Flexible and Robust Pressure Sensor Based on MXene-Incorporated Polyamide 6 Membrane for E-Skin Applications.

Flexible piezoresistive pressure sensors are crucial for next-generation wearable electronics, yet achieving simultaneous high sensitivity, durability, and mechanical robustness remains a challenge. Herein, we report a high-performance piezoresistive sensor fabricated through the integration of two-dimensional MXene nanosheets with a hierarchically structured modified polyamide 6 nanofiber net (D-PA6 NFN) using scalable vacuum filtration. Benefiting from the synergistic combination of MXene's excellent electrical properties, web-like architecture, the composite nanofiber tensile strength (52 MPa), and flexibility (40%), the resulting sensor exhibited good sensitivity (0.

High-fat diet promotes prostate cancer metastasis via RPS27.

Background: Metastasis is the leading cause of death among prostate cancer (PCa) patients. Obesity is associated with both PCa-specific and all-cause mortality. High-fat diet (HFD) is a risk factor contributing to obesity.

PAFAH2 suppresses synchronized ferroptosis to ameliorate acute kidney injury.

Synchronized ferroptosis contributes to nephron loss in acute kidney injury (AKI). However, the propagation signals and the underlying mechanisms of the synchronized ferroptosis for renal tubular injury remain unresolved. Here we report that platelet-activating factor (PAF) and PAF-like phospholipids (PAF-LPLs) mediated synchronized ferroptosis and contributed to AKI.

Prostate cancer cells synergistically defend against CD8 T cells by secreting exosomal PD-L1.

Background: Metastatic castration-resistant prostate cancer (mCRPC) remains fatal and incurable, despite a variety of treatments that can delay disease progression and prolong life. Immune checkpoint therapy is a promising treatment. However, emerging evidence suggests that exosomal programmed necrosis ligand 1 (PD-L1) directly binds to PD-1 on the surface of T cells in the drain lineage lymph nodes or neutralizes administered PD-L1 antibodies, resulting in poor response to anti-PD-L1 therapy in mCRPC.

NRF1-mediated mitochondrial biogenesis antagonizes innate antiviral immunity.

Mitochondrial biogenesis is the process of generating new mitochondria to maintain cellular homeostasis. Here, we report that viruses exploit mitochondrial biogenesis to antagonize innate antiviral immunity. We found that nuclear respiratory factor-1 (NRF1), a vital transcriptional factor involved in nuclear-mitochondrial interactions, is essential for RNA (VSV) or DNA (HSV-1) virus-induced mitochondrial biogenesis.

Saturated fatty acids increase LPI to reduce FUNDC1 dimerization and stability and mitochondrial function.

Ectopic lipid deposition and mitochondrial dysfunction are common etiologies of obesity and metabolic disorders. Excessive dietary uptake of saturated fatty acids (SFAs) causes mitochondrial dysfunction and metabolic disorders, while unsaturated fatty acids (UFAs) counterbalance these detrimental effects. It remains elusive how SFAs and UFAs differentially signal toward mitochondria for mitochondrial performance.

Nondegradable ubiquitinated ATG9A organizes Golgi integrity and dynamics upon stresses.

ATG9A is a highly conserved membrane protein required for autophagy initiation. It is trafficked from the trans-Golgi network (TGN) to the phagophore to act as a membrane source for autophagosome expansion. Here, we show that ATG9A is not just a passenger protein in the TGN but rather works in concert with GRASP55, a stacking factor for Golgi structure, to organize Golgi dynamics and integrity.

Hypoxia-induced proteasomal degradation of DBC1 by SIAH2 in breast cancer progression.

DBC1 has been characterized as a key regulator of physiological and pathophysiological activities, such as DNA damage, senescence, and tumorigenesis. However, the mechanism by which the functional stability of DBC1 is regulated has yet to be elucidated. Here, we report that the ubiquitination-mediated degradation of DBC1 is regulated by the E3 ubiquitin ligase SIAH2 and deubiquitinase OTUD5 under hypoxic stress.

Pt nanoenzyme decorated yolk-shell nanoplatform as an oxygen generator for enhanced multi-modality imaging-guided phototherapy.

The unsatisfactory efficacy of conventional theranostic agents in ablating tumor poses urgent demands on the development of high-performance integrated theranostic agents utilizing rising nanotechnology. To cope with the existing limitations, here we presented an intelligent nanoplatform based on yolk-shell FeO@polydopamine prepared by mussel-inspired polydopamine chemistry and sacrificial template method as well as subsequent incorporation of Pt nanoparticles and chlorine 6 (Ce6) by in situ reduction and electrostatic adsorption for photodynamic therapy (PDT) and photothermal (PTT). The resultant nanoplatform could effectively deliver photosensitizer Ce6 to tumor sites, then promoting the decomposition of endogenous HO to oxygen, finally achieving enhanced PDT therapy, which is demonstrated by in vitro and in vivo evaluations.

Monitoring TFEB translocation.

The transcription factor EB (TFEB) plays a critical role in autophagy induction and lysosomal biogenesis by orchestrating the expression of autophagy- and lysosome-related genes. In response to a series of stresses such as nutrient starvation, TFEB translocates from the cytoplasm to the nucleus, where it exerts its regulatory function. The activity of TFEB is tightly regulated by multiple phosphorylation and acetylation sites.

Recent advances in graphite carbon nitride-based nanocomposites: structure, antibacterial properties and synergies.

Bacterial infections and transmission threaten human health and well-being. Graphite carbon nitride (g-CN), a promising photocatalytic antibacterial nanomaterial, has attracted increasing attention to combat bacterial transmission, due to the outstanding stability, high efficiency and environmental sustainability of this material. However, the antibacterial efficiency of g-CN is affected by several factors, including its specific surface area, rapid electron/hole recombination processes and optical absorption properties.

Receptor-mediated mitophagy regulates EPO production and protects against renal anemia.

Erythropoietin (EPO) drives erythropoiesis and is secreted mainly by the kidney upon hypoxic or anemic stress. The paucity of EPO production in renal EPO-producing cells (REPs) causes renal anemia, one of the most common complications of chronic nephropathies. Although mitochondrial dysfunction is commonly observed in several renal and hematopoietic disorders, the mechanism by which mitochondrial quality control impacts renal anemia remains elusive.

Versatile Nanoplatforms with enhanced Photodynamic Therapy: Designs and Applications.

As an emerging antitumor strategy, photodynamic therapy (PDT) has attracted intensive attention for the treatment of various malignant tumors owing to its noninvasive nature and high spatial selectivity in recent years. However, the therapeutic effect is unsatisfactory on some occasions due to the presence of some unfavorable factors including nonspecific accumulation of PS towards malignant tissues, the lack of endogenous oxygen in tumors, as well as the limited light penetration depth, further hampering practical application. To circumvent these limitations and improve real utilization efficiency, various enhanced strategies have been developed and explored during the past years.

Dynamic PGAM5 multimers dephosphorylate BCL-xL or FUNDC1 to regulate mitochondrial and cellular fate.

Mitochondria are highly dynamic organelles and respond to stress by changing their fission-fusion cycle, undergoing mitophagy, or releasing apoptotic proteins to initiate cell death. The molecular mechanisms that sense different stresses and coordinate distinct effectors still await full characterization. Here, we show that PGAM5, which exists in an equilibrium between dimeric and multimeric states, dephosphorylates BCL-xL to inhibit apoptosis or FUNDC1 to activate mitofission and mitophagy in response to distinct stresses.

The SIAH2-NRF1 axis spatially regulates tumor microenvironment remodeling for tumor progression.

The interactions between tumor cells with their microenvironments, including hypoxia, acidosis and immune cells, lead to the tumor heterogeneity which promotes tumor progression. Here, we show that SIAH2-NRF1 axis remodels tumor microenvironment through regulating tumor mitochondrial function, tumor-associated macrophages (TAMs) polarization and cell death for tumor maintenance and progression. Mechanistically, low mitochondrial gene expression in breast cancers is associated with a poor clinical outcome.

Regulation of mATG9 trafficking by Src- and ULK1-mediated phosphorylation in basal and starvation-induced autophagy.

Autophagy requires diverse membrane sources and involves membrane trafficking of mATG9, the only membrane protein in the ATG family. However, the molecular regulation of mATG9 trafficking for autophagy initiation remains unclear. Here we identified two conserved classic adaptor protein sorting signals within the cytosolic N-terminus of mATG9, which mediate trafficking of mATG9 from the plasma membrane and trans-Golgi network (TGN) via interaction with the AP1/2 complex.

Zyxin-Siah2-Lats2 axis mediates cooperation between Hippo and TGF-β signalling pathways.

The evolutionarily conserved Hippo pathway is a regulator that controls organ size, cell growth and tissue homeostasis. Upstream signals of the Hippo pathway have been widely studied, but how microenvironmental factors coordinately regulate this pathway remains unclear. In this study, we identify LIM domain protein Zyxin, as a scaffold protein, that in response to hypoxia and TGF-β stimuli, forms a ternary complex with Lats2 and Siah2 and stabilizes their interaction.

Mitochondrial outer-membrane E3 ligase MUL1 ubiquitinates ULK1 and regulates selenite-induced mitophagy.

Mitochondria serve as membrane sources and signaling platforms for regulating autophagy. Accumulating evidence has also shown that damaged mitochondria are removed through both selective mitophagy and general autophagy in response to mitochondrial and oxidative stresses. Protein ubiquitination through mitochondrial E3 ligases plays an integrative role in mitochondrial outer membrane protein degradation, mitochondrial dynamics, and mitophagy.

Hypoxia regulates Hippo signalling through the SIAH2 ubiquitin E3 ligase.

The Hippo signalling pathway plays important roles in animal development, physiology and tumorigenesis. Understanding how the activity of this pathway is regulated by the cellular microenvironment remains a major challenge. Here we elucidate a molecular mechanism by which hypoxia deactivates Hippo signalling.

A diterpenoid derivate compound targets selenocysteine of thioredoxin reductases and induces Bax/Bak-independent apoptosis.

We have previously shown that the natural diterpenoid derivative S3 induced Bim upregulation and apoptosis in a Bax/Bak-independent manner. However, the exact molecular target(s) of S3 and the mechanism controlling Bim upregulation are still not clear. Here, we identify that S3 targets the selenoproteins TrxR1 and TrxR2 at the selenocysteine residue of the reactive center of the enzymes and inhibits their antioxidant activities.