Ubiquitin-specific protease 38 promotes atrial fibrillation in diabetic mice by stabilizing iron regulatory protein 2.

BACKGROUND: Atrial fibrillation (AF) is a common cardiovascular disease often observed in diabetes mellitus, and there is currently no satisfactory therapeutic option. Ubiquitin-specific protease 38 (USP38) has been implicated in the degradation of numerous substrate proteins in the myocardium. Herein, we aim to investigate the role of USP38 in AF induced by diabetes. METHODS: Cardiac-specific transgenic USP38 mice and cardiac-specific knockout USP38 mice were constructed, and streptozotocin was used to establish diabetic mouse model. Functional, electrophysiological, histologic, biochemical studies were performed. RESULTS: The expression of USP38 was upregulated in atrial tissues of diabetic mice and HL-1 cells exposed to high glucose. USP38 overexpression increased susceptibility to AF, accompanied by aberrant expression of calcium-handling protein, heightened iron load and oxidation stress in diabetic mice. Conversely, USP38 deficiency reduced vulnerability to AF by hampering ferroptosis. Mechanistically, USP38 bound to iron regulatory protein 2 (IRP2), stabilizing it and remove K48-linked polyubiquitination chains, thereby increasing intracellular iron overload, lipid peroxidation, and ultimately contributing to ferroptosis. In addition, reduced iron overload by deferoxamine treatment alleviated oxidation stress and decreased vulnerability to AF in diabetic mice. CONCLUSION: Overall, our findings reveal the detrimental role of USP38 in diabetes-related AF, manifested by increased level of iron overload and oxidation stress.

Examination of nonlinear associations between pulse pressure index and incident prediabetes susceptibility: a 5-year retrospective cohort investigation.

Prediabetes and related complications constitute significant public health burdens globally. As an indicator closely associated with abnormal glucose metabolism and atherosclerosis, the utility of Pulse Pressure Index (PPI) as a prediabetes risk marker has not been explored. We performed a retrospective cohort analysis to investigate this putative association between PPI and prediabetes hazard. Our analysis encompassed 183,517 Chinese adults ≥ 20 years registered within the Rich Healthcare Group 2010-2016. PPI was defined as (systolic blood pressure - diastolic blood pressure)/systolic blood pressure. The relationship between PPI and prediabetes risk was assessed via Cox proportional hazards regression modeling. Non-linearity evaluations applied cubic spline fitting approaches alongside smooth curve analysis. Inflection points of PPI concerning prediabetes hazard were determined using two-piecewise Cox models. During a median follow-up of 3 years (2.17-3.96 years), new-onset prediabetes was documented in 20,607 patients (11.23%). Multivariate regression analysis showed that PPI was an independent risk factor for prediabetes, and the risk of prediabetes increased by 0.6% for every 1% increase in PPI (Hazard Ratio [HR]: 1.006, 95% Confidence Interval [CI] 1.004-1.008, P < 0.001). This association was non-significant for PPI ≤ 37.41% yet exhibited a sharp upsurge when PPI surpassed 37.41% (HR: 1.013, 95% CI 1.005-1.021, P = 0.0029). Our analysis unveils a positive, non-linear association between PPI and future prediabetes risk. Within defined PPI ranges, this relationship is negligible but dramatically elevates beyond identified thresholds.

Plastome evolution of Engelhardia facilitates phylogeny of Juglandaceae.

BACKGROUND: Engelhardia (Juglandaceae) is a genus of significant ecological and economic importance, prevalent in the tropics and subtropics of East Asia. Although previous efforts based on multiple molecular markers providing profound insights into species delimitation and phylogeography of Engelhardia, the maternal genome evolution and phylogeny of Engelhardia in Juglandaceae still need to be comprehensively evaluated. In this study, we sequenced plastomes from 14 samples of eight Engelhardia species and the outgroup Rhoiptelea chiliantha, and incorporated published data from 36 Juglandaceae and six outgroup species to test phylogenetic resolution. Moreover, comparative analyses of the plastomes were conducted to investigate the plastomes evolution of Engelhardia and the whole Juglandaceae family. RESULTS: The 13 Engelhardia plastomes were highly similar in genome size, gene content, and order. They exhibited a typical quadripartite structure, with lengths from 161,069 bp to 162,336 bp. Three mutation hotspot regions (TrnK-rps16, ndhF-rpl32, and ycf1) could be used as effective molecular markers for further phylogenetic analyses and species identification. Insertion and deletion (InDels) may be an important driving factor for the evolution of plastomes in Juglandoideae and Engelhardioideae. A total of ten codons were identified as the optimal codons in Juglandaceae. The mutation pressure mostly contributed to shaping codon usage. Seventy-eight protein-coding genes in Juglandaceae experienced relaxed purifying selection, only rpl22 and psaI genes showed positive selection (Ka/Ks > 1). Phylogenetic results fully supported Engelhardia as a monophyletic group including two sects and the division of Juglandaceae into three subfamilies. The Engelhardia originated in the Late Cretaceous and diversified in the Late Eocene, and Juglandaceae originated in the Early Cretaceous and differentiated in Middle Cretaceous. The phylogeny and divergence times didn't support rapid radiation occurred in the evolution history of Engelhardia. CONCLUSION: Our study fully supported the taxonomic treatment of at the section for Engelhardia species and three subfamilies for Juglandaceae and confirmed the power of phylogenetic resolution using plastome sequences. Moreover, our results also laid the foundation for further studying the course, tempo and mode of plastome evolution of Engelhardia and the whole Juglandaceae family.

Alternating current electroluminescence devices: recent advances and functional applications.

Wearable smart devices and visualisation sensors based on alternating current electroluminescence (ACEL) have received considerable attention in recent years. Due to the unique properties of ACEL devices, such as high mechanical strength, adaptability to complex environments, and no need for energy level matching, ACEL is suitable for multifunctional applications and visualisation sensing platforms. This review comprehensively outlines the latest developments in ACEL devices, starting with an analysis of the mechanism, classification, and optimisation strategies of ACEL. It introduces the functional applications of ACEL in multicolour displays, high-durability displays, stretchable and wearable displays, and autonomous function displays. Particularly, it emphasises the research progress of ACEL in sensory displays under interactive conditions such as liquid sensing, environmental factor sensing, kinetic energy sensing, and biosensing. Finally, it forecasts the challenges and new opportunities faced by future functional and interactive ACEL devices in fields such as artificial intelligence, smart robotics, and human-computer interaction.

Establishment of a corneal ulcer prognostic model based on machine learning.

Corneal infection is a major public health concern worldwide and the most common cause of unilateral corneal blindness. Toxic effects of different microorganisms, such as bacteria and fungi, worsen keratitis leading to corneal perforation even with optimal drug treatment. The cornea forms the main refractive surface of the eye. Diseases affecting the cornea can cause severe visual impairment. Therefore, it is crucial to analyze the risk of corneal perforation and visual impairment in corneal ulcer patients for making early treatment strategies. The modeling of a fully automated prognostic model system was performed in two parts. In the first part, the dataset contained 4973 slit lamp images of corneal ulcer patients in three centers. A deep learning model was developed and tested for segmenting and classifying five lesions (corneal ulcer, corneal scar, hypopyon, corneal descementocele, and corneal neovascularization) in the eyes of corneal ulcer patients. Further, hierarchical quantification was carried out based on policy rules. In the second part, the dataset included clinical data (name, gender, age, best corrected visual acuity, and type of corneal ulcer) of 240 patients with corneal ulcers and respective 1010 slit lamp images under two light sources (natural light and cobalt blue light). The slit lamp images were then quantified hierarchically according to the policy rules developed in the first part of the modeling. Combining the above clinical data, the features were used to build the final prognostic model system for corneal ulcer perforation outcome and visual impairment using machine learning algorithms such as XGBoost, LightGBM. The ROC curve area (AUC value) evaluated the model's performance. For segmentation of the five lesions, the accuracy rates of hypopyon, descemetocele, corneal ulcer under blue light, and corneal neovascularization were 96.86, 91.64, 90.51, and 93.97, respectively. For the corneal scar lesion classification, the accuracy rate of the final model was 69.76. The XGBoost model performed the best in predicting the 1-month prognosis of patients, with an AUC of 0.81 (95% CI 0.63-1.00) for ulcer perforation and an AUC of 0.77 (95% CI 0.63-0.91) for visual impairment. In predicting the 3-month prognosis of patients, the XGBoost model received the best AUC of 0.97 (95% CI 0.92-1.00) for ulcer perforation, while the LightGBM model achieved the best performance with an AUC of 0.98 (95% CI 0.94-1.00) for visual impairment.

Susceptibility gene identification and risk evaluation model construction by transcriptome-wide association analysis for salt sensitivity of blood pressure.

BACKGROUND: Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. METHODS AND RESULTS: A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets. CONCLUSIONS: Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals.

Scalable weaving of resilient membranes with on-demand superwettability for high-performance nanoemulsion separations.

This study leverages the ancient craft of weaving to prepare membranes that can effectively treat oil/water mixtures, specifically challenging nanoemulsions. Drawing inspiration from the core-shell architecture of spider silk, we have engineered fibers, the fundamental building blocks for weaving membranes, that feature a mechanically robust core for tight weaving, coupled with a CO2-responsive shell that allows for on-demand wettability adjustments. Tightly weaving these fibers produces membranes with ideal pores, achieving over 99.6% separation efficiency for nanoemulsions with droplets as small as 20 nm. They offer high flux rates, on-demand self-cleaning, and can switch between sieving oil and water nanodroplets through simple CO2/N2 stimulation. Moreover, weaving can produce sufficiently large membranes (4800 cm2) to assemble a module that exhibits long-term stability and performance, surpassing state-of-the-art technologies for nanoemulsion separations, thus making industrial application a practical reality.

Achievements, challenges, and perspectives in the design of polymer binders for advanced lithium-ion batteries.

Energy storage devices with high power and energy density are in demand owing to the rapidly growing population, and lithium-ion batteries (LIBs) are promising rechargeable energy storage devices. However, there are many issues associated with the development of electrode materials with a high theoretical capacity, which need to be addressed before their commercialization. Extensive research has focused on the modification and structural design of electrode materials, which are usually expensive and sophisticated. Besides, polymer binders are pivotal components for maintaining the structural integrity and stability of electrodes in LIBs. Polyvinylidene difluoride (PVDF) is a commercial binder with superior electrochemical stability, but its poor adhesion, insufficient mechanical properties, and low electronic and ionic conductivity hinder its wide application as a high-capacity electrode material. In this review, we highlight the recent progress in developing different polymeric materials (based on natural polymers and synthetic non-conductive and electronically conductive polymers) as binders for the anodes and cathodes in LIBs. The influence of the mechanical, adhesion, and self-healing properties as well as electronic and ionic conductivity of polymers on the capacity, capacity retention, rate performance and cycling life of batteries is discussed. Firstly, we analyze the failure mechanisms of binders based on the operation principle of lithium-ion batteries, introducing two models of "interface failure" and "degradation failure". More importantly, we propose several binder parameters applicable to most lithium-ion batteries and systematically consider and summarize the relationships between the chemical structure and properties of the binder at the molecular level. Subsequently, we select silicon and sulfur active electrode materials as examples to discuss the design principles of the binder from a molecular structure point of view. Finally, we present our perspectives on the development directions of binders for next-generation high-energy-density lithium-ion batteries. We hope that this review will guide researchers in the further design of novel efficient binders for lithium-ion batteries at the molecular level, especially for high energy density electrode materials.

Atomic engineering of two-dimensional materials via liquid metals.

Two-dimensional (2D) materials, known for their distinctive electronic, mechanical, and thermal properties, have attracted considerable attention. The precise atomic-scale synthesis of 2D materials opens up new frontiers in nanotechnology, presenting novel opportunities for material design and property control but remains challenging due to the high expense of single-crystal solid metal catalysts. Liquid metals, with their fluidity, ductility, dynamic surface, and isotropy, have significantly enhanced the catalytic processes crucial for synthesizing 2D materials, including decomposition, diffusion, and nucleation, thus presenting an unprecedented precise control over material structures and properties. Besides, the emergence of liquid alloy makes the creation of diverse heterostructures possible, offering a new dimension for atomic engineering. Significant achievements have been made in this field encompassing defect-free preparation, large-area self-aligned array, phase engineering, heterostructures, etc. This review systematically summarizes these contributions from the aspects of fundamental synthesis methods, liquid catalyst selection, resulting 2D materials, and atomic engineering. Moreover, the review sheds light on the outlook and challenges in this evolving field, providing a valuable resource for deeply understanding this field. The emergence of liquid metals has undoubtedly revolutionized the traditional nanotechnology for preparing 2D materials on solid metal catalysts, offering flexible possibilities for the advancement of next-generation electronics.

USP38 exacerbates pressure overload-induced left ventricular electrical remodeling.

BACKGROUND: Ubiquitin-specific protease 38 (USP38), belonging to the USP family, is recognized for its role in controlling protein degradation and diverse biological processes. Ventricular arrhythmias (VAs) following heart failure (HF) are closely linked to ventricular electrical remodeling, yet the specific mechanisms underlying VAs in HF remain inadequately explored. In this study, we examined the impact of USP38 on VAs in pressure overload-induced HF. METHODS: Cardiac-specific USP38 knockout mice, cardiac-specific USP38 transgenic mice and their matched control littermates developed HF induced by aortic banding (AB) surgery. After subjecting the mice to AB surgery for a duration of four weeks, comprehensive investigations were conducted, including pathological analysis and electrophysiological assessments, along with molecular analyses. RESULTS: We observed increased USP38 expression in the left ventricle of mice with HF. Electrocardiogram showed that the USP38 knockout shortened the QRS interval and QTc, while USP38 overexpression prolonged these parameters. USP38 knockout decreased the susceptibility of VAs by shortening action potential duration (APD) and prolonging effective refractory period (ERP). In addition, USP38 knockout increased ion channel and Cx43 expression in ventricle. On the contrary, the increased susceptibility of VAs and the decreased expression of ventricular ion channels and Cx43 were observed with USP38 overexpression. In both in vivo and in vitro experiments, USP38 knockout inhibited TBK1/AKT/CAMKII signaling, whereas USP38 overexpression activated this pathway. CONCLUSION: Our data indicates that USP38 increases susceptibility to VAs after HF through TBK1/AKT/CAMKII signaling pathway, Consequently, USP38 may emerge as a promising therapeutic target for managing VAs following HF.

Biventricular function after Ebstein anomaly repair from a single-center echocardiography study.

OBJECTIVE: We aimed to examine biventricular remodeling and function after Ebstein anomaly (EbA) surgical correction using echocardiographic techniques, particularly, the relations between the biventricular changes and the EbA types. METHODS: From April 2015 to August 2022, 110 patients with EbA were included in this retrospective study based on the Carpentier classification. Echocardiography assessments during the preoperative, early, and mid-term postoperative periods were performed. RESULTS: The 54 patients with types A and B EbA were included in group 1, whereas the 56 patients with types C and D were in group 2. Seventy-eight patients underwent surgical correction of EbA. The median age at operation was 8.8 years. During the mid-term follow-up, only 9.1% of the patients had moderate or severe tricuspid regurgitation. Right ventricular (RV) systolic function worsened in group 2 at discharge (fractional area change: 27.6 ± 11.2 vs. 35.4 ± 11.5 [baseline], P < 0.05; global longitudinal strain: -10.8 ± 4.4 vs. -17.9 ± 4.7 [baseline], P = 0.0001). RV function slowly recovered at a mean of 12 months of follow-up. Regarding left ventricular (LV) and RV systolic function, no statistical difference was found between before and after surgery in group 1. CONCLUSION: A high success rate of surgical correction of EbA, with an encouraging durability of the valve, was noted. Biventricular systolic function was maintained fairly in most patients with types A and B postoperatively. A late increase in RV systolic function after an initial reduction and unchanged LV systolic function were observed in the patients with types C and D postoperatively.

The efficacy and safety of Bazi Bushen Capsule in treating premature aging: A randomized, double blind, multicenter, placebo-controlled clinical trial.

PURPOSE: It is unclear whether traditional Chinese patent medicines can resist premature aging. This prospective study investigated the effects of Bazi Bushen Capsule (BZBS) which is a traditional Chinese patent medicine for tonifying the kidney essence on premature senility symptoms and quality of life, telomerase activity and telomere length. STUDY DESIGN AND METHODS: It was a parallel, multicenter, double-blind, randomized, and placebo-controlled trial. Subjects (n = 530) aged 30-78 years were randomized to receive BZBS or placebo capsules 12 weeks. The primary outcome was the clinical feature of change in kidney deficiency for aging evaluation scale (CFCKD-AES) and tilburg frailty indicator (TFI). The secondary outcomes were SF-36, serum sex hormone level, five times sit-to-stand time (FTSST), 6MWT, motor function test-grip strength, balance test, walking speed, muscle mass measurement, telomerase and telomere length. RESULTS: After 12 weeks of treatment, the CFCKD-AES and TFI scores in the BZBS group decreased by 13.79 and 1.50 respectively (6.42 and 0.58 in the placebo group, respectively); The SF-36 in the BZBS group increased by 98.38 (23.79 in the placebo group). The FTSST, motor function test grip strength, balance test, walking speed, and muscle mass in the elderly subgroup were all improved in the BZBS group. The telomerase content in the BZBS group increased by 150.04 ng/ml compared to the placebo group. The fever led one patient in the placebo group to discontinue the trial. One patient in the placebo group withdrew from the trial due to pregnancy. None of the serious AEs led to treatment discontinuation, and 3 AEs (1.14%) were assessed as related to BZBS by the primary investigator. CONCLUSIONS: BZBS can improve premature aging symptoms, frailty scores, and quality of life, as well as improve FTSST, motor function: grip strength, balance test, walking speed, and muscle mass in elderly subgroups of patients, and enhance telomerase activity, but it is not significantly associated with increasing telomere length which is important for healthy aging. TRIAL REGISTRY: https://www.chictr.org.cn/showproj.html?proj=166181.

Influence of entropy on catalytic performance of high-entropy oxides (NiMgZnCuCoOx) in peroxymonosulfate-mediated acetaminophen degradation.

Developing a high-performance activator is crucial for the practical application of peroxymonosulfate-based advanced oxidation processes (PMS-AOPs). High-entropy oxides (HEOs) have attracted increasing attention due to their stable crystal structure, flexible composition and unique functionality. However, research into the mechanisms by which HEOs function as PMS activators for degrading organic pollutants remains insufficient, and the relationship between entropy and the catalytic performance of HEOs has yet to be clarified. In this study, we synthesized NiMgZnCuCoOx with different levels of entropy as PMS activators for acetaminophen (APAP) degradation, and observed a significant effect for entropy on the catalytic performance. Sulfate radicals (SO4•‒) were identified as the primary reactive oxygen species (ROS), while hydroxyl radicals (•OH) and singlet oxygen (1O2) act as secondary ROS during APAP degradation. Both the Co2+ contents and the oxygen vacancy concentration in NiMgZnCuCoOx are found to increase with the entropy. An increase in the Co2+ sites leads to more activation sites for PMS activation, while excessive oxygen vacancies consume PMS, producing weak oxidation species, and affect the electron-donating ability of Co2+. Consequently, the NiMgZnCuCoOx with middle level of entropy exhibits the optimal performance with APAP degradation rate and mineralization rate reaching 100% and 74.22%, respectively. Furthermore, the degradation intermediates and their toxicities were assessed through liquid chromatography-mass spectrometry and quantitative structure-activity relationship analysis. This work is expected to provide critical insight into the impact of the HEOs entropy on the PMS activation and guide the rational design of highly efficient peroxymonosulfate activators for environmental applications.

Aptamer-Based DNA Allosteric Switch for Regulation of Protein Activity.

Allostery is a fundamental way to regulate the function of biomolecules playing crucial roles in cell metabolism and proliferation and is deemed the second secret of life. Given the limited understanding of the structure of natural allosteric molecules, the development of artificial allosteric molecules brings a huge opportunity to transform the allosteric mechanism into practical applications. In this study, the concept of bionics is introduced into the design of artificial allosteric molecules and an allosteric DNA switch with an activity site and an allosteric site based on two aptamers for selective inhibition of thrombin activity. Compared with the single aptamer, the allosteric switch possesses a significantly enhanced inhibition ability, which can be precisely regulated by converting the switch states. Moreover, the dynamic allosteric switch is further subjected to the control of the DNA threshold circuit for realizing automatic concentration determination and activity inhibition of thrombin. These compelling results confirm that this allosteric switch equipped with self-sensing and information-processing modules puts a new slant on the research of allosteric mechanisms and further application of allosteric tactics in chemical and biomedical fields.

Liposomes in the cosmetics: present and outlook.

Liposomes are small spherical vesicles composed of phospholipid bilayers capable of encapsulating a variety of ingredients, including water- and oil-soluble compound, which are one of the most commonly used piggybacking and delivery techniques for many active ingredients and different compounds in biology, medicine and cosmetics. With the increasing number of active cosmetic ingredients, the concomitant challenge is to effectively protect, transport, and utilize these substances in a judicious manner. Many cosmetic ingredients are ineffective both topically and systemically when applied to the skin, thus changing the method of delivery and interaction with the skin of the active ingredients is a crucial step toward improving their effectiveness. Liposomes can improve the delivery of active ingredients to the skin, enhance their stability, and ultimately, improve the efficacy of cosmetics and and pharmaceuticals. In this review, we summarized the basic properties of liposomes and their recent advances of functionalities in cosmetics and and pharmaceuticals. Also, the current state of the art in the field is discussed and the prospects for future research areas are highlighted. We hope that this review will provide ideas and inspiration on the application and development of cosmetics and pharmaceuticals.

Different reference genomes determine different results: Comparing SNP calling in RAD-seq of Engelhardia roxburghiana using different reference genomes.

Advances in next-generation sequencing (NGS) have significantly reduced the cost and improved the efficiency of obtaining single nucleotide polymorphism (SNP) markers, particularly through restriction site-associated DNA sequencing (RAD-seq). Meanwhile, the progression in whole genome sequencing has led to the utilization of an increasing number of reference genomes in SNP calling processes. This study utilized RAD-seq data from 242 individuals of Engelhardia roxburghiana, a tropical tree of the walnut family (Juglandaceae), with SNP calling conducted using the STACKS pipeline. We aimed to compare both reference-based approaches, namely, employing a closely related species as the reference genome versus the species itself as the reference genome, to evaluate their respective merits and limitations. Our findings indicate a substantial discrepancy in the number of obtained SNPs between using a closely related species as opposed to the species itself as reference genomes, the former yielded approximately an order of magnitude fewer SNPs compared to the latter. While the missing rate of individuals and sites of the final SNPs obtained in the two scenarios showed no significant difference. The results showed that using the reference genome of the species itself tends to be prioritized in RAD-seq studies. However, if this is unavailable, considering closely related genomes is feasible due to their wide applicability and low missing rate as alternatives. This study contributes to enrich the understanding of the impact of SNP acquisition when utilizing different reference genomes.

In situ coupling of carbon dots with zeolitic imidazolate frameworks enabling highly red emission in solid state.

In this work, an extraordinary solid red emissive phosphor was prepared based on red-emitting carbon dots (R-CDs). The synthesis was conducted under an in-situ strategy, with assistance of zeolitic imidazolate frameworks. The obtained phosphor possesses a stronger red emission located at 630 nm in solid state, with CIE coordinate of (0.63, 0.35) and quantum yield of âˆ¼ 45 %. As a consequence, not only aggregation-induced fluorescence quenching of R-CDs is avoided in solid state, but also an enhanced emission with high quantum yield is presented. Fluorescence properties were further explored in detail. The emission is found to be responsive to temperature and applied pressure. Based on the excellent emissive performance, the material has great potentials in anti-counterfeiting, latent fingerprint imaging, and temperature/pressure-sensing. This work provides a facile and promising way of preparing solid carbon-based phosphors for special applications.

Cu/N co-doped biochar activating PMS for selective degrading paracetamol via a non-radical pathway dominated by singlet oxygen and electron transfer.

The non-free radical oxidation pathway (PMS-NOPs) of peroxymonosulfate (PMS) holds significant promise for practical wastewater treatment applications, owing to its low oxidation potential, high PMS utilization rate, and robust anti-interference capability in the degradation of pollutants. A novel activator copper nitrogen co-doped porous biochar (Cu-N-BC) with rich defect edges and functional groups was obtained by adding Cu and N to the biochar matrix generated by sodium alginate through pyrolysis in this study. Under the condition of 1 mM PMS, 30 mg/L activator was used to activate PMS and achieve efficient degradation of 10 mg/L paracetamol (PCT) within 15 min, with a high reaction rate constants (kobs) of 0.391 min-1. The activation mechanism of the Cu-N-BC/PMS/PCT system was a non-radical activation pathway with the dominance of singlet oxygen (1O2) and the presence of catalyst-mediated electron transfer. The graphite nitrogen, pyridine nitrogen, and Cu-N coordination introduced by Cu/N co-doping, as well as the carbon skeleton and CO functional group of biochar, were considered active sites that promote the 1O2 generation. The Cu-N-BC/PMS system exhibits strong stability, eco-friendliness, effective mineralization, and interference resistance across diverse pH levels (3-11) and interfering ions, including Cl-, H2PO4-, NO3-, SO42-, and humic acid. Remarkably, it efficiently degrades PCT in tap and lake water, achieving a notable 63.73% TOC mineralization rate, with leached copper ions below 0.02 mg/L. This research introduces a novel method for obtaining metal nitrogen carbon activators and enhances understanding of PMS non-radical activation pathways and active sites.

Targeting EFHD2 inhibits interferon-γ signaling and ameliorates non-alcoholic steatohepatitis.

BACKGROUND & AIMS: The precise pathomechanisms underlying the development of non-alcoholic steatohepatitis (NASH, also known as metabolic dysfunction-associated steatohepatitis [MASH]) remain incompletely understood. In this study, we investigated the potential role of EF-hand domain family member D2 (EFHD2), a novel molecule specific to immune cells, in the pathogenesis of NASH. METHODS: Hepatic EFHD2 expression was characterized in patients with NASH and two diet-induced NASH mouse models. Single-cell RNA sequencing (scRNA-seq) and double-immunohistochemistry were employed to explore EFHD2 expression patterns in NASH livers. The effects of global and myeloid-specific EFHD2 deletion on NASH and NASH-related hepatocellular carcinoma were assessed. Molecular mechanisms underlying EFHD2 function were investigated, while chemical and genetic investigations were performed to assess its potential as a therapeutic target. RESULTS: EFHD2 expression was significantly elevated in hepatic macrophages/monocytes in both patients with NASH and mice. Deletion of EFHD2, either globally or specifically in myeloid cells, improved hepatic steatosis, reduced immune cell infiltration, inhibited lipid peroxidation-induced ferroptosis, and attenuated fibrosis in NASH. Additionally, it hindered the development of NASH-related hepatocellular carcinoma. Specifically, deletion of myeloid EFHD2 prevented the replacement of TIM4+ resident Kupffer cells by infiltrated monocytes and reversed the decreases in patrolling monocytes and CD4+/CD8+ T cell ratio in NASH. Mechanistically, our investigation revealed that EFHD2 in myeloid cells interacts with cytosolic YWHAZ (14-3-3ζ), facilitating the translocation of IFNγR2 (interferon-γ receptor-2) onto the plasma membrane. This interaction mediates interferon-γ signaling, which triggers immune and inflammatory responses in macrophages during NASH. Finally, a novel stapled α-helical peptide targeting EFHD2 was shown to be effective in protecting against NASH pathology in mice. CONCLUSION: Our study reveals a pivotal immunomodulatory and inflammatory role of EFHD2 in NASH, underscoring EFHD2 as a promising druggable target for NASH treatment. IMPACT AND IMPLICATIONS: Non-alcoholic steatohepatitis (NASH) represents an advanced stage of non-alcoholic fatty liver disease (NAFLD); however, not all patients with NAFLD progress to NASH. A key challenge is identifying the factors that trigger inflammation, which propels the transition from simple fatty liver to NASH. Our research pinpointed EFHD2 as a pivotal driver of NASH, orchestrating the over-activation of interferon-γ signaling within the liver during NASH progression. A stapled peptide designed to target EFHD2 exhibited therapeutic promise in NASH mice. These findings support the potential of EFHD2 as a therapeutic target in NASH.