Attenuated kidney oxidative metabolism in young adults with type 1 diabetes.

BACKGROUNDIn type 1 diabetes (T1D), impaired insulin sensitivity may contribute to the development of diabetic kidney disease (DKD) through alterations in kidney oxidative metabolism.METHODSYoung adults with T1D (n = 30) and healthy controls (HCs) (n = 20) underwent hyperinsulinemic-euglycemic clamp studies, MRI, 11C-acetate PET, kidney biopsies, single-cell RNA-Seq, and spatial metabolomics to assess this relationship.RESULTSParticipants with T1D had significantly higher glomerular basement membrane (GBM) thickness compared with HCs.

Cost-effectiveness of idecabtagene vicleucel compared with conventional care in triple-class exposed relapsed/refractory multiple myeloma patients in Canada and France.

Background: The chimeric antigen receptor (CAR) T-cell therapy idecabtagene vicleucel (ide-cel) is approved for the treatment of adult patients with relapsed/refractory multiple myeloma (RRMM) who have already received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have progressed on their last therapy. The objective of this study was to assess the cost-effectiveness of ide-cel versus conventional care in Canada and France.

Methods: A partitioned survival model was used to estimate the cost-effectiveness of ide-cel (target dose 450 × 10 CAR T cells) in its approved indication in terms of life-years (LYs), quality-adjusted LYs (QALYs), and costs.

Brown-Norway chromosome 1 mitigates the upregulation of proinflammatory pathways in mTAL cells and subsequent age-related CKD in Dahl SS/JrHsdMcwi rats.

Chronic kidney disease (CKD) has a strong genetic component; however, the underlying pathways are not well understood. Dahl salt-sensitive (SS)/Jr rats spontaneously develop CKD with age and are used to investigate the genetic determinants of CKD. However, there are currently several genetically diverse Dahl SS rats maintained at various institutions and the extent to which some exhibit age-related CKD is unclear.

The politics of gifts and reciprocity in South-South Cooperation: The case of India's Covid-19 diplomacy.

Development economists have often argued that South-South flows of capital and aid are devoid of the conditionalities and hierarchies that define North-South flows of the same. Maussians and neo-Maussians maintain that gifting-which allows for the ethos of reciprocity-leads to the formation of more equal international partnerships. This article focusses on India's development diplomacy.

Tubular cells produce FGF2 via autophagy after acute kidney injury leading to fibroblast activation and renal fibrosis.

Following acute kidney injury (AKI), renal tubular cells may stimulate fibroblasts in a paracrine fashion leading to interstitial fibrosis, but the paracrine factors and their regulation under this condition remain elusive. Here we identify a macroautophagy/autophagy-dependent FGF2 (fibroblast growth factor 2) production in tubular cells. Upon induction, FGF2 acts as a key paracrine factor to activate fibroblasts for renal fibrosis.

Cost-Effectiveness of Cemiplimab Versus Standard of Care in the United States for First-Line Treatment of Advanced Non-small Cell Lung Cancer With Programmed Death-Ligand 1 Expression ≥50.

Objectives: This study aimed to evaluate the cost-effectiveness, from a US commercial payer perspective, of cemiplimab versus other first-line treatments for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%.

Methods: A 30-year "partitioned survival" model was constructed. Overall survival and progression-free survival were estimated by applying time-varying hazard ratios from a network meta-analysis of randomized clinical trials.

A review on the application of industrial waste as reinforced earth fills in mechanically stabilized earth retaining walls.

The infrastructure development of a country is focussed on the development of roadways that includes the construction of many bridges and flyovers with retaining walls. The construction of the mechanically stabilized earth (MSE) retaining wall gained momentum since 1960 owing to the various beneficial aspects in terms of its durability, economy, stability, appearance, sustainability aspects, etc. A typical MSE retaining wall is a composite structure made up of compacted backfill and reinforcement elements, fixed to a wall facing.

The reflexive edge strength on some almost regular graphs.

A function with domain and range are respectively the edge set of graph and natural number up to , and a function with domain and range are respectively the vertex set of graph and the even natural number up to are called a total -labeling where . The total -labeling of graph by the condition that every two different edges have different weight is called an edge irregular reflexive -labeling, where for any edge , the weight is . The reflexive edge strength of the graph , denoted by is the minimum for graph which has an edge irregular reflexive -labelling.

OVAT Analysis and Response Surface Methodology Based on Nutrient Sources for Optimization of Pigment Production in the Marine-Derived Fungus 30548 Submerged Fermentation.

Pigment production from filamentous fungi is gaining interest due to the diversity of fungal species, the variety of compounds synthesized, and the possibility of controlled massive productions. The species produce a large panel of metabolites, including azaphilone pigments, with potential use as natural colorants in industrial applications. Optimizing pigment production from fungal strains grown on different carbon and nitrogen sources, using statistical methods, is widespread nowadays.

Proximal tubule LPA1 and LPA2 receptors use divergent signaling pathways to additively increase profibrotic cytokine secretion.

Lysophosphatidic acid (LPA) increases platelet-derived growth factor-B (PDGFB) and connective tissue growth factor (CTGF) production and secretion by proximal tubule (PT) cells through LPA2 receptor-Gα-αβ-integrin-mediated activation of transforming growth factor-β1 (TGFB1). LPA2, β-integrin, PDGFB, and CTGF increase in kidneys after ischemia-reperfusion injury (IRI), coinciding with fibrosis. The TGFB1 receptor antagonist SD-208 prevents increases of β-integrin, TGFB1-SMAD signaling, and PDGFB/CTGF expression after IRI and ameliorates fibrosis (Geng H, Lan R, Singha PK, Gilchrist A, Weinreb PH, Violette SM, Weinberg JM, Saikumar P, Venkatachalam MA.

Proximal tubular epithelial insulin receptor mediates high-fat diet-induced kidney injury.

The role of insulin receptor (IR) activated by hyperinsulinemia in obesity-induced kidney injury is not well understood. We hypothesized that activation of kidney proximal tubule epithelial IR contributes to obesity-induced kidney injury. We administered normal-fat diet (NFD) or high-fat diet (HFD) to control and kidney proximal tubule IR-knockout (KPTIRKO) mice for 4 months.

Proximal Tubular Oxidative Metabolism in Acute Kidney Injury and the Transition to CKD.

The proximal tubule relies on oxidative mitochondrial metabolism to meet its energy needs and has limited capacity for glycolysis, which makes it uniquely susceptible to damage during AKI, especially after ischemia and anoxia. Under these conditions, mitochondrial ATP production is initially decreased by several mechanisms, including fatty acid-induced uncoupling and inhibition of respiration related to changes in the shape and volume of mitochondria. Glycolysis is initially insufficient as a source of ATP to protect the cells and mitochondrial function, but supplementation of tricarboxylic acid cycle intermediates augments anaerobic ATP production, and improves recovery of mitochondrial oxidative metabolism.

Mitochondrial quality control in kidney injury and repair.

Mitochondria are essential for the activity, function and viability of eukaryotic cells and mitochondrial dysfunction is involved in the pathogenesis of acute kidney injury (AKI) and chronic kidney disease, as well as in abnormal kidney repair after AKI. Multiple quality control mechanisms, including antioxidant defence, protein quality control, mitochondrial DNA repair, mitochondrial dynamics, mitophagy and mitochondrial biogenesis, have evolved to preserve mitochondrial homeostasis under physiological and pathological conditions. Loss of these mechanisms may induce mitochondrial damage and dysfunction, leading to cell death, tissue injury and, potentially, organ failure.

ZnO-embedded S-doped g-CN heterojunction: mediator-free Z-scheme mechanism for enhanced charge separation and photocatalytic degradation.

The design of UV-visible light active photocatalysts for organic pollutant removal is a challenging task. Herein, we have developed an LED light active ZnO-embedded S-doped g-CN (SCN) heterojunction by a facile sol-gel assisted calcination method. The heterojunction between ZnO and SCN nanoparticles generates a Z-scheme photocatalyst, which helps to separate the photo-induced charge carriers in the opposite direction, and is beneficial for more visible light absorption for photocatalytic dye degradation.

Statistical Optimization of the Physico-Chemical Parameters for Pigment Production in Submerged Fermentation of 30548.

30548 is a marine-derived pigment producing filamentous fungus, isolated from the La Réunion island, in the Indian Ocean. The objective of this study was to examine and optimize the submerged fermentation (SmF) process parameters such as initial pH (4-9), temperature (21-27 °C), agitation speed (100-200 rpm), and fermentation time (0-336 h), for maximum production of pigments (orange and red) and biomass, using the Box-Behnken Experimental Design and Response Surface Modeling (BBED and RSM). This methodology allowed consideration of multifactorial interactions between a set of parameters.

Pathophysiology of unilateral ischemia-reperfusion injury: importance of renal counterbalance and implications for the AKI-CKD transition.

Unilateral ischemia-reperfusion (UIR) injury leads to progressive renal atrophy and tubulointerstitial fibrosis (TIF) and is commonly used to investigate the pathogenesis of the acute kidney injury-chronic kidney disease transition. Although it is well known that contralateral nephrectomy (CNX), even 2 wk post-UIR injury, can improve recovery, the physiological mechanisms and tubular signaling pathways mediating such improved recovery remain poorly defined. Here, we examined the renal hemodynamic and tubular signaling pathways associated with UIR injury and its reversal by CNX.

Cost-effectiveness analysis of nivolumab for the treatment of squamous cell carcinoma of the head and neck in the United States.

To assess the cost-effectiveness of nivolumab monotherapy for recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) in the US. We constructed a cohort-based partitioned survival model for three health states (progression-free, progressed disease, and death). Using overall survival and progression-free survival data from the nivolumab and investigator's choice (IC) arms of the CheckMate 141 study, the proportion of patients in each health state was estimated by parametric modeling over a 25-year period.

DESI-MSI and METASPACE indicates lipid abnormalities and altered mitochondrial membrane components in diabetic renal proximal tubules.

Introduction: Diabetic kidney disease (DKD) is the most prevalent complication in diabetic patients, which contributes to high morbidity and mortality. Urine and plasma metabolomics studies have been demonstrated to provide valuable insights for DKD. However, limited information on spatial distributions of metabolites in kidney tissues have been reported.

Increased Smad3 and reduced Smad2 levels mediate the functional switch of TGF-β from growth suppressor to growth and metastasis promoter through TMEPAI/PMEPA1 in triple negative breast cancer.

Screening of several TNBC cell lines showed altered Smad2 and Smad3 protein levels compared to normal mammary epithelial cells, suggesting the possibility that it could play an important role in the escape of cancer cells from TGF-β mediated growth inhibition. To assess the functional relevance of these endogenous molecules, Smad2 or Smad3 expression was knocked down individually and assessed their effects on pro-oncogenic properties of TGF-β. Smad3 deficiency reduced growth and invasion capacity of breast cancer cells in comparison to Smad2 which had no effect.