Inactive von Hippel-Lindau (VHL) is linked to metabolic reprogramming and plays pivotal roles in the pathogenesis of clear cell renal cell carcinoma (ccRCC). Here, we identify a previously unknown oncogenic role for inactive VHL in actively triggering histone lactylation to promote ccRCC progression. In patients with ccRCC, inactive VHL positively correlates with the presence of histone lactylation, and high levels of histone lactylation indicates poor patient prognosis. Inactive VHL-triggered histone lactylation contributes to ccRCC progression by activating the transcription of platelet-derived growth factor receptor β (PDGFRβ). In turn, PDGFRβ signaling is shown to stimulate histone lactylation, thereby forming an oncogenic positive feedback loop in ccRCC. Target correction of aberrant histone lactylation represses the growth and metastasis of ccRCC in vivo. More importantly, the combined inhibition of histone lactylation and PDGFRβ significantly reinforces the therapeutic efficacy. This work underscores the importance of histone lactylation in facilitating ccRCC progression and suggests targeting the positive feedback loop between histone lactylation and PDGFRβ signaling might provide a promising therapeutic strategy for ccRCC patients.

This paper aims to investigate the tribo-mechanical behavior of natural fiber reinforced plastic (NFRP) composites with specific consideration of the multiscale complex structure of natural fibers. Understanding the multiscale tribo-mechanical performances of these eco-friendly materials can lead to a better design of their manufacturing processes. Nanoindentation and nanoscratching experiments are conducted on flax fibers reinforced polypropylene composites using a triboindenter at a specific contact scale generated by the tip indenter radius (100 nm). Results confirm the significant effect of the geometric contact scale on the flax fibers stiffness. Moreover, flax fibers friction shows a multiscale behavior where the mechanisms of nano-friction are vastly different from those of micro-friction, which is related to the physical phenomena arisen at each scale.

Here, we demonstrate the assembly of a new stable lanthanide-based metal-organic framework (MOF), Eu(HDPB)(phen) (1) (HDPB = (1,1ʹ:3ʹ,1ʹʹ-terphenyl)-3,3ʹʹ,5,5ʹʹ-tetracarboxylic acid, phen = 1,10-phenanthroline), with a three-dimensional framework under solvothermal conditions. 1...

This study obtained solution-tractable anion-selective membranes with intrinsic porous and highly ionic conductive capabilities by a convenient route. We used the coplanar structure of 9,9-dimethylxanthene to construct a rigid twisted intrinsic microporous all-carbon skeleton PDI with up to 363.4 m 2 g −1 of Brunauer−Emmett−Teller surface, and the pore was filled with a quaternary ammonium salt containing long flexible alkyl chains, which produced an efficient means of OH − transport. The conductivity of the resulting polymer (QPDI-100) is reached as high as 205 mS cm −1 at 80 °C. The size stability was determined to be good at high conductance and swelling ratio is less than 15% at 80 °C. QPDI-a exhibited good stability under alkaline conditions, and 90% of the conductivity of QPDI-100 was retained after being immersed in 1 M NaOH solution at 60 °C for 40 days. The power density of H 2 −O 2 fuel cells at 60 °C was 437.7 mW cm −2 . The prepared intrinsic porous anion exchange membranes (AEMs) demonstrate potential for the development of anion exchange membrane fuel cells. This membrane design strategy paves the way for a new generation of AEMs for the purposes of electrochemical energy conversion and storage.

Background Postoperative cognitive dysfunction (POCD) is a common complication following anesthesia and surgery. General anesthetic isoflurane has potential neurotoxicity and induces cognitive impairments, but the exact mechanism remains unclear. Astrocytes form interconnected networks in the adult brain through gap junctions (GJs), which primarily comprise connexin 43 (Cx43), and play important roles in brain homeostasis and functions such as memory. However, the role of the GJ-Cx43-mediated astrocytic network in isoflurane-induced cognitive dysfunction has not been defined. Methods 4-month-old male C57BL/6 mice were exposure to long-term isoflurane to induce cognitive impairment. To simulate an in vitro isoflurane-induced cognitive dysfunction‐like condition, primary mouse astrocytes were subjected to long-term isoflurane exposure. Cognitive function was assessed by Y-maze and fear conditioning tests. Western blot was used to determine the expression levels of different functional configurations of Cx43. The morphology of the GJs-Cx43 was evaluated by immunofluorescence staining. Levels of IL-1β and IL-6 were examined by ELISA. The ability of GJs-Cx43-mediated intercellular communication was examined by lucifer yellow dye transfer assay. Ethidium bromide uptake assays were used to measure the activity of Cx43 hemichannels. The ultrastructural morphology of astrocyte gap junctions and tripartite synapse were observed by transmission electron microscopy. Results After long-term isoflurane anesthesia, the GJs formed by Cx43 in the mouse hippocampus and primary mouse astrocytes were significantly reduced, GJs function was impaired, hemichannel activity was enhanced, the levels of IL-1β and IL-6 were increased, and mice showed significant cognitive impairment. After treatment with the novel GJ-Cx43 enhancer ZP1609, GJ-Cx43-mediated astrocytic network function was enhanced, neuroinflammation was alleviated, and ameliorated cognition dysfunction induced by long-term isoflurane exposure. However, ZP1609 enhances the astrocytic network by promoting Cx43 to form GJs without affecting hemichannel activity. Additionally, our data showed that long-term isoflurane exposure does not alter the structure of tripartite synapse. Conclusion Our results reveal a novel mechanism of the GJ-Cx43-mediated astrocytic network involved in isoflurane-induced neuroinflammation and cognitive impairments, which provides new mechanistic insight into the pathogenesis of POCD and identifies potential targets for its treatment.

Main-chain non-ether anion-exchange membranes (AEMs) have become a research hotspot in recent years because of their ease of preparation and excellent alkaline stability. However, owing to the limitations of the types of monomers and polymerization mechanisms, preparing main-chain non-ether AEMs with controllable morphology remains challenging. Herein, seven poly(fluorene alkylene) membranes, including random and block-structured membranes with different quaternary ammonium (QA) group distributions on the side chains, with the same ion-exchange capacity (IEC) were designed via superacid-catalyzed polymerization. The properties of the as-synthesized membranes were characterized, and the water-transport mechanism has been discussed in relation to the morphology of the membranes. The formed bicontinuous phase structure based on block biphenyl units possessed multidirectional ion channels and distinct ion clusters favorable to water molecule movement. The conductivity of the optimized membrane with a block biphenyl structure reached 208 mS cm–1 at 80 °C, and the peak power density of an H2/O2 fuel cell based on the as-prepared membrane was 0.92 W cm–2. The reported approach is effective in balancing the content of free and bound water within the membrane, generating maximum hydroxide mobility and water transport suitable for high-performance AEM fuel cells. This study highlights the significance of regulating the block structure and adjusting the segment distribution in AEMs to tune their morphologies and provides an innovative design approach for constructing high-performance AEMs.

Natural fiber reinforced plastic (NFRP) composites are eliciting an increased interest across industrial sectors, as they combine a high degree of biodegradability and recyclability with unique structural properties. These materials are machined to create components that meet the dimensional and surface finish tolerance specifications for various industrial applications. The heterogeneous structure of these materials—resulting from different fiber orientations and their complex multiscale structure—introduces a distinct set of material removal mechanisms that inherently vary over time. This structure has an adverse effect on the surface integrity of machined NFRPs. Therefore, a real-time monitoring approach is desirable for timely intervention for quality assurance. Acoustic emission (AE) sensors that capture the elastic waves generated from the plastic deformation and fracture mechanisms have potential to characterize these abrupt variations in the material removal mechanisms. However, the relationship connecting AE waveform patterns with these NFRP material removal mechanisms is not currently understood. This paper reports an experimental investigation into how the time–frequency patterns of AE signals connote the various cutting mechanisms under different cutting speeds and fiber orientations. Extensive orthogonal cutting experiments on unidirectional flax fiber NFRP samples with various fiber orientations were conducted. The experimental setup was instrumented with a multisensor data acquisition system for synchronous collection of AE and vibration signals during NFRP cutting. A random forest machine learning approach was employed to quantitatively relate the AE energy over specific frequency bands to machining conditions and hence the process microdynamics, specifically, the phenomena of fiber fracture and debonding that are peculiar to NFRP machining. Results from this experimental study suggest that the AE energy over these frequency bands can correctly predict the cutting conditions to ∼95% accuracies, as well as the underlying material removal regimes.

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