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Abstract Background Renal fibrosis significantly contributes to the progressive loss of kidney function in chronic kidney disease (CKD), with alternatively activated M2 macrophages playing a crucial role in this progression. The serum succinate level is consistently elevated in individuals with diabetes and obesity, both of which are critical factors contributing to CKD. However, it remains unclear whether elevated succinate levels can mediate M2 polarization of macrophages and contribute to renal interstitial fibrosis. Methods Male C57/BL6 mice were administered water supplemented with 4% succinate for 12 weeks to assess its impact on renal interstitial fibrosis. Additionally, the significance of macrophages was confirmed in vivo by using clodronate liposomes to deplete them. Furthermore, we employed RAW 264.7 and NRK-49F cells to investigate the underlying molecular mechanisms. Results Succinate caused renal interstitial macrophage infiltration, activation of profibrotic M2 phenotype, upregulation of profibrotic factors, and interstitial fibrosis. Treatment of clodronate liposomes markedly depleted macrophages and prevented the succinate-induced increase in profibrotic factors and fibrosis. Mechanically, succinate promoted CTGF transcription via triggering SUCNR1-p-Akt/p-GSK3β/β-catenin signaling, which was inhibited by SUCNR1 siRNA. The knockdown of succinate receptor (SUCNR1) or pretreatment of anti-CTGF(connective tissue growth factor) antibody suppressed the stimulating effects of succinate on RAW 264.7 and NRK-49F cells. Conclusions The causative effects of succinate on renal interstitial fibrosis were mediated by the activation of profibrotic M2 macrophages. Succinate-SUCNR1 played a role in activating p-Akt/p-GSK3β/β-catenin, CTGF expression, and facilitating crosstalk between macrophages and fibroblasts. Our findings suggest a promising strategy to prevent the progression of metabolic CKD by promoting the excretion of succinate in urine and/or using selective antagonists for SUCNR1.

Objective: To assess prevalence, clinical characteristics, and risk factors associated with low flow state (LFS) in a multiethnic population with normal left ventricular ejection fraction (LVEF). Patients and Methods: The study included 4398 asymptomatic participants undergoing cardiac magnetic resonance from July 17, 2000, to August 29, 2002. Left ventricular (LV) mass, volume, and myocardial contraction fraction were assessed. Low flow state was defined as stroke volume index (SVi of

Objective: To assess the prevalence of low-flow state (LFS) with left ventricular (LV) stroke volume index of less than 35 mL/m2 and the demographics, clinical and echocardiographic characteristics associated with LV remodeling and function in a Hispanic/Latino population. Participants and Methods: The study included 1346 asymptomatic participants from the Hispanic Community Health Study/Study of Latinos with normal LV ejection fraction (≥55%) and no valvular heart disease. LV volume, mass and left atrial volume, LV ejection fraction, global longitudinal strain, and myocardial contraction fraction were measured by echocardiography. The participants were divided into LFS or normal flow state (NFS: stroke volume index ≥35 mL/m2). Demographics, clinical and echocardiographic characteristics, and measures of LV remodeling and function were compared between the LFS and NFS groups. Results: The prevalence of LFS was 41%. In comparison with NFS, the LFS had lower LV mass index (77.2±0.96 g/m2 vs 84.6±0.86 g/m2; P

Intestinal mucositis is a clinically related adverse reaction of antitumor treatment. Majority of patients receiving high-dose chemical therapy, radiotherapy, and bone-marrow transplant suffer from intestinal mucositis. Clinical manifestations of intestinal mucositis mainly include pain, body-weight reduction, inflammatory symptom, diarrhea, hemoproctia, and infection, which all affect regular nutritional input and enteric function. Intestinal mucositis often influences adherence to antitumor treatment because it frequently restricts the sufferer’s capacity to tolerate treatment, thus resulting in schedule delay, interruption, or premature suspension. In certain circumstances, partial and general secondary infections are found, increasing the expenditures on medical care and hospitalization. Current methods of treating intestinal mucositis are provided, which do not always counteract this disorder. Against this background, novel therapeutical measures are extremely required to prevent and treat intestinal mucositis. Plant-derived natural compounds have lately become potential candidates against enteric injury ascribed to the capacity to facilitate mucosal healing and anti-inflammatory effects. These roles are associated with the improvement of intestinal mucosal barrier, suppression of inflammatory response and oxidant stress, and modulation of gut microflora and immune system. The present article aims at systematically discussing the recent progress of plant-derived natural compounds as promising treatments for intestinal mucositis.

Phosphate (Pi) is one of the basic necessities required for sustenance of life and its metabolism largely relies on excretory function of the kidney, a process chiefly under the endocrine control of bone-derived fibroblast growth factor 23 (FGF23). However, knowledge gap exists in understanding the regulatory loop responsible for eliciting phophaturic response to Pi treatment. Here, we reported a novel role of (pro)renin receptor (PRR) in mediating phosphaturic response to Pi treatment via upregulation of FGF23 production. Male Sprague-Dawley rats were pretreated for 5 days via osmotic pump-driven infusion of a PRR antagonist PRO20 or vehicle, and then treated with high Pi (HP) solution as drinking fluid for the last 24 h. PRO20 reduced HP-induced Pi excretion by 42%, accompanied by blunted upregulation of circulating FGF23 and parathyroid hormone (PTH) and downregulation of renal Na/Pi-IIa expression. In cultured osteoblast cells, exposure to HP induced a 1.56-fold increase in FGF23 expression, which was blunted by PRO20 or siRNA against PRR. Together, these results suggest that activation of PRR promotes phosphaturic response through stimulation of FGF23 production and subsequent downregulation of renal Na/Pi-IIa expression.

Aiming at the problem of wind turbine blades' icing, a carbon nanotube composite photothermal coating with both active deicing and passive anti-icing properties was prepared by the spin-coating method. The results indicate that the lubricating coating doped with carbon nanotubes can effectively delay freezing time and reduce ice adhesion strength. The spin-coated 6-layer coating can achieve the best photothermal conversion performance and consume relatively few nanomaterials to maximize the capture of energy in near-infrared light. Under the irradiation of near-infrared light (808 nm), the surface temperature of the coating can reach 97.1°C, which has good photothermal conversion performance. The antifrosting ability of carbon nanotube nanocomposite photothermal coating is related to the content of lubricating oil, and the defrosting performance is related to the content of carbon nanotubes in the coating. Adopting the lubrication-photothermal synergistic deicing method can greatly shorten the deicing time, which is compared with only using photothermal deicing from 392 s to 51 s.

Herein the reaction mechanism and the origin of stereoselectivity of asymmetric hydrogenation of oximes to hydroxylamines catalyzed by the cyclometalated iridium (III) complexes with chiral substituted single cyclopentadienyl ligands (Ir catalysts A1 and B1) under acidic condition were unveiled using DFT calculations. The catalytic cycle for this reaction consists of the dihydrogen activation step and the hydride transfer step. The calculated results indicate that the hydride transfer step is the chirality-determining step and the involvement of methanesulfonate anion (MsO−) in this reaction is of importance in the asymmetric hydrogenation of oximes catalyzed by A1 and B1. The calculated energy barriers for the hydride transfer steps without an MsO− anion are higher than those with an MsO− anion. The differences in Gibbs free energies between TSA5−1fR/TSA5−1fS and TSB5−1fR/TSB5−1fS are 13.8/13.2 (ΔΔG‡ = 0.6 kcal/mol) and 7.5/5.6 (ΔΔG‡ = 1.9 kcal/mol) kcal/mol for the hydride transfer step of substrate protonated oximes with E configuration (E−2a−H+) with MsO− anion to chiral hydroxylamines product R−3a/S−3a catalyzed by A1 and B1, respectively. According to the Curtin–Hammet principle, the major products are hydroxylamines S−3a for the reaction catalyzed by A1 and B1, which agrees well with the experimental results. This is due to the non-covalent interactions among the protonated substrate, MsO− anion and catalytic species. The hydrogen bond could not only stabilize the catalytic species, but also change the preference of stereoselectivity of this reaction.

BackgroundCardiac conduction disturbance requiring new permanent pacemaker implantation (PPI) is an important complication of TAVR that has been associated with increased mortality. It is extremely challenging to optimize the valve size alone to prevent a complete atrioventricular block (AVB).MethodsIn this study, we randomly took 48 patients who underwent TAVR and had been followed for at least 2 years to assess the risk of AVB. CT images of 48 patients with TAVR were analyzed using three-dimensional (3D) anatomical models of the aortic valve apparatus. The stresses were formulated according to loading force and tissue properties. Support vector regression (SVR) was used to model the relationship between AVB risk and biomechanical stresses. To avoid AVB, overlapping regions on the prosthetic valve where AV bundle passes will be removed as cylindrical sector with the angle θ. Thus, the optimization of the valve shape will be predicted with the joint optimization of the θ and valve size R.ResultsThe average AVB risk prediction accuracy was 83.33% in the range from 0.8–0.85 with 95% CI for all cases; specifically, 85.71% for Group A (no AVB), and 80.0% for Group B (undergoing AVB after the TAVR).ConclusionsThis model can estimate the optimal valve size and shape to avoid the risk of AVB after TAVR. This optimization may eliminate the excessive stresses to keep the normal function of both AV bundle and valve leaflets, leading to a favorable clinical outcome. The combination of biomechanical properties and machine learning method substantially improved prediction of surgical results.

Aortic regurgitation as a severe complication of transcatheter aortic valve replacement (TAVR) is usually due to the aortic valve leaflets that carry severity and inhomogeneous distribution of the calcification. However, it is difficult to precisely simulate the post-procedural biomechanical behavior on aortic tissue. This paper presents and validates a reliable system to predict which aortic stenosis patients may suffer aortic regurgitation after TAVR and to identify the best fit for TAVR valve. We randomly chose 22 patients (12 patients without regurgitation and 10 patients have regurgitation) who had been followed for at least 2 years after TAVR. An elastic model is designed to characterize the biomechanical behavior of the aortic tissue for each patient. After calculating the loading force on the tissue, the finite-element method (FEM) is applied to calculate the stresses of each tissue node. The support vector regression (SVR) method is used to model the relationship between the stress information and the risk of aortic regurgitation. Therefore, the risk of regurgitation and the optimal valve size can be predicted by this integrated model prior to the procedure. Leave-one-out cross-validation is implemented to assess the accuracy of our prediction. As a result, the mean prediction accuracy is 90.9% for all these cases, demonstrating the high value of this model as a decision-making assistant for pre-procedural planning of patients who are scheduled to undergo intervention. This method combines a bio-mechanical and machine learning approach to create a procedural planning tool that may support the clinical decision in the future.

To investigate whether people can implicitly learn regularities in a social context, we developed a new implicit sequence learning task combining elements from classic false belief and serial reaction time tasks. Participants learned that protagonists were offered flowers at four locations. The protagonists' beliefs concerning the flowers were true or false, depending on their orientation, respectively, toward the scene (so that the flowers could be seen) or away from it. Unbeknown to the participants, there was a fixed belief-related sequence involving three dimensions (identity of the two protagonists, true-false belief orientation held by the protagonists, and flower location as believed by the protagonists). Participants had to indicate as fast as possible where the flowers were located (Experiment 1), or how many flowers were given (Experiment 2) according to the protagonists. Experiment 1 combined perceptual and motor processes (as both the belief-related sequence and motor responses referred to location), whereas Experiment 2 unconfounded the sequence and motor responses, allowing to investigate pure perceptual implicit learning. For reasons of comparison, two non-social conditions were created in Experiment 2 by replacing the protagonists with two non-social objects—colored cameras or shapes. Results revealed significant implicit sequence learning of all belief-related dimensions in Experiment 1, and of true-false belief orientation in Experiment 2, even without a motor confound. Importantly, there were faster reaction times and stronger sequence learning effects in the social than in the non-social conditions. The present findings demonstrate for the first time that people are able to implicitly learn belief-related sequences.

This study provides the first genetic characterization of the gypsy moth from China (Lymantriadispar), one of the most recognized pests of forests and ornamental trees in the world. We assessed genetic diversity and structure in eight geographic populations of gypsy moths from China using five polymorphic Inter simple sequence repeat markers, which produced reproducible banding patterns. We observed 102 polymorphic loci across the 176 individuals sampled. Overall genetic diversity (Nei's, H) was 0.2357, while the mean genetic diversity within geographic populations was 0.1845 ± 0.0150. The observed genetic distance among the eight populations ranged from 0.0432 to 0.1034. Clustering analysis (using an unweighted pair-group method with arithmetic mean and multidimensional scaling), revealed strong concordance between the strength of genetic relationships among populations and their geographic proximity. Analysis of molecular variance demonstrated that 25.43% of the total variability (F ST = 0.2543, P < 0.001) was attributable to variation among geographic populations. The results of our analyses investigating the degree of polymorphism, genetic diversity (Nei's and Shannon) and genetic structure, suggest that individuals from Hebei may be better able to adapt to different environments and to disperse to new habitats. This study provides crucial genetic information needed to assess the distribution and population dynamics of this important pest species of global concern.

Chronic spinal cord compression (CSCC) is induced by disc herniation and other reasons, leading to movement and sensation dysfunction, with a serious impact on quality of life. Spontaneous disc herniation rarely occurs in rodents, and therefore establishing a chronic spinal cord compression (CSCC) animal model is of crucial importance to explore the pathogenesis and treatment of CSCC. The absence of secreted protein, acidic, and rich in cysteine (SPARC) leads to spontaneous intervertebral disc degeneration in mice, which resembles human disc degeneration. In this study, we evaluated whether SPARC-null mice may serve as an animal model for CSCC. We performed rod rotation test, pain threshold test, gait analysis, and Basso Mouse Scale score. Our results showed that the motor function of SPARC-null mice was weakened, and magnetic resonance images revealed compression at different spinal cord levels, particularly in the lumbar segments. Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes, activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype; it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway. Notably, these findings are characteristics of CSCC. Therefore, we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.