial intelligence, thermally conductive epoxies with self-healing ability will be widely used in flexible electronic materials. Although many compounds containing both performances have been synthesized, there is little systematic theory to explain the coordination mechanism. In this paper, alkyl chains of different lengths were introduced to epoxies to discuss the thermally conductive, the self-healing performance, and the synergistic effect. A series of electronic-grade biphenyl epoxies (4,4'-bis(oxiran-2-ylmethoxy)-1,1'-biphenyl (1), 4,4'-bis(2-(oxiran-2-yl)ethoxy)-1,1'-biphenyl (2), 4,4'-bis(3-(oxiran-2-yl)propoxy)-1,1'-biphenyl (3), and 4,4'-bis(4-(oxiran-2-yl)butoxy)-1,1'-biphenyl (4) were synthesized and characterized. Furthermore, they were cured with decanedioic acid to produce polymers. Results showed that alkyl chains can both affect the two properties, and the epoxies suitable for specific application scenarios can be prepared by adjusting the length of alkyl chains. In terms of thermal conductivity, compound 1 was a most promising material. However, compound 4 was expected to be utilized in flexible electronic devices because of its acceptable thermal conductivity, self-healing ability, transparency, and flexibility.

Aromatic Amino Acids Promote Lipid Metabolism Disorders by Increasing Hepatic Bile Acid Synthesis.

BACKGROUND: Obesity is a progressive metabolic disease that begins with lipid metabolism disorders. Aromatic amino acids (AAAs), including tryptophan, phenylalanine, and tyrosine, have diverse biological activities as nutrients. However, the underlying mechanisms by which AAAs affect lipid metabolism are unclear. OBJECTIVES: This study was designed to investigate the possible roles and underlying molecular mechanisms of AAA in the pathogenesis of lipid metabolism disorders. METHODS: We added an AAA mixture to the high-fat diet (HFD) of mice. Glucose tolerance test was recorded. Protein expression of hepatic bile acid (BA) synthase and mRNA expression of BA metabolism-related genes were determined. Hepatic BA profiles and gut microbial were also determined in mice. RESULTS: The results showed that AAA significantly increased body weight and white adipose tissue, aggravated liver injury, impaired glucose tolerance and intestinal integrity, and significantly increased hepatic BA synthesis by inhibiting intestinal farnesoid X receptor (FXR). Moreover, AAA increased the content of total BA in the liver and altered the hepatic BA profile, with elevated levels of lithocholic acid, glycochenodeoxycholic acid, and glycoursodeoxycholic acid. AAA markedly increased the levels of proteins involved in BA synthesis (cholesterol 7α-hydroxylase and oxysterol 7α-hydroxylase) and inhibited the intestinal FXR. Gut microbial composition also changed, reducing the abundance of some beneficial bacteria, such as Parvibacter and Lactobacillus. CONCLUSIONS: Under HFD conditions, AAAs stimulate BA synthesis in both the classical and alternative pathways, leading to aggravation of liver injury and fat deposition. Excessive intake of AAA disrupts BA metabolism and contributes to the development of lipid metabolism disorders, suggesting that AAA may be a causative agent of lipid metabolism disorders.

Excessive Tryptophan and Phenylalanine Induced Pancreatic Injury and Glycometabolism Disorder in Grower-finisher Pigs.

BACKGROUND: The increase in circulating insulin levels is associated with the onset of type 2 diabetes (T2D), and the levels of branched-chain amino acids and aromatic amino acids (AAAs) are altered in T2D, but whether AAAs play a role in insulin secretion and signaling remains unclear. OBJECTIVES: This study aimed to investigate the effects of different AAAs on pancreatic function and on the use of insulin in finishing pigs. METHODS: A total of 18 healthy finishing pigs (Large White) with average body weight of 100 ± 1.15 kg were randomly allocated to 3 dietary treatments: Con, a normal diet supplemented with 0.68% alanine; Phe, a normal diet supplemented with 1.26% phenylalanine; and Trp, a normal diet supplemented with 0.78% tryptophan. The 3 diets were isonitrogenous. There were 6 replicates in each group. RESULTS: Herein, we investigated the effects of tryptophan and phenylalanine on pancreatic function and the use of insulin in finishing pigs and found that the addition of tryptophan and phenylalanine aggravated pancreatic fat deposition, increased the relative content of saturated fatty acids, especially palmitate (C16:0) and stearate (C18:0), and the resulting lipid toxicity disrupted pancreatic secretory function. We also found that tryptophan and phenylalanine inhibited the growth and secretion of ß-cells, downregulated the gene expression of the PI3K/Akt pathway in the pancreas and liver, and reduced glucose utilization in the liver. CONCLUSIONS: Using fattening pigs as a model, multiorgan combined analysis of the insulin-secreting organ pancreas and the main insulin-acting organ liver, excessive intake of tryptophan and phenylalanine will aggravate pancreatic damage leading to glucose metabolism disorders, providing new evidence for the occurrence and development of T2D.

Cisplatin-based combination therapies: Their efficacy with a focus on ginsenosides co-administration.

Cisplatin, a frequently prescribed chemotherapeutic agent, serves as a clinically therapeutic strategy for a broad range of malignancies. Its primary mode of action centers around interference with DNA replication and RNA transcription, thereby inducing apoptosis in cancer cells. Nevertheless, the clinical utility of cisplatin is constrained by its severe adverse effects and the burgeoning problem of drug resistance. Ginsenosides, potent bioactive constituents derived from ginseng, possess an array of biological activities. Recent scientific investigations underscore the substantial amplification of cisplatin's anticancer potency and the mitigation of its harmful side effects when administered concomitantly with ginsenosides. This review aims to explore the underlying mechanisms at play in this combination therapy. Initially, we provide a concise introduction to the cisplatin. Then, we pivot towards illuminating how ginsenosides bolster the anticancer efficacy of cisplatin and counteract cisplatin resistance, culminating in enhanced therapeutic outcomes. Furthermore, we provide an extensive discussion on the reduction of cisplatin-induced toxicity in the kidneys, liver, gastrointestinal tract, nervous system, and ear, accompanied by immune-fortification with ginsenosides. The existing clinical combined use of cisplatin and ginsenosides is also discussed. We propose several recommendations to propel additional research into the mechanisms governing the synergistic use of ginsenosides and cisplatin, thereby furnishing invaluable insights and fostering advancement in combined modality therapy.

Selective Synthesis of Sulfonamides and Sulfenamides from Sodium Sulfinates and Amines.

An effective method was explored for the selective synthesis of sulfonamides and sulfenamides using sodium sulfinates and amines as starting materials. This method offers mild reaction conditions, a broad substrate scope, high efficiency, and readily accessible materials, making it suitable and an alternative strategy for the preparation of a variety of biologically or pharmaceutically active compounds.

PtCu Alloy-Modified Triptycene-Based Polymer with Charge Separation for Photocatalytic Hydrogen Evolution from Water/Seawater.

Direct photocatalytic hydrogen from earth-abundant seawater is a great potential way to achieve sustainable and clean energy, yet unsatisfactory decomposition and rapid electron-hole pair recombination of catalysts hinder the solar-driven H2 conversion efficiency. Herein, we designed a series of PtCu alloy nanoparticle-modified porous triptycene-based polymers (PtxCu1-TCP) to construct the heterostructure for highly efficient hydrogen generation from photocatalytic water/seawater splitting. Characterizations displayed that TCP with an ultrahigh surface area can confine the agglomeration of PtCu alloy; meanwhile, the PtCu alloy can facilitate the rapid electron transfer from TCP. In addition, TCP with a stable covalent bond structure can resist the corrosion of seawater. Benefiting from these two advantages, Pt7Cu1-TCP showed a remarkably enhanced photocatalytic performance with a maximum H2 evolution rate of 3255 µmol g-1 h-1 in natural seawater with triethanolamine, which is 2.69, 116.25, and 1.08 times that of Pt-TCP, Cu-TCP, and optimal catalyst in pure water, respectively. This study provides an idea for the development of a novel catalytic system for hydrogen production from solar-driven water/seawater splitting.

High-Density CoSe2 Sites Embedded within 2D Porous N-Doped Carbon for High-Performance Oxygen Reduction Reaction Electrocatalysis.

Designing and fabricating efficient and stable nonprecious metal-based oxygen reduction reaction (ORR) electrocatalysts is a pressing and challenging task for the pursuit of sustainable new energy devices. Herein, porous P-CoSe2@NC electrocatalysts with high-density carbon-coated CoSe2 sites were successfully fabricated based on a pyridyl-porphyrinic metal-organic framework (Co-TPyP MOF) via a molten salt-assisted synthesis method. The hierarchical pore and N-doping carbon substrate of P-CoSe2@NC promotes mass transfer and electron-transfer efficiency, which is beneficial to maximize CoSe2 site utilization. Well-designed P-CoSe2@NC exhibits efficient ORR catalytic activity with a high half-wave potential of 0.863 V and excellent catalytic stability. Meanwhile, rechargeable aqueous primary/quasi-solid-state ZABs based on a P-CoSe2@NC air cathode show a high peak power density and exceptional operating stability, catering to the demands of practical applications. The qualified performance and structure stability of the electrocatalytic system may be mainly attributed to the protection of the CoSe2 nanoparticle by the coated carbon layer. Given the rational design of the structure and the component of the electrocatalyst with enhanced ORR activity, we believe that this work has provided a reliable pathway to the development of high-performance transition-metal chalcogenides for energy-storage and -conversion devices.

NiCoP cocatalyst modified g-C3N4 as ohmic junction photocatalyst for efficient degradation of tetracycline under visible light.

Increasing the electron-hole recombination rate in g-C3N4 can effectively improve its photocatalytic performance. In this work, NiCoP/g-C3N4 (NCP/PCN) composites with ohmic junction were formed by embedding granular NiCoP in irregularly porous g-C3N4. There was almost no barrier between the metal and the semiconductor in ohmic junction, which made it easier for electrons to slip from PCN to NCP along the curved energy band, and NCP acted as an electron collector to rapidly capture the slipping electrons. In addition, porous g-C3N4 prepared by supramolecular self-assembly could provide a shorter diffusion path for electrons. Thus, the electron-hole was effectively separated and the photocatalytic performance was improved. The band electronic structure and existence of ohmic junction in 7-NCP/PCN composite were demonstrated by XPS, ESR and DFT calculation. Finally, a reasonable photocatalytic degradation mechanism and possible tetracycline degradation path were proposed. This work has significant potential for providing an effective method for the design of non-precious metal photocatalysts.

Ginger for treating nausea and vomiting: an overview of systematic reviews and meta-analyses.

Ginger may be a potential remedy for nausea and vomiting. This review aimed to assess the reporting and methodological quality, and integrate the evidence in this field. A total of fifteen meta-analyses were analysed and met the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines, providing a relatively complete statement. However, methodological quality, assessed using the Assessment of Multiple Systematic Reviews-2 checklist, was deemed critically low to low. Our review's findings support ginger's effectiveness in managing chemotherapy-induced nausea and vomiting in cancer patients. It also reduces postoperative nausea and vomiting severity, decreasing the need for rescue antiemetics. Furthermore, ginger shows promise in alleviating pregnancy-related nausea and vomiting symptoms. The pooled evidence suggests ginger as a safe botanical option for managing nausea and vomiting, but it is important to improve the scientific quality of published meta-analyses in the future.

Engineering Tunable Ratiometric Dual Emission in Single Emitter-based Amorphous Systems.

Molecular emitters with multi-emissive properties are in high demand in numerous fields, while these properties basically depend on specific molecular conformation and packing. For amorphous systems, special molecular arrangement is unnecessary, but it remains challenging to achieve such luminescent behaviors. Herein, we present a general strategy that takes advantage of molecular rigidity and S1 -T1 energy gap balance for emitter design, which enables fluorescence-phosphorescence dual-emission properties in various solid forms, whether crystalline or amorphous. Subsequently, the amorphism of the emitters based polymethyl methacrylate films endowed an in situ regulation of the dual-emissive characteristics. With the ratiometric regulation of phosphorescence by external stimuli and stable fluorescence as internal reference, highly controllable luminescent color tuning (yellow to blue including white emission) was achieved. There properties together with a persistent luminous behavior is of benefit for an irreplaceable set of optical information combination, featuring an ultrahigh-security anti-counterfeiting ability. Our research introduces a concept of eliminating the crystal-form and molecular-conformational dependence of complex luminescent properties through emitter molecular design. This has profound implications for the development of functional materials.

MiR-184 targeting FOXO1 regulates host-cell oxidative stress induced by Chlamydia psittaci via the Wnt/ß-catenin signaling pathway.

Chlamydia psittaci is a human pathogen that causes atypical pneumonia after zoonotic transmission. We confirmed that C. psittaci infection induces oxidative stress in human bronchial epithelial (HBEs) cells and explored how this is regulated through miR-184 and the Wnt/ß-catenin signaling pathway. miR-184 mimic, miR-184 inhibitor, FOXO1 siRNA, or negative control sequence was transfected into HBE cells cultured in serum-free medium using Lipofectamine 2000. Then, prior to the cells were infected with C. psittaci 6BC, and the cells were treated with or without 30 µM Wnt/ß-catenin inhibitor ICG-001. Quantification of reactive oxygen species, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione was carried out according to the manufacturer's protocol using a corresponding assay kit. The outcome of both protein and gene was measured by western blotting or real-time fluorescence quantitative PCR. In C. psittaci-infected HBE cells, miR-184 was upregulated, while one of its target genes, FOXO1, was downregulated. ROS and MDA levels increased, while SOD and GSH contents decreased after C. psittaci infection. When miR-184 expression was downregulated, the level of oxidative stress caused by C. psittaci infection was reduced, and the Wnt/ß-catenin signaling pathway was inhibited. The opposite results were seen when miR-184 mimic was used. Transfecting with FOXO1 siRNA reversed the effect of miR-184 inhibitor. Moreover, when the Wnt/ß-catenin-specific inhibitor ICG-001 was used, the level of oxidative stress induced by C. psittaci infection was significantly suppressed. miR-184 can target FOXO1 to promote oxidative stress in HBE cells following C. psittaci infection by activation of the Wnt/ß-catenin signaling pathway.

Highly Efficient Room-Temperature Light-Induced Synthesis of Polymer Dots: A Programming Control Paradigm of Polymer Nanostructurization from Single-Component Precursor.

Polymer dots (PDs) have raised considerable research interest due to their advantages of designable nanostructures, high biocompatibility, versatile photoluminescent properties, and recyclability as nanophase. However, there remains a lack of in situ, real-time, and noncontact methods for synthesizing PDs. Here we report a rational strategy to synthesize PDs through a well-designed single-component precursor (an asymmetrical donor-acceptor-donor' molecular structure) by photoirradiation at ambient temperature. In contrast to thermal processes that normally lack atomic economy, our method is mild and successive, based on an aggregation-promoted sulfonimidization triggered by photoinduced delocalized intrinsic radical cations for polymerization, followed by photooxidation for termination with structural shaping to form PDs. This synthetic approach excludes any external additives, rendering a conversion rate of the precursor exceeding 99%. The prepared PDs, as a single entity, can realize the integration of nanocore luminescence and precursor-transferred luminescence, showing 41.5% of the total absolute luminescence quantum efficiency, which is higher than most reported PD cases. Based on these photoluminescent properties, together with the superior biocompatibility, a unique membrane microenvironmental biodetection could be exemplified. This strategy with programming control of the single precursor can serve as a significant step toward polymer nanomanufacturing with remote control, high-efficiency, precision, and real-time operability.

Dietary supplement use among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort Study.

BACKGROUND: Adult survivors of childhood cancer have poor adherence to nutrition guidelines and inadequate intake of dietary vitamins D and E, potassium, fiber, magnesium, and calcium. The contribution of vitamin and mineral supplement use to total nutrient intake in this population is unclear. METHODS: We examined the prevalence and dose of nutrient intake among 2570 adult survivors of childhood cancer participating in the St. Jude Lifetime Cohort Study, and the association of dietary supplement use with treatment exposures, symptom burden, and quality of life. RESULTS: Nearly 40% of the adult survivors of cancer survivors reported regular use of dietary supplements. Although cancer survivors who used dietary supplements were less likely to have inadequate intake of several nutrients, they were also more likely to have excessive intake (total nutrient intake ≥ tolerable upper intake levels) of folate (15.4% vs. 1.3%), vitamin A (12.2% vs. 0.2%), iron (27.8% vs. 1.2%), zinc (18.6% vs. 1%), and calcium (5.1% vs. 0.9%) compared with survivors who did not use dietary supplements (all p < 0.05). Treatment exposures, symptom burden, and physical functioning were not associated with supplement use, whereas emotional well-being and vitality were positively associated with supplement use among childhood cancer survivors. CONCLUSIONS: Supplement use is associated with both inadequate and excessive intake of specific nutrients, but positively impacts aspects of quality of life among childhood cancer survivors.

Pgp3 protein of Chlamydia trachomatis inhibits apoptosis via HO-1 upregulation mediated by PI3K/Akt activation.

As an obligate intracellular pathogen, Chlamydia trachomatis assumes various strategies to inhibit host cells apoptosis, thereby providing a suitable intracellular environment to ensure completion of the development cycle. In the current study, we revealed that Pgp3 protein, one of eight plasmid proteins of C. trachomatis that has been illustrated as the key virulence factor, increased HO-1 expression to suppress apoptosis, and downregulation of HO-1 with siRNA-HO-1 failed to exert anti-apoptosis activity of Pgp3 protein. Moreover, treatment of PI3K/Akt pathway inhibitor and Nrf2 inhibitor evidently reduced HO-1 expression and Nrf2 nuclear translocation was blocked by PI3K/Akt pathway inhibitor. These findings highlight that induction of HO-1 expression by Pgp3 protein is probably due to regulation of Nrf2 nuclear translocation activated by PI3K/Akt pathway, which provide clues on how C. trachomatis adjusts apoptosis.

Target-Induced Electrochemical Sensor Based on Foldable Aptamer and MoS2@MWCNTs-PEI for Enhanced Detection of AFB1 in Peanuts.

Herein, a sensitive and selective electrochemical sensor based on aptamer folding was constructed to detect aflatoxin B1 (AFB1) in peanuts. Specifically, polyethylenimine-functionalized multiwalled carbon nanotubes modified with molybdenum disulfide (MoS2@MWCNTs-PEI) were used as the electrode matrix to enable a large specific surface area, which were characterized by the Randles-Sevcik equation. Additionally, AuNPs were used to immobilize the aptamer via the Au-S covalent bond and provide a favorable microenvironment for signal enhancement. Methylene blue (MB) was modified at the proximal 3' termini of the aptamer as the capture probe, while the signal transduction of the sensor was obtained through changes in conformation and position of MB induced by the binding between AFB1 and the probe. Changes in spatial conformation could be recorded by electrochemical methods more readily. This electrochemical aptasensor demonstrated remarkable sensitivity to AFB1 with an extensive detection range (1 pg/mL to 100 ng/mL) and a lower limit detection (1.0 × 10-3 ng/mL). Moreover, using the constructed aptasensor, AFB1 was identified successfully in peanut samples, with recoveries ranging from 95.83 to 107.53%, illustrating its potential use in determining AFB1 in food.

Carbonized Polymer Dots/Bi/ß-Bi2O3 for Efficient Photosynthesis of H2O2 via Redox Dual Pathways.

A novel heterojunction photocatalyst of carbonized polymer dots (CPDs)/Bi/ß-Bi2O3 is successfully synthesized via a one-pot solvothermal method by adjusting the reaction temperature and time. As a solvent and carbon source, ethylene glycol not only supports the conversion of Bi3+ to ß-Bi2O3 but also undergoes its polymerization, cross-linking, and carbonization to produce CPDs. In addition, partial Bi3+ is reduced to Bi by ethylene glycol. As a result, the CPDs and Bi are deposited in situ on the surface of ß-Bi2O3 microspheres. There are four built-in electric fields in the CPDs/Bi/ß-Bi2O3 system, namely, the n-type semiconductor ß-Bi2O3/H2O interface, the p-type CPDs/H2O interface, the ohmic contact between Bi and ß-Bi2O3, and the Schottky junction between Bi and CPDs. Under the action of four built-in electric fields, the Z-type charge separation mechanism is formed. It promotes the effective separation of the photogenerated electron-hole and greatly improves the yield of H2O2. Under irradiation for 2 h, the H2O2 production is 1590 µmol g-1 h-1. The solar energy to H2O2 conversion efficiency is 0.11%.

Combination of a STING Agonist and Photothermal Therapy Using Chitosan Hydrogels for Cancer Immunotherapy.

Cyclic dinucleotides (CDNs) are a promising class of immune agonists that trigger the stimulator of interferon genes (STING) to activate both innate and acquired immunity. However, the efficacy of CDNs is limited by drug delivery barriers. Therefore, we developed a combined immunotherapy strategy based on injectable reactive oxygen species (ROS)-responsive hydrogels, which sustainably release 5,6-dimethylxanthenone-4-acetic acid (DMXAA) as known as a STING agonist and indocyanine green (ICG) by utilizing a high level of ROS in the tumor microenvironment (TME). The STING agonist combined with photothermal therapy (PTT) can improve the biological efficacy of DMXAA, transform the immunosuppressive TME into an immunogenic and tumoricidal microenvironment, and completely kill tumor cells. In addition, this bioreactive gel can effectively leverage local ROS to facilitate the release of immunotherapy drugs, thereby enhancing the efficacy of combination therapy, improving the TME, inhibiting tumor growth, inducing memory immunity, and protecting against tumor rechallenge.