Metabolic reprogramming in septic acute kidney injury: pathogenesis and therapeutic implications.

Acute kidney injury (AKI) is a frequent and severe complication of sepsis and is characterized by significant mortality and morbidity. However, the pathogenesis of septic acute kidney injury (S-AKI) remains elusive. Metabolic reprogramming, which was originally referred to as the Warburg effect in cancer, is strongly related to S-AKI. At the onset of sepsis, both inflammatory cells and renal parenchymal cells, such as macrophages, neutrophils and renal tubular epithelial cells, undergo metabolic shifts toward aerobic glycolysis to amplify proinflammatory responses and fortify cellular resilience to septic stimuli. As the disease progresses, these cells revert to oxidative phosphorylation, thus promoting anti-inflammatory reactions and enhancing functional restoration. Alterations in mitochondrial dynamics and metabolic reprogramming are central to the energetic changes that occur during S-AKI. In this review, we summarize the current understanding of the pathogenesis of metabolic reprogramming in S-AKI, with a focus on each cell type involved. By identifying relevant key regulatory factors, we also explored potential metabolic reprogramming-related therapeutic targets for the management of S-AKI.

Enhancing radiation-resistance and peroxidase-like activity of single-atom copper nanozyme via local coordination manipulation.

The inactivation of natural enzymes by radiation poses a great challenge to their applications for radiotherapy. Single-atom nanozymes (SAzymes) with high structural stability under such extreme conditions become a promising candidate for replacing natural enzymes to shrink tumors. Here, we report a CuN3-centered SAzyme (CuN3-SAzyme) that exhibits higher peroxidase-like catalytic activity than a CuN4-centered counterpart, by locally regulating the coordination environment of single copper sites. Density functional theory calculations reveal that the CuN3 active moiety confers optimal H2O2 adsorption and dissociation properties, thus contributing to high enzymatic activity of CuN3-SAzyme. The introduction of X-ray can improve the kinetics of the decomposition of H2O2 by CuN3-SAzyme. Moreover, CuN3-SAzyme is very stable after a total radiation dose of 500 Gy, without significant changes in its geometrical structure or coordination environment, and simultaneously still retains comparable peroxidase-like activity relative to natural enzymes. Finally, this developed CuN3-SAzyme with remarkable radioresistance can be used as an external field-improved therapeutics for enhancing radio-enzymatic therapy in vitro and in vivo. Overall, this study provides a paradigm for developing SAzymes with improved enzymatic activity through local coordination manipulation and high radioresistance over natural enzymes, for example, as sensitizers for cancer therapy.

Adenoidectomy in a child with Crouzon syndrome complicated with severe obstructive sleep apnea: Case report and review of literature.

RATIONALE: Crouzon syndrome is an extremely rare craniofacial dysplasia, which is mainly caused by the early ossification and closure of the coronal suture of the skull. Craniofacial deformities can cause stenosis of the nasal cavity and posterior nasal meatus, resulting in sleep apnea. PATIENT CONCERNS: A 9-year-old boy with sleep snoring for 6 years, progressive aggravation in the past 1 month and accompanied by apnea during sleep. DIAGNOSES: This case was diagnosed with Crouzon syndrome complicated with severe obstructive sleep apnea and severe hypoxemia. INTERVENTIONS: After adenoidectomy, he was admitted to the pediatric intensive care unit with ventilator-assisted respiration. During this period, the blood oxygen saturation fluctuated greatly. After trying to extubate, the blood oxygen was difficult to maintain and had to be intubated again. After active treatment, extubation was successful. OUTCOMES: The wound of nasopharynx recovered well and the sleep state was significantly improved 3 months postoperation. LESSONS: It is suggested that the time of ventilator-assisted breathing should be prolonged and the perioperative airway management should be strengthened in order to reduce the risk of postoperative complications.

Influence of Nickel on Microstructure and Mechanical Properties in Medium-Carbon Spring Steel.

The effects of adding nickel on the phase transition temperature, microstructure, and mechanical properties of medium-carbon spring steel have been investigated. The results show that adding nickel reduces the martensite start (Ms) temperature, improves hardenability, and refines the sub-microstructure of the martensite, thereby improving yield stress. The yield strength of martensitic steel increases by approximately 100 MPa due to a synergistic combination of grain refinement strengthening and dislocation strengthening, with an increase in the nickel content from 0 wt.% to 1 wt.%. The cryogenic impact toughness of martensitic steel also improved with a higher nickel content due to packet and block refinement and an increase in the proportion of high-angle grain boundaries (HAGBs).

Octadecyl Gallate and Lipid-Modified MnSe2 Nanoparticles Enhance Radiosensitivity in Esophageal Squamous Cell Carcinoma and Promote Radioprotection in Normal Tissues.

Radiotherapy, a widely used therapeutic strategy for esophageal squamous cell carcinoma (ESCC), is always limited by radioresistance of tumor tissues and side-effects on normal tissues. Herein, a signature based on four core genes of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, is developed to predict prognosis and assess immune cell infiltration, indicating that the cGAS-STING pathway and radiotherapy efficacy are closely intertwined in ESCC. A novel lipid-modified manganese diselenide nanoparticle (MnSe2-lipid) with extraordinarily uniform sphere morphology and tumor microenvironment (TME) responsiveness is developed to simultaneously overcome radioresistance and reduce side-effects of radiation. The uniform MnSe2 encapsulated lipid effectively achieves tumor accumulation. Octadecyl gallate on surface of MnSe2 forming pH-responsive metal-phenolic covalent realizes rapid degradation in TME. The released Mn2+ promotes radiosensitivity by generating reactive oxygen species induced by Fenton-like reaction and activating cGAS-STING pathway. Spontaneously, selenium strengthens immune response by promoting secretion of cytokines and increasing white blood cells, and performs antioxidant activity to reduce side-effects of radiotherapy. Overall, this multifunctional remedy which is responsive to TME is capable of providing radiosensitivity by cGAS-STING pathway-mediated immunostimulation and chemodynamic therapy, and radioprotection of normal tissues, is highlighted here to optimize ESCC treatment.

Intelligent nanomaterials for cancer therapy: recent progresses and future possibilities.

Intelligent nanomedicine is currently one of the most active frontiers in cancer therapy development. Empowered by the recent progresses of nanobiotechnology, a new generation of multifunctional nanotherapeutics and imaging platforms has remarkably improved our capability to cope with the highly heterogeneous and complicated nature of cancer. With rationally designed multifunctionality and programmable assembly of functional subunits, the in vivo behaviors of intelligent nanosystems have become increasingly tunable, making them more efficient in performing sophisticated actions in physiological and pathological microenvironments. In recent years, intelligent nanomaterial-based theranostic platforms have showed great potential in tumor-targeted delivery, biological barrier circumvention, multi-responsive tumor sensing and drug release, as well as convergence with precise medication approaches such as personalized tumor vaccines. On the other hand, the increasing system complexity of anti-cancer nanomedicines also pose significant challenges in characterization, monitoring and clinical use, requesting a more comprehensive and dynamic understanding of nano-bio interactions. This review aims to briefly summarize the recent progresses achieved by intelligent nanomaterials in tumor-targeted drug delivery, tumor immunotherapy and temporospatially specific tumor imaging, as well as important advances of our knowledge on their interaction with biological systems. In the perspective of clinical translation, we have further discussed the major possibilities provided by disease-oriented development of anti-cancer nanomaterials, highlighting the critical importance clinically-oriented system design.