Ceria nanoparticles: biomedical applications and toxicity. / 二氧化铈纳米颗粒：生物医学应用和毒性.

Ceria nanoparticles (CeO2 NPs) have become popular materials in biomedical and industrial fields due to their potential applications in anti-oxidation, cancer therapy, photocatalytic degradation of pollutants, sensors, etc. Many methods, including gas phase, solid phase, liquid phase, and the newly proposed green synthesis method, have been reported for the synthesis of CeO2 NPs. Due to the wide application of CeO2 NPs, concerns about their adverse impacts on human health have been raised. This review covers recent studies on the biomedical applications of CeO2 NPs, including their use in the treatment of various diseases (e.|g., Alzheimer's disease, ischemic stroke, retinal damage, chronic inflammation, and cancer). CeO2 NP toxicity is discussed in terms of the different systems of the human body (e.|g., cytotoxicity, genotoxicity, respiratory toxicity, neurotoxicity, and hepatotoxicity). This comprehensive review covers both fundamental discoveries and exploratory progress in CeO2 NP research that may lead to practical developments in the future.

Passivation Layers in Mg-metal Batteries: Robust Interphases for Li-metal Batteries.

In advanced batteries, interphases serve as the key component in stabilizing the electrolyte with reactive electrode materials far beyond thermodynamic equilibria. While an active interphase facilitates the transport of working ions, an inactive interphase obstructs ion flow, constituting the primary barrier to the realization of battery chemistries. Here, we present a successful transformation of a traditionally inactive passivating layer on Mg-metal anode, characteristic of Mg-metal batteries (MMBs) with typical carbonate electrolytes, into an active and robust interphase in the Li-metal scenario. By further strategically designing magnesiated Li+ electrolytes, we induce the in-situ development of this resilient interphase on Li-metal anodes, imparting enduring stability to Li-metal batteries (LMBs) with nickel-rich cathodes. We identify that the strong affinity between Mg2+ and anions in magnesiated Li+ electrolytes assembles ionic clusters with a bias for reducibility, thereby catalyzing the creation of anion-derived interphases rich in inorganic constituents. The prevalence of ionic clusters induced by magnesiation of electrolytes brought properties only available in high-concentration electrolytes, suggesting a fresh paradigm of tailing electrolytes for highly reversible LMBs. This article is protected by copyright. All rights reserved.

Engineering High-Performance Li Metal Batteries through Dual-Gradient Porous Cu-CuZn Host.

Porous copper (Cu) current collectors show promise in stabilizing Li metal anodes (LMAs). However, insufficient lithiophilicity of pure Cu and limited porosity in three-dimensional (3D) porous Cu structures led to an inefficient Li-Cu composite preparation and poor electrochemical performance of Li-Cu composite anodes. Herein, we propose a porous Cu-CuZn (DG-CCZ) host for Li composite anodes to tackle these issues. This architecture features a pore size distribution and lithiophilic-lithiophobic characteristics designed in a gradient distribution from the inside to the outside of the anode structure. This dual-gradient porous Cu-CuZn exhibits exceptional capillary wettability to molten Li and provides a high porosity of up to 66.05%. This design promotes preferential Li deposition in the interior of the porous structure during battery operation, effectively inhibiting Li dendrite formation. Consequently, all cell systems achieve significantly improved cycling stability, including Li half-cells, Li-Li symmetric cells, and Li-LFP full cells. When paired synergistically with the double-coated LiFePO4 cathode, the pouch cell configured with multiple electrodes demonstrates an impressive discharge capacity of 159.3 mAh g-1 at 1C. We believe this study can inspire the design of future 3D Li anodes with enhanced Li utilization efficiency and facilitate the development of future high-energy Li metal batteries.

Chronoamperometric interrogation of an electrochemical aptamer-based sensor with tetrahedral DNA nanostructure pendulums for continuous biomarker measurements.

Tetrahedral DNA nanostructure (TDN) is highly promising in developing electrochemical aptamer-based (E-AB) sensors for biomolecular detection, owing to its inherit programmability, spatial orientation and structural robustness. However, current interrogation strategies applied for TDN-based E-AB sensors, including enzyme-based amperometry, voltammetry, and electrochemical impedance spectroscopy, either require complicated probe design or suffer from limited applicability or selectivity. In this study, a TDN pendulum-empowered E-AB sensor interrogated by chronoamperometry for reagent-free and continuous monitoring of a blood clotting enzyme, thrombin, was developed. TDN pendulums with extended aptamer sequences at three vertices were immobilized on a gold electrode via a thiolated double-stranded DNA (dsDNA) at the fourth vertex, and their motion is modulated by the bonding of target thrombin to aptamers. We observed a significantly amplified signalling output on our sensor based on the TDN pendulum compared to E-AB sensors modified with linear pendulums. Moreover, our sensor achieved highly selective and rapidly responsive measurement of thrombin in both PBS and artificial urine, with a wide dynamic range from 1 pM to 10 nM. This study shows chronoamperometry-enabled continuous biomarker monitoring on a sub-second timescale with a drift-free baseline, demonstrating a novel approach to accurately detect molecular dynamics in real time.

Guard cell and subsidiary cell sizes are key determinants for stomatal kinetics and drought adaptation in cereal crops.

Climate change-induced drought is a major threat to agriculture. C4 crops have a higher water use efficiency (WUE) and better adaptability to drought than C3 crops due to their smaller stomatal morphology and faster response. However, our understanding of stomatal behaviours in both C3 and C4 Poaceae crops is limited by knowledge gaps in physical traits of guard cell (GC) and subsidiary cell (SC). We employed infrared gas exchange analysis and a stomatal assay to explore the relationship between GC/SC sizes and stomatal kinetics across diverse drought conditions in two C3 (wheat and barley) and three C4 (maize, sorghum and foxtail millet) upland Poaceae crops. Through statistical analyses, we proposed a GCSC-τ model to demonstrate how morphological differences affect stomatal kinetics in C4 Poaceae crops. Our findings reveal that morphological variations specifically correlate with stomatal kinetics in C4 Poaceae crops, but not in C3 ones. Subsequent modelling and experimental validation provide further evidence that GC/SC sizes significantly impact stomatal kinetics, which affects stomatal responses to different drought conditions and thereby WUE in C4 Poaceae crops. These findings emphasize the crucial advantage of GC/SC morphological characteristics and stomatal kinetics for the drought adaptability of C4 Poaceae crops, highlighting their potential as future climate-resilient crops.

From Stress to Screen: Understanding Cyberloafing through Cognitive and Affective Pathways.

This investigation delves into the pervasive yet insufficiently examined phenomenon of "cyberloafing", characterized by employees engaging in non-work-related internet activities during office hours. Despite its frequent occurrence in contemporary work environments, the fundamental mechanisms underpinning cyberloafing remain largely uncharted. This study uses the conservation of resources theory and the cognitive-affective personality system framework to demystify the relationship between role stress and cyberloafing. We developed a dual-path model to assess the mediating roles of perceived insider status and emotional exhaustion. Employing SPSS and Smart PLS for data analysis, our research sampled 210 corporate employees. The findings reveal that role stress predicts perceived insider status and emotional exhaustion significantly. Notably, while perceived insider status negatively correlates with cyberloafing, emotional exhaustion shows a positive correlation. These factors mediate the relationship between role stress and cyberloafing, underscoring a multifaceted dynamic. Our results provide new theoretical insights into the mechanisms of employee counterproductive behavior, specifically in the context of cyberloafing, and broaden our understanding of its determinants. This study illuminates theoretical nuances and offers practical implications for managerial strategies and future scholarly inquiries into organizational behavior.

High-throughput mRNA sequencing of human placenta shows sex differences across gestation.

INTRODUCTION: Fetal sex affects fetal and maternal health outcomes in pregnancy, but this connection remains poorly understood. As the placenta is the route of fetomaternal communication and derives from the fetal genome, placental gene expression sex differences may explain these outcomes. OBJECTIVES: We utilized next generation sequencing to study the normal human placenta in both sexes in first and third trimester to generate a normative transcriptome based on sex and gestation. STUDY DESIGN: We analyzed 124 first trimester (T1, 59 female and 65 male) and 43 third trimester (T3, 18 female and 25 male) samples for sex differences within each trimester and sex-specific gestational differences. RESULTS: Placenta shows more significant sexual dimorphism in T1, with 94 T1 and 26 T3 differentially expressed genes (DEGs). The sex chromosomes contributed 60.6% of DEGs in T1 and 80.8% of DEGs in T3, excluding X/Y pseudoautosomal regions. There were 6 DEGs from the pseudoautosomal regions, only significant in T1 and all upregulated in males. The distribution of DEGs on the X chromosome suggests genes on Xp (the short arm) may be particularly important in placental sex differences. Dosage compensation analysis of X/Y homolog genes shows expression is primarily contributed by the X chromosome. In sex-specific analyses of first versus third trimester, there were 2815 DEGs common to both sexes upregulated in T1, and 3263 common DEGs upregulated in T3. There were 7 female-exclusive DEGs upregulated in T1, 15 female-exclusive DEGs upregulated in T3, 10 male-exclusive DEGs upregulated in T1, and 20 male-exclusive DEGs upregulated in T3. DISCUSSION: This is the largest cohort of placentas across gestation from healthy pregnancies defining the normative sex dimorphic gene expression and sex common, sex specific and sex exclusive gene expression across gestation. The first trimester has the most sexually dimorphic transcripts, and the majority were upregulated in females compared to males in both trimesters. The short arm of the X chromosome and the pseudoautosomal region is particularly critical in defining sex differences in the first trimester placenta. As pregnancy is a dynamic state, sex specific DEGs across gestation may contribute to sex dimorphic changes in overall outcomes.

Tgfb1 deficiency impairs the self-renewal capacity of murine hematopoietic stem/progenitor cells in vivo.

Transforming growth factor ß1 (TGFB1) refers to a pleiotropic cytokine exerting contrasting roles in hematopoietic stem cells (HSCs) functions in vitro and in vivo. However, the understanding of hematopoiesis in vivo, when TGFB1 is constantly deactivated, is still unclear, mainly due to significant embryonic lethality and the emergence of a fatal inflammatory condition, which makes doing these investigations challenging. Our study aims to find the specific role of TGFB1 in regulating hematopoiesis in vivo. We engineered mice strains (Vav1 or Mx1 promoter-driven TGFB1 knockout) with conditional knockout of TGFB1 to study its role in hematopoiesis in vivo. In fetal and adult hematopoiesis, TGFB1 KO mice displayed deficiency and decreased self-renewal capacity of HSCs with myeloid-biased differentiation. The results were different from the regulating role of TGFB1 in vitro. Additionally, our results showed that TGFB1 deficiency from fetal hematopoiesis stage caused more severe defect of HSCs than in the adult stage. Mechanistically, our findings identified TGFB1-SOX9-FOS/JUNB/TWIST1 signal axis as an essential regulating pathway in HSCs homeostasis. Our study may provide a scientific basis for clinical HSC transplantation and expansion.

Molecular classification and tumor microenvironment characteristics in pheochromocytomas.

Pheochromocytomas (PCCs) are rare neuroendocrine tumors that originate from chromaffin cells in the adrenal gland. However, the cellular molecular characteristics and immune microenvironment of PCCs are incompletely understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on 16 tissues from 4 sporadic unclassified PCC patients and 1 hereditary PCC patient with Von Hippel-Lindau (VHL) syndrome. We found that intra-tumoral heterogeneity was less extensive than the inter-individual heterogeneity of PCCs. Further, the unclassified PCC patients were divided into two types, metabolism-type (marked by NDUFA4L2 and COX4I2) and kinase-type (marked by RET and PNMT), validated by immunohistochemical staining. Trajectory analysis of tumor evolution revealed that metabolism-type PCC cells display phenotype of consistently active metabolism and increased metastasis potential, while kinase-type PCC cells showed decreased epinephrine synthesis and neuron-like phenotypes. Cell-cell communication analysis showed activation of the annexin pathway and a strong inflammation reaction in metabolism-type PCCs and activation of FGF signaling in the kinase-type PCC. Although multispectral immunofluorescence staining showed a lack of CD8+ T cell infiltration in both metabolism-type and kinase-type PCCs, only the kinase-type PCC exhibited downregulation of HLA-I molecules that possibly regulated by RET, suggesting the potential of combined therapy with kinase inhibitors and immunotherapy for kinase-type PCCs; in contrast, the application of immunotherapy to metabolism-type PCCs (with antigen presentation ability) is likely unsuitable. Our study presents a single-cell transcriptomics-based molecular classification and microenvironment characterization of PCCs, providing clues for potential therapeutic strategies to treat PCCs.

PHF6 loss reduces leukemia stem cell activity in an acute myeloid leukemia mouse model.

Acute myeloid leukemia (AML) is a malignant hematologic disease caused by gene mutations and genomic rearrangements in hematologic progenitors. The PHF6 (PHD finger protein 6) gene is highly conserved and located on the X chromosome in humans and mice. We found that PHF6 was highly expressed in AML cells with MLL rearrangement and was related to the shortened survival time of AML patients. In our study, we knocked out the Phf6 gene at different disease stages in the AML mice model. Moreover, we knocked down PHF6 by shRNA in two AML cell lines and examined the cell growth, apoptosis, and cell cycle. We found that PHF6 deletion significantly inhibited the proliferation of leukemic cells and prolonged the survival time of AML mice. Interestingly, the deletion of PHF6 at a later stage of the disease displayed a better anti-leukemia effect. The expressions of genes related to cell differentiation were increased, while genes that inhibit cell differentiation were decreased with PHF6 knockout. It is very important to analyze the maintenance role of PHF6 in AML, which is different from its tumor-suppressing function in T-cell acute lymphoblastic leukemia (T-ALL). Our study showed that inhibiting PHF6 expression may be a potential therapeutic strategy targeting AML patients.

High-throughput mRNA-seq atlas of human placenta shows vast transcriptome remodeling from first to third trimester†.

The placenta, composed of chorionic villi, changes dramatically across gestation. Understanding differences in ongoing pregnancies are essential to identify the role of chorionic villi at specific times in gestation and develop biomarkers and prognostic indicators of maternal-fetal health. The normative mRNA profile is established using next-generation sequencing of 124 first trimester and 43 third trimester human placentas from ongoing healthy pregnancies. Stably expressed genes (SEGs) not different between trimesters and with low variability are identified. Differential expression analysis of first versus third trimester adjusted for fetal sex is performed, followed by a subanalysis with 23 matched pregnancies to control for subject variability using the same genetic and environmental background. Placenta expresses 14,979 polyadenylated genes above sequencing noise (transcripts per million > 0.66), with 10.7% SEGs across gestation. Differentially expressed genes (DEGs) account for 86.7% of genes in the full cohort [false discovery rate (FDR) < 0.05]. Fold changes highly correlate between the full cohort and subanalysis (Pearson = 0.98). At stricter thresholds (FDR < 0.001, fold change > 1.5), there remains 50.1% DEGs (3353 upregulated in first and 4155 upregulated in third trimester). This is the largest mRNA atlas of healthy human placenta across gestation, controlling for genetic and environmental factors, demonstrating substantial changes from first to third trimester in chorionic villi. Specific differences and SEGs may be used to understand the specific role of the chorionic villi throughout gestation and develop first trimester biomarkers of placental health that transpire across gestation, which can be used for future development of biomarkers for maternal-fetal health.

Pluripotency state transition of embryonic stem cells requires the turnover of histone chaperone FACT on chromatin.

The differentiation of embryonic stem cells (ESCs) begins with the transition from the naive to the primed state. The formative state was recently established as a critical intermediate between the two states. Here, we demonstrate the role of the histone chaperone FACT in regulating the naive-to-formative transition. We found that the Q265K mutation in the FACT subunit SSRP1 increased the binding of FACT to histone H3-H4, impaired nucleosome disassembly in vitro, and reduced the turnover of FACT on chromatin in vivo. Strikingly, mouse ESCs harboring this mutation showed elevated naive-to-formative transition. Mechanistically, the SSRP1-Q265K mutation enriched FACT at the enhancers of formative-specific genes to increase targeted gene expression. Together, these findings suggest that the turnover of FACT on chromatin is crucial for regulating the enhancers of formative-specific genes, thereby mediating the naive-to-formative transition. This study highlights the significance of FACT in fine-tuning cell fate transition during early development.

Impact of perioperative SARS-CoV-2 Omicron infection on postoperative complications in liver cancer hepatectomy: A single-center matched study.

OBJECTIVES: To explore the effects of perioperative SARS-CoV-2 Omicron infection on postoperative complications in patients with liver cancer. METHODS: A propensity-matched study was conducted, which included patients with primary liver cancer who underwent hepatectomy from September 01, 2022 to January 20, 2023. Patients who infected SARS-CoV-2 Omicron during the perioperative period (7 days before to 30 days after surgery) were matched 1:1 with noninfected patients. The primary outcomes, which were COVID-19-related major complications and liver resection-specific complications, were analyzed using multivariate logistic regression. RESULTS: A total of 243 patients were included, with 63 cases of perioperative infections, of which 62 were postoperative infections. The overall 30-day postoperative mortality rate was 1.6% (4/243). Compared to noninfected patients, those with perioperative infections showed no significant difference in the occurrence of adverse postoperative outcomes. However, they had a higher rate of 30-day readmission after surgery (11.1% vs 0%, P = 0.013). Perioperative SARS-CoV-2 infection was not associated with "major cardiorespiratory complications" or "liver resection-specific complications", but age, pre-existing comorbidities, and tumor type were related to these outcomes. CONCLUSION: Perioperative SARS-CoV-2 Omicron infection did not increase the incidence of postoperative complications in patients with liver cancer. However, those patients had a higher rate of 30-day readmission after surgery.

Enhancing isoprene polymerization with high activity and adjustable monomer enchainment using cyclooctyl-fused iminopyridine iron precatalysts.

In this study, a series of structurally rigid cyclooctyl-fused iminopyridine iron complexes, [L2FeCl][FeCl4] and [2L3Fe][Cl][3FeCl4], was synthesized via a one-pot method and investigated as precatalysts in conjunction with methylaluminoxane for isoprene (Ip) polymerization. Combined characterization through FTIR analysis, elemental analysis and single crystal XRD analysis fully verified the structure of these complexes. The most active iron complex, FeH, exhibited a trisligated nature, with its cation adopting an octahedral geometry around the metal center. In contrast, all the other iron complexes (Fe2Me, Fe2Et, Fe2iPr, Fe3Me, Fe2Et,Me) displayed bisligated configurations, with distorted trigonal bipyramidal geometry of cations. During isoprene polymerization, the extent of steric hindrance of the ligand framework exerted a significant impact on catalytic performance. The FeH precatalyst with less steric hindrance demonstrated excellent performance, producing high molecular weight polyisoprenes with conversions exceeding 99% for 4000 equiv. of monomer. Even at very low catalyst loadings, as low as 0.0025 mol% (Fe/Ip), the polymerization of isoprene could proceed smoothly with an exceptionally high activity of 4.0 × 106 gPI (molFe, h)-1. Moreover, this precatalyst exhibited good thermal stability, maintaining high activity levels (typically 105 gPI (molFe, h)-1) across a broad temperature range from -20 °C to 100 °C. Additionally, by adjusting steric substituents and the reaction temperature, the 1,4/3,4 regioselectivity could be modulated from 9/91 to 69/31 while maintaining a high stereoselectivity of cis-1,4 structures (cis/trans: >99/1).

α-Ketoglutarate-Dependent KDM6 Histone Demethylases and Interferon-Stimulated Gene Expression in Lupus.

OBJECTIVE: We aimed to investigate the hypothesis that interferon (IFN)-stimulated gene (ISG) expression in systemic lupus erythematosus (SLE) monocytes is linked to changes in metabolic reprogramming and epigenetic regulation of ISG expression. METHODS: Monocytes from healthy volunteers and patients with SLE at baseline or following IFNα treatment were analyzed by extracellular flux analysis, proteomics, metabolomics, chromatin immunoprecipitation, and gene expression. The histone demethylases KDM6A/B were inhibited using glycogen synthase kinase J4 (GSK-J4). GSK-J4 was tested in pristane and resiquimod (R848) models of IFN-driven SLE. RESULTS: SLE monocytes had enhanced rates of glycolysis and oxidative phosphorylation compared to healthy control monocytes, as well as increased levels of isocitrate dehydrogenase and its product, α-ketoglutarate (α-KG). Because α-KG is a required cofactor for histone demethylases KDM6A and KDM6B, we hypothesized that IFNα may be driving "trained immune" responses through altering histone methylation. IFNα priming (day 1) resulted in a sustained increase in the expression of ISGs in primed cells (day 5) and enhanced expression on restimulation with IFNα. Importantly, decreased H3K27 trimethylation was observed at the promoters of ISGs following IFNα priming. Finally, GSK-J4 (KDM6A/B inhibitor) resulted in decreased ISG expression in SLE patient monocytes, as well as reduced autoantibody production, ISG expression, and kidney pathology in R848-treated BALB/c mice. CONCLUSION: Our study suggests long-term IFNα exposure alters the epigenetic regulation of ISG expression in SLE monocytes via changes in immunometabolism, a mechanism reflecting trained immunity to type I IFN. Importantly, it opens the possibility that targeting histone-modifying enzymes, such as KDM6A/B, may reduce IFN responses in SLE.

Human Motion Generation: A Survey.

Human motion generation aims to generate natural human pose sequences and shows immense potential for real-world applications. Substantial progress has been made recently in motion data collection technologies and generation methods, laying the foundation for increasing interest in human motion generation. Most research within this field focuses on generating human motions based on conditional signals, such as text, audio, and scene contexts. While significant advancements have been made in recent years, the task continues to pose challenges due to the intricate nature of human motion and its implicit relationship with conditional signals. In this survey, we present a comprehensive literature review of human motion generation, which, to the best of our knowledge, is the first of its kind in this field. We begin by introducing the background of human motion and generative models, followed by an examination of representative methods for three mainstream sub-tasks: text-conditioned, audio-conditioned, and scene-conditioned human motion generation. Additionally, we provide an overview of common datasets and evaluation metrics. Lastly, we discuss open problems and outline potential future research directions. We hope that this survey could provide the community with a comprehensive glimpse of this rapidly evolving field and inspire novel ideas that address the outstanding challenges.

Molecular and phylogenetic evidence of parallel expansion of anion channels in plants.

Aluminum-activated malate transporters (ALMTs) and slow anion channels (SLACs) are important in various physiological processes in plants, including stomatal regulation, nutrient uptake, and in response to abiotic stress such as aluminum toxicity. To understand their evolutionary history and functional divergence, we conducted phylogenetic and expression analyses of ALMTs and SLACs in green plants. Our findings from phylogenetic studies indicate that ALMTs and SLACs may have originated from green algae and red algae, respectively. The ALMTs of early land plants and charophytes formed a monophyletic clade consisting of three subgroups. A single duplication event of ALMTs was identified in vascular plants and subsequent duplications into six clades occurred in angiosperms, including an identified clade, 1-1. The ALMTs experienced gene number losses in clades 1-1 and 2-1 and expansions in clades 1-2 and 2-2b. Interestingly, the expansion of clade 1-2 was also associated with higher expression levels compared to genes in clades that experienced apparent loss. SLACs first diversified in bryophytes, followed by duplication in vascular plants, giving rise to three distinct clades (I, II, and III), and clade II potentially associated with stomatal control in seed plants. SLACs show losses in clades II and III without substantial expansion in clade I. Additionally, ALMT clade 2-2 and SLAC clade III contain genes specifically expressed in reproductive organs and roots in angiosperms, lycophytes, and mosses, indicating neofunctionalization. In summary, our study demonstrates the evolutionary complexity of ALMTs and SLACs, highlighting their crucial role in the adaptation and diversification of vascular plants.

Peptide Gel Electrolytes for Stabilized Zn Metal Anodes.

The rechargeable aqueous Zn ion battery (AZIB) is considered a promising candidate for future energy storage applications due to its intrinsic safety features and low cost. However, Zn dendrites and side reactions (e.g., corrosion, hydrogen evolution reaction, and inactive side product (Zn hydroxide sulfate) formation) at the Zn metal anode have been serious obstacles to realizing a satisfactory AZIB performance. The application of gel electrolytes is a common strategy for suppressing these problems, but the normally used highly cross-linked polymer matrix (e.g., polyacrylamide (PAM)) brings additional difficulties for battery assembly and recycling. Herein, we have developed a gel electrolyte for Zn metal anode stabilization, where a peptide matrix, a highly biocompatible material, is used for gel construction. Various experiments and simulations elucidate the sulfate anion-assisted self-assembly gel formation and its effect in stabilizing Zn metal anodes. Unlike polymer gel electrolytes, the peptide gel electrolyte can reversibly transform between gel and liquid states, thus facilitating the gel-involved battery assembly and recycling. Furthermore, the peptide gel electrolyte provides fast Zn ion diffusion (comparable to conventional liquid electrolyte) while suppressing side reactions and dendrite growth, thus achieving highly stable Zn metal anodes as validated in various cell configurations. We believe that our concept of gel electrolyte design will inspire more future directions for Zn metal anode protection based on gel electrolyte design.

High-performance van der Waals antiferroelectric CuCrP2S6-based memristors.

Layered thio- and seleno-phosphate ferroelectrics, such as CuInP2S6, are promising building blocks for next-generation nonvolatile memory devices. However, because of the low Curie point, the CuInP2S6-based memory devices suffer from poor thermal stability (<42 °C). Here, exploiting the electric field-driven phase transition in the rarely studied antiferroelectric CuCrP2S6 crystals, we develop a nonvolatile memristor showing a sizable resistive-switching ratio of ~ 1000, high switching endurance up to 20,000 cycles, low cycle-to-cycle variation, and robust thermal stability up to 120 °C. The resistive switching is attributed to the ferroelectric polarization-modulated thermal emission accompanied by the Fowler-Nordheim tunneling across the interfaces. First-principles calculations reveal that the good device performances are associated with the exceptionally strong ferroelectric polarization in CuCrP2S6 crystal. Furthermore, the typical biological synaptic learning rules, such as long-term potentiation/depression and spike amplitude/spike time-dependent plasticity, are also demonstrated. The results highlight the great application potential of van der Waals antiferroelectrics in high-performance synaptic devices for neuromorphic computing.

The proteasome component PSMD14 drives myelomagenesis through a histone deubiquitinase activity.

While 19S proteasome regulatory particle (RP) inhibition is a promising new avenue for treating bortezomib-resistant myeloma, the anti-tumor impact of inhibiting 19S RP component PSMD14 could not be explained by a selective inhibition of proteasomal activity. Here, we report that PSMD14 interacts with NSD2 on chromatin, independent of 19S RP. Functionally, PSMD14 acts as a histone H2AK119 deubiquitinase, facilitating NSD2-directed H3K36 dimethylation. Integrative genomic and epigenomic analyses revealed the functional coordination of PSMD14 and NSD2 in transcriptional activation of target genes (e.g., RELA) linked to myelomagenesis. Reciprocally, RELA transactivates PSMD14, forming a PSMD14/NSD2-RELA positive feedback loop. Remarkably, PSMD14 inhibitors enhance bortezomib sensitivity and fosters anti-myeloma synergy. PSMD14 expression is elevated in myeloma and inversely correlated with overall survival. Our study uncovers an unappreciated function of PSMD14 as an epigenetic regulator and a myeloma driver, supporting the pursuit of PSMD14 as a therapeutic target to overcome the treatment limitation of myeloma.