Search

Background: Microglia, the main innate immune cells in the central nervous system, are key drivers of neuroinflammation, which plays a crucial role in the pathogenesis of neurodegenerative diseases. The Sin3/histone deacetylase (HDAC) complex, a highly conserved multiprotein co-repressor complex, primarily performs transcriptional repression via deacetylase activity; however, the function of SDS3, which maintains the integrity of the complex, in microglia remains unclear. Methods: To uncover the regulatory role of the transcriptional co-repressor SDS3 in microglial inflammation, we used chromatin immunoprecipitation to identify SDS3 target genes and combined with transcriptomics and proteomics analysis to explore expression changes in cells following SDS3 knocking down. Subsequently, we validated our findings through experimental assays. Results: Our analysis revealed that SDS3 modulates the expression of the upstream kinase ASK1 of the p38 MAPK pathway, thus regulating the activation of signaling pathways and ultimately influencing inflammation. Conclusions: Our findings provide important evidence of the contributions of SDS3 toward microglial inflammation and offer new insights into the regulatory mechanisms of microglial inflammatory responses. [ABSTRACT FROM AUTHOR]

Yaks live in the Qinghai-Tibet Plateau for a long time where oxygen is scarce, but can ensure the smooth development of testis and spermatogenesis. The key lies in the functional regulation of the Sertoli cells under hypoxia. In this study, we sequenced yak Sertoli cells cultured in normal oxygen concentration (Normoxia) and treated with low oxygen concentration (Hypoxia) by whole transcriptomics, and screened out 194 differentially expressed mRNAs (DEmRNAs), 934 differentially expressed LncRNAs (DELncRNAs) and 129 differentially expressed miRNAs (DEmiRNAs). GO and KEGG analysis showed that these differential genes were mainly concentrated in PI3K-AKT, MAPK, RAS, and other signaling pathways, and were associated with glucose metabolism, tight junction, steroid hormone synthesis, cell fusion, and immunity of yak Sertoli cells. We constructed the gene interaction network of yak Sertoli cells in hypoxia and screened out the relationship pairs related to glucose metabolism and tight junction. The results suggested that the changes in energy metabolism, tight junction, and immune regulation of yak Sertoli cells under hypoxia might provide favorable conditions for spermatogenesis. This study provides data for further study on the role of non-coding RNA in testis development and spermatogenesis of yak. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) is a serious disease that poses a significant threat to the pig industry. This study focused on analyzing the Spike protein of PEDV, which harbors crucial antigenic determinants, in identifying dominant epitopes. Immunoinformatics tools were used to screen for B-cell, CD4+ and CD8+ predominance epitopes. These epitopes were then connected to the N-terminal of ferritin to form a self-assembled nanoparticle vaccine. Various physical and chemical properties of the candidate vaccine were analyzed, including secondary structure prediction, tertiary structure modeling, molecular docking, immune response simulation and computer cloning. The results demonstrated that the candidate vaccine was antigenic, soluble, stable, non-allergic, and formed a stable complex with the target receptor TLR-3. Immune simulation analysis showed that the candidate vaccine effectively stimulated both cellular and humoral reactions, leading to increased related cytokines production. Furthermore, efficient and stable expression of the candidate vaccine was achieved through reverse translation in the Escherichia coli K12 expression system following codon optimization and in silico cloning. The developed nanoparticle candidate vaccine in this study holds promise as an effective PEDV vaccine candidate, offering a new approach for the research, development and improvement of vaccines targeting porcine enteric diarrhea coronavirus. [ABSTRACT FROM AUTHOR]

316 L steel-based human implants play an important role in the biomedical field. In order to address the problem of immune rejection of 316 L steel-based human implants and further improve the machining efficiency, the surface roughness (SR) and hydrophilicity of 316 L workpieces are improved by electrical discharge machining milling (EDM-milling) instead of die-sinking electrical discharge machining (EDM) and by the incorporation of nano hydroxyapatite (NHAP) powder into the dielectric. The effects of powder concentration of NHAP, reference voltage, peak current, pulse width, and pulse interval on the material removal rate (MRR), electrode wear rate (EWR), SR, and contact angle (CA) of 316 L workpiece processed by powder mixed EDM-milling with NHAP (NHAP-PMEDM-milling) are investigated by single-factor experiment, and comparisons are done with the powder mixed die-sinking electrical discharge machining with NHAP (NHAP-PMEDM). According to the results, the MRR, EWR, SR, and CA of 316 L by NHAP-PMEDM-milling are varied regularly with the variation of experiment parameters. The addition of NHAP powder into deionized water (DW) can reduce the CA of the surface of 316 L steel workpiece to a great extent, with a maximum reduction of 27.9%, while affecting MRR, EWR, and SR very little. In addition, NHAP-PMEDM-milling can increase MRR by 115.5% and reduce EWR, SR, and CA by 43.2%, 13.2%, and 15.9%, respectively, compared with NHAP-PMEDM. [ABSTRACT FROM AUTHOR]

This study examined the impact of integrating virtual science inquiry activities with Predict-Observe-Explain (POE) teaching strategies on 5th graders' understanding of science concepts and epistemic beliefs in science. A cohort of 80 5th graders (mean age of 12 years old, 40 boys and 40 girls) from a public primary school in North China took part in the research. The data collected encompassed pre-test and post-test results on understanding of science concepts and epistemic beliefs, along with students' behavioral data during virtual science inquiry. The findings demonstrated that integrating virtual science inquiry activities with POE strategies increased students' understanding of science concepts and epistemic beliefs in science. Furthermore, notable differences were found in observation time and inquiry strategy between high and low achievers, while significant distinctions in page time allocation and page navigation behavior were evident between boys and girls. The results provided empirical support for enhancing the implementation of virtual science inquiry activities in primary school science learning. [ABSTRACT FROM AUTHOR]

Pollution from mineral exploitation is an important risk factor affecting surface water environment in mineral regions. It is urgent to construct a simple and accurate model to assess the surface water pollution risk from mineral exploitation in the regional scale. Thus, taking a mining province namely Liaoning in northeastern China as the study area, we proposed a framework to simulate the transport process of pollutants from mineral exploitation points to the surrounding surface water based on the "source-sink" theory. In our framework, we adopted the regional growth method (RGM) to extract the potential polluted water area as the certain "sink" considering the influence of the topography, and then applied Minimum Cumulative Resistance (MCR) model to assess the surface water pollution risk from mineral exploitation. The results revealed that: (1) 9.5% of the water areas were located at the potential impact area of MEPs. (2) The total value of resistance surface in Liaoning is relatively low, and gradually decreased from west to east. (3) MEPs in Liaoning had a high risk and seriously threatened the surface water environment, among 2125 MEPs, 733 MEPs (32.99%) were assessed as extremely high risk level, and about 35% of the MEPs were distributed within 10KM buffer zone of surface water. (4) Water pollution risk of MEPs in Dalian, Tieling, Fuxin and Dandong need to be emphasized. (5) Compared to previous studies, we considered the topographical influence before applying MCR model directly, so the results of water pollution risk were more reliable. This study provides a methodological support and scientific reference for the water environment protection and regional sustainable development. [ABSTRACT FROM AUTHOR]

Cold-formed thick-walled steel members have a higher bearing capacity and wider applicability in the mid-rise buildings in comparison with the widely-used cold-formed thin-walled steel framing walls in low-rise buildings. To avoid the shortcomings of cold-forming effect, a structure with hinged or semi-rigid joint steel frame using cold-formed thick-walled steel and cold-formed thin-walled steel framing shear wall is one reasonable choices, and it will be very helpful to simplify the on-site assembling processes. In this paper, a cross-shaped joint with adjustable stiffness was proposed, and better seismic performance was investigated and confirmed by tests. By increasing the thickness of the web plates of the cross-shaped joint, the bearing capacity, stiffness, and ductility of the joint can be significantly improved, and the buckling deformation of the web plate will be reduced. Moreover, a strengthening stiffener, Type 2 proposed in the paper, has a significantly effect on the cross-shaped joint for seismic damage and intact specimens. Using ANSYS software and the SOLID185 element, a finite element model was established. With the increasing thickness of the end plate of the stiffener Type 2, both the stiffness and bearing capacity of the cross-shaped joint can be significantly increased. [ABSTRACT FROM AUTHOR]

GJB2 gene mutations are the most common causes of autosomal recessive non-syndromic hereditary deafness. For individuals suffering from severe to profound GJB2-related deafness, cochlear implants have emerged as the sole remedy for auditory improvement. Some previous studies have highlighted the crucial role of preserving cochlear neural components in achieving favorable outcomes after cochlear implantation. Thus, we generated a conditional knockout mouse model (Cx26-CKO) in which Cx26 was completely deleted in the cochlear supporting cells driven by the Sox2 promoter. The Cx26-CKO mice showed severe hearing loss and massive loss of hair cells and Deiter's cells, which represented the extreme form of human deafness caused by GJB2 gene mutations. In addition, multiple pathological changes in the peripheral auditory nervous system were found, including abnormal innervation, demyelination, and degeneration of spiral ganglion neurons as well as disruption of heminodes in Cx26-CKO mice. These findings provide invaluable insights into the deafness mechanism and the treatment for severe deafness in Cx26-null mice. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) stress seriously affects cucumber growth, yield, and quality. Melatonin (MT) can enhance plant resistance to abiotic stresses. However, studies on the mechanism of MT in enhancing plant resistance are limited. To better understand the underlying physiological and molecular mechanisms, the antioxidant defenses, photosynthesis, and transcriptome profiles of cucumber were analyzed under different growth conditions. The results demonstrated that exogenous MT significantly alleviated the Cd-induced damages to cucumber seedlings. Compared with Cd treatment, MT + Cd treatment enhanced antioxidant enzyme activities, suppressed ROS production, and improved photosynthesis in cucumber seedlings. Intriguingly, the scavenging or inhibition of hydrogen peroxide and nitric oxide reversed the positive effects of melatonin described above. RNA-seq identified 1299 differentially expressed genes in MD (MT + Cd) _vs_ D (Cd). Further detailed analyses suggested that MT-regulated genes are mainly related to photosynthesis, membrane lipid peroxidation, and plant hormone metabolism. In addition, some transcription factors and heavy metal transporters were involved in MT-induced Cd tolerance in cucumber seedlings. The results laid the foundation for further elucidation of the mechanism of exogenous MT-mediated Cd tolerance in cucumber and provided a theoretical reference for the future utilization of melatonin to improve Cd tolerance in cucumber. [ABSTRACT FROM AUTHOR]

Landscape stability is a paramount concern within the field of landscape ecology. Indices of landscape patterns not only facilitate an effective analysis of land use transformations but also delve into the mechanisms of landscape disturbances across various spatial and temporal dimensions. Utilizing land use data spanning from 2014 to 2022 for the Shibing and Libo-Huanjiang South China Karst (SCK) World Heritage Sites (WHSs), this study delves into the landscape dynamics of these areas over the past 8 years. This investigation employs landscape pattern indices and a moving window technique to construct a landscape stability evaluation model, incorporating indices such as the Contagion Index, Patch Density, and Total Edge Contrast. Moreover, the study employs Moran's I, a spatial autocorrelation index, to scrutinize the shifts in geographical heterogeneity of landscape stability within the said period. The findings reveal: (1) Between 2014 and 2022, the landscape patterns of the Shibing and Libo-Huanjiang WHSs have undergone significant transformations, with Woodland emerging as the predominant landscape type and its area exhibiting an upward trend in recent years. (2) The level of fragmentation within the research area has decreased, landscape diversity has diminished, and the aggregation index has risen, according to the landscape pattern indices from 2014 to 2022, indicating that conservation measures have significantly influenced the evolution of landscape patterns. (3) Throughout most of the study period, landscape stability predominantly remained at a relatively stable level, albeit with noticeable fluctuations in years heavily impacted by human activities. (4) The areas of high-high agglomeration and the hotspots of the heritage sites were primarily concentrated within the core zones of these sites, suggesting focused areas of conservation and landscape integrity. [ABSTRACT FROM AUTHOR]

Exploring the method for rational design of hierarchical structures such as hollow, sphere, and core–shell structures is a crucial challenge for enhancing the electrochemical performance of supercapacitor electrodes. In this study, we demonstrate a facile method for controllable preparation of hydrangea-shaped CoAl-LDHs/CoF2 composite and used as a positive electrode for supercapacitor. A series of contrast tests are performed to select optimal experiment condition. CoAl-LDHs obtained at a metal ratio of 2:1, reacting 8 h with the addition of NH4F, display optimal performance associated with the hierarchical structure, where NH4F plays a vital role in regulating this uniform generation process. The fabricated working electrode shows a high specific capacitance of 827.8 Fg−1, with excellent capacitance retention of 62.8% after current density increases ten times. At last, an asymmetric supercapacitor using C2A1-8 h sample as positive electrode and activated carbon as negative electrode is assembled and delivers an outstanding energy density of 53.7 Wh kg−1 at a power density of 239.9 kW kg−1, and energy density reaches 27.8 Wh kg−1 at maximum power density of 12,000 W kg−1, indicating C2A1-8 h is a potential candidate for energy storage and conversion systems. [ABSTRACT FROM AUTHOR]

A complication of pediatric systemic lupus erythematosus (pSLE) is immune thrombocytopenia (ITP). Although corticosteroids and immunoglobulins are frequently used as preliminary treatments, some patients do not respond to them. Rituximab has been reported to be safe and effective in the treatment of pSLE complicated with refractory ITP. Research is currently underway to determine the optimal rituximab dose for these individuals. We report a case of a child with SLE-associated ITP (SLE-ITP) who was successfully treated with rituximab. Rituximab is likely the most viable therapeutic option for refractory SLE-ITP. Furthermore, a comprehensive review of the relevant literature was performed and a concise overview of the pathogenesis and available treatment modalities for pediatric patients diagnosed with SLE and concurrent ITP was provided. [ABSTRACT FROM AUTHOR]

Lysine lactylation (Kla) links metabolism and gene regulation and plays a key role in multiple biological processes. However, the regulatory mechanism and functional consequence of Kla remain to be explored. Here, we report that HBO1 functions as a lysine lactyltransferase to regulate transcription. We show that HBO1 catalyzes the addition of Kla in vitro and intracellularly, and E508 is a key site for the lactyltransferase activity of HBO1. Quantitative proteomic analysis further reveals 95 endogenous Kla sites targeted by HBO1, with the majority located on histones. Using site-specific antibodies, we find that HBO1 may preferentially catalyze histone H3K9la and scaffold proteins including JADE1 and BRPF2 can promote the enzymatic activity for histone Kla. Notably, CUT&Tag assays demonstrate that HBO1 is required for histone H3K9la on transcription start sites (TSSs). Besides, the regulated Kla can promote key signaling pathways and tumorigenesis, which is further supported by evaluating the malignant behaviors of HBO1- knockout (KO) tumor cells, as well as the level of histone H3K9la in clinical tissues. Our study reveals HBO1 serves as a lactyltransferase to mediate a histone Kla-dependent gene transcription. The regulatory mechanism and functional consequence of lysine lactylation remain to be explored. Here, the authors identify HBO1 as a lysine lactyltransferase and suggest a potential role of HBO1 in tumorigenesis through H3K9la-mediated transcription regulation. [ABSTRACT FROM AUTHOR]

This research aimed to investigate effects of different yeast culture (YC) levels on in vitro fermentation characteristics and bacterial and fungal community under high concentrate diet. A total of 5 groups were included in the experiment: control group without YC (CON), YC1 (0.5% YC proportion of substrate dry matter), YC2 (1%), YC3 (1.5%) and YC4 (2%). After 48 h of fermentation, the incubation fluids and residues were collected to analyze the ruminal fermentation parameters and bacterial and fungal community. Results showed that the ruminal fluid pH of YC2 and YC4 groups was higher (P < 0.05) than that of CON group. Compared with CON group, the microbial protein, propionate and butyrate concentrations and cumulative gas production at 48 h of YC2 group were significantly increased (P < 0.05), whereas an opposite trend of ammonia nitrogen and lactate was observed between two groups. Microbial analysis showed that the Chao1 and Shannon indexes of YC2 group were higher (P < 0.05) than those of CON group. Additionally, YC supplementation significantly decreased (P < 0.05) Succinivibrionaceae_UCG-001, Streptococcus bovis and Neosetophoma relative abundances. An opposite tendency of Aspergillus abundance was found between CON and YC treatments. Compared with CON group, the relative abundances of Prevotella, Succiniclasticum, Butyrivibrio and Megasphaera elsdenii were significantly increased (P < 0.05) in YC2 group, while Apiotrichum and unclassified Clostridiales relative abundances were decreased (P < 0.05). In conclusion, high concentrate substrate supplemented with appropriate YC (1%) can improve ruminal fermentation and regulate bacterial and fungal composition. [ABSTRACT FROM AUTHOR]

Nitrogen-containing disinfection by-products (N-DBPs) produced in the process of drinking water disinfection are widely concerning due to the high cytotoxicity and genotoxicity. It is due to the difficulty of natural degradation of N-DBPs in water and the fact that conventional treatment systems do not effectively treat N-DBPs in drinking water. In this study, N-nitrosopyrrolidine (NPYR) in water was electrocatalytically degraded by a three-dimensional electrode reactor (3DER). This system applied graphite plates as anode and cathode. The granular activated carbon (GAC) was used as third electrode. The degradation of NPYR using a continuous flow three-dimensional electrode reactor was investigated by examining the effects of flow rate, current density, electrolyte concentration, and pollutant concentration on the degradation efficiency, energy consumption, and reaction kinetics of GAC particle electrodes. The results showed that the optimal operating conditions were flow rate = 0.45 mL/min, current density = 6 mA/cm2, Na2SO4 concentration = 0.28 mol/L, and NPYR concentration = 20 mg/L. Under optimal conditions, the degradation of NPYR exceeded 58.84%. The main contributor of indirect oxidation was deduced from free radical quenching experiments. NPYR concentration was measured by GC–MS with DB-5 capillary column, operating in full scan monitoring mode for appropriate quantification of NPYR and intermediates. Based on the identification of reaction intermediates, a possible pathway for the electrochemical oxidation of NPYR on GAC particle electrodes was proposed. [ABSTRACT FROM AUTHOR]

As a four-electron transfer reaction, oxygen evolution reaction (OER) is limited by large overpotential and slow kinetics. Here, we in-situ synthesized two-dimensional (2D) Ni-Fe metal-organic framework nanosheets on nickel foam (NixFe-TPA/NF, TPA = terephthalic acid) for oxygen evolution in alkaline and alkaline seawater electrolytes. In 1 M KOH, Ni3Fe-TPA/NF shows a low overpotential (η10) of 189 mV at 10 mA·cm−2 and an ultra-low overpotential of only 260 mV at 500 mA·cm−2. In alkaline seawater, Ni3Fe-TPA/NF still provides impressive OER performance, with an η10 of 265 mV. In-situ Raman characterization results show that the phase transition occurs during the OER, and Ni3FeOOH with more oxygen vacancies is in-situ formed, reducing the OER energy barrier. Density functional theory (DFT) reveals that the synergy between Ni and Fe reduces the energy barrier and accelerates the rate-determining step. In addition, the ultra-thin 2D sheet structure and the close combination of Ni3FeOOH and highly conductive NF support ensure the high catalytic OER activity. Therefore, the surface reconstruction and structural modification strategy can be used to design and prepare high-performance OER electrocatalysts for energy-related applications. [ABSTRACT FROM AUTHOR]

Pure organic phosphorescence resonance energy transfer is a research hotspot. Herein, a single-molecule phosphorescence resonance energy transfer system with a large Stokes shift of 367 nm and near-infrared emission is constructed by guest molecule alkyl-bridged methoxy-tetraphenylethylene-phenylpyridines derivative, cucurbit[n]uril (n = 7, 8) and β-cyclodextrin modified hyaluronic acid. The high binding affinity of cucurbituril to guest molecules in various stoichiometric ratios not only regulates the topological morphology of supramolecular assembly but also induces different phosphorescence emissions. Varying from the spherical nanoparticles and nanorods for binary assemblies, three-dimensional nanoplate is obtained by the ternary co-assembly of guest with cucurbit[7]uril/cucurbit[8]uril, accompanying enhanced phosphorescence at 540 nm. Uncommonly, the secondary assembly of β-cyclodextrin modified hyaluronic acid and ternary assembly activates a single intramolecular phosphorescence resonance energy transfer process derived from phenyl pyridines unit to methoxy-tetraphenylethylene function group, enabling a near-infrared delayed fluorescence at 700 nm, which ultimately applied to mitochondrial targeted imaging for cancer cells.Phosphorescence resonance energy transfer systems have potential in light-harvesting and bioimaging, but host-guest systems are rarely explored. Here, the authors report the development of a macrocyclic host-guest system for targeted cell imaging. [ABSTRACT FROM AUTHOR]

This paper examines the potential of using ammonia (NH 3 ) as a primary fuel in heavy-duty engines for decarbonization, with some challenges yet to be addressed. It presents a numerical study of a Reactivity Controlled Compression Ignition engine, where pilot diesel is used to ignite the premixed ammonia/air mixture. The numerical model and combustion mechanism are validated against engine experimental results using methanol and iso-octane fuels and ignition delay times of ammonia/n-heptane mixtures measured in a rapid compression machine. The findings show that the engine can effectively operate with up to 50% of the total energy supplied by premixed ammonia, albeit with slightly elevated NO emissions compared to a diesel-fueled engine. Increasing ammonia further leads to lower combustion efficiency. Hydrogen can be utilized in the ammonia engine to enhance ammonia combustion; however, NO emissions increase further. Ammonia leakage primarily originates from regions near the cold wall, the center of the cylinder, and the crevice. N 2 O mainly forms at the ammonia flame front. Emission of N 2 O is therefore mainly due to flame front quenching near the wall. [ABSTRACT FROM AUTHOR]

Purpose: Tegafur (TF) is one of the most important clinical antitumor drugs with poor water solubility, severely reducing its bioavailability. This work develops new cocrystals to improve the solubility of TF and systematically investigates the intermolecular interactions to provide new insights into the formation of cocrystal and changes in physicochemical properties. Method: In this paper, two new 1:1 cocrystals of TF with 2,4 dihydroxybenzoic acid (2,4HBA) and p-nitrophenol (PNP) were synthesized. The cocrystal products were identified and characterized by various solid state analysis techniques. And the high performance liquid chromatography (HPLC) was conducted to determine the solubility and dissolution rate of TF and cocrystals. Moreover, the quantum chemistry calculations of crystal structure provided theoretical support for the results. Result: Compared with pure TF, the solubility and dissolution rate of TF-2,4HBA is significantly increased in a pH 6.8 buffer at 37°C. Under accelerated storage conditions (40°C, 75% RH), all cocrystal exhibits excellent stability over 8 weeks. Hirshfeld surface (HS) analysis, atoms in molecules (AIM) analysis, interaction region indicator (IRI) analysis, molecular electrostatic potential surface (MEPS) analysis and frontier molecular orbital (HOMO–LUMO) analysis were integrated to understand the hydrogen bonding interaction more comprehensively. The simulation results are in good agreement with the experimental data. The results show that the analysis of physical and chemical properties of TF-PNP cocrystal and TF crystal by quantum chemistry method is reliable at molecular level. Conclusion: These results are helpful to provide guiding methods in the cocrystal development and theoretical study of tegafur. [ABSTRACT FROM AUTHOR]

Gastric cancer is the fifth most common malignancy worldwide having the fourth highest mortality rate. Energy metabolism is key and closely linked to tumour development. Most important in the reprogramming of cancer metabolism is the Warburg effect, which suggests that tumour cells will utilise glycolysis even with normal oxygen levels. Various molecules exert their effects by acting on enzymes in the glycolytic pathway, integral to glycolysis. Second, mitochondrial abnormalities in the reprogramming of energy metabolism, with consequences for glutamine metabolism, the tricarboxylic acid cycle and oxidative phosphorylation, abnormal fatty acid oxidation and plasma lipoprotein metabolism are important components of tumour metabolism. Third, inflammation-induced oxidative stress is a danger signal for cancer. Fourth, patterns of signalling pathways involve all aspects of metabolic transduction, and many clinical drugs exert their anticancer effects through energy metabolic signalling. This review summarises research on energy metabolism genes, enzymes and proteins and transduction pathways associated with gastric cancer, and discusses the mechanisms affecting their effects on postoperative treatment resistance and prognoses of gastric cancer. We believe that an in-depth understanding of energy metabolism reprogramming will aid the diagnosis and subsequent treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

With the rapid development of intelligent and connected vehicles, the experimental road test for the advanced driving assistance system (ADAS) is dramatically increasing around the world. Considering its high cost and hazardous situations, simulation test based on a dummy model is becoming a promising way for ADAS road test practice to reduce the experiment expanses. This study proposed a methodology for the evaluation of the performance of human and dummies with distinct designed materials based on the data extracted from the Doppler effect of millimeter-wave radar. Echo data of 8 different angles from 0 to 360 degrees, with the an interval of 45 degrees, at the same distance between the test object and the signal source is collected. Meanwhile, the echo energy is collected for correlation modeling and analysis among groups. By evaluating the performance of humans and dummies via statistical analysis, a close correlation was found which results verified the substitutability of the dummy for the ADAS experiment test. The correlation coefficient between human and dummies ranges from 0.75 to 0.93. The support vector machine (SVM) model was developed and fitted to predict the echo energy in diverse environments. The mean average error (MAE) is 5.42–11.42 in the training and testing datasets while root mean square error (RMSE) is 0.43–0.90. The methods developed in the study can simulate the real ADAS road test environment and support future experimental research. [ABSTRACT FROM AUTHOR]

Given that combination with multiple biomarkers may well raise the predictive value of wound age, it appears critically essential to identify new features under the limited cost. For this purpose, the present study explored whether the gene expression ratios provide unique time information as an additional indicator for wound age estimation not requiring the detection of new biomarkers and allowing full use of the available data. The expression levels of four wound-healing genes (Arid5a, Ier3, Stom, and Lcp1) were detected by real-time polymerase chain reaction, and a total of six expression ratios were calculated among these four genes. The results showed that the expression levels of four genes and six ratios of expression changed time-dependent during wound repair. The six expression ratios provided additional temporal information, distinct from the four genes analyzed separately by principal component analysis. The overall performance metrics for cross-validation and external validation of four typical prediction models were improved when six ratios of expression were added as additional input variables. Overall, expression ratios among genes provide temporal information and have excellent potential as predictive markers for wound age estimation. Combining the expression levels of genes with ratio-expression of genes may allow for more accurate estimates of the time of injury. [ABSTRACT FROM AUTHOR]

Background: Uveal melanoma (UVM) is an aggressive malignant tumor originating from melanocytes in the eye. Here, we screened the possible genes involved in the development and prognosis of UVM, and identified that FOXM1 and MET were associated with the prognosis of UVM patients. Forkhead box protein M1 (FOXM1) is a transcription factor that regulates the expression of cell cycle-related genes that are necessary for DNA duplication. However, the regulatory mechanism of FOXM1 in UVM was still not clear. Here, we investigated the regulation of FOXM1 in the malignant phenotype of UVM cells and its effect on the prognosis of UVM patients. Methods: UVM gene expression profiles were obtained using GSE22138 data from the gene expression omnibus (GEO). Weighted gene co-expression network analysis (WGCNA) was used to construct a key module gene for metastasis, which was strongly correlated with UVM prognosis. The latent biological pathways were identified through gene ontology analysis. Protein–protein interaction (PPI) networks and hub shared gene authentication were performed. GEPIA and UALCAN databases were used for the analysis of relationship between candidate genes (FOXM1 or MET) and the prognosis of UVM patients. The abundance of FOXM1 was examined by quantitative real time polymerase chain reaction (qRT-PCR) and western blot. Colony formation and cell counting kit-8 (CCK-8) assays for cell proliferation, wound healing assay for migration, and transwell invasion analysis for invasion were performed. Results: GEO database showed the differentially expressed genes between UVM samples with or without metastasis, and a key module gene for metastasis was constructed by WGCNA. The PPI network revealed that seven candidate genes (VEGFA, KRAS, MET, SRC, EZR, FOXM1, and CCNB1) were closely associated with UVM metastasis. GEPIA and UALCAN analyzes suggested that FOXM1 and MET are related to the prognosis of patients with UVM. These experimental results suggested that FOXM1 was highly expressed in UVM cells. FOXM1 deficiency represses the proliferative, migratory, and invasive abilities of UVM cells. Conclusions: FOXM1 silencing may hinder UVM cell progression, providing a novel theoretical basis and new insights for UVM treatment. [ABSTRACT FROM AUTHOR]

The serine/threonine kinase, PINK1, and the E3 ubiquitin ligase, Parkin, are known to facilitate LC3-dependent autophagosomal encasement and lysosomal clearance of dysfunctional mitochondria, and defects in this process contribute to a variety of cardiometabolic and neurological diseases. Although recent evidence indicates that dynamic actin remodeling plays an important role in PINK1/Parkin-mediated mitochondrial autophagy (mitophagy), the underlying signaling mechanisms remain unknown. Here, we identify the RhoGAP GRAF1 (Arhgap26) as a PINK1 substrate that regulates mitophagy. GRAF1 promotes the release of damaged mitochondria from F-actin anchors, regulates mitochondrial-associated Arp2/3-mediated actin remodeling and facilitates Parkin-LC3 interactions to enhance mitochondria capture by autophagosomes. Graf1 phosphorylation on PINK1-dependent sites is dysregulated in human heart failure, and cardiomyocyte-restricted Graf1 depletion in mice blunts mitochondrial clearance and attenuates compensatory metabolic adaptations to stress. Overall, we identify GRAF1 as an enzyme that coordinates cytoskeletal and metabolic remodeling to promote cardioprotection. Cytoskeletal remodeling is known to facilitate mitophagy, but the mechanism is not fully understood. Here, the authors show that damaged mitochondria recruit a RhoA GTPase activating protein that promotes their capture and encasement by autophagosomes. [ABSTRACT FROM AUTHOR]

It has been demonstrated that the ATP-gated ion channel P2X7 receptor is involved in tumor progression and plays an important role in regulating tumor cell growth, invasion, migration and angiogenesis. However, P2X7 receptors have been relatively poorly studied in non-small cell lung cancer (NSCLC) cells. Therefore, the aim of this study was to investigate the effects of P2X7 receptor on A549 cells (NSCLC cell line) migration and invasion and to reveal the molecular mechanisms mediated by it. We detected the expression and function of P2X7 receptor in A549 cells. The effects and mechanisms of P2X7 receptor on A549 cells migration, invasion, and epithelial-mesenchymal transition were detected in vitro and in vivo. The results showed P2X7 receptor expressed by A549 cells had ion channel and macropore formation function. In addition, activation of P2X7 receptor by adenosine triphosphate (ATP) or 2′(3′)-O-(4-Benzoylbenzoyl)-adenosine-5'-triphosphate (BzATP) promoted Epithelial-mesenchymal transition (EMT), migration and invasion of A549 cells, which was attenuated by treatment of cells with P2X7 receptor antagonist A438079 and Oxidized ATP. Furthermore, activation of P2X7 receptor increased phosphorylated protein kinase B (p-Akt) levels, and the phosphatidylinositol-tris–phosphate kinase 3 (PI3K)/protein kinase B (Akt) inhibitor LY294002 blocked migration and invasion of A549 cells induced by ATP or BzATP. At the same time, in vivo results showed that P2X7 receptor could also promote EMT and PI3K/Akt expression in transplanted tumors. Our study indicated that P2X7 receptor promotes A549 cells migration and invasion through the PI3K/Akt signaling pathway, suggesting that P2X7 receptor may be a potential therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

The inter-particle bonding (IPB) mechanism of cold-sprayed titanium alloy during heat treatment (HT) is not clear. The interfacial microstructure and bonding characteristics at the interface of cold-sprayed Ti6Al4V after HT were studied at the micro- and nano-scale. As a result, the nanocrystallization at IPB during cold spray (CS) cannot cause obvious metallurgical bonding between Ti6Al4V particles. The average Young's modulus of CS Ti6Al4V is 57% higher than that of powder, but the average Young's modulus of HT sample decreases by 16%. The internal stress and dislocation distribution of interfacial microstructure can lead to various microstructure features and non-uniform rates of microstructure growth at deformed transition layer and IPB during HT. The nanograins at the IPB grow into micron-equiaxed grains. On the contrary, the micron martensitic laths at deformed transition layer adjacent to IPB show the characteristics of equiaxed nanograins transformation under the action of grain boundary bulges induced by dislocation entanglement. [ABSTRACT FROM AUTHOR]

Studies have reported that typical nanomaterials (NMs) have been applied on a large scale to various human consumer products due to their rapid development. Nanoparticles (NPs) flowing into the environment inevitably exhibit toxicological effects on organisms at the physiological and molecular levels. To identify the mechanisms of phytotoxicity regulation of typical metal-based engineered NPs, a review of ecotoxicological effects and environmental risks of particles is required. The biological transport of NPs in cells frequently affects the physiological state of plants, resulting in growth restriction of seedlings and structural damage to cellular tissues. Subsequently, excessive accumulation of reactive oxygen species (ROS) enhances oxidative stress, metabolic disorders, cell death, and DNA damage. The transcriptome and metabolome of the antioxidant system were also highly activated to resist ROS, which inevitably caused cytotoxicity and dysregulation of metabolic activity. At the biological process, protein folding, imbalance of calcium homeostasis, impaired mitosis, abnormal electron transport in photosynthesis, and dysregulation of TCA cycle in respiration have been extensively explored in the nanotoxicology field. Trophic transfer in the food chain indicates that ingested NPs are highly probable to accumulate in aquatic and terrestrial food chains and eventually pose potential threats to human health. Overall, this review aims to emphasize the toxicological effects of typical NMs on plants, reveal the toxicity mechanisms of plant cells with metal-based NPs in the environment, and discuss potential risks of particles in aquatic and terrestrial food chains, paving a bright path for environmental risk studies of NMs. [ABSTRACT FROM AUTHOR]

This paper provides a detailed description of reduced embedded questions in Chakhar Mongolian and proposes to analyze them in terms of so-called pseudo-sluicing. It has been noted in the literature that the comparable construction in Khalkha Mongolian does not exhibit the so-called case-matching effect, a phenomenon in which the case of a remnant interrogative phrase matches that of its correlate in the preceding context. We show that it also holds in Chakhar Mongolian. We argue that reduced embedded questions in the language have a pseudo-sluicing structure, which straightforwardly accounts for the absence of the relevant effect. Our proposal is supported by the appearance of a copula and pronominal subjects in those reduced questions and by the fact that reduced questions can be pragmatically controlled. [ABSTRACT FROM AUTHOR]

Due to its exceptional performance, the Ti6Al4V alloy finds extensive use in aviation, biomedical, and petrochemical sectors. Nonetheless, its limited machinability and subpar wear resistance have hindered its widespread application. Therefore, this study underlooks a novel approach by employing nitrogen (N2) gas–assisted electrical discharge machining (NA-EDM) to machine Ti6Al4V. In this context, N2 gas serves a dual purpose. On the one hand, the flow of N2 has a beneficial impact on enhancing the surface properties of the workpiece. On the other hand, N2 reacts with titanium (Ti) to create titanium nitride (TiN), enhancing the component's performance. Also, this study focuses on investigating how peak current, pulse-on time, electrode rotation speed, and gas pressure influence various aspects, including surface morphology, surface roughness, the microstructure of the recast layer, the microhardness of the recast layer, the thickness of the recast layer, and material removal rate (MRR). Experimental findings show that the NA-EDM process results in a smoother surface morphology, a uniform recast layer, and a reduced MRR. The microhardness in NA-EDM exceeds that of EDM by 42.1%, attributed to the formation of TiN and martensite. Ra is decreased by 21.2% compared to EDM. This study offers novel insights into machining Ti6Al4V alloy, opening up possibilities for broader-scale applications. [ABSTRACT FROM AUTHOR]

Gear disengaging, back-side tooth contact or poor dynamic behavior during operating leads to dynamic instability in planetary gear trains (PGTs). A novel nonlinear dynamic model of PGTs with internal and external gear pairs considering multi-state engagement induced by backlash and contact ratio is established. An improved time-varying meshing stiffness model including temperature stiffness is analytically derived. The time-varying meshing stiffness with temperature effect, friction, backlash, time-varying pressure angle, and time-varying friction arm are to be incorporated into the dynamic model of PGTs. Multi-state engaging behavior is efficiently identified by constructing different Poincaré mappings. A method to calculate dynamic instability is proposed in the time-domain trace. The intrinsic relationship between multi-state engaging and dynamic instability is investigated via multi-section bifurcation plots and phase trajectory topology. The global dynamic instability is revealed based on the bifurcation and evolution of coexistence behavior under the parameter-state synergy. The results show that the multi-state engagement is heavily depending on bifurcation and phase trajectory topology, which whereby affects the dynamic instability. Two special phenomena, complete and incomplete bifurcations, are discovered under parameter-state synergy. Complete bifurcation causes global instability and incomplete bifurcation results in local instability and yields coexistence responses. Incomplete bifurcation brings about new bifurcation branches. [ABSTRACT FROM AUTHOR]

The HIV-1 Tat protein hijacks the Super Elongation Complex (SEC) to stimulate viral transcription and replication. However, the mechanisms underlying Tat activation and inactivation, which mediate HIV-1 productive and latent infection, respectively, remain incompletely understood. Here, through a targeted complementary DNA (cDNA) expression screening, we identify PRMT2 as a key suppressor of Tat activation, thus contributing to proviral latency in multiple cell line latency models and in HIV-1-infected patient CD4+ T cells. Our data reveal that the transcriptional activity of Tat is oppositely regulated by NPM1-mediated nucleolar retention and AFF4-induced phase separation in the nucleoplasm. PRMT2 preferentially methylates Tat arginine 52 (R52) to reinforce its nucleolar sequestration while simultaneously counteracting its incorporation into the SEC droplets, thereby leading to its functional inactivation to promote proviral latency. Thus, our studies unveil a central and unappreciated role for Tat methylation by PRMT2 in connecting its subnuclear distribution, liquid droplet formation, and transactivating function, which could be therapeutically targeted to eradicate latent viral reservoirs. The mechanisms regulating Tat function for HIV-1 replication remain poorly understood. Here, the authors reveal that the transcriptional activity of Tat is modulated by a PRMT2-licensed switch between its nucleolar sequestration and phase separation into the nucleoplasmic Super Elongation Complex (SEC) droplets. [ABSTRACT FROM AUTHOR]

Carpal tunnel syndrome (CTS) is one of the most common work-related musculoskeletal disorders. The present study sought to identify putative causal proteins for CTS. We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal association between 2859 plasma proteins (N = 35,559) and CTS (N = 1,239,680) based on the published GWAS summary statistics. Then we replicated the significant associations using an independent plasma proteome GWAS (N = 10,708). Sensitivity analyses were conducted to validate the robustness of MR results. Multivariate MR and mediation analyses were conducted to evaluate the mediation effects of body mass index (BMI), type 2 diabetes (T2D), and arm tissue composition on the association between putative causal proteins and CTS. Colocalization analysis was used to examine whether the identified proteins and CTS shared causal variant(s). Finally, we evaluated druggability of the identified proteins. Ten plasma proteins were identified as putative causal markers for CTS, including sCD14, PVR, LTOR3, CTSS, SIGIRR, IFNL3, ASPN, TM11D, ASIP, and ITIH1. Sensitivity analyses and reverse MR analysis validated the robustness of their causal effects. Arm tissue composition, BMI, and T2D may play a fully/partial mediating role in the causal relationships of ASIP, TM11D, IFNL3, PVR, and LTOR3 with CTS. The association of ASPN and sCD14 with CTS were supported by colocalization analysis. Druggability assessment demonstrated that sCD14, CTSS, TM11D, and IFNL3 were potential drug therapeutic targets. The present study identified several potential plasma proteins that were causally associated with CTS risk, providing new insights into the pathogenesis of protein-mediated CTS and offering potential targets for new therapies. [ABSTRACT FROM AUTHOR]

Tunnelling in urban areas should be aware of deviations from the design tunnel axis, referred to also as 'misalignment'. Significant misalignment can cause unfavourable soil deformations, threatening adjacent properties, and sustainable development of underground space. In this study, the potential of applying machine learning (ML) and deep learning (DL) algorithms to EPB shield posture prediction and anomaly detection was explored. A framework, including data pre-processing, development of prediction models, performance evaluation, and anomaly detection, was proposed to tackle the said issue. The principal component analysis (PCA) was introduced not only to eliminate outliers but also to isolate salient data features using the Pearson's correlation coefficient (PCC). Also, the partial dependence analysis aimed to marginalize other features and established the relationship between an individual tunnelling parameter and EPB shield position. Then the feature-based subseries were normalized for training and examining the DL-based Long Short-Term Memory (LSTM) and ML-based ensemble EPB shield position predictors. On the other hand, three anomaly detectors founded on three ML algorithms were developed to prevent snakelike advance. Results showed that the DL-based LSTM predictor outperformed the ML-based ensemble predictor owing to its relative insensitivity to lags of unknown duration between important events. The thrust force dominated EPB shield position. The LSTM model prevented the accuracy of EPB shield position prediction from disturbing by gravels surrounding the design tunnel axis or artificial intervention. [ABSTRACT FROM AUTHOR]

Main conclusion: Overexpression of JcSEUSS1 resulted in late flowering, reduced flower number, wrinkled kernels, and decreased seed yield in Jatopha curcas, while downregulation of JcSEUSS1 increased flower number and seed production. The seed oil of Jatropha curcas is suitable as an ideal alternative for diesel fuel, yet the seed yield of Jatropha is restricted by its small number of female flowers and low seed setting rate. Therefore, it is crucial to identify genes that regulate flowering and seed set, and hence improve seed yield. In this study, overexpression of JcSEUSS1 resulted in late flowering, fewer flowers and fruits, and smaller fruits and seeds, causing reduced seed production and oil content. In contrast, the downregulation of JcSEUSS1 by RNA interference (RNAi) technology caused an increase in the flower number and seed yield. However, the flowering time, seed number per fruit, seed weight, and size exhibited no obvious changes in JcSEUSS1-RNAi plants. Moreover, the fatty acid composition also changed in JcSEUSS1 overexpression and RNAi plants, the percentage of unsaturated fatty acids (FAs) was increased in overexpression plants, and the saturated FAs were increased in RNAi plants. These results indicate that JcSEUSS1 played a negative role in regulating reproductive growth and worked redundantly with other genes in the regulation of flowering time, seed number per fruit, seed weight, and size. [ABSTRACT FROM AUTHOR]

Background: The proliferation marker Ki67 is associated with the progression and prognosis of melanoma. However, its prognostic impact on acral melanoma (AM) remains unclear. Methods: A total of 314 AM patients were enrolled from a cohort of 5758 patients with melanoma at Peking University Cancer Hospital between 2006 and 2018. The patients were divided into Ki67 high- and low-expressing groups using a cut-off value of 30%. The associations between Ki67 and clinicopathologic characteristics as well as survival were analyzed. Cox proportional regression analysis was used to establish a nomogram to predict the survival probabilities of AM. Results: Among 314 patients, the Ki67-high group (Ki67 ≥ 30%) included 49.4% of patients at diagnosis. Patients in the Ki67-high group had lower median melanoma-specific survival (MSS) than those in the Ki67-low group (60.7 months vs. not reached, p < 0.001). In multivariate analyses, Ki67, lymph node metastasis and primary site were independent prognostic factors for MSS. The nomogram showed that Ki67 had the fourth greatest impact on survival, following Breslow thickness, lymph node metastasis and primary site. The C-index of the nomogram was 0.765 and 0.758 in the training and validation cohort, respectively. Area under the curve values were both near 0.8 in the training and validation cohorts. Net reclassification improvement and integrated discrimination improvement demonstrated that the predictive nomogram performed better than the traditional AJCC staging system. Conclusion: Ki67 expression is an independent prognostic factor for MSS in AM. A predictive model incorporating Ki67 and clinical factors was constructed to predict the prognosis of AM. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the incidence of malignancies in acromegaly and to identify risk factors for newly-diagnostic cancers, especially the excessive growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Methods: A retrospective cohort including 1738 consecutive hospitalized patients with acromegaly in a single referral center between 2012 and 2020 (mean follow-up 4.3 years). A gender- and age-matched case-control study (280 patients from the cohort) was performed for risk factor analysis. Results: One hundred thirteen malignancies (67 diagnosed after acromegaly) were observed. The overall newly-diagnostic cancer risk of acromegaly was higher than the general population (standardized incidence ratio (SIR) 2.81; 95% CI 2.18–3.57). The risk of thyroid cancer (n = 33, SIR 21.42; 95% CI 13.74–30.08) and colorectal cancer (n = 8, SIR 3.17; 95% CI 1.37–6.25) was elevated. In the overall cohort, IGF-1 (ULN: 1.27 vs. 0.94, p = 0.057), GH (1.30 vs. 1.00 ng/ml, p = 0.12), and disease-controlled rate (34.9% vs. 45.9%, p = 0.203) at the last visit did not reach significance between patients with and without post-diagnostic cancer. In the case-control study, GH (1.80 vs. 0.90 ng/ml, p = 0.018) and IGF-1 (ULN: 1.27 vs. 0.91, p = 0.003) at the last visit were higher in patients with post-diagnostic cancers, with a lower disease-controlled rate. Elder age was a risk factor for cancer. Other metabolic comorbidities and the size of pituitary tumors were similar. Conclusion: The risk of malignancies, especially thyroid cancer, was increased in patients with acromegaly in our center. More cancer screening should be considered when managing acromegaly, especially in patients with higher posttreatment GH and IGF-1. [ABSTRACT FROM AUTHOR]

Underground mining activities can easily trigger surface subsidence and cause damage to surface soil. However, there is still a lack of studies on damaged soil, restricting ecological remediation in mining-induced subsidence regions to a certain degree. Focusing on the particular example of No. 4 Mine in Yili, Xinjiang, China, this study comprehensively combined field sampling, laboratory experiments, and data analysis to investigate the variation rules of basic physical properties and shear characteristics of soil samples. The latter had different subsidence degrees (0, 0–20, 20–40, and above 40 cm) and various depths (0– 10, 10–20, 20– 40, 40–60, and 60–80 cm). The experimental results show that: First, the natural density and dry unit weight of shallow soil in the serious-subsidence region were more significantly affected by mining-induced subsidence than the conditions in the deep layer, which also dropped with the increase in subsidence degree (with a mean drop rate of 7%). Second, serious subsidence could greatly counteract the positive effect of slight and moderate subsidence on the soil shear strength, with a drop rate of up to 30.7%. Third, compared with soil physical indices, mining-induced subsidence more easily affected shear strength indices. In particular, the soil samples taken from 0 to 10 cm depth in the slight subsidence area and 60–80 cm depth in the moderate subsidence area were most significantly affected by mining-induced subsidence, with PCA comprehensive scores of over 1.5. The present study can con-tribute to gaining in-depth knowledge of the damage characteristics of surface soil under mining-induced subsidence and provide a theoretical foundation for formulating reasonable coal mining strategies and ecological protection measures. [ABSTRACT FROM AUTHOR]

Endometrial cancer is known to be an estrogen-dependent cancer, and it is believed that exposure to estrogens increases the risk of developing endometrial cancer in the absence of progesterone. Estrogens and estrogen metabolites may help to predict the risk of endometrial hyperplasia (EH) with atypia. Estrogens and estrogen metabolites were measured by high-performance liquid chromatography–mass spectrometry (HPLC–MS/MS) in the first morning urine sample collected from 150 patients with EH and 50 healthy premenopausal women in the study. In healthy premenopausal women, the level of 16α-hydroxyestrone (16α-OHE1) in the overweight group was significantly higher than that in the lean group (p < 0.05). The levels of 4-hydroxyestradiol (4-OHE2) and 16α-OHE1 were elevated in the AEH group as compared to that in the control group (p < 0.05). Overweight is related to EH incidence as it causes an imbalance of estrogen metabolites. This study provides identifies potential biomarkers for estrogen-induced AEH. [ABSTRACT FROM AUTHOR]

Activation of mixed lineage kinase 3 (MLK3) by phosphorylation at Thr277/Ser281 stimulates downstream apoptotic pathways and ultimately leads to cell injury. MLK3 is reported to localize to both the cytoplasm and nucleus in human ovarian cancer cells and immortalized ovarian epithelial cells (T80 and T90 cells), and phosphorylation at Thr477 is required for the cytoplasmic retention of MLK3 in T80 cells. However, the subcellular distribution of MLK3 in other cell types has rarely been reported, and whether phosphorylation of MLK3 at Thr277/Ser281 affects its subcellular distribution is unknown. Here, our bioinformatics analysis predicted that MLK3 was mainly distributed in the cytoplasm and nucleus. In the human HEK293T embryonic kidney cell line and murine HT22 hippocampal neuronal cell line, endogenous MLK3 was more abundant in the cytoplasm and less abundant in the nucleus. In addition, overexpressed Myc-tagged MLK3 and EGFP-tagged MLK3 were also observed to localize mainly to the cytoplasm. MLK3 that was activated by phosphorylation at Thr277/Ser281 was mainly distributed in the cytoplasm, and phosphorylation deficient (T277A/S281A) and mimic (T277E/S281E) mutants both showed distributions similar to that of wild type (wt) MLK3, further proving that phosphorylation at Thr277/Ser281 was not involved in regulating MLK3 subcellular localization. In HEK293T cells, H2O2 stimulation accelerated MLK3 phosphorylation (activation), and this phosphorylation was reduced by the antioxidant N-acetylcysteine in a dose-dependent manner. Overexpressing wt MLK3 promoted the production of intracellular reactive oxygen species and increased cell apoptosis, both of which were enhanced by the phosphorylation-mimic (T277E/S281E) MLK3 variant but not by the phosphorylation-deficient (T277A/S281A) MLK3 variant. These findings provided additional evidence for the cytoplasmic and nuclear distribution of MLK3 in HEK293T cells or HT22 cells and revealed the pivotal role of MLK3 in the positive feedback loop of oxidative stress injury. [ABSTRACT FROM AUTHOR]

Calreticulin (CRT) is a multifunctional protein found within the endoplasmic reticulum (ER). In addition, CRT participates in the formation and development of tumors and promotes the proliferation and migration of tumor cells. When a malignant tumor occurs in the human body, cancer cells that die from immunogenic cell death (ICD) expose CRT on their surface, and CRT that is transferred to the cell surface represents an "eat me" signal, which promotes dendritic cells to phagocytose the tumor cells, thereby increasing the sensitivity of tumors to anticancer immunotherapy. Expression of CRT in tumor tissues is higher than in normal tissues and is associated with disease progression in many malignant tumors. Thus, the dysfunctional production of CRT can promote tumorigenesis because it disturbs not only the balance of healthy cells but also the body's immune surveillance. CRT may be a diagnostic marker and a therapeutic target for cancer, which is discussed extensively in this review. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) remains a global challenge due to its high morbidity and mortality rates especially in Asia as well as poor response to treatment. As a member of the adhesion protein family and transmembrane glycoprotein, EpCAM expressed excessively in cancer cells including GC cells. The database assay showed that EpCAM is excessively expressed and easily mutated in cancers, especially in early stage of GC. Methods: To explore the roles EpCAM plays in oncogenesis and progression of GC, the expression of EpCAM was deleted in GC cells with CRISPR/Cas9 method, and then the changes of cell proliferation, apoptosis, motility and motility associated microstructures in EpCAM-deleted GC cells (EpCAM-/-SGC7901) were detected to evaluate the rules EpCAM played. Results: The results showed that EpCAM deletion caused cell proliferation, motility and the development of motility-relevant microstructures inhibited significantly, apoptotic trend and contact inhibition enhanced in EpCAM-deleted GC cells. The results of western blot suggested that EpCAM modulates the expression of epithelial/endothelial mesenchymal transition (EMT) correlated genes. All results as above indicated that EpCAM plays important roles to enhance the oncogenesis, malignancy and progression as a GC enhancer. Conclusions: Combining our results and published data together, the interaction of EpCAM with other proteins was also discussed and concluded in the discussion. Our results support that EpCAM can be considered as a novel target for the diagnosis and therapy of GC in future. [ABSTRACT FROM AUTHOR]

Urban park green spaces (UPGS) constitute a vital component of urban ecosystems, and the unequal distribution of UPGS can significantly impact the well-being of residents. Therefore, investigating the spatial delineation methods of UPGS service levels from the perspective of opportunity equity contributes to enhancing people's quality of life and promoting social harmony. Taking the Yingze District of Taiyuan City as an example, this study uses a modified accessibility measurement method of UPGS with the smallest clustered unit (building) as the service demand point and the UPGS entrance/exit as the service provision point, to establish a micro-scale evaluation framework for spatial equity considering the service radius and service quality of UPGS. The findings are as follows: after setting different service radius for UPGS at different levels, additional areas not covered by UPGS service were identified compared to setting the same service radius uniformly, which could prevent these areas from being overlooked in urban plans. After considering the quality of UPGS services, additional areas with low and high UPGS service levels were identified. Accurate spatial delineation of UPGS service level can avoid wasting public resources by including areas with high service levels in the scope of new UPGS requirements, while areas with low service levels lose opportunities for consideration in future urban infrastructure planning. This study emphasizes the residents' demand for both the quantity and quality of UPGS, facilitating an accurate assessment of whether urban residents can enjoy UPGS, the number of UPGS options available to them, and evaluate the quality of UPGS services experienced. Overall, this research provides new insights for evaluating the spatial equity of urban public facilities. [ABSTRACT FROM AUTHOR]

Developing transition metal-nitrogen-carbon materials (M-N-C) as electrocatalysts for the oxygen evolution reaction (OER) is significant for low-cost energy conversion systems. Further d-orbital adjustment of M center in M-N-C is beneficial to the improvement of OER performance. Herein, we synthesize a single-Mn-atom catalyst based on carbon skeleton (Mn1-N2S2CX) with isolated Mn-N2S2 sites, which exhibits high alkaline OER activity (η10 = 280 mV), low Tafel slope (44 mV·dec−1), and excellent stability. Theoretical calculations reveal the pivotal function of isolated Mn-N2S2 sites in promoting OER, including the adsorption kinetics of intermediates and activation mechanism of active sites. The doping of S causes the increase in both charge density and work function of active Mn center, and ortho-Mn1-N2S2CX expresses the fastest OER kinetics due to the asymmetric plane. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the deadliest types of cancer, with a death rate nearly equal to the incidence. The P2X7 receptor (P2X7R) is a kind of extracellular adenosine triphosphate (ATP)-gated ion channel with special permeability, which exists in most tissues of human body and mediates inflammation-related signaling pathways and immune signal transduction after activation. P2X7R is also present on the surface of several tumor cells and is involved in tumor growth and progression. P2X7R expression in pancreatic cancer has also been identified in recent studies. Activation of P2X7R in pancreatic cancer can support the proliferation of pancreatic stellate cells, participate in protein interactions, and mediate ERK1/2, IL-6/STAT3, hCAP-18/LL-37, PI3K/AKT signaling pathways to promote pancreatic cancer progression. Inhibitors targeting P2X7R can inhibit the development of pancreatic cancer and are expected to be used in clinical therapy. Therefore, P2X7R is promising as a potential therapeutic target for pancreatic cancer. This article reviews the progress of research on P2X7R in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Canine parvovirus (CPV) is an acute and highly infectious virus causing disease in puppies and, thus, affecting the global dog industry. The current CPV detection methods are limited by their sensitivity and specificity. Hence, the current study sought to develop a rapid, sensitive, simple, and accurate immunochromatographic (ICS) test to detect and control the spread and prevalence of CPV infection. More specifically, 6A8, a monoclonal antibody (mAb) with high specificity and sensitivity, was obtained by preliminary screening. The 6A8 antibody was labelled with colloidal gold particles. Subsequently, 6A8 and goat anti-mouse antibodies were coated onto a nitrocellulose membrane (NC) as the test and control lines, respectively. Furthermore, 6A8 and rabbit IgG antibodies were labelled with fluorescent microspheres and evenly sprayed onto a glass fibre membrane. Both strips could be prepared in 15 min with no noticeable cross-reactivity with other common canine intestinal pathogens. The strips were simultaneously used to detect CPV in 60 clinical samples using real-time quantitative PCR, hemagglutination, and hemagglutination inhibition assays. The colloidal gold (fluorescent) ICS test strip was stable for 6 (7) and 4 (5) months at 4 °C and room temperature (18–25 °C). Both test strips were easy to prepare and rapidly detected CPV with high sensitivity and specificity. Moreover, the results were easily interpretable. This study establishes a simple method for two CPV diseases, colloidal gold and fluorescent immunochromatographic (ICS) test strips. Key points: • CPV test strips do not exhibit cross-reactivity with other canine intestinal pathogens. • The strips are stable for months at 4 °C and at room temperature (18–25 °C). • These strips are a promising approach for the timely diagnosis and treatment of CPV. [ABSTRACT FROM AUTHOR]

Mammalian cardiomyocytes (CMs) undergo maturation during postnatal heart development to meet the increased demands of growth. Here, we found that omentin-1, an adipokine, facilitates CM cell cycle arrest and metabolic maturation. Deletion of omentin-1 causes mouse heart enlargement and dysfunction in adulthood and CM maturation retardation in juveniles, including delayed cell cycle arrest and reduced fatty acid oxidation. Through RNA sequencing, molecular docking analysis, and proximity ligation assays, we found that omentin-1 regulates CM maturation by interacting directly with bone morphogenetic protein 7 (BMP7). Omentin-1 prevents BMP7 from binding to activin type II receptor B (ActRIIB), subsequently decreasing the downstream pathways mothers against DPP homolog 1 (SMAD1)/Yes-associated protein (YAP) and p38 mitogen-activated protein kinase (p38 MAPK). In addition, omentin-1 is required and sufficient for the maturation of human embryonic stem cell-derived CMs. Together, our findings reveal that omentin-1 is a pro-maturation factor for CMs that is essential for postnatal heart development and cardiac function maintenance. [ABSTRACT FROM AUTHOR]