CuCo2O4 Nanoflowers with Multiple Enzyme Activities for Treating Bacterium-Infected Wounds via Cuproptosis-like Death.

Nanozyme-driven catalytic therapy provides a promising treatment strategy for bacterial biofilm-infected wounds. However, the single functionality and limited catalytic efficiency of nanozyme-based materials often restrict the effectiveness of wound infection treatment. In this study, CuCo2O4 nanoflowers with multiple enzymatic activities were prepared for antibacterial/antibiofilm treatment by cuproptosis-like death. CuCo2O4 exhibited peroxidase-like (POD-like) and oxidase-like (OXD-like) dual enzyme activities that generated large amounts of •OH and O2•-. Moreover, the glutathione peroxidase-like (GSH-Px-like) activity of CuCo2O4 was able to reduce the overexpression of GSH in the wound microenvironment, enhancing the therapeutic effects of reactive oxygen species (ROS). The morphology of CuCo2O4 was modified using a hydrothermal method with PEG4000 as the solvent, resulting in the exposure of more active center sites and a significant improvement in enzyme catalytic activity. The in vitro results demonstrated the pronounced disruption effect of CuCo2O4 on biofilms formed by bacteria. In vivo, CuCo2O4 significantly promoted angiogenesis, collagen deposition, and cell proliferation. Transcriptome sequencing revealed that elevated ROS levels in bacteria led to cell membrane damage and metabolic disruption. In addition, Cu2+ overload in bacteria induces lipid peroxidation accumulation and disrupts the respiratory chain and tricarboxylic acid (TCA) cycle, ultimately leading to bacterial cuproptosis-like death. This therapeutic strategy, which combines the synergistic effects of multiple enzyme-like activities with cuproptosis-like death, provides an approach for treating biofilm infections.

Stability evaluation of open-pit mine slope based on Bayesian optimization 1D-CNN.

As mechanized open-pit coal mining intensifies, assessing and predicting slope stability has become increasingly important. To address the limitations of traditional mechanical calculations, numerical simulations, and physical experiments, this paper identifies the key factors impacting slope stability in open-pit mines and develops a multi-parameter sample data set. The study employs hyperparameters optimized using a Bayesian algorithm, introduces additional convolutional layers, and combines the Adam optimizer with dropout techniques to enhance the feature extraction and performance of one-dimensional convolutional neural networks (1D-CNN). This leads to a Bayesian-optimized one-dimensional convolutional neural network (B-1D MCNN) model for predicting slope stability.The study evaluates the classification performance and accuracy of various models for slope stability, including BP neural networks, genetic algorithm-optimized convolutional neural networks, 1D-CNN, and B-1D MCNN, using accuracy, precision, and F1-score as metrics. The analysis also examines the influence of factor indicators and training set length on the model's output to assess its generalization capabilities.The research findings suggest that: (1) the B-1D MCNN model for evaluating slope stability demonstrates the capability to accurately depict the nonlinear correlation between influencing factors and slope stability. (2) Compared with other models, the B-1D MCNN model has shown enhancements of 10.96% to 27.85%, 10.26% to 28.55%, and 8.98% to 25.05% in terms of Accuracy, F1-Score, and Precision, respectively. (3) As the length of the training dataset increases, the performance of the model improves accordingly. (4) The B-1D MCNN model shows a generalization power of 87.5%.

Combined clinical significance of MRI and serum mannose-binding lectin in the prediction of spinal tuberculosis.

BACKGROUND: Spinal tuberculosis (STB) is a local manifestation of systemic infection caused by Mycobacterium tuberculosis, accounting for a significant proportion of joint tuberculosis cases. This study aimed to explore the diagnostic value of MRI combined with mannose-binding lectin (MBL) for STB. METHODS: 124 patients suspected of having STB were collected and divided into STB and non-STB groups according to their pathological diagnosis. Serum MBL levels were measured using ELISA and a Pearson analysis was constructed to determine the correlation between MBL and STB. ROC was plotted to analyze their diagnostic value for STB. All the subjects included in the study underwent an MRI. RESULTS: The sensitivity of MRI for the diagnosis of STB was 84.38% and specificity was 86.67%. The serum MBL levels of the patients in the STB group were significantly lower than the levels in the non-STB group. ROC analysis results indicated that serum MBL's area under the curve (AUC) for diagnosis of STB was 0.836, with a sensitivity of 82.3% and a specificity was 77.4%. The sensitivity of MRI combined with MBL diagnosis was 96.61%, and the specificity was 92.31%, indicating that combining the two diagnostic methods was more effective than using either one alone. CONCLUSIONS: Both MRI and MBL had certain diagnostic values for STB, but their combined use resulted in a diagnostic accuracy than either one alone.

Methanogen-methanotroph community has a more consistent and integrated structure in rice rhizosphere than in bulk soil and rhizoplane.

Methanogenic and methanotrophic microbes together determine the net methane flux from rice fields. Despite much research on them as separate communities, there has been little study of combined community patterns, and how these vary between the rhizoplane (root surface), rhizosphere (soil surrounding the root) and bulk soil around rice plants, especially at larger spatial scale. We collected samples from 32 geographically scattered rice fields in east central China, amplicon targeting the mcrA gene for methanogenesis and pmoA gene for methanotrophy by using high-throughput sequencing. Distinct communities of both methanogens and methanotrophs occurred in each of the three compartments, and predominantly positive links were found between methanogens and methanotrophs in all compartments indicating cross-feeding or consortia relationships. Methanogens were acting as the network hub in the bulk soil, and methanotrophs in rhizoplane. Network complexity and stability was greater in the rhizosphere than rhizoplane and bulk soil, with no network hubs detected, suggesting the strongest effect of homeostatic influence by plant occurred in the rhizosphere. The proportion of determinism (homogeneous selection) and distance-decay relation (DDR) in rhizoplane was consistently lower than that in the rhizosphere for both communities, indicating weaker phylogenetic clustering in rice root surface. Our results have provided a better understanding of CH4 oxidation and emission in rice paddy fields and future agriculture management could take into consideration of the subtle variation among different soil compartments and interactions within methanogenic and methanotrophic communities.

Semi-Supervised Medical Image Segmentation Based on Deep Consistent Collaborative Learning.

In the realm of medical image analysis, the cost associated with acquiring accurately labeled data is prohibitively high. To address the issue of label scarcity, semi-supervised learning methods are employed, utilizing unlabeled data alongside a limited set of labeled data. This paper presents a novel semi-supervised medical segmentation framework, DCCLNet (deep consistency collaborative learning UNet), grounded in deep consistent co-learning. The framework synergistically integrates consistency learning from feature and input perturbations, coupled with collaborative training between CNN (convolutional neural networks) and ViT (vision transformer), to capitalize on the learning advantages offered by these two distinct paradigms. Feature perturbation involves the application of auxiliary decoders with varied feature disturbances to the main CNN backbone, enhancing the robustness of the CNN backbone through consistency constraints generated by the auxiliary and main decoders. Input perturbation employs an MT (mean teacher) architecture wherein the main network serves as the student model guided by a teacher model subjected to input perturbations. Collaborative training aims to improve the accuracy of the main networks by encouraging mutual learning between the CNN and ViT. Experiments conducted on publicly available datasets for ACDC (automated cardiac diagnosis challenge) and Prostate datasets yielded Dice coefficients of 0.890 and 0.812, respectively. Additionally, comprehensive ablation studies were performed to demonstrate the effectiveness of each methodological contribution in this study.

A live attenuated influenza B virus vaccine expressing RBD elicits protective immunity against SARS-CoV-2 in mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to human health globally. It is crucial to develop a vaccine to reduce the effect of the virus on public health, economy, and society and regulate the transmission of SARS-CoV-2. Influenza B virus (IBV) can be used as a vector that does not rely on the current circulating influenza A strains. In this study, we constructed an IBV-based vector vaccine by inserting a receptor-binding domain (RBD) into a non-structural protein 1 (NS1)-truncated gene (rIBV-NS110-RBD). Subsequently, we assessed its safety, immunogenicity, and protective efficacy against SARS-CoV-2 in mice, and observed that it was safe in a mouse model. Intranasal administration of a recombinant rIBV-NS110-RBD vaccine induced high levels of SARS-CoV-2-specific IgA and IgG antibodies and T cell-mediated immunity in mice. Administering two doses of the intranasal rIBV-NS110-RBD vaccine significantly reduced the viral load and lung damage in mice. This novel IBV-based vaccine offers a novel approach for controlling the SARS-CoV-2 pandemic.

Identification of PTPN12 Phosphatase as a Novel Negative Regulator of Hippo Pathway Effectors YAP/TAZ in Breast Cancer.

The Hippo pathway plays crucial roles in governing various biological processes during tumorigenesis and metastasis. Within this pathway, upstream signaling stimuli activate a core kinase cascade, involving MST1/2 and LATS1/2, that subsequently phosphorylates and inhibits the transcriptional co-activators YAP and its paralog TAZ. This inhibition modulates the transcriptional regulation of downstream target genes, impacting cell proliferation, migration, and death. Despite the acknowledged significance of protein kinases in the Hippo pathway, the regulatory influence of protein phosphatases remains largely unexplored. In this study, we conducted the first gain-of-functional screen for protein tyrosine phosphatases (PTPs) regulating the Hippo pathway. Utilizing a LATS kinase biosensor (LATS-BS), a YAP/TAZ activity reporter (STBS-Luc), and a comprehensive PTP library, we identified numerous novel PTPs that play regulatory roles in the Hippo pathway. Subsequent experiments validated PTPN12, a master regulator of oncogenic receptor tyrosine kinases (RTKs), as a previously unrecognized negative regulator of the Hippo pathway effectors, oncogenic YAP/TAZ, influencing breast cancer cell proliferation and migration. In summary, our findings offer valuable insights into the roles of PTPs in the Hippo signaling pathway, significantly contributing to our understanding of breast cancer biology and potential therapeutic strategies.

Inactivation of hydrogenase-3 leads to enhancement of 1,3-propanediol and 2,3-butanediol production by Klebsiella pneumoniae.

Klebsiella pneumoniae can use glucose or glycerol as carbon sources to produce 1,3-propanediol or 2,3-butanediol, respectively. In the metabolism of Klebsiella pneumoniae, hydrogenase-3 is responsible for H2 production from formic acid, but it is not directly related to the synthesis pathways for 1,3-propanediol and 2,3-butanediol. In the first part of this research, hycEFG, which encodes subunits of the enzyme hydrogenase-3, was knocked out, so K. pneumoniae ΔhycEFG lost the ability to produce H2 during cultivation using glycerol as a carbon source. As a consequence, the concentration of 1,3-propanediol increased and the substrate (glycerol) conversion ratio reached 0.587 mol/mol. Then, K. pneumoniae ΔldhAΔhycEFG was constructed to erase lactic acid synthesis which led to the further increase of 1,3-propanediol concentration. A substrate (glycerol) conversion ratio of 0.628 mol/mol in batch conditions was achieved, which was higher compared to the wild type strain (0.545 mol/mol). Furthermore, since adhE encodes an alcohol dehydrogenase that catalyzes ethanol production from acetaldehyde, K. pneumoniae ΔldhAΔadhEΔhycEFG was constructed to prevent ethanol production. Contrary to expectations, this did not lead to a further increase, but to a decrease in 1,3-propanediol production. In the second part of this research, glucose was used as the carbon source to produce 2,3-butanediol. Knocking out hycEFG had distinct positive effect on 2,3-butanediol production. Especially in K. pneumoniae ΔldhAΔadhEΔhycEFG, a substrate (glucose) conversion ratio of 0.730 mol/mol was reached, which is higher compared to wild type strain (0.504 mol/mol). This work suggests that the inactivation of hydrogenase-3 may have a global effect on the metabolic regulation of K. pneumoniae, leading to the improvement of the production of two industrially important bulk chemicals, 1,3-propanediol and 2,3-butanediol.

Highly Enantioselective Catalysis by Enzyme Encapsulated in Metal Azolate Frameworks with Micelle-Controlled Pore Sizes.

Encapsulating enzymes within metal-organic frameworks has enhanced their structural stability and interface tunability for catalysis. However, the small apertures of the frameworks restrict their effectiveness to small organic molecules. Herein, we present a green strategy directed by visible linker micelles for the aqueous synthesis of MAF-6 that enables enzymes for the catalytic asymmetric synthesis of chiral molecules. Due to the large pore aperture (7.6 Å), double the aperture size of benchmark ZIF-8 (3.4 Å), MAF-6 allows encapsulated enzyme BCL to access larger substrates and do so faster. Through the optimization of surfactants' effect during synthesis, BCL@MAF-6-SDS (SDS = sodium dodecyl sulfate) displayed a catalytic efficiency (Kcat/Km) that was 420 times greater than that of BCL@ZIF-8. This biocomposite efficiently catalyzed the synthesis of drug precursor molecules with 94-99% enantioselectivity and nearly quantitative yields. These findings represent a deeper understanding of de novo synthetic encapsulation of enzyme in MOFs, thereby unfolding the great potential of enzyme@MAF catalysts for asymmetric synthesis of organics and pharmaceuticals.

Study on Laser Polishing of Ti6Al4V Fabricated by Selective Laser Melting.

Laser-based additive manufacturing has garnered significant attention in recent years as a promising 3D-printing method for fabricating metallic components. However, the surface roughness of additive manufactured components has been considered a challenge to achieving high performance. At present, the average surface roughness (Sa) of AM parts can reach high levels, greater than 50 µm, and a maximum distance between the high peaks and the low valleys of more than 300 µm, which requires post machining. Therefore, laser polishing is increasingly being utilized as a method of surface treatment for metal alloys, wherein the rapid remelting and resolidification during the process significantly alter both the surface quality and subsurface material properties. In this paper, the surface roughness, microstructures, microhardness, and wear resistance of the as-received, continuous wave laser polishing (CWLP), and pulsed laser polishing (PLP) processed samples were investigated systematically. The results revealed that the surface roughness (Sa) of the as-received sample was 6.29 µm, which was reduced to 0.94 µm and 0.84 µm by CWLP and PLP processing, respectively. It was also found that a hardened layer, about 200 µm, was produced on the Ti6Al4V alloy surface after laser polishing, which can improve the mechanical properties of the component. The microhardness of the laser-polished samples was increased to about 482 HV with an improvement of about 25.2% compared with the as-received Ti6Al4V alloy. Moreover, the coefficient of friction (COF) was slightly reduced by both CWLP and LPL processing, and the wear rate of the surface layer was improved to 0.790 mm3/(N∙m) and 0.714 mm3/(N∙m), respectively, under dry fraction conditions.

Improved anti-cancer effects of luteolin@ZIF-8 in cervical and prostate cancer cell lines.

Luteolin, a naturally occurring pharmaceutical compound with significant antitumor properties, faces challenges in clinical applications due to its low solubility in water and limited bioavailability. To address these issues, a one-step synthesis method was employed to encapsulate luteolin within ZIF-8. The successful preparation of luteolin@ ZIF-8 nanoparticles was confirmed through various analytical techniques, including fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), laser size distribution analysis, X-ray diffraction (XRD), and release curve assessment. Results indicate that the formulated luteolin@ ZIF-8 nanoparticles exhibited high drug loading (1360 mg/g) and demonstrated selective drug release in acidic microenvironments. Furthermore, the encapsulation of luteolin increased the size of ZIF-8 from 168.4 ± 0.2 nm to 384.7 ± 1.4 nm, but did not change its crystalline structure significantly. Notably, the results of in vitro anti-cervical and prostate cancers experiments revealed that luteolin@ ZIF-8 had better efficacy in inhibiting the proliferation and migration of HeLa and PC3 cells than free luteolin. The antitumor activity of luteolin@ ZIF-8 was sustained for 72 h, with a particularly pronounced inhibitory effect on HeLa cells as compared to PC3 cells. This study underscores the effective enhancement of luteolin's antitumor activity through encapsulation in ZIF-8, offering substantial implications for improving its clinical applications.

Precision Cellulose from Living Cationic Polymerization of Glucose 1,2,4-Orthopivalates.

Cellulose serves as a sustainable biomaterial for a wide range of applications in biotechnology and materials science. While chemical and enzymatic glycan assembly methods have been developed to access modest quantities of synthetic cellulose for structure-property studies, chemical polymerization strategies for scalable and well-controlled syntheses of cellulose remain underdeveloped. Here, we report the synthesis of precision cellulose via living cationic ring-opening polymerization (CROP) of glucose 1,2,4-orthopivalates. In the presence of dibutyl phosphate as an initiator and triflic acid as a catalyst, precision cellulose with well-controlled molecular weights, defined chain-end groups, and excellent regio- and stereospecificity was readily prepared. We further demonstrated the utility of this method through the synthesis of precision native d-cellulose and rare precision l-cellulose.

Insight into the improvement mechanism of gel properties of pea protein isolate based on the synergistic effect of cellulose nanocrystals and calcium ions.

Here, the influence and potential mechanism by which cellulose nanocrystals (CNC) collaborated with Ca2+ enhancing the heat-induced gelation of pea protein isolate (PPI) were investigated. It was found that the combination of 0.45% CNC and 15 mM Ca2+ synergistically increased the gel strength (from 14.18 to 65.42 g) and viscoelasticity of PPI while decreased the water holding capacity. The improved particle size, turbidity, and thermostability as well as the reduced solubility, crystallinity, and gel porosity were observed in CNC/CaCl2 composite system. CNC fragments bind to specific amino acids in 11S legumin and 7S vicilin mainly through hydrogen bonding and van der Waals forces. Moreover, changes in the protein secondary structure and enhancement of the molecular interaction induced by CNC and Ca2+ could favor the robust gel network. The results will provide a new perspective on the functional regulation of pea protein and the creation of pea protein gel-based food.

Remodeling mechanism of gel network structure of soy protein isolate amyloid fibrils mediated by cellulose nanocrystals.

The differences in the gelling properties of soy protein isolate (SPI) and soy protein isolate amyloid fibrils (SAFs) as well as the role of cellulose nanocrystals (CNC) in regulating their gel behaviors were investigated in this study. The binding of CNC to ß-conglycinin (7S), glycinin (11S), and SAFs was predominantly driven by non-covalent interactions. CNC addition reduced the particle size, turbidity, subunit segments, and crystallinity of SPI and SAFs, promoted the conversion of α-helix to ß-sheet, improved the thermal stability, exposed more tyrosine and tryptophan residues, and enhanced the intermolecular interactions. A more regular and ordered lamellar network structure was formed in the SAFs-CNC composite gel, which could be conducive to the improvement of gel quality. This study would provide theoretical reference for the understanding of the regulatory mechanism of protein amyloid fibrils gelation as well as the high-value utilization of SAFs-CNC complex as a functional protein-based material or food ingredient in food field.

Characterization of ATG8-family protein phosphorylation by Phos-tag gel for autophagy study.

Autophagy supports cell survival under different stress conditions, where ATG8-family proteins are required for autophagosome biogenesis/maturation and selective autophagy. Here, we present a protocol for studying ATG8-family protein phosphorylation using Phos-tag gel, a modified SDS-PAGE system, when the related phosphorylation site information and/or specific phospho-antibody are unavailable. We describe steps for generating GST-ATG8 proteins in bacteria, purifying S protein-Flag-SBP protein (SFB)-tagged kinasefrom cells, preparing gel, and an in vitro kinase assay. We then detail procedures for western blotting and image processing. For complete details on the use and execution of this protocol, please refer to Seo et al.1.

Efficacy and safety of two-stage revision for patients with culture-negative versus culture-positive periprosthetic joint infection: a single-center retrospective study.

BACKGROUND: The safety and efficacy of two-stage revision for culture-negative PJI remain controversial. This study analyzed outcomes after two-stage revision in patients with culture-negative and culture-positive periprosthetic joint infection (PJI) during follow-up lasting at least two years. METHODS: Data were retrospectively analysed patients who underwent hip or knee revision arthroplasty from January 2008 to October 2020 at our medical center. The primary outcome was the re-revision rate, while secondary outcomes were the rates of reinfection, readmission, and mortality. Patients with culture-negative or culture-positive PJI were compared in terms of these outcomes, as well as survival time without reinfection or revision surgery, based on Kaplan‒Meier analysis. RESULTS: The final analysis included 87 patients who were followed up for a mean of 72.3 months (range, 24-123 months). The mean age was 58.1 years in the culture-negative group (n = 24) and 59.1 years in the culture-positive group (n = 63). The two groups (culture-negative versus culture-positive) did not differ significantly in rates of re-revision (0.0% vs. 3.2%, p > 0.05), reinfection (4.2% vs. 3.2%, p > 0.05), readmission (8.4% vs. 8.0%, p > 0.05), or mortality (8.3% vs. 7.9%, p > 0.05). They were also similar in survival rates without infection-related complications or revision surgery at 100 months (91.5% in the culture-negative group vs. 87.9% in the culture-positive group; Mantel‒Cox log-rank χ2 = 0.251, p = 0.616). CONCLUSION: The two-stage revision proves to be a well-tolerated and effective procedure in both culture-negative and culture-positive PJI during mid to long-term follow-up.

Microbubble Biointerfacing by Regulation of the Platelet Membrane Surfactant Activity at the Gas-Liquid Interface for Acute Thrombosis Targeting.

Biointerfacing nanomaterials with cell membranes has been successful in the functionalization of nanoparticles or nanovesicles, but microbubble functionalization remains challenging due to the unique conformation of the lipid monolayer structure at the gas-liquid interface that provides insufficient surfactant activity. Here, we describe a strategy to rationally regulate the surfactant activity of platelet membrane vesicles by adjusting the ratio of proteins to lipids through fusion with synthetic phospholipids (i.e., liposomes). A "platesome" with the optimized protein-to-lipid ratio can be assembled at the gas-liquid interface in the same manner as pulmonary surfactants to stabilize a microsized gas bubble. Platesome microbubbles (PMBs) inherited 61.4 % of the platelet membrane vesicle proteins and maintained the active conformation of integrin αIIbß3 without the talin 1 for fibrin binding. We demonstrated that the PMBs had good stability, long circulation, and superior functionality both in vitro and in vivo. Moreover, by molecular ultrasound imaging, the PMBs provide up to 11.8 dB of ultrasound signal-to-noise ratio enhancement for discriminating between acute and chronic thrombi. This surface tension regulating strategy may provide a paradigm for biointerfacing microbubbles with cell membranes, offering a potential new approach for the construction of molecular ultrasound contrast agents for the diagnosis of different diseases.

Near-Unity Green Luminescent Hybrid Manganese Halides as X-ray Scintillators.

The increasing demands in optoelectronic applications have driven the advancement of organic-inorganic hybrid metal halides (OIMHs), owing to their exceptional optical and scintillation properties. Among them, zero-dimensional (0D) low-toxic manganese-based scintillators have garnered significant interest due to their exceptional optical transparency and elevated photoluminescence quantum yields (PLQYs), making them promising for colorful light-emitting diodes and X-ray imaging applications. In this study, two OIMH single crystals of (Br-PrTPP)2MnBr4 (Br-PrTPP = (3-bromopropyl) triphenylphosphonium) and (Br-BuTPP)2MnBr4 (Br-BuTPP = (4-bromobutyl) triphenylphosphonium) were prepared via a facile saturated crystallization method. Benefiting from the tetrahedrally coordinated [MnBr4]2- polyhedron, both of them exhibited strong green emissions peaked at 517 nm owing to the d-d electron transition of Mn2+ with near-unity PLQYs of 99.33 and 86.85%, respectively. Moreover, benefiting from the high optical transparencies and remarkable luminescence properties, these manganese halides also exhibit excellent radioluminescent performance with the highest light yield of up to 68,000 photons MeV-1, negligible afterglow (0.4 ms), and linear response to X-ray dose rate with the lowest detection limit of 45 nGyair s-1. In X-ray imaging, the flexible film made by the composite of (Br-PrTPP)2MnBr4 and PDMS shows an ultrahigh spatial resolution of 12.78 lp mm-1, which provides a potential visualization tool for X-ray radiography.

MAP4K2 connects the Hippo pathway to autophagy in response to energy stress.

As a key regulator of development, organ size, tissue homeostasis and cancer, the Hippo pathway is tightly regulated by various growth-related signaling events. Among them, energy stress activates the Hippo pathway to inhibit its downstream effector YAP1. Our recent work reported a YAP1-independent role of the Hippo pathway in promoting macroautophagy/autophagy and cell survival in response to energy stress, a process mediated by Hippo kinase MAP4K2. MAP4K2 interacts with and phosphorylates MAP1LC3A/LC3A at S87, which in turn drives autophagosome-lysosome fusion via the RAB3GAP-RAB18 axis. Energy stress activates MAP4K2 by reducing its association with the Hippo phosphatase complex STRIPAK component STRN4. Moreover, MAP4K2 is highly expressed in head and neck cancer, while MAP4K2 and its mediated autophagy are required for head and neck cancer development. Taken together, our study not only reveals a noncanonical role of the Hippo pathway in energy stress response, but also suggests Hippo kinase MAP4K2 as a potential therapeutic target for head and neck cancer treatment.Abbreviation: AMPK: 5'-AMP-activated protein kinase; Atg8: autophagy related 8; LATS1: large tumor suppressor 1; LIR: microtubule-associated protein 1 light chain 3-interacting region; MAP1LC3A/LC3A: microtubule-associated protein 1 light chain 3 alpha; MAP4K2: mitogen-activated protein kinase kinase kinase kinase 2; PPP2/PP2A: protein phosphatase 2; RAB3GAP: RAB3 GTPase activating protein; RAB18: RAB18, member RAS oncogene family; SLMAP: sarcolemma associated protein; STK3/MST2: serine/threonine kinase 3; STK4/MST1: serine/threonine kinase 4; STRIPAK: striatin-interacting phosphatase and kinase; STRN4: striatin, calmodulin binding protein 4; SQSTM1/p62: sequestosome 1; TEAD: TEA domain family member; ULK1: unc-51 like kinase 1; WWTR1/TAZ: WW domain containing transcription regulator 1; YAP1: yes-associated protein 1.

Copper Nanodots-Based Hybrid Hydrogels with Multiple Enzyme Activities for Acute and Infected Wound Repair.

Effectively controlling bacterial infection, reducing the inflammation and promoting vascular regeneration are all essential strategies for wound repair. Nanozyme technology has potential applications in the treatment of infections because its non-antibiotic dependent, topical and noninvasive nature. In wound management, copper-based nanozymes have emerged as viable alternatives to antibiotics. In this study, an ultrasmall cupric enzyme with high enzymatic activity is synthesized and added to a nontoxic, self-healing, injectable cationic guar gum (CG) hydrogel network. The nanozyme exhibits remarkable antioxidant properties under neutral conditions, effectively scavenging reactive nitrogen and oxygen species (RNOS). Under acidic conditions, Cu NDs have peroxide (POD) enzyme-like activity, which allows them to eliminate hydrogen peroxides and produce free radicals locally. Antibacterial experiments show that they can kill bacteria and remove biofilms. It reveals that low concentrations of Cu ND/CG decrease the expression of the inflammatory factors in cells and tissues, effectively controlling inflammatory responses. Cu ND/CG hydrogels also inhibit HIF-1α and promote VEGF expression in the wound with the ability to promote vascular regeneration. In vivo safety assessments reveal a favorable biosafety profile. Cu ND/CG hydrogels offer a promising solution for treating acute and infected wounds, highlighting the potential of innovative nanomaterials in wound healing.