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The ATP responsive P2 purinergic receptors can be subdivided into metabotropic P2X family and ionotropic P2Y family. Among these, P2X3 is a type of P2X receptor which is specifically expressed on nerves, especially on pre-ganglionic sensory fibers. This study investigates whether gefapixant possesses the potential of inhibiting cardiac sympathetic hypersensitivity to protect against cardiac remodeling in the context of myocardial infarction.The Sprague-Dawley rats were divided randomly into three groups: sham group-myocardial infarction group, and myocardial infarction with gefapixant treatment group. Myocardial infarction was induced by left anterior descending branch ligation. The gefapixant solution was intraperitoneally injected each time per day for 7 days and the appropriate dosage of gefapixant was determined according to the results of hematoxylin-eosin (HE) staining and myocardial injury biomarkers. Conditions of cardiac function were assessed by echocardiograph and cardiac fibrosis was evaluated by Western blotting and immunofluorescence staining of collagen I and collagen III. The sympathetic innervation was detected by norepinephrine concentration (pg/mL), in-vivo electrophysiology, and typical sympathetic biomarkers. Inflammatory cell infiltration was shown from immunofluorescence staining and pro-inflammatory signaling pathway activation was checked by immunohistology, quantitative realtime PCR (qPCR) and Western blotting.It was found that gefapixant injection of 10 mg/kg per day had the highest dosage-efficacy ratio. Furthermore, gefapixant treatment improved cardiac pump function as shown by increased LVEF and LVFS, and decreased LVIDd and LVIDs. The expression levels of collagen I and collagen III, and TNF-α were all decreased by P2X3 inhibition. Mechanistically, the decreased activation of nucleotide-binding and oligomerization domain-like receptors family pyrin-domain-containing 3 (NLRP3) inflammasome and subsequent cleavage of caspase-1 which modulated interleukin-1β (IL-1β) and IL-18 level in heart after gefapixant treatment were associated with the suppressed cardiac inflammation.It is suggested that P2X3 inhibition by gefapixant ameliorates post-infarct autonomic nervous imbalance, cardiac dysfunction, and remodeling possibly via inactivating NLRP3 inflammasome.

Carbon dots has becoming one of the most promising fluorescence sensors to determine the trace level of heavy metals in environments because of their advantages in optical properties, response time, and convenient operation procedures. Herein, a novel nitrogen and sulfur co-doped carbon dots (NS-CDs) were prepared though microwave assisted approach using DL-malic acid and allyl thiourea for the first time. Due to the existence of nitrogen and sulfur, the as-prepared NS-CDs exhibited bright blue fluorescence at 430 nm upon 330 nm excitation, with a fluorescence quantum yield of 19.8%. The sensitivity study of NS-CDs against metal ions and organic molecules has approved that the fluorescence could be further quenched by Ce

To investigate microvascular alterations in the Glisson system of biliary atresia (BA) patients after Kasai portoenterostomy (KP) using three-dimensional (3D) virtual histopathology based on X-ray phase-contrast CT (PCCT).Liver explants from BA patients were imaged using PCCT, and 32 subjects were included and divided into two groups: KP (n = 16) and non-KP (n = 16). Combined with histological analysis and 3D visualization technology, 3D virtual histopathological assessment of the biliary, arterial, and portal venous systems was performed. According to loop volume ratio, 3D spatial density, relative surface area, tortuosity, and other parameters, pathological changes of microvasculature in the Glisson system were investigated.In the non-KP group, bile ducts mostly manifested as radial multifurcated hyperplasia and twisted into loops. In the KP group, the bile duct hyperplasia was less, and the loop volume ratio of bile ducts decreased by 13.89%. Simultaneously, the arterial and portal venous systems presented adaptive alterations in response to degrees of bile duct hyperplasia. Compared with the non-KP group, the 3D spatial density of arteries in the KP group decreased by 3.53%, and the relative surface area decreased from 0.088 ± 0.035 to 0.039 ± 0.015 (p.01). Deformed portal branches gradually recovered after KP, with a 2.93% increase in 3D spatial density and a decrease in tortuosity from 1.17 ± 0.06 to 1.14 ± 0.04 (p.01) compared to the non-KP group.3D virtual histopathology via PCCT clearly reveals the microvascular structures in the Glisson system of BA patients and provides key insights into the morphological mechanism of microvascular adaptation induced by biliary tract dredging after KP in BA disease.• 3D virtual histopathology via X-ray phase-contrast computed tomography clearly presented the morphological structures and pathological changes of microvasculature in the Glisson system of biliary atresia patients. • The morphological alterations of microvasculature in the Glisson system followed the competitive occupancy mechanism in the process of biliary atresia.

Ambient fine particulate matter (PM2.5) exposures during pregnancy could lead to adverse birth outcomes, including neurobehavioral development defects. However, limited studies explored the effects and potential epigenetic mechanisms of maternal PM2.5 exposure on offspring spatial memory defects. This study aims to explore the effects and underlying epigenetic mechanisms of maternal concentrated ambient PM2.5 exposure in male mice offspring with spatial memory defects. Pregnant female C57BL/6 mice were exposed daily to concentrated ambient PM2.5 (CAP) or filtered air (FA) throughout gestation, with the concentration of particulates (102.99 ± 78.74 μg/m3) and (2.78 ± 1.19 μg/m3), respectively. Adult male mice offspring were subsequently assessed for spatial learning and memory ability using Morris Water Maze tests and locomotor activities in open field tests. The hippocampus of the male mice offspring was harvested to test mRNA expression and DNA methylation. Results from the probe test of Morris Water Maze showed that the mice offspring in the CAP group had shorter swimming distance travelled in the target quadrant, shorter duration in the target quadrant, and less number of entries into the target quadrant (p 2.5 induced long-lasting spatial memory defects in male mice offspring. The underlying biological mechanism might be mediated by an inflammatory reaction which is regulated by DNA methylation.

In this article, we study the boundedness properties of the averaging operatorStγon Triebel-Lizorkin spaces$$\dot F_{p,q}^\alpha \left( {{\mathbb{R}^n}} \right)$$F˙p,qα(ℝn)for variousp,q. As an application, we obtain the norm convergence rate forStγ(f) on Triebel-Lizorkin spaces and the relation between the smoothness imposed on functions and the rate of norm convergence ofStγis given.

Air pollution exposure is an important environmental risk factor involved in the development of systemic lupus erythematosus (SLE). This study was conducted to investigate the relationships between particulate matter (PM) air pollutants exposure and the risk of SLE admission in Xi'an, China. The records of SLE admission, air pollutants and meteorological data were retrieved from the First Affiliated Hospital of Xi'an Jiaotong University, the Xi'an Environmental Monitoring Station and China Meteorological Data Network, respectively. A distributed lagged nonlinear model combined with Poisson generalized linear regression was used to evaluate the effect of air pollution on SLE admission. Exposure-response curves showed positive associations of PM ≤ 2.5 (PM

Unlike classic spins, quantum magnets are spin systems that interact via the exchange interaction and exhibit collective quantum behaviours, such as fractional excitations. Molecular magnetism often stems from d/f-transition metals, but their spin-orbit coupling and crystal field induce a significant magnetic anisotropy, breaking the rotation symmetry of quantum spins. Thus, it is of great importance to build quantum nanomagnets in metal-free systems. Here we have synthesized individual quantum nanomagnets based on metal-free multi-porphyrin systems. Covalent chains of two to five porphyrins were first prepared on Au(111) under ultrahigh vacuum, and hydrogen atoms were then removed from selected carbons using the tip of a scanning tunnelling microscope. The conversion of specific porphyrin units to their radical or biradical state enabled the tuning of intra- and inter-porphyrin magnetic coupling. Characterization of the collective magnetic properties of the resulting chains showed that the constructed S = 1/2 antiferromagnets display a gapped excitation, whereas the S = 1 antiferromagnets exhibit distinct end states between even- and odd-numbered spin chains, consistent with Heisenberg model calculations.

A large number of pathogenic bioaerosols are generated during the treatment process of wastewater treatment plants (WWTPs), and they can pose potential risks to human health. Therefore, this study systematically analyzed the emission characteristics of Staphylococcus aureus bioaerosols released from an inverted umbrella aeration tank, a microporous aeration tank, and a residual sludge storage yard in a WWTP, and quantitatively evaluated the health risks of four kinds of exposed populations with nasal/oral breathing patterns under optimistic and conservative estimations. The results displayed that the bioaerosol concentration in inverted umbrella aeration tank was higher than that in microporous aeration tank and residual sludge storage yard. Aerosolization ratio in residual sludge storage yard was an order of magnitude lower than that in aeration tanks. Sludge workers were at higher health risks than the other three exposed populations. The health risks of nasal breathers (infection risk: 1.62 × 10

Promoting brown fat-like phenotype in white adipose tissue has been a promising strategy for the treatment of obesity. Vitamin D3 (VD3) has been indicated to affect differentiation of white and brown adipocytes. Nevertheless, its potential mechanism involved in obesity development is unclear. Oil red O staining was utilized to detect lipid formation in 3T3-L1 adipocytes. CKK-8 assay was used for measurement of cell viability. RT-qPCR and western blotting were implemented for expression detection of markers for white adipocyte browning, autophagy- and PI3K/Akt/mTOR/p53 signaling-associated proteins. Immunofluorescence staining was conducted for assessment of autophagy. An obese mouse model was established by high-fat VD deficient diet. VD3 suppressed lipid formation in 3T3-L1 adipocytes. VD3 downregulated markers for white adipocyte browning (PPAR-γ, PGC-1α, UCP1), enhanced autophagy, activated p53 signaling and inactivated PI3K/Akt/mTOR signaling in 3T3-L1 adipocytes and HF-VDD-induced mice. VD3 suppressed HF-VDD-induced weight gain in mice. VD3 inhibits the expression of markers for white adipocyte browning in vitro and in vivo by enhancing autophagy and regulating PI3K/Akt/mTOR/p53 signaling pathway.

Amyotrophic lateral sclerosis (ALS) is one of the most common fatal neurodegenerative diseases in adults. ALS pathogenesis is associated with toxic SOD1 aggregates generated by mutant SOD1. Since autophagy is responsible for the clearance of toxic protein aggregates including SOD1 aggregates, autophagy induction has been considered as a potential strategy for treating ALS. Autophagic signaling is initiated by unc-51 like autophagy activating kinase 1 (ULK1) complex. We previously identified that BL-918 as a specific ULK1 activator, which exerted cytoprotective effect against Parkinson's disease in vitro and in vivo. In this study we investigated whether BL-918 exerted a therapeutic effect against ALS, and characterized its pharmacokinetic profile in rats. In hSOD

Phytoremediation of heavy metal-contaminated sites has been widely used. Nonetheless, the destruction of chloroplasts and plant growth enzymes by heavy metals leads to a low germination rate and high mortality of plants. To address these issues, an experiment was conducted in which plants were grown with (SHC) and without humic acid (SC) in actual Cd-contaminated soil from the site of an industrial pollution source. The results showed that the average germination rates of SC and SHC samples were 94.17% and 98.33%, respectively, and the plant heights were approximately 5 and 7 cm after 42 days of planting, respectively. It was discovered that humic acid (HA) enhanced plant growth by increasing urease and invertase content of the soil. The Shannon index and Venn diagram revealed that SHC had the richer population diversity. High-throughput analysis demonstrated that HA increased the content of plant growth-promoting bacteria in the soil from 5.01 to 34.27%. The experimental results revealed that HA increased microbial activity and diversity, thereby providing a favorable environment for plants to thrive. This study develops an effective method to enhance the phytoremediation performance of heavy metal-contaminated soils.

Offshore oil and gas development plays an important part in the global energy sector. Offshore platforms and flexible pipes are the key equipments in the whole offshore oil and gas development system. Because of the randomness and uncertainty of wave and current loads in the ocean environment, the structural design and mechanical analysis of the marine equipment can be highly complicated. Therefore, this paper reviews the recent works of the theoretical model, numerical simulation, and experimental test in three research areas: hydrodynamic analysis of offshore platforms, structural mechanics analysis of flexible pipe and cable, and monitoring technology of offshore floating structures under marine loads. By analyzing their main research methods and key technical difficulties, this paper provides theoretical basis and technical support for the reliability engineering application of offshore platforms and flexible pipelines. Also, China is relatively backward in the design of marine floating platform, the design, analysis and testing of flexible pipeline and cable, as well as the marine equipment prototype monitoring technology research. Calling for breakthroughs at the earliest possible stage in the above fields, prime research should be focused on and strategic planning should be made to deal with “key areas and stranglehold problems”. It is of great significance for the development of China’s deep-sea energy and resource development of independent technology and on time to achieve the “carbon peak” national strategic objectives.

Tumor mutation burden (TMB) level is identified as a useful predictor in multiple tumors including colon adenocarcinoma (COAD). However, the function of TMB related genes has not been explored previously. In this study, we obtained patients’ expression and clinical data from The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI). TMB genes were screened and subjected to differential expression analysis. Univariate Cox and LASSO analyses were utilized to construct the prognostic signature. The efficiency of the signature was tested by using a receiver operating characteristic (ROC) curve. A nomogram was further plotted to assess the overall survival (OS) time of patients with COAD. In addition, we compared the predictive performance of our signature with other four published signatures. Functional analyses indicated that patients in the low-risk group have obviously different enrichment of tumor related pathways and tumor infiltrating immune cells from that of high-risk patients. Our findings suggested that the ten genes’ prognostic signature could exert undeniable prognostic functions in patients with COAD, which might provide significant clues for the development of personalized management of these patients.

Mechanical sensing Piezo2 channel in primary sensory neurons has been shown contribute to mechanical allodynia in somatic chronic pain conditions. Interstitial cystitis (IC)-associated pain is often triggered by bladder filling, a presentation that mimics the mechanical allodynia. In the present study, we aimed to examine the involvement of sensory Piezo2 channel in IC-associated mechanical allodynia using a commonly employed cyclophosphamide (CYP)-induced IC model rat. Piezo2 channels in dorsal root ganglia (DRGs) was knocked down by intrathecal injections of Piezo2 anti-sense oligodeoxynucleotides (ODNs) in CYP-induced cystitis rats, and mechanical stimulation–evoked referred bladder pain was measured in the lower abdomen overlying the bladder using von Frey filaments. Piezo2 expression at the mRNA, protein, and functional levels in DRG neurons innervating the bladder was detected by RNA-fluorescence in situ hybridization, western blotting, immunofluorescence, and Ca2+ imaging, respectively. We found that Piezo2 channels were expressed on most (> 90%) of the bladder primary afferents, including afferents that express CGRP, TRPV1 and stained with isolectin B4. CYP-induced cystitis was associated with Piezo2 upregulation in bladder afferent neurons at the mRNA, protein, and functional levels. Knockdown of Piezo2 expression in DRG neurons significantly suppressed mechanical stimulation–evoked referred bladder pain as well as bladder hyperactivity in CYP rats compared to CYP rats treated with mismatched ODNs. Our results suggest upregulation of Piezo2 channels is involved in the development of bladder mechanical allodynia and bladder hyperactivity in CYP-induced cystitis. Targeting Piezo2 might be an attractive therapeutic approach for IC-related bladder pain.