Does epigenetic aging mediate the associations between phthalate exposure and renal function?

Emerging evidence suggests that phthalate ester (PAE) exposure accelerates epigenetic aging and impairs kidney function. However, very few epidemiological studies have explored the associations between PAE exposure, epigenetic age acceleration (EAA), and kidney function. The present cross-sectional study investigated whether EAA mediates the effect of PAE exposure on kidney function and assessed the potential interaction effects of PAE exposure and EAA on kidney function.

Cytoreductive nephroureterectomy for treatment of upper urinary tract urothelial carcinoma initially diagnosed as node-positive.

Urothelial carcinomas of the upper urinary tract (UTUC) are rare tumors with a high malignancy degree. Radical nephroureterectomy (RNU) with bladder cuff excision remains one of the standard treatments in clinically localized or locally advanced UTUCs. However, the role of cytoreductive RNU in treating clinically lymph node-positive (N+) UTUCs remains unclear.

Inflammation and Obesity Correlate in Pulmonary Hypertension but Associate with Diverging Outcomes.

Rationale & Objectives: Inflammation is associated with all types of Pulmonary Hypertension (PH) both as a known cause and/or a putative confounder. The most common marker of inflammation, C-reactive protein (CRP), has not been widely studied in PH. This study set out to clarify if CRP informed clinical endotyping and outcomes.

Aluminum Cations Stabilized by Hybrid N-Heterocyclic Imine Ligand as Catalysts for Guanidine Synthesis from Carbodiimides and Anilines.

In this study, we developed a facile method for synthesizing four-coordinated aluminum cations using hybrid N-heterocyclic imine ligands. These ligands enhance the stability of the aluminum cations while preserving their reactivity in catalyzing guanidine synthesis from carbodiimides and anilines. Mechanistic studies revealed that the aluminum cation operates as a highly reactive system under mild conditions, exhibiting rapid kinetics and robust stability.

Identification and validation of interferon-driven gene signature as a predictor of response to methotrexate in juvenile idiopathic arthritis.

Objectives: To identify and validate gene expression biomarkers of response to methotrexate (MTX) treatment in peripheral blood of children with juvenile idiopathic arthritis (JIA) measured before starting MTX treatment.

Methods: RNA sequencing was performed on sorted CD4+, CD8+, CD14+, and CD19+ cells, as well as peripheral blood mononuclear cells (PBMC) taken pre-treatment in a discovery cohort (n = 97) and 2 validation cohorts (n = 26 and n = 47, respectively) of patients with non-systemic JIA. Clinical data were recorded at baseline (timepoint 1) prior to treatment and 6 months (timepoint 2) of MTX treatment.

Engineering a protease-stable, oral single-domain antibody to inhibit IL-23 signaling.

Interleukin (IL)-23 is a validated therapeutic target in inflammatory bowel disease. While antibodies targeting IL23 demonstrate clinical efficacy, they face challenges such as high costs, safety risks, and the necessity of parenteral administration. Here, we present a workflow to simultaneously enhance the affinity and protease stability of an inhibitory anti-IL23R VHH for oral use.

Development and validation of a prediction model for early recurrence in upper tract urothelial carcinoma treated with radical nephroureterectomy.

Background: Most cases of upper tract urothelial carcinoma (UTUC) exhibit recurrence within the first year following surgery. The time from surgery to recurrence significantly impacts cancer-specific survival. In this study, we analyzed patients with localized UTUC (pTis-3N0/xcM0) who experienced postoperative recurrence to identify an appropriate early recurrence time point and the associated risk factors.

Preoperative ECOG performance status as a predictor of outcomes in upper tract urothelial cancer surgery.

Eastern Cooperative Oncology Group performance status (ECOG-PS) is a widely used functional status measure in oncology, yet its prognostic value in upper tract urothelial carcinoma remains unclear. In this multicenter study of 2473 patients undergoing radical nephroureterectomy, ECOG-PS ≥ 2 was independently associated with worse overall survival (hazard ratio [HR] 2.53, p < 0.

Penalised regression improves imputation of cell-type specific expression using RNA-seq data from mixed cell populations compared to domain-specific methods.

Gene expression studies often use bulk RNA sequencing of mixed cell populations because single cell or sorted cell sequencing may be prohibitively expensive. However, mixed cell studies may miss expression patterns that are restricted to specific cell populations. Computational deconvolution can be used to estimate cell fractions from bulk expression data and infer average cell-type expression in a set of samples (e.

Sustainable Synthesis of Polyfluoro-Pyrimido [1,2-] Benzimidazole Derivatives Using a Tandem Strategy─Ultrasound and an Integrated Continuous Flow System.

We have developed a novel ultrasound technique that generates significant amounts of CF-substituted benzo[4,5] imidazo [1,2-]pyrimidine analogues from easily accessible starting materials in an ecologically friendly and efficient approach. This method is notably helpful for producing physiologically relevant compounds containing the imidazopyrimidine unit, which serves as a versatile building block for the synthesis of -fused heterocycles and is devoid of metals, solvents, additives, and catalysts. Additionally, utilizing ultrasound in an open-air environment, a range of polyfluoro-ynones were successfully reacted with 2-aminobenzimidazole, generating a diverse array of polyfluoroimidazo[1,2-]pyrimidine derivatives.

Epidemiology and practice patterns of achalasia in Taiwan: A nationwide population-based cohort study.

Background: Achalasia is a rare disease of gastrointestinal motility characterized by impaired esophageal peristalsis and reduced esophageal sphincter relaxation. However, data on its epidemiology and outcomes in Taiwan are limited. This study aimed to assess the incidence, characteristics, and clinical management of achalasia in Taiwan.

Efficacy of Zinc Supplementation in the Management of Primary Dysmenorrhea: A Systematic Review and Meta-Analysis.

Background/objectives: Primary dysmenorrhea (PD) is a common condition affecting up to 90% of menstruating women, which often results in significant pain without an underlying pathology. Zinc, recognized for its anti-inflammatory and antioxidant effects through inhibiting prostaglandin production and superoxide dismutase 1 (SOD1) upregulation, alleviates menstrual pain by preventing uterine spasms and enhancing microcirculation in the endometrium, suggesting its potential as an alternative treatment for primary dysmenorrhea. The goal of this systematic review and meta-analysis was to assess the efficacy and safety of zinc supplementation in reducing pain severity among women with PD and to explore the influence of dosage and treatment duration.

Aglaia elliptifolia Leaf Extract Inhibits Autophagy-Related 4B Protease and Suppresses Malignancies of Colorectal Cancer Cells.

Autophagy is a self-eating pathway for maintaining normal cellular physiology, while dysregulation of autophagy is associated with cancer progression. Autophagy-related 4B gene (ATG4B) is a cysteine protease to regulate autophagosome formation and is positively correlated with poor prognosis of colorectal cancer (CRC) patients. An increasing number of reports have implied that ATG4B might be an attractive drug target for CRC.

Carvedilol through ß1-Adrenoceptor blockade ameliorates glomerulonephritis via inhibition of oxidative stress, apoptosis, autophagy, ferroptosis, endoplasmic reticulum stress and inflammation.

Glomerulonephritis (GN) is one of the main causes of end stage renal disease and requires an effective treatment for inhibiting GN. Renal nerves through efferent (RENA) and afferent (RANA) innervation to glomeruli regulate the glomerular function. We delineated the role of RENA and RANA on anti-Thy1.

AviTrap: A novel solution to achieve complete biotinylation.

Site specific biotinylation of AviTagged recombinant proteins using BirA enzyme is a widely used protein labeling technology. However, due to the incomplete biotinylation reactions and the lack of a purification method specific for the biotinylated proteins, it is challenging to purify the biotinylated sample when mixed with the non-biotinylated byproduct. Here, we have developed a monoclonal antibody that specifically recognizes the non-biotinylated AviTag but not the biotinylated sequence.

Base-promoted triple cleavage of CClBr: a direct one-pot synthesis of unsymmetrical oxalamide derivatives.

We present a novel, eco-friendly and one-pot approach for synthesizing unsymmetrical oxalamides with the aid of dichloroacetamide and amine/amides in the presence of CBr in a basic medium. The use of water as a potent supplement for the oxygen atom source and the detailed mechanism have been disclosed. Moreover, the protocol involves triple cleavage of CClBr and the formation of new C-O/C-N bonds, with the advantage of achieving selective bromination using CBr with good to excellent yield under mild conditions.

Prognostic factors of intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.

Purpose: To evaluate predictive factors of increasing intravesical recurrence (IVR) rate in patients with upper tract urothelial carcinoma (UTUC) after receiving radical nephroureterectomy (RNUx) with bladder cuff excision (BCE).

Materials And Methods: A total of 2114 patients were included from the updated data of the Taiwan UTUC Collaboration Group. It was divided into two groups: IVR-free and IVR after RNUx, with 1527 and 587 patients, respectively.

Novel Selective Quantification of Zinpentraxin Alfa Biotherapeutic in the Presence of Endogenous Isomer in Plasma Samples of Idiopathic Pulmonary Fibrosis Patients Using Immunoaffinity LC-MS.

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal interstitial lung disease that affects three million patients worldwide and currently without an effective cure. Zinpentraxin alfa, a recombinant human pentraxin-2 (rhPTX-2) protein, has been evaluated as a potential drug candidate for the treatment of IPF. Clinical pharmacokinetic analysis of zinpentraxin alfa has been challenging historically due to interference from serum amyloid P component (SAP), an endogenous human pentraxin-2 protein.

Spatial variability of nitrogen cycling in the sediments of the Danshuie River Estuary (Northern Taiwan).

Dissolved N species, TOC and total N (TN) in sediment cores (SC) collected from an eutrophic estuary were analyzed to understand the N geochemical variation in SC of the eutrophic estuary. Extremely higher concentrations of ammonium (6550 μM) and DON (2050 μM) were observed in pore water of the upper estuary and both concentrations generally accounted for 65-99 % and 1-34 % of the dissolved total N pool, respectively, in the three sediment pore waters. The DON and TN concentrations decreased with increasing depth in SC of the upper estuary, opposite the ammonium profile, suggesting that the mineralization of DON and TN provided the ammonium source to the SC.

An Active-Matrix Organic Light-Emitting Diode Pixel Circuit Featuring Mobility Compensation for Portable Applications.

A 6T1C pixel circuit based on low-temperature polycrystalline oxide (LTPO) technology for portable active-matrix organic light-emitting diode (AMOLED) display applications is proposed in this paper. For superior high-end portable applications including 4K high resolution and high PPI (pixels per inch), the proposed pixel circuit employs a single storage capacitor and signal sharing switch-control design and provides low-voltage driving and immunity to the IR-drop issue and OLED degradation. Furthermore, the threshold voltage and mobility-compensating capabilities are improved by both compensation mechanisms, which are based on a negative feedback system, and mobility-related compensation parameters.

FeCl-Catalyzed Decyanative [4 + 2] Annulation of α-Aminonitriles with Alkynes: Access to 2,4-Diaryl Quinolines in Batch and Continuous-Flow Processes.

FeCl-catalyzed decyanation of α-aminonitriles followed by a [4 + 2] annulation with terminal alkynes has been developed to synthesize 2,4-diaryl quinolines. A broad range of aniline, aldehyde, and arylacetylene derivatives were well tolerated to access 2,4-diaryl quinolines in moderate to good yields. The control experiment studies suggested that the reaction proceeds through a nonradical pathway involving Povarov-type [4 + 2] annulation from the generated iminium species.

Inhibiting membrane rupture with NINJ1 antibodies limits tissue injury.

Plasma membrane rupture (PMR) in dying cells undergoing pyroptosis or apoptosis requires the cell-surface protein NINJ1. PMR releases pro-inflammatory cytoplasmic molecules, collectively called damage-associated molecular patterns (DAMPs), that activate immune cells. Therefore, inhibiting NINJ1 and PMR may limit the inflammation that is associated with excessive cell death.

Preoperative hydronephrosis is an independent protective factor of renal function decline after nephroureterectomy for upper tract urothelial carcinoma.

Objectives: To evaluate the predictive role of pre-nephroureterectomy (NU) hydronephrosis on post-NU renal function (RF) change and preserved eligibility rate for adjuvant therapy in patients with upper tract urothelial carcinoma (UTUC).

Patients And Methods: This retrospective study collected data of 1018 patients from the Taiwan UTUC Collaboration Group registry of 26 institutions. The patients were divided into two groups based on the absence or presence of pre-NU hydronephrosis.