Chromosome-level genome provides insights into evolution and diving adaptability in the vulnerable common pochard (Aythya ferina).

The common pochard (Aythya ferina) is a freshwater diving duck found in the Palearctic region that has been classified as vulnerable by the IUCN due to continuous and rapid population declines across their distribution. To gain a better understanding of its genetic mechanism of adaptive evolution, we successfully sequenced and assembled the first high-quality chromosome-level genome of A. ferina using Illumina, Nanopore and Hi-C sequencing technologies. A total assembly length of 1,130.78 Mbp was obtained, with over 98.81% (1,117.37Mbp) of sequence anchored to 35 pseudo-chromosomes. We predicted 17,232 protein-coding genes, 95.9% of which were functionally annotated. We identified 339 expanded and 937 contracted gene families in the genome of A. ferina, and detected 95 genes that have been positively selected. The significantly enriched Gene Ontology and enriched pathways were related to energy metabolism, immune, nervous, and sensory systems, suggests that these factors likely played an important role in its evolution. Importantly, we recovered signatures of positive selection on genes related to vasoconstriction that may be associated with thermoregulatory adaptations of A. ferina for underwater diving. Overall, the high-quality genome assembly and annotation in this study provides valuable genomic resources for ecological and evolutionary studies, as well as toward the conservation of A. ferina.

Evaluation of a plasma cell-free DNA methylation test for colorectal cancer diagnosis: a multicenter clinical study.

BACKGROUND: A blood-based diagnostic test is a promising strategy for colorectal cancer (CRC). The MethyDT test (IColohunter), which detects methylation levels of NTMT1 and MAP3K14-AS1, exhibited potential in discriminating CRC, but its clinical performance needs to be validated in large-scale populations. METHODS: A multicenter, double-blinded, cross-sectional study that enrolled 1194 participants was performed. Plasma samples were collected to detect methylation levels of NTMT1 and MAP3K14-AS1 using quantitative methylation-specific PCR with the MethyDT test, and the accuracy was further evaluated by Sanger sequencing. RESULTS: The sensitivities of the MethyDT test for detecting CRC, early stages of CRC (I and II), advanced adenoma (AA), and high-grade intraepithelial neoplasia (HGIN) were 91.2% (95% confidence interval [CI], 88.4-94.0), 87.4% (95% CI, 82.5-92.2), 43.5% (95% CI, 35.7-51.4), and 72.7% (95% CI, 57.5-87.9), respectively. The specificities for participants with non-AA, interfering diseases (ID), and no evidence of disease (NED) were 85.0% (95% CI, 78.8-91.3), 93.7% (95% CI, 91.4-95.9) and 97.3% (95% CI, 90.5-99.7), respectively, and its overall specificity for all-controls was 92.4% (95% CI, 90.3-94.4). The consistency of the MethyDT test with pathology for CRC was high with a kappa value of 0.830 (95% CI, 0.795-0.865). Additionally, the MethyDT test was comparable to Sanger sequencing for detecting methylation with kappa values > 0.97. CONCLUSIONS: The MethyDT test demonstrates excellent sensitivity and specificity for CRC and high consistency with Sanger sequencing for methylation, suggesting it may serve as a potential noninvasive diagnostic tool for the detection of CRC. TRIAL REGISTRATION: This clinical trial has been registered in ClinicalTrials.gov (NCT05508503).

AXIN1 boosts antiviral response through IRF3 stabilization and induced phase separation.

Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.

TRIM33 promotes glycolysis through regulating P53 K48-linked ubiquitination to promote esophageal squamous cell carcinoma growth.

Esophageal squamous cell carcinoma (ESCC) is a common fatal malignant tumor of the digestive tract; however, its pathogenic mechanism is unknown and lacks specific molecular diagnosis and treatment. Therefore, it is particularly important to identify new tumor biomarkers to enhance the early diagnosis and molecular-targeted therapy of ESCC. Here, we found that the E3 ubiquitin ligase Tripartitemotif-containing33 (TRIM33) is highly expressed in ESCC tissues and cell lines, and is associated with adverse clinical outcomes. We determined that TRIM33 drives aerobic glycolysis to promote tumor growth in vivo and in vitro. In terms of mechanism, TRIM33 binds to p53 to inhibit its stability and promote the expression of downstream glycolysis target genes GLUT1, HK2, PKM2, and LDHA. In addition, TRIM33 promotes the polyubiquitination of P53 K48-linked and proteasome degradation. Further studies have shown that the K351 site of P53 is the key site mediating the ubiquitination of P53 K48-linked to promote aerobic glycolysis in ESCC and tumor cell growth. Our results reveal that the TRIM33-P53 signal axis regulates glycolysis during ESCC and may provide a new perspective for the diagnosis and treatment of ESCC.

Optimizing coolant loop design across the stator core: A research study.

Liquid cooling is widely used on high power motors. Optimal design of the coolant loop could help rise the power density. The coolant channels are placed across the stator core in this research. The heat dissipation performances of the coolant channel with different designs are compared and analyzed through simulation. Experiments were carried out to verify the simulation results and the feasibility of the cooling method. The results show that the coolant loop should be placed tightly close to the slots. The heat dissipation performance of the optimized coolant loop is efficient compared to the jacket cooling design. The coolant channels across the stator core could remain sealed under a 0.5 Mpa pressure at least according to the air proof test. The coolant pressure within the channels could be reduced efficiently through increasing the parallel loop number or moving the channels away from the slots properly. The winding temperature of the measured values and the simulated results of the motor with jacket cooling is within 2 °C.

Targeted gene sequencing and transcriptome sequencing reveal characteristics of NUP98 rearrangement in pediatric acute myeloid leukemia.

BACKGROUND: NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. METHODS: Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. RESULTS: Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P < 0.001 and P = 0.001, respectively). Multivariate Cox regression analyses demonstrated that patients harboring NUP98-r (P < 0.001) and WT1 mutations (P = 0.030) had worse relapse-free survival, and patients harboring NUP98-r (P < 0.008) presented lower overall survival. CONCLUSIONS: These investigations contribute to the understanding of the molecular characteristics, risk stratification, and prognostic evaluation of pediatric AML patients.

Evaluation of Active Oxygen Species Derived from Water Splitting for Electrocatalytic Organic Oxidation.

Active oxygen species (OH*/O*) derived from water electrolysis are essential for the electrooxidation of organic compounds into high-value chemicals, which can determine activity and selectivity, whereas the relationship between them remains unclear. Herein, using glycerol (GLY) electrooxidation as a model reaction, we systematically investigated the relationship between GLY oxidation activity and the formation energy of OH* (ΔGOH*). We first identified that OH* on Au demonstrates the highest activity for GLY electrooxidation among various pure metals, based on experiments and density functional theory, and revealed that ΔGOH* on Au-based alloys is influenced by the metallic composition of OH* coordination sites. Moreover, we observed a linear correlation between the adsorption energy of GLY (Eads) and the d-band center of Au-based alloys. Comprehensive microkinetic analysis further reveals a volcano relationship between GLY oxidation activity, the ΔGOH* and the adsorption free energy of GLY (ΔGads). Notably, Au3Pd and Au3Ag alloys, positioned near the peak of the volcano plot, show excellent activity, attributed to their moderate ΔGOH* and ΔGads, striking a balance that is neither too high nor too low. This research provides theoretical insights into modulating active oxygen species from water electrolysis to enhance organic electrooxidation reactions.

Nd: YAG laser irradiation in the treatment of live pulp preservation in pediatric cariogenic pulpitis.

BACKGROUND: Dental pulpitis significantly impacts oral function and quality of life. Treatments like direct pulp capping aim to preserve pulp vitality. OBJECTIVE: This study aims to investigate the application value of Nd:YAG laser irradiation in preserving pulp vitality in children with caries-induced pulpitis. METHODS: This study, conducted from June 2019 to June 2023, included 89 children undergoing pulp vitality preservation treatment for caries-induced pulpitis. The children were divided into two groups using sealed envelopes: 44 in the control group received pulp capping treatment, while the study group received Nd:YAG laser-assisted pulp capping treatment. The efficacy, oral indicators, oral function, changes in root apex diameter and root length, changes in gingival crevicular fluid inflammatory factors, and incidence of complications were compared between the two groups before and 3 months after treatment. RESULTS: The total effective rates were 97.78% in the study group and 95.45% in the control group, with no significant difference between the groups (p> 0.05). Before treatment, there were no differences in gingival index, plaque index, and probing bleeding index between the groups (p> 0.05). After treatment, both groups showed decreased periodontal indexes compared to before treatment, with the study group showing lower values than the control group (p< 0.05). Chewing and biting function scores were similar between the groups before and after treatment (p> 0.05), but both groups showed decreased scores after treatment (p< 0.05). The study group had a higher percentage decrease in root apex diameter and a greater increase in root length compared to the control group (p< 0.05). During treatment, one case of tooth discoloration occurred in the study group (2.27%), while the control group had two cases of tooth discoloration and one case of secondary caries, resulting in a complication rate of 6.67%. There was no significant difference in the incidence of complications between the groups (p> 0.05). CONCLUSION: Nd:YAG laser irradiation effectively preserves pulp vitality in children with caries-induced pulpitis, improving periodontal health, reducing root apex diameter, and increasing root length with high safety.

[Early gait analysis after total knee arthroplasty based on artificial intelligence dynamic image recognition].

OBJECTIVE: To explore early postoperative gait characteristics and clinical outcomes after total knee arthroplasty (TKA). METHODS: From February 2023 to July 2023, 26 patients with unilateral knee osteoarthritis (KOA) were treated with TKA, including 4 males and 22 females, aged from 57 to 85 years old with an average of (67.58±6.49) years old;body mass index (BMI) ranged from 18.83 to 38.28 kg·m-2 with an average of (26.43±4.15) kg·m-2;14 patients on the left side, 12 patients on the right side;according to Kellgren-Lawrence(K-L) classification, 6 patients with grade Ⅲ and 20 patients with grade IV;the courses of disease ranged from 1 to 14 years with an average of (5.54±3.29) years. Images and videos of standing up and walking, walking side shot, squatting and supine kneeling were taken with smart phones before operation and 6 weeks after operation. The human posture estimation framework OpenPose were used to analyze stride frequency, step length, step length, step speed, active knee knee bending angle, stride length, double support phase time, as well as maximum hip flexion angle and maximum knee bending angle on squatting position. Western Ontario and McMaster Universities (WOMAC) arthritis index and Knee Society Score (KSS) were used to evaluate clinical efficacy of knee joint. RESULTS: All patients were followed up for 5 to 7 weeks with an average of (6.00±0.57) weeks. The total score of WOMAC decreased from (64.85±11.54) before operation to (45.81±7.91) at 6 weeks after operation (P<0.001). The total KSS was increased from (101.19±9.58) before operation to (125.50±10.32) at 6 weeks after operation (P<0.001). The gait speed, stride frequency and stride length of the affected side before operation were (0.32±0.10) m·s-1, (96.35±24.18) steps·min-1, (0.72±0.14) m, respectively;and increased to (0.48±0.11) m·s-1, (104.20±22.53) steps·min-1, (0.79±0.10) m at 6 weeks after operation (P<0.05). The lower limb support time and active knee bending angle decreased from (0.31±0.38) s and (125.21±11.64) ° before operation to (0.11±0.04) s and (120.01±13.35) ° at 6 weeks after operation (P<0.05). Eleven patients could able to complete squat before operation, 13 patients could able to complete at 6 weeks after operation, and 9 patients could able to complete both before operation and 6 weeks after operation. In 9 patients, the maximum bending angle of crouching position was increased from 76.29° to 124.11° before operation to 91.35° to 134.12° at 6 weeks after operation, and the maximum bending angle of hip was increased from 103.70° to 147.25° before operation to 118.61° to 149.48° at 6 weeks after operation. CONCLUSION: Gait analysis technology based on artificial intelligence image recognition is a safe and effective method to quantitatively identify the changes of patients' gait. Knee pain of KOA was relieved and the function was improved, the supporting ability of the affected limb was improved after TKA, and the patient's stride frequency, stride length and stride speed were improved, and the overall movement rhythm of both lower limbs are more coordinated.

Optimal timing of invasive intervention for high-risk non-ST-segment-elevation myocardial infarction patients.

OBJECTIVE: To compare the immediate, early, and delayed percutaneous coronary intervention (PCI) strategies in non-ST-segment-elevation myocardial infarction (NSTEMI) patients with high-risk. METHODS: Medical records of patients treated at the Daping Hospital, Third Military Medical University, Chongqing, China between 2011 and 2021 were retrospectively reviewed. Only patients with complete available information were included. All patients assigned into three groups based on the timing of PCI including immediate (< 2 h), early (2-24 h) and delayed (≥ 24 h) intervention. Multivariable Cox hazards regression and simpler nonlinear models were performed. RESULTS: A total of 657 patients were included in the study. The median follow-up length was 3.29 (interquartile range: 1.45-4.85) years. Early PCI strategy improved the major adverse cardiac event (MACE) outcome compared to the immediate or delayed PCI strategy. Early PCI, diabetes mellitus, and left main or/and left anterior descending or/and left circumflex stenosis or/and right coronary artery ≥ 99% were predictors for MACE outcome. The optimal timing range for PCI to reduce MACE risk is 3-14 h post-admission. For high-risk NSTEMI patients, early PCI reduced primary clinical outcomes compared to immediate or delayed PCI, and the optimal timing range was 3-14 h post-admission. Delayed PCI was superior for NSTEMI with chronic kidney injury. CONCLUSIONS: Delayed invasive strategy was helpful to reduce the incidence of MACE for high-risk NSTEMI with chronic kidney injury. An immediate PCI strategy might increase the rate of MACE.

Tumor Microenvironment-Derived Exosomes: A Double-Edged Sword for Advanced T Cell-Based Immunotherapy.

The tumor microenvironment (TME) plays a crucial role in cancer progression and immune evasion, partially mediated by the activity of the TME-derived exosomes. These extracellular vesicles are pivotal in shaping immune responses through the transfer of proteins, lipids, and nucleic acids between cells, facilitating a complex interplay that promotes tumor growth and metastasis. This review delves into the dual roles of exosomes in the TME, highlighting both their immunosuppressive functions and their emerging therapeutic potential. Exosomes can inhibit T cell function and promote tumor immune escape by carrying immune-modulatory molecules, such as PD-L1, yet they also hold promise for cancer therapy as vehicles for delivering tumor antigens and costimulatory signals. Additionally, the review discusses the intricate crosstalk mediated by exosomes among various cell types within the TME, influencing both cancer progression and responses to immunotherapies. Moreover, this highlights current challenges and future directions. Collectively, elucidating the detailed mechanisms by which TME-derived exosomes mediate T cell function offers a promising avenue for revolutionizing cancer treatment. Understanding these interactions allows for the development of targeted therapies that manipulate exosomal pathways to enhance the immune system's response to tumors.

The genomics and physiology of abiotic stressors associated with global elevational gradients in Arabidopsis thaliana.

Phenotypic and genomic diversity in Arabidopsis thaliana may be associated with adaptation along its wide elevational range, but it is unclear whether elevational clines are consistent among different mountain ranges. We took a multi-regional view of selection associated with elevation. In a diverse panel of ecotypes, we measured plant traits under alpine stressors (low CO2 partial pressure, high light, and night freezing) and conducted genome-wide association studies. We found evidence of contrasting locally adaptive regional clines. Western Mediterranean ecotypes showed low water use efficiency (WUE)/early flowering at low elevations to high WUE/late flowering at high elevations. Central Asian ecotypes showed the opposite pattern. We mapped different candidate genes for each region, and some quantitative trait loci (QTL) showed elevational and climatic clines likely maintained by selection. Consistent with regional heterogeneity, trait and QTL clines were evident at regional scales (c. 2000 km) but disappeared globally. Antioxidants and pigmentation rarely showed elevational clines. High elevation east African ecotypes might have higher antioxidant activity under night freezing. Physiological and genomic elevational clines in different regions can be unique, underlining the complexity of local adaptation in widely distributed species, while hindering global trait-environment or genome-environment associations. To tackle the mechanisms of range-wide local adaptation, regional approaches are thus warranted.

La diversidad fenotípica y genómica en Arabidopsis thaliana puede estar asociada con la adaptación a lo largo de su amplio rango de elevación, pero no está claro si la variación asociada a la elevación es consistente entre diferentes cadenas montañosas. Investigamos la selección asociada con la elevación tomando una visión multiregional. En un panel diverso de ecotipos, medimos fenotipos bajo condiciones estresantes alpinas (baja presión parcial de CO2, mucha luz y congelación nocturna) y realizamos estudios de asociación con el genoma. Encontramos evidencia de clinas de elevación regionales contrastantes. Los ecotipos del Mediterráneo occidental mostraron una eficiencia de uso de agua baja/floración temprana en elevaciones bajas y una eficiencia de uso de agua alta/floración tardía en elevaciones altas. Los ecotipos de Asia Central mostraron el patrón opuesto. Mapeamos diferentes genes candidatos para cada región, y algunos locus mostraron variación en elevación probablemente mantenida por selección. De acuerdo con heterogeneidad regional, las clinas de fenotipo y de frecuencia alélica fueron evidentes a escalas regionales (~2000 km) pero desaparecieron a nivel global. Los antioxidantes y la pigmentación rara vez mostraron clinas, aunque los ecotipos de alta elevación del este de África podrían tener una mayor actividad antioxidante bajo congelación nocturna. Las clinas de elevación fisiológicas y genómicas en diferentes regiones pueden ser únicas, lo que subraya la complejidad de la adaptación local en especies ampliamente distribuidas, al tiempo que obstaculiza las asociaciones globales fenotipo­ambiente o genoma­ambiente. Por lo tanto, para abordar los mecanismos de adaptación local a gran escala, se necesitan enfoques regionales.

Mechanisms of Mechanical Stimulation in the Development of Respiratory System Diseases.

During respiration, mechanical stress can initiate biological responses that impact the respiratory system. Mechanical stress plays a crucial role in the development of the respiratory system. However, pathological mechanical stress can impact the onset and progression of respiratory diseases by influencing the extracellular matrix and cell transduction processes. In this article, we explore the mechanisms by which mechanical forces communicate with and influence cells. We outline the basic knowledge of respiratory mechanics, elucidating the important role of mechanical stimulation in influencing respiratory system development and differentiation from a microscopic perspective. We also explore the potential mechanisms of mechanical transduction in the pathogenesis and development of respiratory diseases such as asthma, lung injury, pulmonary fibrosis, and lung cancer. Finally, we look forward to new research directions in cellular mechanotransduction, aiming to provide fresh insights for future therapeutic research on respiratory diseases.

Ultrasonic features of hidradenoma papilliferum: An unexpected mass in the vulvar.

Hidradenoma papilliferum is a rare superficial mass with distinct ultrasonic features. It originates from mammary structures and is commonly observed in the anogenital region of women. We report a hidradenoma papilliferum with clear ultrasound images which have never be described before.

Gut microbiota contributes to high-altitude hypoxia acclimatization of human populations.

BACKGROUND: The relationship between human gut microbiota and high-altitude hypoxia acclimatization remains highly controversial. This stems primarily from uncertainties regarding both the potential temporal changes in the microbiota under such conditions and the existence of any dominant or core bacteria that may assist in host acclimatization. RESULTS: To address these issues, and to control for variables commonly present in previous studies which significantly impact the results obtained, namely genetic background, ethnicity, lifestyle, and diet, we conducted a 108-day longitudinal study on the same cohort comprising 45 healthy Han adults who traveled from lowland Chongqing, 243 masl, to high-altitude plateau Lhasa, Xizang, 3658 masl, and back. Using shotgun metagenomic profiling, we study temporal changes in gut microbiota composition at different timepoints. The results show a significant reduction in the species and functional diversity of the gut microbiota, along with a marked increase in functional redundancy. These changes are primarily driven by the overgrowth of Blautia A, a genus that is also abundant in six independent Han cohorts with long-term duration in lower hypoxia environment in Shigatse, Xizang, at 4700 masl. Further animal experiments indicate that Blautia A-fed mice exhibit enhanced intestinal health and a better acclimatization phenotype to sustained hypoxic stress. CONCLUSIONS: Our study underscores the importance of Blautia A species in the gut microbiota's rapid response to high-altitude hypoxia and its potential role in maintaining intestinal health and aiding host adaptation to extreme environments, likely via anti-inflammation and intestinal barrier protection.

Fully automated hybrid approach on conventional MRI for triaging clinically significant liver fibrosis: A multi-center cohort study.

Establishing reliable noninvasive tools to precisely diagnose clinically significant liver fibrosis (SF, ≥F2) remains an unmet need. We aimed to build a combined radiomics-clinic (CoRC) model for triaging SF and explore the additive value of the CoRC model to transient elastography-based liver stiffness measurement (FibroScan, TE-LSM). This retrospective study recruited 595 patients with biopsy-proven liver fibrosis at two centers between January 2015 and December 2021. At Center 1, the patients before December 2018 were randomly split into training (276) and internal test (118) sets, the remaining were time-independent as a temporal test set (96). Another data set (105) from Center 2 was collected for external testing. Radiomics scores were built with selected features from Deep learning-based (ResUNet) automated whole liver segmentations on MRI (T2FS and delayed enhanced-T1WI). The CoRC model incorporated radiomics scores and relevant clinical variables with logistic regression, comparing routine approaches. Diagnostic performance was evaluated by the area under the receiver operating characteristic curve (AUC). The additive value of the CoRC model to TE-LSM was investigated, considering necroinflammation. The CoRC model achieved AUCs of 0.79 (0.70, 0.86), 0.82 (0.73, 0.89), and 0.81 (0.72-0.91), outperformed FIB-4, APRI (all p < 0.05) in the internal, temporal, and external test sets and maintained the discriminatory power in G0-1 subgroups (AUCs range, 0.85-0.86; all p < 0.05). The AUCs of joint CoRC-LSM model were 0.86 (0.79-0.94), and 0.81 (0.72-0.90) in the internal and temporal sets (p = 0.01). The CoRC model was useful for triaging SF, and may add value to TE-LSM.

Accelerated healing of intractable biofilm-infected diabetic wounds by trypsin-loaded quaternized chitosan hydrogels that disrupt extracellular polymeric substances and eradicate bacteria.

Complex and stubborn bacterial biofilm infections significantly hinder diabetic wound healing and threaten public health. Therefore, a dressing material that effectively clears biofilms and promotes wound healing is urgently required. Herein, we introduce a novel strategy for simultaneously dispersing extracellular polymeric substances and eradicating drug-resistant bacteria. We prepared an ultrabroad-spectrum and injectable quaternized chitosan (QCS) hydrogel loaded with trypsin, which degrades biofilm extracellular proteins. Increased temperature initiated QCS gelation to form the hydrogel, enabling the sustained release of trypsin and effective adherence of the hydrogel to irregularly shaped wounds. To reproduce clinical scenarios, biofilms formed by a mixture of Staphylococcus aureus (S. aureus), Methicillin-resistant S. aureus, and Pseudomonas aeruginosa were administered to the wounds of rats with streptozotocin-induced diabetes. Under these severe infection conditions, the hydrogel efficiently suppressed inflammation, promoted angiogenesis, and enhanced collagen deposition, resulting in accelerated healing of diabetic wounds. Notably, the hydrogel demonstrates excellent biocompatibility without cytotoxicity. In summary, we present a trypsin-loaded QCS hydrogel with tremendous clinical applications potential for the treatment of chronic infected wounds.