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Objective: To investigate the changes in fractional exhaled nitric oxide (FeNO) after treatment and the association between FeNO changes and the prognosis and lung function of children with asthma. Methods: A total of 144 children newly enrolled with non-standardized treatment of asthma were recruited between September 2020 and December 2021. The children were divided into two groups according to the initial FeNO (0 day), and the changes in FeNO after Budesonide/Formoterol Inhalation Powder Mist (B/FIPM) treatment were observed in different subgroups in correlation with future outcomes after 1 year (well controlled or partly controlled) and lung function. Results: The study showed that B/FIPM therapy significantly reduced FeNO levels and eosinophils (EOS) counts, improving pulmonary function (P 0 (72.73 %) than that in the ΔFeNO ≤0 group (53.85 %) (P = 0.042). Conclusion: B/FIPM is effective in reducing FeNO levels and EOS counts and restoring lung function in children with asthma. In addition, post-treatment changes in FeNO were predictive of prognosis and correlated with post-treatment lung function.

Antibiotic resistance is an escalating global health concern, exacerbated by the pervasive presence of antibiotic resistance genes (ARGs) in natural environments. The Yangtze River, the world's third-longest river, traversing areas with intense human activities, presents a unique ecosystem for studying the impact of these genes on human health. Here, we explored ARGs in the Yangtze River, examining 204 samples from six distinct habitats of approximately 6000 km of the river, including free-living and particle-associated settings, surface and bottom sediments, and surface and bottom bank soils. Employing shotgun sequencing, we generated an average of 13.69 Gb reads per sample. Our findings revealed a significantly higher abundance and diversity of ARGs in water-borne bacteria compared to other habitats. A notable pattern of resistome coalescence was observed within similar habitat types. In addition, we developed a framework for ranking the risk of ARG and a corresponding method for calculating the risk index. Applying them, we identified water-borne bacteria as the highest contributors to health risks, and noted an increase in ARG risks in particle-associated bacteria correlating with heightened anthropogenic activities. Further analysis using a weighted ARG risk index pinpointed the Chengdu–Chongqing and Yangtze River Delta urban agglomerations as regions of elevated health risk. These insights provide a critical new perspective on ARG health risk assessment, highlighting the urgent need for strategies to mitigate the impact of ARGs on human health and to preserve the ecological and economic sustainability of the Yangtze River for future human use.

Abstract The world is transitioning into an aging society, a phenomenon that escalates the risk of age‐related diseases, posing a significant threat to human health. Addressing how to delay aging or achieve healthy aging has become an urgent and pivotal issue. Presently, diverse anti‐aging drugs are under development and entering clinical validation stages. However, the absence of specific aging biomarkers has hindered the identification of corresponding targets for diagnosing and treating aging and age‐related diseases. Aptamer, a novel molecular recognition tool, has found broad application in diagnosing and treating various diseases. Additionally, cell‐based selection holds the potential to identify unidentified molecules that could serve as biomarkers for diseases. Recent years have seen a surge in attention towards aging and age‐related diseases, with the application of aptamer in this domain rapidly advancing. Consequently, this review will provide a concise overview of the aging, with a focus on the utilisation of aptamer in aging and age‐related diseases.

Abstract Purpose Numerous clinical studies have explored sodium–glucose cotransporter 2 inhibitor (SGLT2i) in patients with chronic heart failure (CHF), with or without type 2 diabetes mellitus (T2DM), and SGLT2i were proved to significantly reduce CHF hospitalization, cardiovascular death, cardiovascular mortality, all-cause mortality and myocardial infarction in patients with or without T2DM. However, only a limited few have investigated the effects of SGLT-2i on HF disease-specific health status and cardiac function. This meta-analysis aims to assess the effects of SGLT2i on disease-specific health status and cardiac function in CHF patients. Methods A comprehensive search was conducted of trials by searching in PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, and two Chinese databases (CNKI and Wanfang), Clinical Trials ( http://www.clinicaltrials.gov ) were also searched. Results A total of 18 randomized controlled trials (RCTs) involving 23,953 participants were included in the meta-analysis. The effects of SGLT2 inhibitors were compared with control or placebo groups in CHF with or without T2DM. The SGLT2 inhibitors group exhibited a significant reduction in pro b-type natriuretic peptide (NT-proBNP) levels by 136.03 pg/ml (95% confidence interval [CI]: −253.36, − 18.70; P = 0.02). Additionally, a greater proportion of patients in the SGLT2 inhibitors group showed a ≥ 20% decrease in NT-proBNP (RR = 1.45, 95% CI [0.92, 2.29], p = 0.072). However, no statistically significant difference was observed for the effects on B-type natriuretic peptide (BNP). The use of SGLT-2 inhibitors led to a noteworthy improvement in LVEF by 2.79% (95% CI [0.18, 5.39];P = 0.036). In terms of health status, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and 6-minute walk distance, SGLT2 inhibitors led to a significant improvement in KCCQ clinical summary (KCCQ-CS) score (WMD = 1.7, 95% CI [1.67, 1.73], P

In this study, Gd2O3 and Yb2O3 co-doped YSZ (GYYSZ) ceramic coatings were prepared via atmospheric plasma spraying (APS). The GYYSZ ceramic coatings were subjected to heat treatment at different temperatures for 5 h to analyze their high-temperature phase stability and sintering resistance. The thermophysical properties of GYYSZ, YSZ, and composite coatings were compared. Three types of thermal barrier coatings (TBCs) were designed: GYYSZ (TBC-1), YSZ/GYYSZ (TBC-2), and YSZ/Composite/GYYSZ (TBC-3). The failure mechanisms of these three TBCs were investigated. The results indicate that both the powder and the sprayed GYYSZ primarily maintain a homogeneous cubic phase c-ZrO2, remaining stable at 1500 °C after annealing. The sintering and densification of the coatings are influenced by the annealing temperature; higher temperatures lead to faster sintering rates. At 1500 °C, the grain size and porosity of GYYSZ are 4.66 μm and 9.9%, respectively. At 1000 °C, the thermal conductivity of GYYSZ is 1.35 W·m−1 K−1, which is 44% lower than that of YSZ. The thermal conductivity of the composite material remains between 1.79 W·m−1 K−1 and 1.99 W·m−1 K−1 from room temperature to 1000 °C, positioned between GYYSZ and YSZ. In the TBC thermal shock water quenching experiment, TBC-3 demonstrated an exceptionally long thermal shock lifetime of 246.3 cycles, which is 5.8 times that of TBC-1 and 1.8 times that of TBC-2. The gradient coating structure effectively reduces the thermal mismatch stress between layers, while the dense surface microcracks provide a certain toughening effect. Failure analysis of the TBC reveals that TBC-3 exhibits a mixed failure mode characterized by both spallation and localized peeling. The ultimate failure was attributed to the propagation of transverse cracks during the final stage of water quenching, which led to the eventual spallation of the ceramic blocks.

In this study, a series of CoCrFeMnNiSix (x = 0, 0.3, 0.6, 0.9) high-entropy alloys (HEAs) were prepared by suspension melting of cold crucible, annealed at 1000 °C, and then quenched at 900 °C. The changes in the microstructure of the HEAs after the addition of Si were analyzed using X-ray diffraction (XRD), metallographic microscope, scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS), and electron backscatter diffraction (EBSD). The hardness, room-temperature friction, and wear behavior, room-temperature compressive properties, and corrosion resistance of the annealed CoCrFeMnNiSix HEAs were also studied. The results show that when the Si content is 0 and 0.3, the annealed CoCrFeMnNiSix HEA exhibits a single face-centered cubic (FCC) structure. As the silicon content increases, a face-centered orthorhombic (FCO) phase appears. At a Si content of 0.9, a hexagonal close-packed (HCP) phase is observed. After heat treatment, the hardness of the CoCrFeMnNiSix HEAs increases continuously with the addition of Si. The HEA with a Si content of 0.9 achieves the highest hardness of 974.8 ± 30.2 HV. The HEA with a Si content of 0.6 reaches the highest compressive strength and yield strength, which are 1990.3 MPa and 1327.5 MPa. When the Si content is 0.9, the HEA shows the smoothest surface after wear, with the best wear resistance, achieving a value of 0.21 mm−1. In the CoCrFeMnNiSix HEAs after 900 °C heat treatment, the HEA with a Si content of 0.6 exhibits the lowest self-corrosion current density of 0.23 µA/cm2 and the highest pitting potential of 157.65 mV, indicating the best corrosion resistance.

Electric multirotor plant protection unmanned aerial vehicles (UAVs) are widely used in China for efficient and precise plant protection at low altitude for low volumes. Unstructured farmland in China has various types of obstacles, and UAVs usually use a detour path to avoid obstacles due to flight altitude limitations. However, existing UAV spray systems do not spray when in obstacle neighborhoods during obstacle avoidance, resulting in insufficient droplet coverage and reduced plant protection quality in the area. To improve the droplet coverage in obstacle neighborhoods, this article carries out a study of side spray technology with an electric quadrotor UAV, and proposes the design and development of a side spray device. The relationship between the obstacle avoidance path of the UAV and the spray pattern of the side spray device and their effect on droplet coverage in obstacle neighborhoods was explored. An accurate measurement method of the relative position between the UAV and obstacles was proposed. Spray angle calculations and nozzle selection for the side spray device were carried out in conjunction with the relative position. A rotor wind field simulation model was designed based on the lattice Boltzmann method (LBM), and the spatial layout of the side spray device on the UAV was designed based on the simulation results. To explore suitable spray patterns for the side spray device, comparative experiments of droplet coverage in obstacle neighborhoods were carried out under different environments, spray patterns, and flight parameter combinations. The relationship between the flight parameter combinations and the distribution uniformity of droplets and the effective swath width of the side spray device was explored. The experimental results were analyzed by an analysis of variance (ANOVA) and a relationship model was obtained. The results showed that the side spray device can effectively improve droplet coverage in obstacle neighborhoods compared to a device without side spray using the same flight parameter combinations. The effective swath width in obstacle neighborhoods can be increased by a minimum of 6.35%, maximum of 35.32%, and average of 15.25% using the side spray device. The error between the predicted values of the relational model and the field experiment results was less than 15%. The results verify the effectiveness and rationality of the method proposed in this article. This study can provide technical and theoretical references for improving the plant protection quality of UAVs in obstacle environments.

In this study, Mo2NiB2 coatings were prepared by the laser cladding technique and the relationship between coating microstructure and corrosion resistance with cladding power was analyzed. The results showed that Mo2NiB2 was reactively generated in all coatings while Mo2FeB2 and (Fe, Ni) were also present in the coatings due to dilution of the substrate. There was a good metallurgical bond between the coating and the substrate. The white cermet phase and black Fe-rich phase alternated within the coatings. As observed from the surface, the ceramic phase spreads out in a flattened shape and the black Fe-rich phase was present in a large number of pores. Due to the overdilution of the substrate, the volume of the ceramic phase decreased at a power of 800 W and the Fe content within the coating increased. The corrosion resistance of the coatings increased as the laser power increased from 500 to 700 W. Then the corrosion resistance of the coatings decreased at 800 W due to the excess Fe content and the decrease in the relative content of Mo2NiB2 and (Fe, Ni). Mo2NiB2 coating prepared at 700 W has the best corrosion resistance.

Abstract Aim Early mobilization (EM) improves critical illness survivors' clinical outcomes. This study examines ICU quasi‐specialty nurses' EM‐related knowledge, attitudes and practices (KAP). Design This cross‐sectional study was conducted at a provincial ICU specialty nurse training site from 2019 to 2021. KAP data were collected using a self‐report questionnaire. Methods Participants were registered nurses enrolled in the training programme; 485 nurses from 188 hospitals completed the questionnaire. Results Of the participants, 37.7% had EM training, and 30.7% reported their wards performed EM. Median (IQR) scores for knowledge, attitudes and practices were 14.0 (4.0), 47.0 (9.0) and 37.0 (8.0), belonging to medium, high and medium levels. Scores were lowest for EM scope, implementation indicators and out‐of‐bed mobilization. There were significant deviations in KAP scores amongst nurses at different levels of hospitals with EM training and whose departments performed EM. Significant positive correlations between knowledge and practice, and attitude and practice were identified.

The presence of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) in the environment is of great concern to human health. This study developed a new combination of high-frequency electromagnetic field (HEMF) and low-dosage chlorine disinfection to reduce the abundance of extracellular ARG (eARG) sul2 and intracellular ARG (iARG) adeF. The removal efficiencies of sul2 and adeF from sulfamethoxazole- and multidrug-resistant Acinetobacter junii were measured by quantitative PCR (qPCR). Compared to chlorine disinfection alone, the combination of HEMF treatment exhibited significantly improved ARG removal efficiency. The highest removal efficiencies of sul2 and adeF under the combination were 75.7% and 91.4%, respectively. Treatment time and the dosage of chlorine played pivotal roles in the removal efficiency of ARGs via HEMF treatment and chlorine disinfection, respectively. Importantly, a combination of low-dose chlorine with HEMF treatment could serve as a viable alternative to high-dose chlorine disinfection. This work offers essential process parameters for optimizing the elimination of iARGs and eARGs and presents a viable solution for addressing the issue of ARG contamination.

Abstract Background Riverine ecosystems are one of the most important reservoirs of antibiotic resistance genes (ARGs) in the environment, but the occurrence and controlling factors of ARG distribution in different habitats of riverine ecosystems remain poorly understood. In this study, a metagenomic approach was used to characterize ARG types and their abundance in different habitats (rhizosphere soil, surface bulk soil, bottom bulk soil, and sediment) of riverine ecosystems in eastern China. Sampling sites were located along different rivers of eastern China, which are geographically isolated. Differences in bacterial communities, mobile genetic elements (MGEs), pattern and intensity of human activities, climate, and other environmental factors at the sampling sites and habitats were expected to affect ARG occurrence. Results ARGs were observed with high variations in diversity (44–206 subtypes) and abundance (6.85–105.68 ×/Gb). There were significant south-north differences in ARG occurrence in the same habitat, except for surface bulk soil. And the significant difference was found in ARGs among four southern habitats. South–north differences in ARGs of the same habitat were mainly attributed to the combination of different occurrence frequencies and habitat selections of ARGs. Differences in ARG profiles among the four habitats in the south and the north were both mainly attributed to the different occurrence frequencies of ARGs. Bacterial communities and MGEs (Mobile genetic elements) could account for the observed variance in the resistome of riverine ecosystems across eastern China. The co-occurrences of specific ARGs with bacterial communities and MGEs were more frequent at the northern sampling sites than in the south, and co-occurrence patterns (i.e. ARGs and bacterial communities or ARGs and MGEs) varied between the habitats. Moreover, building land in all habitats, except bulk soils, showed significant positive correlations with ARG abundance. Conclusion This study reveals a high variance in the resistome of riverine ecosystems in eastern China and its controlling factors. We appeal to the importance of assessment of ARGs in the riverine ecosystem and the need for future prevention and intervention of ARG spread.

Aiming to address the problems of low working efficiency and high damage rate of high and low roller peeling equipment in the process of fresh corn harvesting in China, this paper theoretically analyzes the mechanical motion process between the peeling device and the corn ear, and a high–low roll peeling structure is proposed. This structure incorporates elastomeric rubber material, a roller segmentation design, and an adjustable spiral frame, and the selection of relevant parameters is given. To determine the optimal operating parameters for the fresh-corn-peeling device, a three-factor, three-level orthogonal test was conducted using the Box–Behnken central grouping method in Design-Expert 12 software. The test factors were peeling roller speed, peeling roller tilt angle, and vibrating plate frequency. The evaluation indices considered were the bract peeling rate (BPR) and the grain breaking rate (GBR). Based on the theoretical analysis results, a test bench for the fresh-corn-ear-peeling device was established and the parameter combination for optimal peeling quality was determined according to the actual work situation. The results show that the impact on the BPR and GBR, from large to small, is in the following order: peeling roller speed, peeling roller tilt angle, and frequency vibration plate. The optimization module was used to optimize the operating parameters and used the following integers to obtain the optimal operating parameter combination: the peeling roller speed was 480 r·min−1; the peeling roller tilt angle was 8°; the vibrating plate frequency was 260 times·min−1; the corresponding BPR was 91.75%, which was 0.66% points lower than the optimal value; and the GBR was 1.55%, which was 0.08% points higher than the optimal value. Notably, this fresh-corn-peeling equipment exhibited superior performance in terms of peeling fracture results compared with standard peeling equipment. Therefore, this study provides valuable technical support for the optimal design and selection of fresh-corn-peeling equipment.

Systemic vascular impairment is the most common complication of diabetes. Advanced glycation end products (AGEs) can exacerbate diabetes-related vascular damage by affecting the intima and media through a variety of mechanisms. In the study, we demonstrated that AGEs and their membrane receptor RAGE could induce the differentiation of EPCs into osteoblasts under certain circumstances, thereby promoting accelerated atherosclerosis. Differentiation into osteoblasts was confirmed by positive staining for DiI-acetylated fluorescently labeled low-density lipoprotein and FITC-conjugated Ulex europaeus agglutinin. During differentiation, expression of receptor for AGE (RAGE) was significantly upregulated. This upregulation was attenuated by transfection with RAGE-targeting small interfering (si)RNA. siRNA-mediated knockdown of RAGE expression significantly inhibited the upregulation of AGE-induced calcification-related proteins, such as runt-related transcription factor 2 (RUNX2) and osteoprotegerin (OPG). Additional experiments showed that AGE induction of EPCs significantly induced ERK, p38MAPK, and JNK activation. The AGE-induced upregulation of osteoblast proteins (RUNX2 and OPG) was suppressed by treatment with a p38MAPK inhibitor (SB203580) or JNK inhibitor (SP600125), but not by treatment with an ERK inhibitor (PD98059), which indicated that AGE-induced osteoblast differentiation from EPCs may be mediated by p38MAPK and JNK signaling, but not by ERK signaling. These data suggested that AGEs may bind to RAGE on the EPC membrane to trigger differentiation into osteoblasts. The underlying mechanism appears to involve the p38MAPK and JNK1/2 pathways, but not the ERK1/2 pathway.

Myelination of neuronal axons in the central nervous system (CNS) by oligodendrocytes (OLs) enables rapid saltatory conductance and axonal integrity, which are crucial for normal brain functioning. Previous studies suggested that different subtypes of oligodendrocytes in the CNS form different types of myelin determined by the diameter of axons in the unit. However, the molecular mechanisms underlying the developmental association of different types of oligodendrocytes with different fiber sizes remain elusive. In the present study, we present the evidence that the intracellular Ca2+ release channel associated receptor (Itpr2) contributes to this developmental process. During early development, Itpr2 is selectively up-regulated in oligodendrocytes coinciding with the initiation of myelination. Functional analyses in both conventional and conditional Itpr2 mutant mice revealed that Itpr2 deficiency causes a developmental delay of OL differentiation, resulting in an increased percentage of CAII+ type I/II OLs which prefer to myelinate small-diameter axons in the CNS. The increased percentage of small caliber myelinated axons leads to an abnormal compound action potentials (CAP) in the optic nerves. Together, these findings revealed a previously unrecognized role for Itpr2-mediated calcium signaling in regulating the development of different types of oligodendrocytes.

A tractor electro-hydraulic hitch system is considered one of the most important systems that play a strategic role in the power transmission and operation depth control of a tractor’s field operation. Its performance directly affects the operation quality of the whole work unit of the tractor. Furthermore, a tractor electro-hydraulic hitch system has gained the interest of many in the agricultural machinery sector because of its stable performance, high production efficiency, good operation quality and its low energy consumption. To fully benefit from the potential of the tractor electro-hydraulic hitch system, it is significant to understand and address the problems and challenges associated with it. This study, therefore, aims to contribute to the development of the tractor electro-hydraulic hitch system by investigating the research methods, technical characteristics and emerging trends in three key aspects that include the tillage depth adjustment method, the tillage depth control algorithm and the core components of the electro-hydraulic hitch system. The characteristics and applicable conditions of the different tillage depth adjustment methods of the electro-hydraulic hitch system were summarized. The realization methods and the control characteristics of the different algorithms were elaborated and discussed for both the PID control algorithm and the intelligent control algorithm. The working characteristics of the core components of the electro-hydraulic hitch system were analyzed based on the hydraulic control valves and sensing elements. The results have shown that the multi-parameter tillage depth adjustment method met the operation quality standard while taking the engine load stability and traction efficiency into account, and it has a greater research significance and value. The working quality can be improved effectively by introducing the intelligent algorithm. In addition, the study of smart valves with built-in sensing elements and how to improve the anti-interference ability of sensing elements, are the aspects that requires further consideration. Aiming to improve the working quality and reduce energy consumption, further research into the tractor electro-hydraulic hitch system is necessary. The results of this comprehensive review provide a reference for the intelligent operation of tractors under the precision agriculture.

An experimental method for preparing high-entropy thin films with gradient changes of alloying elements by magnetron sputtering co-deposition is proposed in this work to evaluate the effect of alloying element composition changes on the properties of non-equal molar ratio high-entropy alloys. The (TiVCr)x-(TaW)1-x binary system thin films were deposited by a magnetron sputtering system with two intermediate alloy targets. The surface morphology, element composition, roughness, and phase structure of the coatings were studied with scanning electron microscope (SEM), energy dispersive X-ray (EDX), X-ray diffractometer (XRD), atomic force microscope (AFM), and transmission electron microscope (TEM). The results show that at x = 0.51, the films had the best mechanical properties under the action of multiple strengthening mechanisms, and the hardness and modulus reached 27.61 GPa and 274.42 GPa, respectively. Due to higher hardness and special surface morphology, the films showed a lower average friction coefficient and had excellent wear resistance with wear rates of 0.34 and 5.01 × 10−9 mm3/(N·mm), respectively. On the other hand, it was found that forming a BCC polycrystalline structure and an amorphous-mixed structure can improve the radiation resistance of the material.

Background. Hyperglycemia plays a vital role in diabetic nephropathy (DN); autophagy and its potential upregulator receptor-interacting protein kinase 2 (RIPK2) are associated with ROS, which play a potential role in regulating NLRP3, and may be involved in inflammation in DN. Aim. In this study, we aimed to explore the mechanisms mediated by RIPK2 in autophagy and the relationship with ROS-NLRP3 of DN, by investigating the levels of RIPK2 and autophagy in glomerular mesangial cells (GMCs) stimulated with high glucose. Material and Methods. GMCs were divided into the following groups: normal group (NC), high glucose group (HG), and RIPK2 siRNA group. RIPK2, LC3, caspase1, and IL-1β levels were measured by western blotting and RT-PCR. Autophagosomes were measured by GFP-RFP-LC3; ROS were detected by DCFH-DA. Results. High glucose upregulated RIPK2 and LC3 in GMCs during short periods (0-12 h) (p

Foreign body removal is a challenging procedure. Firstly we have to identify properly the foreign body and the position of the obstruction. Secondly we have to choose the proper removal equipment and finally the appropriate method of patient ventilation during the procedure. In our case report we present a challenging procedure with the removal of a metallic needle with minimum resources and equipment in a young girl in Djibouti, Africa. Keywords: Foreign body, Bronchoscopy, Biopsy forceps

In this study, high-entropy alloy films, namely, AlCrTaTiZr/AlCrTaTiZr-N, were deposited on the n-type (100) silicon substrate. Then, a copper film was deposited on the high-entropy alloy films. The diffusion barrier performance of AlCrTaTiZr/AlCrTaTiZr-N for Cu/Si connect system was investigated after thermal annealing for an hour at 600 °C, 700 °C, 800 °C, and 900 °C. There were no Cu-Si intermetallic compounds generated in the Cu/AlCrTaTiZr/AlCrTaTiZr-N/Si film stacks after annealing even at 900 °C through transmission electron microscopy (TEM) and atomic probe tomography (APT) analysis. The results indicated that AlCrTaTiZr/AlCrTaTiZr-N alloy films can prevent copper diffusion at 900 °C. The reason was investigated in this work. The amorphous structure of the AlCrTaTiZr layer has lower driving force to form intermetallic compounds; the lattice mismatch between the AlCrTaTiZr and AlCrTaTiZ-rN layers increased the diffusion distance of the Cu atoms and the difficulty of the Cu atom diffusion to the Si substrate.

Background. Sumoylation is extensively involved in the regulation of NF-κB signaling. PIASy, as a SUMO E3 ligase, has been proved to mediate sumoylation of IκB kinase γ (IKKγ) and contribute to the activation of NF-κB under genotoxic agent stimulation. However, the association of PIASy and NF-κB signaling in the pathogenesis of diabetic nephropathy (DN) has not been defined. Methods. Rat glomerular mesangial cells (GMCs) were stimulated by high glucose; siRNA was constructed to silence the expression of PIASy; the expression of PIASy, SUMO isoforms (SUMO1, SUMO2/3), and NF-κB signaling components was analyzed by Western blot; the interaction between IKKγ and SUMO proteins was detected by coimmunoprecipitation; and the release of inflammatory cytokines MCP-1 and IL-6 was assayed by ELISA. Results. High glucose significantly upregulated the expression of PIASy, SUMO1, and SUMO2/3 in a dose- and time-dependent manner (P

Background. Inflammation and fibrosis are the important pathophysiologic processes in diabetic nephropathy (DN). Maresin 1 is a potential anti-inflammatory lipid mediator, which has displayed powerful proresolving activities. Aim. We determine whether maresin 1 has protective effect on mouse glomerular mesangial cells (GMCs) induced by high glucose. Methods. We cultured GMCs stimulated by high glucose and categorized as follows: normal glucose group (5.6 mmol/L), high glucose group (30 mmol/L), mannitol group, maresin 1 intervention group (1, 10, and 100 nmol/L), maresin 1 and normal glucose group, and the N-acetylcysteine (NAC) intervention group (10 μmol/L NAC). After 24 h, the expression of ROS, NLRP3, caspase-1, procaspase-1, IL-1β, and pro-IL-1β was detected by western-blot, RT-PCR, and immunofluorescence. After 48 h, the expression of TGF-β1 and FN was detected by RT-PCR and ELISA. Results. Compared with normal glucose group, the expression of ROS, NLRP3, caspase-1, IL-1β, TGF-β1, and FN increased in high glucose group (P

Although NG2 is known to be selectively expressed in oligodendrocyte precursor cells (OPCs) for many years, its expressional regulation and functional involvement in oligodendrocyte differentiation have remained elusive. Here, we report that the surface-bound NG2 proteoglycan can physically bind to PDGF-AA and enhances PDGF receptor alpha (PDGFRa) activation of downstream signaling. During differentiation stage, NG2 protein is cleaved by A disintegrin and metalloproteinase with thrombospondin motifs type 4 (Adamts4), which is highly upregulated in differentiating OPCs but gradually downregulated in mature myelinating oligodendrocytes. Genetic ablation of Adamts4 gene impedes NG2 proteolysis, leading to elevated PDGFRa signaling but impaired oligodendrocyte differentiation and axonal myelination in both sexes of mice. Moreover, Adamts4 deficiency also lessens myelin repair in adult brain tissue following Lysophosphatidylcholine-induced demyelination. Thus, Adamts4 could be a potential therapeutic target for enhancing oligodendrocyte differentiation and axonal remyelination in demyelinating diseases. [ABSTRACT FROM AUTHOR]