Enhancing Performance and Stability of p-i-n Perovskite Solar Cells with Ag-Cu Codeposited Alloy Electrodes.

In the development of back electrodes for perovskite solar cells (PSCs), the major challenges are stability and cost. To address this, we present an innovative approach: Simultaneous evaporation of two independently controlled sources of metal materials was performed to achieve a uniform distribution of the alloy electrodes. In this study, Ag-Cu alloys (the molar ratio of Ag/Cu is 7/3) with a high-index crystal face (111) and a work function matching perovskite were prepared using a codeposition technique. These properties mitigate nonradiative carrier recombination at the interface and reduce the energy barrier for carrier migration. Consequently, compared to Ag based PSCs (22.77%), the implementation of Ag-Cu alloy (Ag/Cu is 7/3)-based PSCs resulted in a power conversion efficiency of 23.72%. In a 1500 h tracking test in ambient air, the Ag-Cu alloy (Ag/Cu is 7/3)-based PSCs maintained their initial efficiency of 86%. This can be attributed to almost no migration of elements from the Ag-Cu alloy electrode to the perovskite layer. Our work presents a vital strategy for improving the stability of PSCs and reducing the costs associated with the back electrode in PSCs.

Androgen receptor-mediated pharmacogenomic expression quantitative trait loci: implications for breast cancer response to AR-targeting therapy.

BACKGROUND: Endocrine therapy is the most important treatment modality of breast cancer patients whose tumors express the estrogen receptor α (ERα). The androgen receptor (AR) is also expressed in the vast majority (80-90%) of ERα-positive tumors. AR-targeting drugs are not used in clinical practice, but have been evaluated in multiple trials and preclinical studies. METHODS: We performed a genome-wide study to identify hormone/drug-induced single nucleotide polymorphism (SNP) genotype - dependent gene-expression, known as PGx-eQTL, mediated by either an AR agonist (dihydrotestosterone) or a partial antagonist (enzalutamide), utilizing a previously well characterized lymphoblastic cell line panel. The association of the identified SNPs-gene pairs with breast cancer phenotypes were then examined using three genome-wide association (GWAS) studies that we have published and other studies from the GWAS catalog. RESULTS: We identified 13 DHT-mediated PGx-eQTL loci and 23 Enz-mediated PGx-eQTL loci that were associated with breast cancer outcomes post ER antagonist or aromatase inhibitors (AI) treatment, or with pharmacodynamic (PD) effects of AIs. An additional 30 loci were found to be associated with cancer risk and sex-hormone binding globulin levels. The top loci involved the genes IDH2 and TMEM9, the expression of which were suppressed by DHT in a PGx-eQTL SNP genotype-dependent manner. Both of these genes were overexpressed in breast cancer and were associated with a poorer prognosis. Therefore, suppression of these genes by AR agonists may benefit patients with minor allele genotypes for these SNPs. CONCLUSIONS: We identified AR-related PGx-eQTL SNP-gene pairs that were associated with risks, outcomes and PD effects of endocrine therapy that may provide potential biomarkers for individualized treatment of breast cancer.

Prokaryotic expression of DFP1 and DFP2 in Dermatophagoides farinae and their responses to temperature stress.

The functions of highly expressed genes DFP1 and DFP2 in Dermatophagoides farinae remain unknown. DFP1 and DFP2 have been abundantly annotated and were up-regulated under temperature stress at 43 °C and -10 °C in our previous RNA-seq study, indicating that DFP1 and DFP2 may have temperature stress response function. Here, we amplified, cloned, and sequenced to obtain the complete coding sequences of DFP1 and DFP2 and predicted their protein characteristics using bioinformatics analysis. Then, prokaryotic expression systems were constructed and found that DFP1 was expressed in Escherichia coli Rosetta-gami 2 (DE3) but not BL21 (DE3); DFP2 was expressed in both BL21 (DE3) and Rosetta-gami 2 (DE3), with higher expression in BL21 (DE3). Finally, the growth curves of bacteria were drawn and indicated that the DFP1- and DFP2-pET32a carrying recombinant bacteria grew better than the respectiveonly pET32a carrying control bacteria after heat and cold stress. This study confirms for the first time that DFP1 and DFP2 respond to temperature stress at the protein level. The constructed prokaryotic expression systems will provide an experimental foundation for future antibody preparation for western blotting detection to confirm the temperature-stress response functions of DFP1 and DFP2.

Application and progress of artificial intelligence technology in the segmentation of hyperreflective foci in OCT images for ophthalmic disease research.

With the advancement of retinal imaging, hyperreflective foci (HRF) on optical coherence tomography (OCT) images have gained significant attention as potential biological biomarkers for retinal neuroinflammation. However, these biomarkers, represented by HRF, present pose challenges in terms of localization, quantification, and require substantial time and resources. In recent years, the progress and utilization of artificial intelligence (AI) have provided powerful tools for the analysis of biological markers. AI technology enables use machine learning (ML), deep learning (DL) and other technologies to precise characterization of changes in biological biomarkers during disease progression and facilitates quantitative assessments. Based on ophthalmic images, AI has significant implications for early screening, diagnostic grading, treatment efficacy evaluation, treatment recommendations, and prognosis development in common ophthalmic diseases. Moreover, it will help reduce the reliance of the healthcare system on human labor, which has the potential to simplify and expedite clinical trials, enhance the reliability and professionalism of disease management, and improve the prediction of adverse events. This article offers a comprehensive review of the application of AI in combination with HRF on OCT images in ophthalmic diseases including age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) and other retinal diseases and presents prospects for their utilization.

Carrimycin inhibits coronavirus replication by decreasing the efficiency of programmed -1 ribosomal frameshifting through directly binding to the RNA pseudoknot of viral frameshift-stimulatory element.

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity. Here, we show that carrimycin, a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials, decreases the efficiency of programmed -1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion. Carrimycin binds directly to the coronaviral frameshift-stimulatory element (FSE) RNA pseudoknot, interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes. Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses. Because the FSE mechanism is essential in all coronaviruses, carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA. This finding may open a new direction in antiviral drug discovery for coronavirus variants.

Bioinspired Genetic and Chemical Engineering of Protein Hydrogels for programable Multi-responsive Actuation.

Protein hydrogels with tailored stimuli-responsive features and tunable stiffness have garnered considerable attention due to the growing demand for biomedical soft robotics. However, integrating multiple responsive features toward intelligent yet biocompatible actuators remains challenging. Here, we report a facile approach that synergistically combines genetic and chemical engineering for the design of protein hydrogel actuators with programable complex spatial deformation. Genetically engineered silk-elastin-like proteins (SELPs) were encoded with stimuli-responsive motifs and enzymatic crosslinking sites via simulation-guided genetic engineering strategies. Chemical modifications of the recombinant proteins were also used as secondary control points to tailor material properties, responsive features, and anisotropy in SELP hydrogels. As a proof-of-concept example, diazonium coupling chemistry was exploited to incorporate sulfanilic acid groups onto the tyrosine residues in the elastin domains of SELPs to achieve patterned SELP hydrogels. These hydrogels can be programmed to perform various actuations, including controllable bending, buckling, and complex deformation under external stimuli, such as temperature, ionic strength, or pH. With the inspiration of genetic and chemical engineering in natural organisms, this work offers a predictable, tunable, and environmentally sustainable approach for the fabrication of programmed intelligent soft actuators, with implications for a variety of biomedical materials and bio-robotics needs. This article is protected by copyright. All rights reserved.

Occurrence and spatiotemporal distribution of arsenic biotransformation genes in urban dust.

Microbially-mediated arsenic biotransformation plays a pivotal role in the biogeochemical cycling of arsenic; however, the presence of arsenic biotransformation genes (ABGs) in urban dust remains unclear. To investigate the occurrence and spatiotemporal distributions of ABGs, a total of one hundred and eighteen urban dust samples were collected from different districts of Xiamen city, China in summer and winter. Although inorganic arsenic species, including arsenate [As(V)] and arsenite [As(III)], were found to be predominant, the methylated arsenicals, particularly trimethylarsine oxide [TMAs(V)O] and dimethylarsenate [DMAs(V)], were detected in urban dust. Abundant ABGs were identified in urban dust via AsChip analysis (a high-throughput qPCR chip for ABGs), of which As(III) S-adenosylmethionine methyltransferase genes (arsM), As(V) reductase genes (arsC), As(III) oxidase genes (aioA), As(III) transporter genes (arsB), and arsenic-sensing regulator genes (arsR) were the most prevalent, collectively constituting more than 90 % of ABGs in urban dust. Microbes involved in arsenic methylation were assigned to bacteria (e.g., Actinomycetes and Alphaproteobacteria), archaea (e.g., Halobacteria), and eukaryotes (e.g., Chlamydomonadaceae) in urban dust via the arsM amplicon sequencing. Temperature, a season-dependent environmental factor, profoundly affected the abundance of ABGs and the composition of microbes involved in arsenic methylation. This study provides new insights into the presence of ARGs within the urban dust.

Conserved A-to-I RNA editing with non-conserved recoding expands the candidates of functional editing sites.

Adenosine-to-inosine (A-to-I) RNA editing recodes the genome and confers flexibility for the organisms to adapt to the environment. It is believed that RNA recoding sites are well suited for facilitating adaptive evolution by increasing the proteomic diversity in a temporal-spatial manner. The function and essentiality of a few conserved recoding sites are recognized. However, the experimentally discovered functional sites only make up a small corner of the total sites, and there is still the need to expand the repertoire of such functional sites with bioinformatic approaches. In this study, we define a new category of RNA editing sites termed 'conserved editing with non-conserved recoding' and systematically identify such sites in Drosophila editomes, figuring out their selection pressure and signals of adaptation at inter-species and intra-species levels. Surprisingly, conserved editing sites with non-conserved recoding are not suppressed and are even slightly overrepresented in Drosophila. DNA mutations leading to such cases are also favoured during evolution, suggesting that the function of those recoding events in different species might be diverged, specialized, and maintained. Finally, structural prediction suggests that such recoding in potassium channel Shab might increase ion permeability and compensate the effect of low temperature. In conclusion, conserved editing with non-conserved recoding might be functional as well. Our study provides novel aspects in considering the adaptive evolution of RNA editing sites and meanwhile expands the candidates of functional recoding sites for future validation.

Glycogen synthase kinase 3 activity enhances liver inflammation in MASH.

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by excessive circulating toxic lipids, hepatic steatosis, and liver inflammation. Monocyte adhesion to liver sinusoidal endothelial cells (LSECs) and transendothelial migration (TEM) are crucial in the inflammatory process. Under lipotoxic stress, LSECs develop a proinflammatory phenotype known as endotheliopathy. However, mediators of endotheliopathy remain unclear. Methods: Primary mouse LSECs isolated from C57BL/6J mice fed chow or MASH-inducing diets rich in fat, fructose, and cholesterol (FFC) were subjected to multi-omics profiling. Mice with established MASH resulting from a choline-deficient high-fat diet (CDHFD) or FFC diet were also treated with two structurally distinct GSK3 inhibitors (LY2090314 and elraglusib [9-ING-41]). Results: Integrated pathway analysis of the mouse LSEC proteome and transcriptome indicated that leukocyte TEM and focal adhesion were the major pathways altered in MASH. Kinome profiling of the LSEC phosphoproteome identified glycogen synthase kinase (GSK)-3ß as the major kinase hub in MASH. GSK3ß-activating phosphorylation was increased in primary human LSECs treated with the toxic lipid palmitate and in human MASH. Palmitate upregulated the expression of C-X-C motif chemokine ligand 2, intracellular adhesion molecule 1, and phosphorylated focal adhesion kinase, via a GSK3-dependent mechanism. Congruently, the adhesive and transendothelial migratory capacities of primary human neutrophils and THP-1 monocytes through the LSEC monolayer under lipotoxic stress were reduced by GSK3 inhibition. Treatment with the GSK3 inhibitors LY2090314 and elraglusib ameliorated liver inflammation, injury, and fibrosis in FFC- and CDHFD-fed mice, respectively. Immunophenotyping using cytometry by mass cytometry by time of flight of intrahepatic leukocytes from CDHFD-fed mice treated with elraglusib showed reduced infiltration of proinflammatory monocyte-derived macrophages and monocyte-derived dendritic cells. Conclusion: GSK3 inhibition attenuates lipotoxicity-induced LSEC endotheliopathy and could serve as a potential therapeutic strategy for treating human MASH. Impact and Implications: LSECs under lipotoxic stress in MASH develop a proinflammatory phenotype known as endotheliopathy, with obscure mediators and functional outcomes. The current study identified GSK3 as the major driver of LSEC endotheliopathy, examined its pathogenic role in myeloid cell-associated liver inflammation, and defined the therapeutic efficacy of pharmacological GSK3 inhibitors in murine MASH. This study provides preclinical data for the future investigation of GSK3 pharmacological inhibitors in human MASH. The results of this study are important to hepatologists, vascular biologists, and investigators studying the mechanisms of inflammatory liver disease and MASH, as well as those interested in drug development.

Does coevolution in refugia drive mimicry in bumble bees? Insights from a South Asian mimicry group.

Müllerian mimicry was proposed to be an example of a coevolved mutualism promoted by population isolation in glacial refugia. This, however, has not been well supported in butterfly models. Here, we use genomic data to test this theory while examining the population genetics behind mimetic diversification in a pair of co-mimetic bumble bees, Bombus breviceps Smith and Bombus trifasciatus Smith. In both lineages, populations were structured by geography but not as much by color pattern, suggesting sharing of color alleles across regions of restricted gene flow and formation of mimicry complexes in the absence of genetic differentiation. Demographic analyses showed mismatches between historical effective population size changes and glacial cycles, and niche modeling revealed only mild habitat retraction during glaciation. Moreover, mimetic subpopulations of the same color form in the two lineages only in some cases exhibit similar population history and genetic divergence. Therefore, the current study supports a more complex history in this comimicry than a simple refugium-coevolution model.

IL17RB genetic variants are associated with acamprosate treatment response in patients with alcohol use disorder: A proteomics-informed genomics study.

Acamprosate is a Food and Drug Administration (FDA) approved medication for the treatment of alcohol use disorder (AUD). However, only a subset of patients achieves optimal treatment outcomes. Currently, no biological measures are utilized to predict response to acamprosate treatment. We applied our established pharmaco-omics informed genomics strategy to identify potential biomarkers associated with acamprosate treatment response. Specifically, our previous open-label acamprosate clinical trial recruited 442 patients with AUD who were treated with acamprosate for three months. We first performed proteomics using baseline plasma samples to identify potential biomarkers associated with acamprosate treatment outcomes. Next, we applied our established "proteomics-informed genome-wide association study (GWAS)" research strategy, and identified 12 proteins, including interleukin-17 receptor B (IL17RB), associated with acamprosate treatment response.​ A GWAS for IL17RB concentrations identified several genome-wide significant signals. Specifically, the top hit single nucleotide polymorphism (SNP) rs6801605 with a minor allele frequency of 38% in the European American population mapped 4 kilobase (Kb) upstream of IL17RB, and intron 1 of the choline dehydrogenase (CHDH) gene on chromosome 3 (p: 4.8E-20). The variant genotype (AA) for the SNP rs6801605 was associated with lower IL17RB protein expression. In addition, we identified a series of genetic variants in IL17RB that were associated with acamprosate treatment outcomes. Furthermore, the variantgenotypes for all of those IL17RB SNPs were protective for alcohol relapse. Finally, we demonstrated that the basal level of mRNA expression of IL17RB was inversely correlated with those of nuclear factor-κB (NF-κB) subunits, and a significantly higher expression of NF-κB subunits was observed in AUD patients who relapsed to alcohol use. In summary, this study illustrates that IL17RB genetic variants might contribute to acamprosate treatment outcomes. This series of studies represents an important step toward generating functional hypotheses that could be tested to gain insight into mechanisms underlying acamprosate treatment response phenotypes. (The ClinicalTrials.gov Identifier: NCT00662571).

Engineering Core/Ligands Interfacial Anchors of Nanoparticles for Efficiently Inhibiting Both Aß and Amylin Fibrillization.

Accurate construction of artificial nano-chaperones' structure is crucial for precise regulation of protein conformational transformation, facilitating effective treatment of proteopathy. However, how the ligand-anchors of nano-chaperones affect the spatial conformational changes in proteins remains unclear, limiting the development of efficient nano-chaperones. In this study, three types of gold nanoparticles (AuNPs) with different core/ligands interface anchor structures (Au─NH─R, Au─S─R, and Au─C≡C─R, R = benzoic acid) are synthesized as an ideal model to investigate the effect of interfacial anchors on Aß and amylin fibrillization. Computational results revealed that the distinct interfacial anchors imparted diverse distributions of electrostatic potential on the nanointerface and core/ligands bond strength of AuNPs, leading to differential interactions with amyloid peptides. Experimental results demonstrated that all three types of AuNPs exhibit site-specific inhibitory effects on Aß40 fibrillization due to preferential binding. For amylin, amino-anchored AuNPs demonstrate strong adsorption to multiple sites on amylin and effectively inhibit fibrillization. Conversely, thiol- and alkyne-anchored AuNPs adsorb at the head region of amylin, promoting folding and fibrillization. This study not only provided molecular insights into how core/ligands interfacial anchors of nanomaterials induce spatial conformational changes in amyloid peptides but also offered guidance for precisely engineering artificial-chaperones' nanointerfaces to regulate the conformational transformation of proteins.

Effects of organophosphorus flame retardant EHDPP on mouse retinal photoreceptor cells: Oxidative stress, apoptosis, and proinflammatory response.

2-Ethylhexyl diphenyl phosphate (EHDPP) is a frequently utilized organophosphorus flame retardant (OPFR) and has been extensively detected in environmental media. Prolonged daily exposure to EHDPP has been linked to potential retinal damage, yet the adverse impacts on the retina are still generally underexplored. In this research, we explored oxidative stress, inflammation, and the activating mechanisms initiated by EHDPP in mouse retinal photoreceptor (661 W) cells following a 24 h exposure period. Our research demonstrated that EHDPP led to a decline in cell viability that was directly proportional to its concentration, with the median lethal concentration (LC50) being 88 µM. Furthermore, EHDPP was found to elevate intracellular and mitochondrial levels of reactive oxygen species (ROS), trigger apoptosis, induce cell cycle arrest at the G1 phase, and modulate the expression of both antioxidant enzymes (Nrf2, HO-1, and CAT) and pro-inflammatory mediators (TNF-α, IL-1ß, and IL-6) within 661 W cells. These findings indicate that retinal damage triggered by EHDPP exposure could be mediated via the Nrf2/HO-1 signaling pathway in these cells. Collectively, our investigation revealed that oxidative stress induced by EHDPP is likely a critical factor in the cytotoxic response of 661 W cells, potentially leading to damage in retinal photoreceptor cells.

Assessing the genetic relationship between phimosis and 26 urogenital diseases: a Mendelian randomization study.

Purpose: This study aims to investigate the impacts of phimosis on the health of the genitourinary system through Mendelian random analysis. Material and method: A dual-sample Mendelian randomization (MR) analysis was conducted using the publicly available genome-wide association study (GWAS) data. The inverse variance weighted based on the random effects model (Re-IVW) method was used as the main statistical analysis. Complementary methods, including weighted median, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), were applied to detect or correct the impact of horizontal pleiotropy. Result: Re-IVW showed a genetic predictive causal relationship of phimosis on glomerulonephritis (odds ratio [OR]: 1.37 [1.13-1.65], p = 0.00149) and IgA glomerulonephritis (OR: 1.57 [1.18-2.09), p = 0.00187). Suggestive evidence indicated that phimosis was associated with chronic nephritis syndrome (OR: 1.23 (1.00-1.51), p = 0.0481], acute nephritis syndrome (OR: 1.50 [1.13-2.01], p = 0.0058), and impotence (OR: 1.39 [1.11-1.73], p = 0.0035). Kidney and ureteral stone (OR: 1.14 [1.04-1.26], p = 0.0069), urethral strictures (OR: 1.26 [1.07-1.48], p = 0.0050), benign prostatic hyperplasia (OR: 1.07 [1.01-1.13], p = 0.0242), and decreased testicular function (OR: 0.72 [0.56-0.94], p = 0.0141) have genetically predictive causal relationships. Conclusion: In summary, we employed a series of reliable analytical methods to investigate the association between phimosis and 26 urogenital diseases. We have reported several strong associations, but more research is needed to evaluate whether this discovery is replicated in other environments and to gain a better understanding of potential mechanisms.

Based on systematic druggable genome-wide Mendelian randomization identifies therapeutic targets for diabetes.

Purpose: Diabetes and its complications cause a heavy burden of disease worldwide. In recent years, Mendelian randomization (MR) has been widely used to discover the pathogenesis and epidemiology of diseases, as well as to discover new therapeutic targets. Therefore, based on systematic "druggable" genomics, we aim to identify new therapeutic targets for diabetes and analyze its pathophysiological mechanisms to promote its new therapeutic strategies. Material and method: We used double sample MR to integrate the identified druggable genomics to evaluate the causal effect of quantitative trait loci (eQTLs) expressed by druggable genes in blood on type 1 and 2 diabetes (T1DM and T2DM). Repeat the study using different data sources on diabetes and its complications to verify the identified genes. Not only that, we also use Bayesian co-localization analysis to evaluate the posterior probabilities of different causal variations, shared causal variations, and co-localization probabilities to examine the possibility of genetic confounding. Finally, using diabetes markers with available genome-wide association studies data, we evaluated the causal relationship between established diabetes markers to explore possible mechanisms. Result: Overall, a total of 4,477 unique druggable genes have been gathered. After filtering using methods such as Bonferroni significance (P<1.90e-05), the MR Steiger directionality test, Bayesian co-localization analysis, and validation with different datasets, Finally, 7 potential druggable genes that may affect the results of T1DM and 7 potential druggable genes that may affect the results of T2DM were identified. Reverse MR suggests that C4B may play a bidirectional role in the pathogenesis of T1DM, and none of the other 13 target genes have a reverse causal relationship. And the 7 target genes in T2DM may each affect the biomarkers of T2DM to mediate the pathogenesis of T2DM. Conclusion: This study provides genetic evidence supporting the potential therapeutic benefits of targeting seven druggable genes, namely MAP3K13, KCNJ11, REG4, KIF11, CCNE2, PEAK1, and NRBP1, for T2DM treatment. Similarly, targeting seven druggable genes, namely ERBB3, C4B, CD69, PTPN22, IL27, ATP2A1, and LT-ß, has The potential therapeutic benefits of T1DM treatment. This will provide new ideas for the treatment of diabetes and also help to determine the priority of drug development for diabetes.

Support based metal incorporated layered nanomaterials for photocatalytic degradation of organic pollutants.

An effective approach to producing sophisticated miniaturized and nanoscale materials involves arranging nanomaterials into layered hierarchical frameworks. Nanostructured layered materials are constructed to possess isolated propagation assets, massive surface areas, and envisioned amenities, making them suitable for a variety of established and novel applications. The utilization of various techniques to create nanostructures adorned with metal nanoparticles provides a secure alternative or reinforcement for the existing physicochemical methods. Supported metal nanoparticles are preferred due to their ease of recovery and usage. Researchers have extensively studied the catalytic properties of noble metal nanoparticles using various selective oxidation and hydrogenation procedures. Despite the numerous advantages of metal-based nanoparticles (NPs), their catalytic potential remains incompletely explored. This article examines metal-based nanomaterials that are supported by layers, and provides an analysis of their manufacturing, procedures, and synthesis. This study incorporates both 2D and 3D layered nanomaterials because of their distinctive layered architectures. This review focuses on the most common metal-supported nanocomposites and methodologies used for photocatalytic degradation of organic dyes employing layered nanomaterials. The comprehensive examination of biological and ecological cleaning and treatment techniques discussed in this article has paved the way for the exploration of cutting-edge technologies that can contribute to the establishment of a sustainable future.

Zebra-Patterned Stretchable Helical Yarn for Triboelectric Self-Powered Multifunctional Sensing.

Smart textiles capable of both energy harvesting and multifunctional sensing are highly desirable for next-generation portable electronics. However, there are still challenges that need to be conquered, such as the innovation of an energy-harvesting model and the optimization of interface bonding between fibers and active materials. Herein, inspired by the spiral structure of natural vines, a highly stretchable triboelectric helical yarn (TEHY) was manufactured by twisting the carbon nanotube/polyurethane nanofiber (CNT/PU NF) Janus membrane. The TEHY had a zebra-stripe-like design that was composed of black interval conductive CNTs and white insulative PU NFs. Due to the different electron affinity, the zebra-patterned TEHY realized a self-frictional triboelectric effect because the numerous microscopic CNT/PU triboelectric interfaces generated an alternating current in the external conductive circuit without extra external friction layers. The helical geometry combined with the elastic PU matrix endowed TEHY with superelastic stretchability and outstanding output stability after 1000 cycles of the stretch-release test. By virtue of the robust mechanical and electrical stability, the TEHY can not only be used as a high-entropy mechanical energy harvester but also serve as a self-powered sensor to monitor the stretching or deforming stimuli and human physiological activities in real time. These merits manifested the versatile applications of TEHY in smart fabrics, wearable power supplies, and human-machine interactions.

Upregulation of Hepatic Glutathione S-Transferase Alpha 1 Ameliorates Metabolic Dysfunction-Associated Steatosis by Degrading Fatty Acid Binding Protein 1.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common metabolic disease of the liver, characterized by hepatic steatosis in more than 5% of hepatocytes. However, despite the recent approval of the first drug, resmetirom, for the management of metabolic dysfunction-associated steatohepatitis, decades of target exploration and hundreds of clinical trials have failed, highlighting the urgent need to find new druggable targets for the discovery of innovative drug candidates against MASLD. Here, we found that glutathione S-transferase alpha 1 (GSTA1) expression was negatively associated with lipid droplet accumulation in vitro and in vivo. Overexpression of GSTA1 significantly attenuated oleic acid-induced steatosis in hepatocytes or high-fat diet-induced steatosis in the mouse liver. The hepatoprotective and anti-inflammatory drug bicyclol also attenuated steatosis by upregulating GSTA1 expression. A detailed mechanism showed that GSTA1 directly interacts with fatty acid binding protein 1 (FABP1) and facilitates the degradation of FABP1, thereby inhibiting intracellular triglyceride synthesis by impeding the uptake and transportation of free fatty acids. Conclusion: GSTA1 may be a good target for the discovery of innovative drug candidates as GSTA1 stabilizers or enhancers against MASLD.

EDTA enables to alleviate impacts of metal ions on conjugative transfer of antibiotic resistance genes.

Various heavy metals are reported to be able to accelerate horizontal transfer of antibiotic resistance genes (ARGs). In real water environmental settings, ubiquitous complexing agents would affect the environmental behaviors of heavy metal ions due to the formation of metal-organic complexes. However, little is known whether the presence of complexing agents would change horizontal gene transfer due to heavy metal exposure. This study aimed to fill this gap by investigating the impacts of a typical complexing agent ethylenediaminetetraacetic acid (EDTA) on the conjugative transfer of plasmid-mediated ARGs induced by a range of heavy metal ions. At the environmentally relevant concentration (0.64 mg L-1) of metal ions, all the tested metal ions (Mg2+, Ca2+, Co2+, Pb2+, Ni2+, Cu2+, and Fe3+) promoted conjugative transfer of ARGs, while an inhibitory effect was observed at a relatively higher concentration (3.20 mg L-1). In contrast, EDTA (0.64 mg L-1) alleviated the effects of metal ions on ARGs conjugation transfer, evidenced by 11 %-66 % reduction in the conjugate transfer frequency. Molecular docking and dynamics simulations disclosed that this is attributed to the stronger binding of metal ions with the lipids in cell membranes. Under metal-EDTA exposure, gene expressions related to oxidative stress response, cell membrane permeability, intercellular contact, energy driving force, mobilization, and channels of plasmid transfer were suppressed compared with the metal ions exposure. This study offers insights into the alleviation mechanisms of complexing agents on ARGs transfer induced by free metal ions.