Scutellarin inhibits ferroptosis by promoting cellular antioxidant capacity through regulating Nrf2 signaling.

Ferroptosis is a lytic form of regulated cell death that is driven by iron-dependent lipid peroxidation and has been implicated in various diseases, including acute kidney injury (AKI). Scutellarin is a flavonoid isolated from (Vant.) Hand.

USP30 inhibition augments mitophagy to prevent T cell exhaustion.

The exhaustion of tumor-infiltrating CD8 T cells poses a substantial challenge in cancer immunotherapy, with mitochondrial health essential for sustaining T cell functionality. Mitophagy, a critical process for mitochondrial quality control, is severely impaired in exhausted CD8 T cells, yet the underlying mechanisms remain unclear. We identified ubiquitin-specific protease 30 (USP30), a mitochondrial deubiquitinase that inhibits mitophagy, as a key factor up-regulated in exhausted CD8 T cells.

Fully printable integrated multifunctional sensor arrays for intelligent lithium-ion batteries.

Monitoring battery health states and predicting potential hazards are crucial technologies for ensuring the safe operation of battery packs. Current battery risk control often lacks indicators and timeliness for the accidents due to complexity in convoluted and distinct electrochemical behaviors of diverse cell chemistries. Here, we enable lithium-ion batteries with intelligence by integrating a conformal array of multifunctional sensors into the packing foil.

Mitophagy mitigates mitochondrial fatty acid β-oxidation deficient cardiomyopathy.

The healthy heart relies on mitochondrial fatty acid β-oxidation (FAO) to sustain its high energy demands. FAO deficiencies can cause muscle weakness, cardiomyopathy, and, in severe cases, neonatal/infantile mortality. Although FAO deficits are thought to induce mitochondrial stress and activate mitophagy, a quality control mechanism that eliminates damaged mitochondria, the mechanistic link in the heart remains unclear.

Immunometabolic interplay and molecular characterization of hepcidins reveal ferroptosis mechanisms to Edwardsiella piscicida infection in black rockfish Sebastes schlegeli.

Edwardsiella piscicida infection represents a major pathogenic threat in aquaculture, yet the molecular mechanisms underlying host-pathogen interactions is still not fully understood. Here, we investigated the pathophysiological response of black rockfish Sebastes schlegeli to E. piscicida infection through an integrated approach combining immune-metabolism analysis and molecular characterization.

Revealing the Degradation Mechanism of Lithium-Ion Batteries for Electric Aircraft.

The widespread adoption of electric vehicles has spurred the exploration of airworthy lithium-ion batteries (LIBs) for electric-powered aircraft. However, LIBs used for aviation exhibit rapid aging and shortened service life due to the harsh conditions of aviation, posing significant risks to flight safety. In this study, a comprehensive analysis is conducted under simulated flight conditions to reveal the degradation mechanism of aviation batteries.

Theaflavin suppresses necroptosis by attenuating RIPK1-RIPK3-MLKL signaling and mitigates cisplatin-induced kidney injury in mice.

Necroptosis is a lytic form of regulated cell death (RCD) that is dependent on receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain like pseudokinase (MLKL). This form of RCD has been implicated in various inflammatory diseases and organ injuries including cisplatin-induced acute kidney injury (AKI), thus representing a therapeutic target for such diseases. Theaflavin is an ingredient of black tea that exhibits beneficial effects on human health and has been shown to regulate pyroptosis, but its effects on necroptosis and cisplatin-induced AKI remain unclear.

Mx of Sebastes schlegelii: expression pattern, antibacterial activity and antiviral mechanism.

Myxovirus resistance (Mx) is a classical antiviral molecule that has been well understood in mammals. However, very limited studies on Mx antiviral activities have been documented in teleosts. In the present study, a novel Mx (SsMx) was cloned from black rockfish (Sebastes schlegelii) and the immunological activities of SsMx were examined in vitro and in vivo.

The NAE1-mediated neddylation operates as an essential post-translational modification checkpoint for effector CD8 T cells.

Optimal activation of CD8+ T cells is crucial for immunity-mediated destruction of cancer, requiring a substantial amount of proteins involved in metabolism, proliferation, and effector function. Despite extensive studies emphasizing the role of transcriptional regulation in this process, paired transcriptomic and proteomic analyses reveal that the RNA profile is poorly correlated with protein levels. This discrepancy underscores the importance of post-translational modifications (PTMs) in controlling protein abundance during activation.

A Multifunctional Bioadhesive for Bone Augmentation: Tissue Integration Combined with Antioxidant and Antibacterial Effects.

Guided bone regeneration (GBR) is a widely used clinical method for bone augmentation that features a barrier membrane that prevents soft tissue interference with osteogenesis. However, the most used collagen membranes and bone granules often struggle to maintain a stable bone formation space and create a microenvironment conducive to bone regeneration. In this study, a multifunctional bioadhesive (nSF@TA) is obtained from the reaction between nanofiber fibroin (nSF) and tannic acid (TA), which exhibits excellent wet adhesion properties on various substances and maintains a stable osteogenic space through tissue integration.

Targeting metabolic sensing switch GPR84 on macrophages for cancer immunotherapy.

Introduction: As one of the major components of the tumor microenvironment, tumor-associated macrophages (TAMs) possess profound inhibitory activity against T cells and facilitate tumor escape from immune checkpoint blockade therapy. Converting this pro-tumorigenic toward the anti-tumorigenic phenotype thus is an important strategy for enhancing adaptive immunity against cancer. However, a plethora of mechanisms have been described for pro-tumorigenic differentiation in cancer, metabolic switches to program the anti-tumorigenic property of TAMs are elusive.

A self-activating electron transfer antibacterial strategy: CoO/TiO P-N heterojunctions combined with photothermal therapy.

Implant-associated infections are significant impediments to successful surgical outcomes, often resulting from persistent bacterial contamination. It has been hypothesized that bacteria can transfer electrons to semiconductors with comparable potential to the biological redox potential (BRP). Building on this concept, we developed an antibiotic-free bactericidal system, CoO/TiO-Ti, capable of achieving real-time and sustainable bactericidal effects.

A Biomimetic Nanogenerator to Enhance Bone Regeneration by Restoring Electric Microenvironments.

Piezoelectric materials have received increasing attention in bone regeneration due to their prominent role in bioelectricity in bone homeostasis. This study aimed to develop bioactive barium titanate-chitosan-graphene oxide piezoelectric nanoparticles (BCG-NPs) to improve biocompatibility and stimulate bone repair. Butterfly loops, hysteresis loops, and microcurrent studies on BCG-NPs confirmed their good piezoelectric properties.

RAB7 deficiency impairs pulmonary artery endothelial function and promotes pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a devastating and progressive disease with limited treatment options. Endothelial dysfunction plays a central role in the development and progression of PAH, yet the underlying mechanisms are incompletely understood. The endosome-lysosome system is important to maintain cellular health, and the small GTPase RAB7 regulates many functions of this system.

RAB7 deficiency impairs pulmonary artery endothelial function and promotes pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a devastating and progressive disease with limited treatment options. Endothelial dysfunction plays a central role in development and progression of PAH, yet the underlying mechanisms are incompletely understood. The endosome-lysosome system is important to maintain cellular health and the small GTPase RAB7 regulates many functions of this system.

Molecular signature of cardiac remodeling associated with Polymerase Gamma mutation.

Aims: Metabolic function/dysfunction is central to aging biology. This is well illustrated by the Polymerase Gamma (POLG) mutant mouse where a key residue of the mitochondrial DNA polymerase is mutated (D257A), causing loss of mitochondrial DNA stability and dramatically accelerated aging processes. Given known cardiac phenotypes in the POLG mutant, we sought to characterize the course of cardiac dysfunction in the POLG mutant to guide future intervention studies.

The Mitochondrial Deubiquitinase USP30 Regulates AKT/mTOR Signaling.

Mitophagy is an intracellular mechanism to maintain mitochondrial health by removing dysfunctional mitochondria. The E3 ligase Parkin ubiquitinates the membrane proteins on targeted mitochondria to initiate mitophagy, whereas USP30 antagonizes Parkin-dependent mitophagy by removing ubiquitin from Parkin substrates. The AKT/mTOR signaling is a master regulator of cell proliferation, differentiation, apoptosis, and autophagy.

Assessment of mitophagy in human iPSC-derived cardiomyocytes.

Defective mitophagy contributes to normal aging and various neurodegenerative and cardiovascular diseases. The newly developed methodologies to visualize and quantify mitophagy allow for additional progress in defining the pathophysiological significance of mitophagy in various model organisms. However, current knowledge regarding mitophagy relevant to human physiology is still limited.

Berberine reverses multidrug resistance in Candida albicans by hijacking the drug efflux pump Mdr1p.

Clinical use of antimicrobials faces great challenges from the emergence of multidrug-resistant pathogens. The overexpression of drug efflux pumps is one of the major contributors to multidrug resistance (MDR). Reversing the function of drug efflux pumps is a promising approach to overcome MDR.

Hyper-Synergistic Antifungal Activity of Rapamycin and Peptide-Like Compounds against Orthogonally via Tor1 Kinase.

is a life-threatening, opportunistic fungal pathogen with a high mortality rate, especially within the immunocompromised populations. Multidrug resistance combined with limited antifungal drugs even worsens the situation. Given the facts that the current drug discovery strategies fail to deliver sufficient antifungals for the emerging multidrug resistance, we urgently need to develop novel approaches.

Significance of mitochondrial activity in neurogenesis and neurodegenerative diseases.

Mitochondria play a multidimensional role in the function and the vitality of the neurological system. From the generation of neural stem cells to the maintenance of neurons and their ultimate demise, mitochondria play a critical role in regulating our neural pathways' homeostasis, a task that is critical to our cognitive health and neurological well-being. Mitochondria provide energy via oxidative phosphorylation for the neurotransmission and generation of an action potential along the neuron's axon.

Pharmacological inhibition of USP30 activates tissue-specific mitophagy.

Aim: Mitophagy is the regulated process that targets damaged or dysfunctional mitochondria for lysosomal-mediated removal. This process is an essential element of mitochondrial quality control, and dysregulation of mitophagy may contribute to a host of diseases, most notably neurodegenerative conditions such as Parkinson's disease. Mitochondria targeted for mitophagic destruction are molecularly marked by the ubiquitination of several outer mitochondrial membrane (OMM) proteins.

Zika Virus-Induced Neuronal Apoptosis via Increased Mitochondrial Fragmentation.

The 2015 to 2016 outbreak of Zika virus (ZIKV) infections in the Americas coincided with a dramatic increase in neurodevelopmental abnormalities, including fetal microcephaly, in newborns born to infected women. In this study, we observed mitochondrial fragmentation and disrupted mitochondrial membrane potential after 24 h of ZIKV infection in human neural stem cells and the SNB-19 glioblastoma cell line. The severity of these changes correlated with the amount of ZIKV proteins expressed in infected cells.