One-Week Kava Dietary Supplementation Increases Both Urinary N- and O-Glucuronides of NNAL, a Lung Carcinogen Major Metabolite, among Smokers.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (commonly known as NNK) is one of the most prevalent and potent pulmonary carcinogens in tobacco products that increases the human lung cancer risk. Kava has the potential to reduce NNK and tobacco smoke-induced lung cancer risk by enhancing urinary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, the major metabolite of NNK) and thus reducing NNK-induced DNA damage. In this study, we quantified N-glucuronidated NNAL (NNAL-N-gluc), O-glucuronidated NNAL (NNAL-O-gluc), and free NNAL in the urine samples collected before and after 1-week kava dietary supplementation. The results showed that kava increased both NNAL-N-glucuronidation and O-glucuronidation. Since NNAL-N-glucuronidation is dominantly catalyzed by UGT2B10, its representative single-nucleotide polymorphisms (SNPs) were analyzed among the clinical trial participants. Individuals with any of the four analyzed SNPs appear to have a reduced basal capacity in NNAL-N-glucuronidation. Among these individuals, kava also resulted in a smaller extent of increases in NNAL-N-glucuronidation, suggesting that participants with those UGT2B10 SNPs may not benefit as much from kava with respect to enhancing NNAL-N-glucuronidation. In summary, our results provide further evidence that kava enhances NNAL urinary detoxification via an increase in both N-glucuronidation and O-glucuronidation. UGT2B10 genetic status has not only the potential to predict the basal capacity of the participants in NNAL-N-glucuronidation but also potentially the extent of kava benefits.

Metal-doped biochar for selective recovery and reuse of phosphate from water: Modification design, removal mechanism, and reutilization strategy.

Phosphorus (P) plays a crucial role in plant growth, which can provide nutrients for plants. Nonetheless, excessive phosphate can cause eutrophication of water, deterioration of aquatic environment, and even harm for human health. Therefore, adopting feasible adsorption technology to remove phosphate from water is necessary. Biochar (BC) has received wide attention for its low cost and environment-friendly properties. However, undeveloped pore structure and limited surface groups of primary BC result in poor uptake performance. Consequently, this work introduced the synthesis of pristine BC, parameters influencing phosphate removal, and corresponding mechanisms. Moreover, multifarious metal-doped BCs were summarized with related design principles. Meanwhile, mechanisms of selective phosphate adsorption by metal-doped BC were investigated deeply, and the recovery of phosphate from water, and the utilization of phosphate-loaded adsorbents in soil were critically presented. Finally, challenges and prospects for widespread applications of selective phosphate adsorption were proposed in the future.

Identifying and evaluating a disulfidptosis-related gene signature to predict prognosis in colorectal adenocarcinoma patients.

Disulfidptosis, a regulated form of cell death, has been recently reported in cancers characterized by high SLC7A11 expression, including invasive breast carcinoma, lung adenocarcinoma, and hepatocellular carcinoma. However, its role in colon adenocarcinoma (COAD) has been infrequently discussed. In this study, we developed and validated a prognostic model based on 20 disulfidptosis-related genes (DRGs) using LASSO and Cox regression analyses. The robustness and practicality of this model were assessed via a nomogram. Subsequent correlation and enrichment analysis revealed a relationship between the risk score, several critical cancer-related biological processes, immune cell infiltration, and the expression of oncogenes and cell senescence-related genes. POU4F1, a significant component of our model, might function as an oncogene due to its upregulation in COAD tumors and its positive correlation with oncogene expression. In vitro assays demonstrated that POU4F1 knockdown noticeably decreased cell proliferation and migration but increased cell senescence in COAD cells. We further investigated the regulatory role of the DRG in disulfidptosis by culturing cells in a glucose-deprived medium. In summary, our research revealed and confirmed a DRG-based risk prediction model for COAD patients and verified the role of POU4F1 in promoting cell proliferation, migration, and disulfidptosis.

Clinical significance of PLT for diagnosis and treatment monitoring in imported malaria.

To evaluate the clinical significance of PLT, MPV, and PDW in monitoring malaria treatment efficacy and predicting disease progression. A total of 31 patients with imported malaria were selected as the observation group, while 31 non-malaria patients with fever were selected as controls. The observation group was subdivided into a complication group and a non-complication group according to the occurrence of complications during treatment. Additionally, on the 1st day (within 24 h), the 3rd day, and the 5th day following admission, a comprehensive blood routine examination, Plasmodium microscopic examination, and colloidal gold assay were conducted. The blood routine examination results were compared before and after treatment among patients in the observation group and the control group. Moreover, the study involved dynamic monitoring and analysis of the levels and variations in PLT, MPV, and PDW within both the complication group and the non-complication group. The Plasmodium density was negatively correlated with PLT before treatment. There were significant differences were observed in PLT, MPV, and PDW (P < 0.05) within the observation group before and after treatment. Notably, there were no significant alterations in red blood cell (RBC), hemoglobin (Hb), and white blood cell (WBC) counts (P > 0.05) within the observation group before and after treatment. The PLT, MPV, and PDW levels in the complication group and the non-complication group exhibited an upward trend after treatment. Further, the PLT of patients in the complication group was significantly lower than that in the non-complication group. Additionally, the PLT, MPV, and PDW levels in the complication group and the non-complication group increased gradually from the time of admission to the 3rd and 5th day of treatment. Notably, the PLT in the complication group was consistently lower than that in the non-complication group. The continuous monitoring of PLT, MPV, and PDW changes plays a crucial role in assessing malaria treatment efficacy and prognosis in these individuals.

Metagenomic comparison of intestinal microbiota between normal and liver fibrotic rhesus macaques (Macaca mulatta).

Liver fibrosis is an important pathological process in chronic liver disease and cirrhosis. Recent studies have found a close association between intestinal microbiota and the development of liver fibrosis. To determine whether there are differences in the intestinal microbiota between rhesus macaques with liver fibrosis (MG) and normal rhesus macaques (MN), fecal samples were collected from 8 male MG and 12 male MN. The biological composition of the intestinal microbiota was then detected using 16S rRNA gene sequencing. The results revealed statistically significant differences in ASVs and Chao1 in the alpha-diversity and the beta-diversity of intestinal microbiota between MG and MN. Both groups shared Prevotella and Lactobacillus as common dominant microbiota. However, beneficial bacteria such as Lactobacillus were significantly less abundant in MG (P = 0.02). Predictive functional analysis using PICRUSt2 gene prediction revealed that MG exhibited a higher relative abundance of functions related to substance transport and metabolic pathways. This study may provide insight into further exploration of the mechanisms by which intestinal microbiota affect liver fibrosis and its potential future use in treating liver fibrosis.

Risk evaluation for diabetic retinopathy in Chinese renal-biopsied type 2 diabetes mellitus patients.

AIM: To investigate diabetic retinopathy (DR) prevalence in Chinese renal-biopsied type 2 diabetes mellitus (T2DM) patients with kidney dysfunction, and to further evaluate its relationship with diabetic nephropathy (DN) incidence and the risk factors for DR development in this population. METHODS: A total of 84 renal-biopsied T2DM patients were included. Fundus and imaging examinations were employed for DR diagnosis. Demographic information and clinical measures along with renal histopathology were analyzed for comparisons between the DR and non-DR groups. Risk factors on DR development were analyzed with multiple logistic regression. RESULTS: DR prevalence was 50% in total. The incidences of DN, non-diabetic renal disease (NDRD) and mixed-type pathology were 47.6%, 19.0% and 33.3% in the DR group respectively, while 11.9%, 83.3% and 4.8% in the non-DR group. Systolic blood pressure, ratio of urinary albumin to creatine ratio, urinary albumin, 24-hours urinary protein, the incidence and severity of DN histopathology were found statistically increased in the DR group. Multiple logistic regression analysis showed histopathological DN incidence significantly increased the risk of DR development [odds ratio (OR)=21.664, 95% confidential interval (CI) 5.588 to 83.991, P<0.001 for DN, and OR=45.475, 95%CI 6.949 to 297.611, P<0.001 for mixed-type, respectively, in reference to NDRD)], wherein DN severity positively correlated. CONCLUSION: Renal histopathological evidence indicates DN incidence and severity increases the risk of DR development in Chinese T2DM patients inexperienced of regular fundus examinations.

Constructing Favorable Microenvironment on Copper Grain Boundaries for CO2 Electro-conversion to Multicarbon Products.

The electrochemical CO2 reduction reaction (eCO2RR) to multicarbon chemicals provides a promising avenue for storing renewable energy. Herein, we synthesized small Cu nanoparticles featuring enriched tiny grain boundaries (RGBs-Cu) through spatial confinement and in situ electroreduction. In-situ spectroscopy and theoretical calculations demonstrate that small-sized Cu grain boundaries significantly enhance the adsorption of the *CO intermediate, owing to the presence of abundant low-coordinated and disordered atoms. Furthermore, these grain boundaries, generated in situ under high current conditions, exhibit excellent stability during the eCO2RR process, thereby creating a stable *CO-rich microenvironment. This high local *CO concentration around the catalyst surface can reduce the energy barrier for C-C coupling and significantly increase the Faradaic efficiency (FE) for multicarbon products across both neutral and alkaline electrolytes. Specifically, the developed RGBs-Cu electrocatalyst achieved a peak FE of 77.3% for multicarbon products and maintained more than 134 h stability at a constant current density of -500 mA cm-2.

Boosting Electrochemical Urea Synthesis via Constructing Ordered Pd-Zn Active Pair.

Electrochemical co-reduction of nitrate (NO3-) and carbon dioxide (CO2) has been widely regarded as a promising route to produce urea under ambient conditions, however the yield rate of urea has remained limited. Here, we report an atomically ordered intermetallic pallium-zinc (PdZn) electrocatalyst comprising a high density of PdZn pairs for boosting urea electrosynthesis. It is found that Pd and Zn are responsible for the adsorption and activation of NO3- and CO2, respectively, and thus the co-adsorption and co-activation NO3- and CO2 are achieved in ordered PdZn pairs. More importantly, the ordered and well-defined PdZn pairs provide a dual-site geometric structure conducive to the key C-N coupling with a low kinetical barrier, as demonstrated on both operando measurements and theoretical calculations. Consequently, the PdZn electrocatalyst displays excellent performance for the co-reduction to generate urea with a maximum urea Faradaic efficiency of 62.78% and a urea yield rate of 1274.42 µg mg-1 h-1, and the latter is 1.5-fold larger than disordered pairs in PdZn alloys. This work paves new pathways to boost urea electrosynthesis via constructing ordered dual-metal pairs.

Research trends and hotspot analysis of age-related hearing loss: A bibliometric analysis from 2019 to 2023.

BACKGROUND: Age-related hearing loss (ARHL) - also termed presbycusis - is prevalent among older adults, leading to a range of issues. Although considerable progress in the understanding of ARHL over the decades, available reports lack data from recent years and do not comprehensively reflect the latest advancements and trends. Therefore, our study sought to assess research hotspots and trends in ARHL over the past 5 years to provide the basis for future research. MATERIALS AND METHODS: The Web of Science Core Collection database was searched and screened from January 1, 2019 to October 21, 2023, according to the inclusion criteria. CiteSpace (5.8.R3), VOSviewer (1.6.19), and Microsoft Excel 2019 were employed for bibliometric analysis and visualization. RESULTS: 3084 articles from 92 countries led by the United States and China were included. There has been a steady upward trend in the number of publications from 2019 to 2023. The most productive institutions, authors, and journals are Johns Hopkins University (n = 113), Lin FR (n = 66), and Ear and Hearing (n = 135), respectively. Trend topic analyses revealed that "cochlear synaptopathy" and "dementia" were the predominant foci. Keywords, including "individuals" and "national health", began to appear. CONCLUSION: Over the past 5 years, the annual number of publications has increased significantly and will continue to do so. Research on the mechanism of ARHL, represented by "oxidative stress", is a continuing focus. Emerging topics such as "individual differences" and "national health" may be potential future hotspots in this field.

Two Mn(II)-Bridged Silverton-Type [UMo12O42]8- Polyoxometalates with Catalytic Activity for the Synthesis of Pyrazoles.

Two Mn(II)-bridged Silverton-type {UMo12O42}-based polyoxomolybdates with different three-dimensional structures, Na6(H2O)12[Mn(UMo12O42)] (NaMn) and (NH4)2[K2Na6(µ4-O)2(H2O)1.2Mn(UMo12O42)]·4.6H2O (KMn), were hydrothermally synthesized and further characterized, demonstrating a feasible strategy for the assembly of Silverton-type polyoxomolybdates. Additionally, NaMn is demonstrated to be a good heterogeneous catalyst in the condensation cyclization reaction of hydrazines and 1,3-diketones, and a range of valuable pyrazoles were produced in up to 99% yield.

A study on the factors influencing the vulnerability of women of childbearing age to health poverty in rural western China.

The health of women of childbearing age in rural areas is crucial for the development of individuals, families, and society. Research on the identification and influencing factors of health vulnerability in impoverished and disadvantaged groups is important for adjusting and implementing health poverty alleviation policies. However, there is limited research on the health vulnerability of women of childbearing age in rural Western China. Based on panel data from the Rural Residents' Family Health Status Survey in 2019 and 2022, the vulnerability to health poverty of women of childbearing age in rural areas was constructed using the three-stage feasible generalized least squares method. Variables from four dimensions-physical capital, financial capital, social capital, and human capital-were included in the sustainable livelihood analysis framework for analysis. The Tobit model was used to analyze the influencing factors of vulnerability to health poverty among women of childbearing age in rural Western China, and the contribution rates of various factors were studied using the Shapley value decomposition method. In 2019 and 2022, under the poverty line standards of $1.90 and $2.15, respectively, the vulnerability to health poverty among rural women of childbearing age exceeded 20%. Tobit regression analysis revealed that the type of drinking water being well water significantly increased the vulnerability to health poverty of rural women of childbearing age (P < 0.05), whereas the separation of housing and kitchen, registered poor households, household loans, annual per capita household income, expenditures on social interactions, educational level, self-assessed health status, respondent age, and the utilization of hospital services significantly reduced the vulnerability to health poverty of rural women of childbearing age (P < 0.05). Shapley's decomposition shows that annual per capita household income, expenditures on social interactions, respondent age, and household loans are the factors contributing most to the vulnerability to health poverty of rural women of childbearing age, while other variables have a smaller contribution rate. The health poverty situation of women of childbearing age in rural Western China is not optimistic. Preintervention for health poverty should be strengthened among rural women of childbearing age, early warning mechanisms for the risk of falling back into poverty due to illness should be established, the precise identification of highly vulnerable rural women of childbearing age should be improved, and the medical insurance system for rural women of childbearing age should be enhanced to help improve their current health poverty situation.

Different concentrations of hyaluronic acid eye drops for dry eye syndrome: a systematic review and Meta-analysis.

AIM: To compare high or low concentration of hyaluronic acid eye drops (HY) for dry eye syndromes (DES). METHODS: Randomized controlled trials (RCTs) comparing various concentrations of HY were searched in PubMed, Embase, Web of Science, Cochrane, SinoMed, CNKI, Wanfang Database, CQVIP, and Chinese journals databases between inception and July 2023. Pooled standardized mean differences (SMD) or weighted mean difference (WMD) with 95% confidence intervals (CI) from RCTs evaluating Schirmer's I test (SIT), corneal fluorescein staining score (CFS), tear breakup time (TBUT), DES score (DESS), and Ocular Surface Disease Index (OSDI) were calculated. Sensitivity analysis, Egger's test and Meta-regression analysis were performed for all indicators. RESULTS: We conducted a Meta-analysis of 10 RCTs that met the inclusion criteria, involving 1796 cases. High-concentrations group significantly improved the outcome of CFS according to random effects modelling (SMD, -3.37; 95%CI, -5.25 to -1.48; P=0.0005). The rest of the results were not statistically significant, including indicators such as SIT, TBUT, DESS and OSDI. CONCLUSION: For dry eyes with positive corneal staining, a high concentration of HY is recommended, whereas in other cases, a high concentration of HY does not offer a more pronounced advantage over a low concentration of HY in the treatment of dry eyes.

The role of minimal residual disease and serum free light chain ratio in the management of multiple myeloma.

Multiple myeloma (MM) denotes a cancerous growth characterized by abnormal proliferation of plasma cells. Growing evidence suggests that the complexity in addressing MM lies in the presence of minimal residual disease (MRD) within the body. MRD assessment is becoming increasingly important for risk assessment in patients with MM. Similarly, the levels of serum free protein light chain and their ratio play a crucial role in assessing the disease burden and changes in MM. In this paper, we review and explore the utilization of MRD and serum free light chain ratio in the treatment of MM, delving into their respective characteristics, advantages, disadvantages, and their interrelation.

NiS ultrafine nanorod with translational and rotational symmetry.

Anisotropy is a significant and prevalent characteristic of materials, conferring orientation-dependent properties, meaning that the creation of original symmetry enables key functionality that is not found in nature. Even with the advancements in atomic machining, synthesis of separated symmetry in different directions within a single structure remains an extraordinary challenge. Here, we successfully fabricate NiS ultrafine nanorods with separated symmetry along two directions. The atomic structure of the nanorod exhibits rotational symmetry in the radial direction, while its axial direction is characterized by divergent translational symmetry, surpassing the conventional crystalline structures known to date. It does not fit the traditional description of the space group and the point group in three dimensions, so we define it as a new structure in which translational symmetry and rotational symmetry are separated. Further corroborating the atomic symmetric separation in the electronic structure, we observed the combination of stripe and vortex magnetic domains in a single nanorod with different directions, in accordance with the atomic structure. The manipulation of nanostructure at the atomic level introduces a novel approach to regulate new properties finely, leading to the proposal of new nanotechnology mechanisms.

Network Pharmacology, Molecular Docking, and Experimental Validation of the Mechanism of Jiedu Xiaoliu Formula against Diffuse Large B-Cell Lymphoma.

INTRODUCTION: Diffuse Large B-Cell Lymphoma (DLBCL) is the most common Bcell lymphoma type. Detoxification and tumor elimination formula, a herbal compound, can potentially treat lymphoma. In this study, network pharmacology and molecular docking approaches were utilized to reveal the potential mechanism of the Jiedu Xiaoliu formula (JDXLF) against DLBCL. METHODS: Active compounds and targets of JDXLF were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Targets related to DLBCL were retrieved from GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Protein- Protein Interaction (PPI) networks were established to screen core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using R 4.2.2. Model interactions between potential disease targets and pharmacologically active compounds were determined by molecular docking. RESULTS: Screening of 14 herbal active ingredients yielded 129 active compounds and 1414 disease targets for DLBCL. GO annotations showed that the effects of JDXLF were related to protein phosphorylation and reactive oxygen species response. KEGG pathway enrichment analysis indicated that the detoxification and elimination of tumors formula mainly regulated apoptosis pathways. Nobiletin showed good interaction with AKT1, TP53, and CASP3, and the cell counting kit-8 (CCK-8) assay confirmed that nobiletin inhibited the proliferation of SU-DHL-4 cells. Western blot analysis showed that nobiletin downregulated the expressions of p-PI3K, p- AKT, and BCL-2 proteins and upregulated those of cleaved-caspase3 and BAX. CONCLUSION: Our findings preliminarily suggested that the active ingredient of JDXLF, nobiletin, may induce apoptosis in Diffuse Large B-Cell Lymphoma SU-DHL-4 cells by regulating the PI3K/AKT signaling pathway.

The performance of quaternary-ammonium chitosan in wastewater treatment: The overlooked role of solubility.

Quaternary-ammonium chitosan (CT-CTA) is a popular water treatment agent, and its electropositivity and cation strength are improved compared with chitosan. The use of CT-CTA is widely advocated to remove suspended particles and organic matter from wastewater. However, the solubility of CT-CTA is an important factor affecting the performance of CT-CTA, which is a neglected problem in previous studies. In the study, CT-CTA with different solubilities were prepared by adjusting pH from 2 to 7 in preparation, and their applications were explored in wastewater. When the pH was 2, 2.5, or 3, the obtained CT-CTA was a dissolved state. The turbidity and color removal were 95 % - 98 % and 60 % - 74 %, respectively. When the pH was 4, 5, 6, or 7, the obtained CT-CTA was a solid state. The turbidity and color removal were 30 % - 63 % and 90 % - 97 %, respectively. For domestic-wastewater treatment, CT-CTA in a dissolved state removed 92 % of turbidity and 50 % of chemical oxygen demand (COD). CT-CTA in a solid state removed 86 % of turbidity and 64 % of COD with poly aluminum chloride (PAC). The results illustrated the performance of CT-CTA with different solubilities, which can broaden its application in wastewater treatment.

Enhancement of silicon vacancy fluorescence intensity in silicon carbide using a dielectric cavity.

Over the past decades, spin qubits in silicon carbide (SiC) have emerged as promising platforms for a wide range of quantum technologies. The fluorescence intensity holds significant importance in the performance of quantum photonics, quantum information process, and sensitivity of quantum sensing. In this work, a dual-layer Au/SiO2 dielectric cavity is employed to enhance the fluorescence intensity of a shallow silicon vacancy ensemble in 4H-SiC. Experimental results demonstrate an effective fourfold augmentation in fluorescence counts at saturating laser power, corroborating our theoretical predictions. Based on this, we further investigate the influence of dielectric cavities on the contrast and linewidth of optically detected magnetic resonance (ODMR). There is a 1.6-fold improvement in magnetic field sensitivity. In spin echo experiments, coherence times remain constant regardless of the thickness of dielectric cavities. These experiments pave the way for broader applications of dielectric cavities in SiC-based quantum technologies.

Prophylactic Effects of n-Acethylcysteine on Inflammation-induced Depression-like Behaviors in Mice.

Depression, affecting individuals worldwide, is a prevalent mental disease, with an increasing incidence. Numerous studies have been conducted on depression, yet its pathogenesis remains elusive. Recent advancements in research indicate that disturbances in synaptic transmission, synaptic plasticity, and reduced neurotrophic factor expression significantly contribute to depression's pathogenesis. In our study, we utilized adult male C57BL/6J mice. Lipopolysaccharide (LPS) can induce both chronic and acute depression-like symptoms in mice, a widely used model for studying depression associated with inflammation. N-acetylcysteine (NAC) exhibits anti-inflammatory and ameliorative effects on depressive symptoms. This study sought to determine whether NAC use could mitigate inflammatory depressive behavior through the enhancement of synaptic transmission, synaptic plasticity, and increasing levels of brain-derived neurotrophic factor (BDNF). In this study, we discovered that in mice modeled with depression-like symptoms, the expression levels of dendrites, BDNF, and miniature excitatory postsynaptic potential (mEPSC) in glutamatergic neurons, as well as the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid glutamate receptors (AMPARs) GluA1 and GluA2 subunits, were significantly decreased. These findings suggest an impairment in the synaptic transmission of glutamatergic neurons. Following treatment with NAC, the previously mentioned levels improved, indicating an enhancement in both synaptic transmission and synaptic plasticity. Our results suggest that NAC exerts a protective effect on mouse models of inflammatory depression, potentially through the enhancement of synaptic transmission and plasticity, as well as the restoration of neurotrophic factor expression. These findings offer vital animal experimental evidence supporting NAC's role in mitigating inflammatory depressive behaviors.

Efficient Neutral H2O2 Electrosynthesis from Favorable Reaction Microenvironments via Porous Carbon Carrier Engineering.

The efficient electrosynthesis of hydrogen peroxide (H2O2) via two-electron oxygen reduction reaction (2e- ORR) in neutral media is undoubtedly a practical route, but the limited comprehension of electrocatalysts has hindered the system advancement. Herein, we present the design of model catalysts comprising mesoporous carbon spheres-supported Pd nanoparticles for H2O2 electrosynthesis at near-zero overpotential with approximately 95 % selectivity in a neutral electrolyte. Impressively, the optimized Pd/MCS-8 electrocatalyst in a flow cell device achieves an exceptional H2O2 yield of 15.77 mol gcatalyst -1 h-1, generating a neutral H2O2 solution with an accumulated concentration of 6.43 wt %, a level sufficiently high for medical disinfection. Finite element simulation and experimental results suggest that mesoporous carbon carriers promote O2 enrichment and localized pH elevation, establishing a favorable microenvironment for 2e- ORR in neutral media. Density functional theory calculations reveal that the robust interaction between Pd nanoparticles and the carbon carriers optimized the adsorption of OOH* at the carbon edge, ensuring high active 2e- process. These findings offer new insights into carbon-loaded electrocatalysts for efficient 2e- ORR in neutral media, emphasizing the role of carrier engineering in constructing favorable microenvironments and synergizing active sites.

A rare case of TFEB/6p21/VEGFA-amplified renal cell carcinoma diagnosed by whole-exome sequencing: clinicopathological and genetic feature report and literature review.

BACKGROUND: TFEB/6p21/VEGFA-amplified renal cell carcinoma (RCC) is rare and difficult to diagnose, with diverse histological patterns and immunohistochemical and poorly defined molecular genetic characteristics. CASE PRESENTATION: We report a case of a 63-year-old male admitted in 2017 with complex histomorphology, three morphological features of clear cell, eosinophilic and papillary RCC and resembling areas of glomerular and tubular formation. The immunophenotype also showed a mixture of CD10 and P504s. RCC with a high suspicion of collision tumors was indicated according to the 2014 WHO classification system; no precise diagnosis was possible. The patient was diagnosed at a different hospital with poorly differentiated lung squamous cell carcinoma one year after RCC surgery. We exploited molecular technology advances to retrospectively investigate the patient's molecular genetic alterations by whole-exome sequencing. The results revealed a 6p21 amplification in VEGFA and TFEB gene acquisition absent in other RCC subtypes. Clear cell, papillary, chromophobe, TFE3-translocation, eosinophilic solid and cystic RCC were excluded. Strong TFEB and Melan-A protein positivity prompted rediagnosis as TFEB/6p21/VEGFA-amplified RCC as per 2022 WHO classification. TMB-L (low tumor mutational load), CCND3 gene acquisition and MRE11A and ATM gene deletion mutations indicated sensitivity to PD-1/PD-L1 inhibitor combinations and the FDA-approved targeted agents Niraparib (Grade C), Olaparib (Grade C), Rucaparib (Grade C) and Talazoparib (Class C). GO (Gene Ontology) and KEGG enrichment analyses revealed major mutations and abnormal CNVs in genes involved in biological processes such as the TGF-ß, Hippo, E-cadherin, lysosomal biogenesis and autophagy signaling pathways, biofilm synthesis cell adhesion substance metabolism regulation and others. We compared TFEB/6p21/VEGFA-amplified with TFEB-translocated RCC; significant differences in disease onset age, histological patterns, pathological stages, clinical prognoses, and genetic characteristics were revealed. CONCLUSION: We clarified the patient's challenging diagnosis and discussed the clinicopathology, immunophenotype, differential diagnosis, and molecular genetic information regarding TFEB/6p21/VEGFA-amplified RCC via exome analysis and a literature review.