Loss of HD-PTP function results in lipodystrophy, defective cellular signaling, and altered lipid homeostasis.

His Domain Protein Tyrosine Phosphatase (HD-PTP) facilitates function of the endosomal sorting complexes required for transport (ESCRTs) during multivesicular body (MVB) formation. To uncover its role in physiological homeostasis, embryonic lethality caused by a complete lack of HD-PTP was bypassed through generation of hypomorphic mice expressing reduced protein, resulting in animals that are viable into adulthood. These mice exhibited marked lipodystrophy and decreased receptor-mediated signaling within white adipose tissue (WAT), involving multiple prominent pathways including RAS/MAPK, PI3K/AKT and RTKs such as EGFR. EGFR signaling was dissected in vitro to assess the nature of defective signaling, revealing decreased trans-autophosphorylation and downstream effector activation, despite normal EGF binding. This corresponds to decreased plasma membrane cholesterol and increased lysosomal cholesterol, likely resulting from defective endosomal maturation necessary for cholesterol trafficking and homeostasis. ESCRT components Vps4 and HRS have previously been implicated in cholesterol homeostasis, thus these findings expand knowledge on which ESCRT subunits are involved in cholesterol homeostasis and highlight a non-canonical role for HD-PTP in signal regulation and adipose tissue homeostasis.

Lipids, lipid-modified drug target genes, and the risk of male infertility: a Mendelian randomization study.

Background: Previous observational studies have reported a possible association between circulating lipids and lipid-lowering drugs and male infertility (MIF), as well as the mediating role of circulating vitamin D. Then, due to issues such as bias, reverse causality, and residual confounding, inferring causal relationships from these studies may be challenging. Therefore, this study aims to explore the effects of circulating lipids and lipid-lowering drugs on MIF through Mendelian randomization (MR) analysis and evaluate the mediating role of vitamin D. Method: Genetic variations related to lipid traits and the lipid-lowering effect of lipid modification targets are extracted from the Global Alliance for Lipid Genetics Genome-Wide Association Study. The summary statistics for MIF are from the FinnGen 9th edition. Using quantitative expression feature loci data from relevant organizations to obtain genetic variations related to gene expression level, further to explore the relationship between these target gene expression levels and MIF risk. Two-step MR analysis is used to explore the mediating role of vitamin D. Multiple sensitivity analysis methods (co-localization analysis, Egger intercept test, Cochrane's Q test, pleiotropy residuals and outliers (MR-PRESSO), and the leave-one-out method) are used to demonstrate the reliability of our results. Result: In our study, we observed that lipid modification of four lipid-lowering drug targets was associated with MIF risk, the LDLR activator (equivalent to a 1-SD decrease in LDL-C) (OR=1.94, 95% CI 1.14-3.28, FDR=0.040), LPL activator (equivalent to a 1-SD decrease in TG) (OR=1.86, 95% CI 1.25-2.76, FDR=0.022), and CETP inhibitor (equivalent to a 1-SD increase in HDL-C) (OR=1.28, 95% CI 1.07-1.53, FDR=0.035) were associated with a higher risk of MIF. The HMGCR inhibitor (equivalent to a 1-SD decrease in LDL-C) was associated with a lower risk of MIF (OR=0.38, 95% CI 0.17-0.83, FDR=0.39). Lipid-modifying effects of three targets were partially mediated by serum vitamin D levels. Mediation was 0.035 (LDLR activator), 0.012 (LPL activator), and 0.030 (CETP inhibitor), with mediation ratios of 5.34% (LDLR activator), 1.94% (LPL activator), and 12.2% (CETP inhibitor), respectively. In addition, there was no evidence that lipid properties and lipid modification effects of six other lipid-lowering drug targets were associated with MIF risk. Multiple sensitivity analysis methods revealed insignificant evidence of bias arising from pleiotropy or genetic confounding. Conclusion: This study did not support lipid traits (LDL-C, HDL-C, TG, Apo-A1, and Apo-B) as pathogenic risk factors for MIF. It emphasized that LPL, LDLR, CETP, and HMGCR were promising drug targets for improving male fertility.

Comparative genomic analyses on assassin bug Rhynocoris fuscipes (Hemiptera: Reduviidae) reveal genetic bases governing the diet-shift.

Genetic basis underlying the biodiversity and phenotypic plasticity are fascinating questions in evolutionary biology. Such molecular diversity can be achieved at multi-omics levels. Here, we sequenced the first chromosome-level genome of assassin bug Rhynocoris fuscipes, a polyphagous generalist predator for biological control of agroecosystems. Compared to non-predatory true bugs Apolygus lucorum and Riptortus pedestris, the R. fuscipes-specific genes were enriched in diet-related genes (e.g., serine proteinase, cytochrome P450) which had higher expression level and more exons than non-diet genes. Extensive A-to-I RNA editing was identified in all three species and showed enrichment in genes associated with diet in R. fuscipes, diversifying the transcriptome. An extended analysis between five predaceous and 27 phytophagous hemipteran species revealed an expansion of diet-related genes in R. fuscipes. Our findings bridge the gap between genotype and phenotype, and also advance our understanding on genetic and epigenetic bases governing the diet shifts in ture bugs.

Interference with ENO2 promotes ferroptosis and inhibits glycolysis in clear cell renal cell carcinoma by regulating Hippo­YAP1 signaling.

Glycolytic enzyme enolase 2 (ENO2) is dysregulated in various cancer types. Nevertheless, the role and underlying mechanism of ENO2 in clear cell renal cell carcinoma (ccRCC) remain unclear. Therefore, the current study investigated the effect and mechanism of ENO2 in ccRCC. ENO2 expression in a ccRCC cell line was assessed using reverse transcription-quantitative PCR and western blotting. Analysis of glycolysis was performed by estimating the extracellular acidification rate, lactic acid concentration, glucose uptake and the expression of glucose transporter 1, pyruvate kinase muscle isozyme M2 and hexokinase 2. Moreover, ferroptosis was assessed by detecting the level of total iron, lipid peroxide, reactive oxygen species and the expression of ferroptosis-related protein. In addition, mitochondrial function was assessed using JC-1 staining and detection kits. The results indicated that ENO2 is expressed at high levels in ccRCC cell lines, and interference with ENO2 expression inhibits glycolysis, promotes ferroptosis and affects mitochondrial function in ccRCC cells. Further investigation demonstrated that interference with ENO2 expression affected ferroptosis levels in ccRCC cells by inhibiting the glycolysis process. Mechanistically, the present results indicated that ENO2 may affect ferroptosis, glycolysis and mitochondrial functions by regulating Hippo-yes-associated protein 1 (YAP1) signaling in ccRCC cells. In conclusion, the present study showed that ENO2 affects ferroptosis, glycolysis and mitochondrial functions in ccRCC cells by regulating Hippo-YAP1 signaling, hence demonstrating its potential as a therapeutic target in ccRCC.

Efficient reduction of antibiotic resistance genes and mobile genetic elements in organic waste composting via fenton-like treatment.

Livestock manure harbors antibiotic resistance genes (ARGs), and aerobic composting (AC) is widely adopted for waste management. However, mitigating ARG resurgence in later stages remains challenging. This work aims to curb ARGs rebounding through a Fenton-like reaction during food waste and swine manure co-composting. Results revealed that 0.025 % zerovalent iron (ZVI) + 0.5 % hydrogen peroxide (H2O2) facilitated maximum ARG, mobile genetic elements (MGEs), and 16 s rRNA removal with reductions of 2.68, 2.69, and 1.4 logs. Spectroscopic analysis confirmed Fenton-like reaction and cell apoptosis analysis indicated that 0.025 % ZVI and 0.5 % H2O2 treatment had the maximum early apoptosis, least observed, and normal cells on day 30. Redundancy analysis highlighted the influence of bacterial communities and physicochemical properties on ARGs, with MGEs playing a crucial role in Fenton treatments. Our findings suggest incorporating ZVI and H2O2 in composting can significantly reduce ARGs and enhance waste management practices.

Exploring high-emission driving behaviors of heavy-duty diesel vehicles based on engine principles under different road grade levels.

To reveal the outstanding high-emission problems that occur when heavy-duty diesel vehicles (HDDV) pass uphill and downhill, this study proposes a method to depict the nitrogen oxides (NOx) and carbon dioxide (CO2) high-emission driving behaviors caused by slopes from the perspective of engine principles. By calculating emission and grade data of HDDV based on on-board diagnostic (OBD) data and digital elevation model (DEM) data, the 262 short trips including uphill, flat-road and downhill are firstly obtained through the rule-based short trip segmentation method, and the significant correlation between the road grade and emissions of the short trips is verified by Kendall's Tau and K-means clustering. Secondly, by comparing the distribution changes of three speed categories (acceleration state, constant speed state and deceleration state), the differences in HDDV operating states under different grade levels are discussed. Finally, the machine learning models (Random Forest, XGBoost and Elastic Net), are used to develop the NOx and CO2 emission estimation model, identifying high-emission driving behaviors, particularly during uphill driving, which showed the highest proportion of high-emission. Explained by the feature importance and SHapley Additive exPlanations (SHAP) model that large accelerator pedal opening, frequent aggressive acceleration, and high engine load have positive effects both on NOx and CO2 emissions. The difference is in the air-fuel ratio that the engine in the rich or slightly lean burning state will increase CO2 emissions and the lean burning state will increase NOx emissions. In addition, due to the uncertainty of the actual uphill, drivers often undergo a rapid "deceleration-uniform-acceleration" process, which significantly contributes to high NOx and CO2 emissions from the engine perspective. The findings provide insights for designing driving strategies in slope scenarios and offer a novel perspective on depicting driving behaviors.

Early reapplication of prone position during venovenous ECMO for acute respiratory distress syndrome: a prospective observational study and propensity-matched analysis.

BACKGROUND: A combination of prone positioning (PP) and venovenous extracorporeal membrane oxygenation (VV-ECMO) is safe, feasible, and associated with potentially improved survival for severe acute respiratory distress syndrome (ARDS). However, whether ARDS patients, especially non-COVID-19 patients, placed in PP before VV-ECMO should continue PP after a VV-ECMO connection is unknown. This study aimed to test the hypothesis that early use of PP during VV-ECMO could increase the proportion of patients successfully weaned from ECMO support in severe ARDS patients who received PP before ECMO. METHODS: In this prospective observational study, patients with severe ARDS who were treated with VV-ECMO were divided into two groups: the prone group and the supine group, based on whether early PP was combined with VV-ECMO. The proportion of patients successfully weaned from VV-ECMO and 60-day mortality were analyzed before and after propensity score matching. RESULTS: A total of 165 patients were enrolled, 50 in the prone and 115 in the supine group. Thirty-two (64%) and 61 (53%) patients were successfully weaned from ECMO in the prone and the supine groups, respectively. The proportion of patients successfully weaned from VV-ECMO in the prone group tended to be higher, albeit not statistically significant. During PP, there was a significant increase in partial pressure of arterial oxygen (PaO2) without a change in ventilator or ECMO settings. Tidal impedance shifted significantly to the dorsal region, and lung ultrasound scores significantly decreased in the anterior and posterior regions. Forty-five propensity score-matched patients were included in each group. In this matched sample, the prone group had a higher proportion of patients successfully weaned from VV-ECMO (64.4% vs. 42.2%; P = 0.035) and lower 60-day mortality (37.8% vs. 60.0%; P = 0.035). CONCLUSIONS: Patients with severe ARDS placed in PP before VV-ECMO should continue PP after VV-ECMO support. This approach could increase the probability of successful weaning from VV-ECMO. TRIAL REGISTRATION: ClinicalTrials.Gov: NCT04139733. Registered 23 October 2019.

Deciphering tumour microenvironment and elucidating the origin of cancer cells in ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (CCC) has an East Asian preponderance. It is associated with endometriosis, a benign condition where endometrial (inner lining of the uterus) tissue is found outside the uterus and on the peritoneal surface, in the abdominal or pelvic space. CCC is relatively more resistant to conventional chemotherapy compared to other ovarian cancer subtypes and is associated with a poorer prognosis. In this study, we recruited and obtained tumour tissues from seven patients across the four stages of CCC. The tumour and the tumour microenvironment (TME) from 7 CCC patients spanning clinical stages 1-4 were transcriptionally profiled using high-resolution scRNA-seq to gain insight into CCC's biological mechanisms. Firstly, we built a scRNA-seq resource for the CCC tumour microenvironment (TME). Secondly, we identified the different cell type proportions and found high levels of immune infiltration in CCC. Thirdly, since CCC is associated with endometriosis, we compared CCC with two publicly available endometriosis scRNA-seq datasets. The CCC malignant cells showed similarities with glandular secretory and ciliated epithelial cells found in endometriosis. Finally, we determined the differences in cell-cell communication between various cell types present in CCC TME and endometriosis conditions to gain insights into the transformations in CCC.

Synthesis of C-Alkyl Glycosides from Alkyl Bromides and Glycosyl Carboxylic Acids via Ni/Photoredox Dual Catalysis.

C-Alkyl glycosides, an important class of C-glycosides, are widely found in various drugs and natural products. The synthesis of C-alkyl glycosides has attracted considerable attention. Herein, we developed a Ni/photoredox catalyzed decarboxylative C(sp3)-C(sp3) coupling reaction of stable glycosylcarboxylic acids with simple aliphatic bromides to generate C-alkyl glycosides. The method successfully linked several functional molecular fragments (natural products or drugs) to a sugar moiety, showing the extensive application prospects of this transformation. Controlled experiments and DFT calculations demonstrated that the reaction pathway contains a free radical process, and a possible mechanism is proposed.

Learning from the Codon Table: Convergent Recoding Provides Novel Understanding on the Evolution of A-to-I RNA Editing.

Adenosine-to-inosine (A-to-I) RNA editing recodes the genetic information. Apart from diversifying the proteome, another tempting advantage of RNA recoding is to correct deleterious DNA mutation and restore ancestral allele. Solid evidences for beneficial restorative editing are very rare in animals. By searching for "convergent recoding" under a phylogenetic context, we proposed this term for judging the potential restorative functions of particular editing site. For the well-known mammalian Gln>Arg (Q>R) recoding site, its ancestral state in vertebrate genomes was the pre-editing Gln, and all 470 available mammalian genomes strictly avoid other three equivalent ways to achieve Arg in protein. The absence of convergent recoding from His>Arg, or synonymous mutations on Gln codons, could be attributed to the strong maintenance on editing motif and structure, but the absence of direct A-to-G mutation is extremely unexpected. With similar ideas, we found cases of convergent recoding in Drosophila genus, reducing the possibility of their restorative function. In summary, we defined an interesting scenario of convergent recoding, the occurrence of which could be used as preliminary judgements for whether a recoding site has a sole restorative role. Our work provides novel insights to the natural selection and evolution of RNA editing.

Silencing endomucin in bone marrow sinusoids improves hematopoietic stem and progenitor cell homing during transplantation.

Efficient homing of infused hematopoietic stem and progenitor cells (HSPCs) into the bone marrow (BM) is the prerequisite for successful hematopoietic stem cell transplantation. However, only a small part of infused HSPCs find their way to the BM niche. A better understanding of the mechanisms that facilitate HSPC homing will help to develop strategies to improve the initial HSPC engraftment and subsequent hematopoietic regeneration. Here, we show that irradiation upregulates the endomucin expression of endothelial cells in vivo and in vitro. Furthermore, depletion of endomucin in irradiated endothelial cells with short interfering RNA (siRNA) increases the HSPC-endothelial cell adhesion in vitro. To abrogate the endomucin of BM sinusoidal endothelial cells (BM-SECs) in vivo, we develop a siRNA-loaded bovine serum albumin nanoparticle for targeted delivery. Nanoparticle-mediated siRNA delivery successfully silences endomucin expression in BM-SECs and improves HSPC homing during transplantation. These results reveal that endomucin plays a critical role in HSPC homing during transplantation and that gene-based manipulation of BM-SEC endomucin in vivo can be exploited to improve the efficacy of HSPC transplantation.

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.

Shale pore characteristics and their impact on the gas-bearing properties of the Longmaxi Formation in the Luzhou area.

Deep shale has the characteristics of large burial depth, rapid changes in reservoir properties, complex pore types and structures, and unstable production. The whole-rock X-ray diffraction (XRD) analysis, reservoir physical property parameter testing, scanning electron microscopy (SEM) analysis, high-pressure mercury intrusion testing, CO2 adsorption experimentation, and low-temperature nitrogen adsorption-desorption testing were performed to study the pore structure characteristics of marine shale reservoirs in the southern Sichuan Basin. The results show that the deep shale of the Wufeng Formation Longyi1 sub-member in the Luzhou area is superior to that of the Weiyuan area in terms of factors controlling shale gas enrichment, such as organic matter abundance, physical properties, gas-bearing properties, and shale reservoir thickness. SEM is utilized to identify six types of pores (mainly organic matter pores). The porosities of the pyrobitumen pores reach 21.04-31.65%, while the porosities of the solid kerogen pores, siliceous mineral dissolution pores, and carbonate dissolution pores are low at 0.48-1.80%. The pores of shale reservoirs are mainly micropores and mesopores, with a small amount of macropores. The total pore volume ranges from 22.0 to 36.40 µL/g, with an average of 27.46 µL/g, the total pore specific surface area ranges from 34.27 to 50.39 m2/g, with an average of 41.12 m2/g. The pore volume and specific surface area of deep shale gas are positively correlated with TOC content, siliceous minerals, and clay minerals. The key period for shale gas enrichment, which matches the evolution process of shale hydrocarbon generation, reservoir capacity, and direct and indirect cap rocks, is from the Middle to Late Triassic to the present. Areas with late structural uplift, small uplift amplitude, and high formation pressure coefficient characteristics favor preserving shale gas with high gas content and production levels.

A paradigm shift in diagnosis and treatment innovation for mucinous cystic neoplasms of the liver.

This study comprehensively explores the clinical characteristics, diagnostic approaches, and treatment methods for liver mucinous cystic neoplasms (MCN). A retrospective analysis was conducted on seven individuals diagnosed with MCN, admitted to the Fifth Medical Center of the PLA General Hospital between October 2016 and May 2023. Preoperative AFP was negative, while CA19-9 was elevated in two cases. Surgical resection was performed for all patients. The patients showed favorable postoperative recovery. Follow-up revealed an excellent overall survival rate, except for one case of invasive carcinoma resulting in tumor recurrence and metastasis 6 months after surgery. MCN poses a diagnostic challenge due to the absence of distinct clinical and radiological features, leading to potential misdiagnosis and inappropriate treatment. Patients with suspected liver cystic diseases should consider the possibility of MCN. Surgical resection has proven to be a practical approach with satisfactory therapeutic outcomes.

Recombinant humanized type I collagen remodels decidual immune microenvironment at maternal-fetal interface by modulating Th17/Treg imbalance.

Disruption of the extracellular matrix and dysregulation of the balance between Th17 and regulatory T cells are recognized as risk factors for recurrent spontaneous abortion (RSA). However, the interaction between matrix components and the Th17/Treg axis remains poorly elucidated. The result of this study revealed that the absence of type I collagen in the decidua is linked to Th17/Treg imbalance in RSA. Furthermore, we discovered that biomaterial recombinant humanized type I collagen (rhCOLI) promoted T cell differentiation into Tregs by inhibition the Notch1/Hes1 signaling pathway and enhanced the immunosuppressive function of Tregs, as indicated by increased secretion level of IL-10 and TGF-ß. Importantly, this study is the first to demonstrate that rhCOLI can modulate the Th17/Treg imbalance, reduce embryo resorption rates, reshape the immune microenvironment at the maternal-fetal interface, and improve fertility in an RSA mouse model. Collectively, these findings suggest that type I collagen deficiency may contribute to, rather than result from, RSA, and propose a potential intervention for RSA using rhCOLI.

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.

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.

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).

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.