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Various factors, including fatty liver and macrophage alterations, influence colorectal cancer (CRC). This study explores the mechanistic role of fatty liver in CRC progression, focusing on macrophage polarization and lipid metabolism. A murine fatty liver model was created with a high-fat diet (HFD), and CRC was induced using AOM and DSS. Single-cell transcriptome sequencing (scRNA-seq) identified MAPKAP1 as a critical gene promoting CRC via M2 macrophage polarization and lipid metabolism reprogramming. Prognosis analysis on the TCGA-CRC dataset confirmed MAPKAP1′s significance. In vitro and in vivo experiments demonstrated that EVs from fatty liver cells enhanced MAPKAP1 expression, accelerating CRC development and metastasis. HFD exacerbated CRC, but fatty acid inhibitors delayed progression. Fatty liver upregulates MAPKAP1, driving M2 macrophage polarization and lipid metabolism changes, worsening CRC. These findings suggest potential therapeutic strategies for CRC, particularly targeting lipid metabolism and macrophage-mediated tumor promotion.

The utilization of thermal reflective materials on the building surface is one of the most promising methods for energy-saving in tropical and subtropical regions. In this work, nano TiO2 (NT) is used to enhance the mechanical properties and thermal reflectance of inorganic decorative panels, which are widely used for building exterior walls in China. The obtained results show that NT can modify the pore size distribution of the decorative panels and reduce the presence of macropores, and the compressive strength of the decorative panels with 2% NT increased by 4.78%. The thermal reflective properties of the decorative panels initially increased and then decreased with increasing NT content and particle size. Notably, the panels made of 6% NT with a particle size of 100 nm exhibited higher thermal reflectivity, resulting in a surface temperature decrease of 3.9 °C compared to the reference sample. Furthermore, compounding different particle sizes NT is employed to produce the decorative panels, and about a 4.5 °C decrease can be observed in this study. Mid- and far-infrared absorption spectroscopy results show that the thermal emissivity is improved in the mid- and far-infrared region of 2.5–25 μm when 100-nm and 25-nm NT were compounded at a weight ratio of 1:1. Additionally, to further evaluate the energy-saving of the decorative panels, the Designer’s Simulation Toolkit (DeST) is employed, which demonstrates that the thermal reflective decorative panels with 6% NT can save 7.19% of building air-conditioning energy consumption and reduce the indoor temperature by 1.5 °C.

Eco-friendly concrete becomes research hotspots since concrete production emits 8–10% of the total anthropogenic CO2 emissions worldwide. Industry solid waste modification exhibits great potentials on mitigating aggregates depletion and carbon emissions. Coal gangue aggregate (CGA) coated by silica fume manually (CGACM) and in a desiccator (CGACD) are utilised to optimize the 3D printing concrete. Specimens were printed by a 3D printing robotic arm with a 25 mm-diameter nozzle. The compressive strength of CGACM and CGACD increases by 49% and 44% than non-activated series. For splitting tensile strength, the figures are 43% and 36%. The density of activation series decreases over 16% compared with standard sand. However, both surface pretreated methods make negative effects on structure compactness. From the SEM, SiO2 particles filles defects of aggregates, resulting in a denser internal structure and promoting secondary hydration reaction. However, excessive SiO2 particles agglomerated on CGA leads to the lubricant film among particles. These results expand recycle methods for CG and promotes 3D printing technology application on mine.

The boron nitride (BN) particle dispersed silicon carbide (SiC) materials were fabricated by liquid phase sintering (LPS) with Al2O3 and Y2O3 sintering additives as the reference matrix material for SiC composites. They were irradiated to 0.1/1/3/10 dpa by 5.1 MeV Si2+ ions at 800 °C. Raman spectra indicated that the pure h-BN structure was partially destroyed following irradiation, while yttrium aluminum garnet (YAG) structure at grain boundaries formed from the sintering additives wasn’t destroyed. TEM images and diffraction patterns indicated that the mechanism of microstructure evolution of SiC after irradiation up to high fluence at 800 °C was defect clusters induced by irradiation.

Perfluorobutanesulfonic acid (PFBS), a short-chain alternative to perfluorooctanesulfonic acid (PFOS), is widely used in various products and is increasingly present in environmental media and human bodies. Recent epidemiological findings have raised concerns about its potential adverse health effects, although the specific toxic mechanism remains unclear. This study aimed to investigate the metabolic toxicity of gestational PFBS exposure in maternal rats. Pregnant Sprague Dawley (SD) rats were randomly assigned to three groups and administered either 3% starch gel (control), 5, or 50 mg/kg bw·d PFBS. Oral glucose tolerance tests (OGTT) and lipid profiles were measured, and integrated omics analysis (transcriptomics and non-targeted metabolomics) was employed to identify changes in genes and metabolites and their relationships with metabolic phenotypes. The results revealed that rats exposed to 50 mg/kg bw·d PFBS exhibited a significant decrease in 1-h glucose levels and the area under the curve (AUC) of OGTT compared with the starch group. Transcriptomics analysis indicated significant alterations in gene expression related to cytochrome P450 exogenous metabolism, glutathione metabolism, bile acid secretion, tumor pathways, and retinol metabolism. Differentially expressed metabolites (DEMs) were enriched in pathways such as pyruvate metabolism, the glucagon signaling pathway, central carbon metabolism in cancer, and the citric acid cycle. Co-enrichment analysis and pairwise correlation analysis among genes, metabolites, and outcomes identified several differentially expressed genes (DEGs), including Gstm1, Kit, Adcy1, Gck, Ppp1r3c, Ppp1r3d, and DEMs such as fumaric acid, L-lactic acid, 4-hydroxynonenal, and acetylvalerenolic acid. These DEGs and DEMs may play a role in the modulation of glucolipid metabolic pathways. In conclusion, our results suggest that gestational exposure to PFBS may induce molecular perturbations in glucose homeostasis. These findings provide insights into the potential mechanisms contributing to the heightened risk of abnormal glucose tolerance associated with PFBS exposure.

The selection of the finest possible embryo in in-vitro fertilization (IVF) was crucial and revolutionary, particularly when just one embryo is transplanted to lessen the possibility of multiple pregnancies. However, practical usefulness of currently used methodologies may be constrained. Here, we established a novel non-invasive embryo evaluation method that combines non-invasive chromosomal screening (NICS) and Timelapse system along with artificial intelligence algorithms. With an area under the curve (AUC) of 0.94 and an accuracy of 0.88, the NICS-Timelapse model was able to predict blastocyst euploidy. The performance of the model was further evaluated using 75 patients in various clinical settings. The clinical pregnancy and live birth rates of embryos predicted by the NICS-Timelapse model, showing that embryos with higher euploid probabilities were associated with higher clinical pregnancy and live birth rates. These results demonstrated the NICS-Timelapse model's significantly wider application in clinical IVF due to its excellent accuracy and noninvasiveness.

We investigated the prevalence and species diversity of dsRNA mycoviruses in Beauveria bassiana isolates from the China's Guniujiang Nature Preserve. Among the 28 isolates analyzed, electropherotyping revealed viral infections in 28.6 % (8 out of 28) of the isolates. Metatranscriptomic identification and RT-PCR confirmed the presence of six putative virus species, including two novel species: Beauveria bassiana victorivirus 2 (BbV-2) and Beauveria bassiana bipartite mycovirus 2 (BbBV-2). Four previously characterized mycoviruses were also identified: Beauveria bassiana polymycovirus 4 (BbPmV4), Beauveria bassiana partitivirus 1 (BbPV-1), Beauveria bassiana bipartite mycovirus 1 (BbBV-1), and Beauveria bassiana chrysovirus 2 (BbCV-2). BbPmV4 was found to be the prevailing mycovirus among the infected isolates, and three isolates showed co-infection with both BbPmV4 and BbBV-2. This study enhances our understanding of fungal viral taxonomy and diversity, providing insights into mycovirus infections in B. bassiana populations in China's Guniujiang Nature Preserve. Furthermore, the study on the diversity of B. bassiana viruses lays the foundation for recognizing fungal viruses as potential enhancers of biocontrol agents.

Background: Information on the relation of air pollution with non-alcoholic fatty liver disease (NAFLD) is scarce. We thus conducted a large cross-sectional study in Asia to investigate the role of air pollution in NAFLD. Methods: We recruited 329,048 adults (mean age: 41.0 years) without other liver disease (hepatitis and cirrhosis) or excessive alcohol consumption in Taiwan and Hong Kong from 2001 to 2018. The concentrations of nitrogen dioxide (NO2) and ozone (O3) were estimated using a space–time regression model, and the concentrations of fine particulate matter (PM2.5) was evaluated using a satellite-based spatio-temporal model. NAFLD was determined using either the fatty liver index (FLI) or the hepatic steatosis index (HSI). The NAFLD-related advanced fibrosis was defined according to BARD score or the fibrosis-4 (FIB-4). A logistic regression model was adopted to explore the relationships of ambient air pollution with the odds of NAFLD and NAFLD-related advanced fibrosis. Results: We found positive relationships between PM2.5 and the odds of NAFLD and advanced fibrosis, with every standard deviation (SD, 7.5 µg/m3) increases in PM2.5 exposure being associated with a 10% (95% confidence interval [CI]: 9%–11%) increment in the prevalence of NAFLD and an 8% (95% CI: 7%–9%) increment in the prevalence of advanced fibrosis. Similarly, the prevalence of NAFLD and advanced fibrosis increased by 8% (95% CI: 7%–9%) and 7% (95% CI: 6%–8%) with per SD (18.9 µg/m3) increasement in NO2 concentration, respectively. Additionally, for every SD (9.9 µg/m3) increasement in O3 concentration, the prevalence of NAFLD and advanced fibrosis decreased by 12% (95% CI: 11%–13%) and 11% (95% CI: 9%–12%), respectively. Conclusion: Higher ambient PM2.5 and NO2 are linked with higher odds of NAFLD and advanced fibrosis. Our findings indicate that reducing PM2.5 and NO2 concentrations may be an effective way for preventing NAFLD. Further studies on O3 are warranted.

Urban functional zoning offers valuable insights into urban morphology and sustainable development. However, the conventional fixed spatial units, such as blocks and grids, cannot easily capture the morphological characteristics inherent in functional union and separation during urban evolution. In this paper, by taking advantage of remote sensing images and geospatial big data, we propose a minimum identification unit (MIU)-based urban functional zoning model. This approach integrates the deep embedded clustering of buildings to generate the spatial unit segmentation, and then identifies the urban function by generating semantic vectors with the Word2Vec model. The effectiveness of the proposed method was tested in the city of Wuhan in China. The results highlight that MIUs provide a more flexible and suitable unit for segmenting urban functional zones compared to traditional street blocks. The proposed method is a feasible way to deal with the semantic redundancy of volunteered geographic information (VGI) data when identifying urban function, and the quality issue only has a significant impact on the minor functional types. Moreover, the building clustering results can effectively reveal the fine-scale urban structure, especially for the administration, manufacturing, and residential types. This demonstrates the potential of our approach in enhancing the understanding of urban morphology and supporting sustainable urban development.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer, with a highly aggressive phenotype and poor prognosis. RNA binding proteins (RBPs) play crucial roles in post-transcriptional gene regulation and have been implicated in tumorigenesis. RBPs have the potential to become a new therapeutic target for ccRCC. In this study, we screened and validated that insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) as an RBP, was down-regulated in ccRCC tissues and cell lines. Functionally, we verified that IGF2BP2 significantly suppressed the migration and invasion ability of ccRCC in vitro and in vivo. Mechanistically, RIP-seq and actinomycin D experiments results showed that IGF2BP2 enhanced the expression of Creatine Kinase B (CKB) by binding to CKB mRNA and enhancing its mRNA stability. Thus, IGF2BP2 inhibited ccRCC metastasis through enhancing the expression of CKB. Taken together, these finding suggests that IGF2BP2 is a novel metastasis suppressor of ccRCC and may serve as a potential therapeutic target.

The increasing concern over electromagnetic wave (EMW) contamination has led to the emergence of the EMW-absorbing superstructure element. Cementitious composites typically possess poor electromagnetic wave reflectivity, but this was improved through 3D printing technology, which offers greater productivity and design flexibility. In this study, a new wave-shaped EMW absorbing superstructure was manufactured using 3D cement printing, and mechanical testing showed a significant improvement in flexural and shearing strength. Molecular dynamic simulation was utilized to investigate the mechanism of the enhanced mechanical properties at the molecular scale. The EMW absorption performance of the printed specimens was analyzed from 1 GHz to 18 GHz through the Naval Research Laboratory (NRL) equipment, exhibiting a significant improvement in reflectance, especially in the low-frequency domain. Based on experimental results, the optimized design of the superstructure was proposed, which possesses an average reflection loss of −25 dB, a peak reflectivity of −37.4 dB, and an absorbing bandwidth of 17 GHz. These findings suggest that the 3D-printed EMW absorber element has great potential for use in minimizing electromagnetic contamination in various applications.

Background: Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome (Barakat syndrome) is a rare autosomal dominant disorder caused by mutations in the gene encoding GATA3 on chromosome 10p14. Method: Informed consent was obtained from a 38-year-old female patient. 5 mL of venous blood was collected and sent for whole-exome sequencing. GATA3 constructs of both wild-type and mutant were transfected into HEK-293 T cells. Three-dimensional modeling, luciferase-reporter gene test, western blotting and cellular immunofluorescence were used to evaluate the effect of the mutation. Results: A novel frameshift mutation c. 677dup(p.Pro227AlafsTer77), named P227Afs, was found in GATA3. Three-dimensional modeling revealed that the mutation caused the loss of the dual zinc finger structures 1 and 2 (ZNF1 and ZNF2) of the synthesized protein. Expression of wild-type GATA3 produced a six-fold increase in luciferase activity when compared with pcDNA3.1 vector only (P

The advancement of molecular pathology techniques has led to the discovery of rare EGFR mutations for targeted therapy in lung cancer. Additionally, a substantial body of evidence indicates a connection between the development of lung cancer and genetic variations in the EGFR gene. Here, we present a case report of a patient with multifocal lung adenocarcinoma who possessed a rare germline mutation, EGFR R776H. An investigation into the family history of the patient exposed the notable incidence of lung adenocarcinoma, indicating a plausible genetic vulnerability to the ailment. To be specific, the patient's older brother and sister both suffered from lung cancer, which underlines the hereditary predisposition. Furthermore, it should be noted that the patient's daughter has inherited the germline mutation and also presented with multiple lung ground-glass nodules, emphasizing the clinical importance of this genetic variation. Following the lobectomy, the patient received treatment with almonertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), and at the latest follow-up, the patient has achieved partial remission. This case highlights the significance of taking into account germline possibilities when multiple lesions carry the same mutation. It stresses the importance of acquiring a comprehensive family history and performing genetic testing on leukocytes. Moreover, for the infrequent EGFR R776H mutation, third generation EGFR-TKIs may be a viable option.

Objective: The lung is a common organ for colon cancer metastasis, and the objective of this experiment was to explore the protective effect of berberine on lung tissue or alveolar epithelial cells induced by colon cancer. Methods: Thirty-six BALB/c nude mice were used to establish a xenograft model of colon cancer with the HT29 cell line and were treated with berberine and probiotics. Human bronchial epithelial BEAS-2B cells were induced by conditioned medium (CM) from the colon cancer cell lines HT29 and RKO and were treated with berberine. Lung tissues were collected to detect the changes in the microbiota using 16S rDNA sequencing and the expression of inflammatory cytokines. The expression of E-cadherin and N-cadherin in BEAS-2B cells was detected by cellular immunofluorescence. The changes in cell proliferation were detected by the CCK-8 assay. Western blotting was used to detect E-cadherin, N-cadherin, collagen I, fibronectin, PDGF-β, and RAD51 expression in BEAS-2B cells. Results: The richness and evenness of the microbiota in the lung tissues of mice with colon cancer were significantly lower than those of the control group. Berberine significantly increased the abundances of Bacteroidetes, Bacteroidia, Bacteroidales, Lactobacillaceae, Lactobacillus and Acinetobacter in the lung tissue of mice with colon cancer, with reduced abundances of Actinobacteria, Bacillales, Staphylococcaceae and Staphylococcus. Berberine or probiotics significantly increased the alpha diversity of the lung microbiota. Compared with probiotics, berberine significantly enhanced the abundance of microbiota involved in the metabolism of lysosomes, flavone and flavonol biosynthesis, glycosaminoglycan degradation, and glycosphingolipid biosynthesis-ganglio. Berberine increased IL-6 and IL-10 and decreased IL-17 and IFN-γ expression in lung tissue (P > 0.05), but berberine-probiotics significantly decreased IL-17 and IFN-γ and increased IL-10 expression (P

Epidemiological and experimental research has indicated an association between perfluorooctane sulfonate (PFOS) exposure and liver disease. However, the potential hepatotoxic effects and mechanisms of low-level prenatal PFOS exposure in offspring remain ambiguous. The objective of this research was to examine the alterations in liver transcriptomic and metabolomic profiles in offspring rats at postnatal day (PND) 30 following gestational and lactational exposure to PFOS (from gestational day 1 to 20 and PND 1 to 21). Pregnant Sprague-Dawley rats were separated into a control group (3% starch gel solution, oral gavage) and a PFOS exposure group (0.03 mg/kg body weight per day, oral gavage). Histopathological changes in liver sections were observed by hematoxylin and eosin staining. Biochemical analysis was conducted to evaluate changes in glucose and lipid metabolism. Transcriptomic and metabolomic analyses were utilized to identify significant genes and metabolites associated with alterations of liver glucose and lipid metabolism through an integrated multi-omics analysis. No significant differences were found in the measured biochemical parameters. In total, 167 significant differentially expressed genes (DEGs) related to processes such as steroid biosynthesis, PPAR signaling pathway, and fat digestion and absorption were identified in offspring rats in the PFOS exposure group. Ninety-five altered metabolites were exhibited in the PFOS exposure group, such as heptaethylene glycol, lysoPE (0:0/18:0), lucidenic acid K, and p-Cresol sulfate. DEGs associated with steroid biosynthesis, PPAR signaling pathway, fat digestion and absorption were significantly upregulated in the PFOS exposure group (P

Background: Intervertebral disc degeneration (IDD) is the most common chronic disease. Oxidative stress and apoptosis of nucleus pulposus (NP) cells disrupt intervertebral disc (IVD) homeostasis, which is the main cause of IDD. Glioma-associated oncogene 1 (Gli1) is an important transcription factor in the Hedgehog (Hh) pathway. Depletion of Gli1 accelerates the occurrence and development of degenerative diseases. This study aimed to explore the role of aging related Gli1 depletion in the progression of IDD. Methods: The relationship between aging related Gli1 depletion and IDD was studied in the NP tissues of human and rats of different ages, and the levels of oxidative stress and NP cell apoptosis during IDD were explored. Gli1 depletion of NP cells were established by targeting inhibitor GANT61 or lentivirus-coated Gli1 sh-RNA (sh-Gli1) to explore the role of Gli1 in NP cells and underlying mechanism. Exogenous Gli1 depletion induced IDD of rats was established by intraperitoneal injection of GANT61. Also, the roles of Fos in the Gli1 depletion induced NP cell oxidative stress, apoptosis and IDD were investigated. Results: Gli1 was down-regulated in the tissues of degenerative NP, and the level of Gli1 was negatively correlated with the severity of aging related IDD in human and rats. Furthermore, we found enhanced oxidative stress and apoptosis in degenerative NP tissues. Gli1 depletion promoted oxidative stress and apoptosis of NP cells and resulted in the degradation of extracellular matrix (ECM) and decreased ECM synthesis. Transcriptome sequencing showed that Gli1 depletion caused Fos activation in NP cells. the effect of Gli1 depletion on the oxidative stress and apoptosis of NP cells were retarded by Fos inhibitor. In vivo, Fos inhibition alleviated the IDD induced by exogenous Gli1 depletion. Conclusions: This study revealed for the first time that Gli1 is gradually depleted in NP with IDD progression. Exogenous Gli1 depletion causes oxidative stress and apoptosis of NP cells both in vivo and in vitro. Fos suppression effectively retards the destructive effects of Gli1 depletion on IVD homoeostasis.The translational potential of this article: This study may provide new potential targets for preventing and reversing IDD. Maintaining Gli1 expression in NP and suppressing Fos activation may be an effective treatment strategy for IDD.

Pulmonary fibrosis (PF) is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration (LAR). Here, we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells (AEC2s). The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells (AEC1s). We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s, which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK, two critical kinases supporting LAR, leading to LAR failure. TRIB3, a stress sensor, interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination. Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF. Our study reveals a mechanism of the TRIB3–MDM2–SLUG–SLC34A2 axis causing the LAR failure in PF, which confers a potential strategy for treating patients with fibroproliferative lung diseases.

Alpine grasslands are vital in regulating carbon balance on the Qinghai-Tibetan Plateau (QTP) because of the large soil organic carbon (SOC) stocks, while persistent disturbance from the endemic small semifossorial herbivore, plateau pika (Ochotona curzoniae, hereafter pika), may break this balance. Pika affect the soil microclimate by creating a heterogeneous underlying surface, which is expected to alter soil microbial communities and eventually SOC stocks. However, our knowledge regarding the potential influence mechanism is still limited. Here, we investigated vegetation biomass, soil properties and soil microbes among 4 different surfaces (i.e., original vegetation, new pika pile, old pika pile and bare patch) of typical alpine grasslands to reveal soil microbial communities and the associated effect on SOC in response to pika bioturbation. Our results showed that pika bioturbation increased both bacterial and fungal diversity and their phyla abundance for SOC decomposition. Vegetation biomass, electrical conductivity and NH4+-N accounted for the variation in both bacterial and fungal community compositions and diversity. SOC stocks were 15–30% lower in pika piles and bare patches than in the original vegetation, which was mainly attributed to the reduced soil organic matter input from vegetation and the enhanced SOC consumption by soil microbial communities. Overall, we conclude that pika bioturbation altered the diversity and composition of soil microbial communities, which was associated with SOC loss and positive carbon feedback in alpine grasslands. Our findings provide insights into the role of small semifossorial herbivores in the carbon cycle of global grasslands.

Summary: The sodium-activated Slo2.2 channel is abundantly expressed in the brain, playing a critical role in regulating neuronal excitability. The Na+-binding site and the underlying mechanisms of Na+-dependent activation remain unclear. Here, we present cryoelectron microscopy (cryo-EM) structures of human Slo2.2 in closed, open, and inhibitor-bound form at resolutions of 2.6–3.2 Å, revealing gating mechanisms of Slo2.2 regulation by cations and a potent inhibitor. The cytoplasmic gating ring domain of the closed Slo2.2 harbors multiple K+ and Zn2+ sites, which stabilize the channel in the closed conformation. The open Slo2.2 structure reveals at least two Na+-sensitive sites where Na+ binding induces expansion and rotation of the gating ring that opens the inner gate. Furthermore, a potent inhibitor wedges into a pocket formed by pore helix and S6 helix and blocks the pore. Together, our results provide a comprehensive structural framework for the investigation of Slo2.2 channel gating, Na+ sensation, and inhibition.

As an advanced material, ceramic matrix composites have attracted attention due to their superior properties, such as low density, high strength, and high-temperature resistance. However, it is also a typical difficult-to-cut material with the reinforcement and matrix material being of high hardness and brittleness, which makes the manufacturing of this kind of material an urgent problem. Ultrasonic vibration-assisted machining technique has advantages in decreasing cutting force, reducing tool wear, and improving machinability, making it suitable for machining hard and brittle difficult-to-cut materials. This paper has investigated ultrasonic vibration-assisted milling-grinding SiC fiber reinforced ceramic matrix composite. It aims to understand the feasibility of machining this advanced material and tool performance. Experimental results found that the ultrasonic vibration-assisted machining technique with the proper tool would be a suitable method for this advanced material. The self-designed polycrystalline diamond compact tool had a better performance and tool life. Its tool life was 4.11 times, 12 times, and 50.63 times as long as commonly used 50 mesh brazed diamond tool, 200 mesh brazed diamond tool and 100 mesh electroplated diamond tool, respectively. For a smaller cutting force and tool wear, machining parameters of a more considerable spindle speed, lower feed speed, and small cutting depth would be suggested, with ultrasonic amplitude being 4 μm and frequency being 30 kHz.

The increasing anthropogenic heat, which is emitted from human activities and energy consumption in urban areas and migrates to the atmosphere, significantly alters surface energy balances and the local climate and in turn generates urban heat islands (UHIs). Anthropogenic heat flux (AHF) has been estimated with energy balance residual and inventory methods. However, these methods have large uncertainty and fail to further explore the spatial distribution of anthropogenic heat at large scales due to limited data availability and the complexities of human activities, urban geometry, landscapes and building thermal properties. From the heat sources of the UHIs and based on thermodynamics, this study deduces that the AHE difference between urban and surrounding rural areas can be quantified as the residual of the heat for increasing UHIs and the heat difference from natural radiation between urban and rural areas. Thus, an urban anthropogenic heat index (UAHI) is proposed to quantify the contribution of AHF to UHIs, as a proxy of AHF. The UAHI is generated using the normalized differences in urban–rural land surface temperature (LST) and albedo derived from both Landsat and MODIS data. We investigate the spatial and temporal association between the UAHI and AHF in Beijing. The results demonstrated that the average annual UAHIs in Beijing ranged from 0.168 to 0.208 and steadily improved in the last decade. The UAHI can represent detailed spatial heterogeneity and temporal variations in AHF with correlation coefficients in the range from 35% to 50%. UAHI can also identify the dynamics of AHF hotspots and the heating and cooling sources in Beijing. Overall, the UAHI is a convincing indicator of the contribution of urban anthropogenic heat to UHIs, providing a new option for quantifying AHF dynamics and improving the knowledge of urban thermal environments.

Emerging epidemiological evidence has linked per- and polyfluoroalkyl substances (PFAS) exposure could be linked to the disturbance of gestational glucolipid metabolism, but the toxicological mechanism is unclear, especially when the exposure is at a low level. This study examined the glucolipid metabolic changes in pregnant rats treated with relatively low dose perfluorooctanesulfonic acid (PFOS) through oral gavage during pregnancy [gestational day (GD): 1–18]. We explored the molecular mechanisms underlying the metabolic perturbation. Oral glucose tolerance test (OGTT) and biochemical tests were performed to assess the glucose homeostasis and serum lipid profiles in pregnant Sprague-Dawley (SD) rats randomly assigned to starch, 0.03 and 0.3 mg/kg·bw·d groups. Transcriptome sequencing combined with non-targeted metabolomic assays were further performed to identify differentially altered genes and metabolites in the liver of maternal rats, and to determine their correlation with the maternal metabolic phenotypes. Results of transcriptome showed that differentially expressed genes at 0.03 and 0.3 mg/kg·bw·d PFOS exposure were related to several metabolic pathways, such as peroxisome proliferator-activated receptors (PPARs) signaling, ovarian steroid synthesis, arachidonic acid metabolism, insulin resistance, cholesterol metabolism, unsaturated fatty acid synthesis, bile acid secretion. The untargeted metabolomics identified 164 and 158 differential metabolites in 0.03 and 0.3 mg/kg·bw·d exposure groups, respectively under negative ion mode of Electrospray Ionization (ESI-), which could be enriched in metabolic pathways such as α-linolenic acid metabolism, glycolysis/gluconeogenesis, glycerolipid metabolism, glucagon signaling pathway, glycine, serine and threonine metabolism. Co-enrichment analysis indicated that PFOS exposure may disturb the metabolism pathways of glycerolipid, glycolysis/gluconeogenesis, linoleic acid, steroid biosynthesis, glycine, serine and threonine. The key involved genes included down-regulated Ppp1r3c and Abcd2, and up-regulated Ogdhland Ppp1r3g, and the key metabolites such as increased glycerol 3-phosphate and lactosylceramide were further identified. Both of them were significantly associated with maternal fasting blood glucose (FBG) level. Our findings may provide mechanistic clues for clarifying metabolic toxicity of PFOS in human, especially for susceptible population such as pregnant women.

Despite increasing concerns about the detrimental effects of air pollution on respiratory health, limited evidence is available on these effects in the Hong Kong population, especially in children. In this prospective cohort study between 2012 and 2017, we aimed to investigate the associations between exposure to air pollution (concentrations of fine particulate matter [PM2.5] and nitrogen dioxide [NO2]) and respiratory health (lung function parameters and respiratory diseases and symptoms) in schoolchildren. We recruited 5612 schoolchildren aged 6–16 years in Hong Kong. We estimated the annual average concentrations of ambient PM2.5 and NO2 at each participant’s address using spatiotemporal models. We conducted spirometry tests on all participants to measure their lung function parameters and used a self-administered questionnaire to collect information on their respiratory diseases and symptoms and a wide range of covariates. Linear mixed models were used to investigate the associations between exposure to air pollution and lung function. Mixed-effects logistic regression models with random effects were used to investigate the associations of exposure to air pollution with respiratory diseases and symptoms. In all of the participants, every 5-μg/m3 increase in the ambient PM2.5 concentration was associated with changes of − 13.90 ml (95 % confidence interval [CI]: −23.65 ml, −4.10 ml), − 4.20 ml (−15.60 ml, 7.15 ml), 27.20 ml/s (−3.95 ml/s, 58.35 ml/s), and − 19.80 ml/s (−38.35 ml/s, −1.25 ml/s) in forced expiratory volume in 1 s, forced vital capacity, peak expiratory flow, and maximal mid-expiratory flow, respectively. The corresponding lung function estimates for every 5-μg/m3 increase in the ambient NO2 concentration were − 2.70 ml (−6.05 ml, 0.60 ml), − 1.40 ml (−5.40 ml, 2.60 ml), − 6.60 ml/s (−19.75 ml/s, 6.55 ml/s), and − 3.05 ml/s (−11.10 ml/s, 5.00 ml/s), respectively. We did not observe significant associations between PM2.5/NO2 exposure and most respiratory diseases and symptoms. Stratified analyses by sex and age showed that the associations between exposure to air pollution and lung function parameters were stronger in male participants and older participants (11–14 year old group) than in female participants and younger participants (6–10 year old group), respectively. Our results suggest that chronic exposure to air pollution is detrimental to the respiratory health of schoolchildren, especially that of older boys. Our findings reinforce the importance of air pollution mitigation to protect schoolchildren’s respiratory health.

Ground-level ozone (O3) pollution has received widespread attention because its rising trend and adverse ecological impacts. However, the extremely strong photochemical reactions of its precursor volatile organic compounds (VOCs) increase the difficulty of reducing VOCs emissions to alleviate O3. Here, we carried out a one-year comprehensive observation in two representative cities, Tianjin (TJ, Northern China) and Guangzhou (GZ, Southern China). By revealing the concentration characteristics of three different types of VOCs, i.e., initial VOCs without photochemical reaction (In-VOCs), consumed VOCs (C-VOCs), and measured VOCs after the reaction (M-VOCs), we elucidated the important role of C-VOCs in the formation of O3. Although the overall trends were similar in both cities, the average concentration level of VOCs in GZ was 8.2 ppbv higher than that in TJ, and the photochemical loss of VOCs was greater by 2.2 ppbv. In addition, various drivers affecting O3 generation from C-VOCs were specifically explored, and it was found that most alkenes of TJ were key substances for rapid O3 formation compared to aromatics of GZ. Meanwhile, favorable meteorological conditions such as high temperature (T > 31 °C in TJ, and T > 33 °C in GZ), low relative humidity (56% in TJ and 45% in GZ), and stable atmospheric environment (proper pressure and gentle wind speed) also contribute to the generation of O3. More importantly, we combined chemical kinetics and receptor model to quantify the three-type VOCs source contributions and assess the potential impact of C-VOCs sources on O3 production, thus proposing environmental abatement technologies corresponding to the three types of VOCs. The differences in the comparison results of the three-type VOCs highlight the need to reduce O3 pollution from C-VOCs sources, which provides insights for future clean air policies development.

Understanding changes of ecosystem services and their influencing factors is crucial for more sustainable ecosystem management and conservation of nature contributions to people, especially in regions suffering high pressure from climate change and human activities, such as the Nordic countries. In this study, we assess multiple ecosystem services and their influencing factors in Denmark, Finland, Norway, and Sweden. We analyze changes in ecosystem services such as habitat quality, sediment retention, water yield, carbon sequestration, crop and roundwood production between 2003 and 2018. The relationships between ecosystem services and the main influencing factors (temperature, precipitation, elevation, population, livestock, and land use change) are assessed by means of the Spearman’s correlation coefficient and a new method that unravels synergies or tradeoffs at a grid level. Given the importance of forest management in the study region, an advanced land cover dataset that includes maps of forest harvest is produced and used as a basis for the analysis. Results show the large changes in ecosystem services during the study period and their spatial variations. Overall, the habitat quality is decreased, especially in the sites affected by forest management and agricultural production. Water yield and sediment retention increased due to higher precipitation (mainly in Norway). Higher temperature and forest management have generally increased carbon sequestration and provisioning services. The relationship between ecosystem services and their potential influencing factors differs across space. There are 10 out of 15 pairs of ecosystem services that predominantly show a tradeoff relationship, while the rest shows a synergy. In general, our results show the importance to monitor ecosystem services and understand the main drivers of their changes, so to design more sustainable resource management strategies that can secure a long-term delivery of ecosystem services.

KRAS is the most commonly mutated oncogene in human cancers with limited therapeutic options, thus there is a critical need to identify novel targets and inhibiting agents. The 78-kDa glucose-regulated protein GRP78, which is upregulated in KRAS cancers, is an essential chaperone and the master regulator of the unfolded protein response (UPR). Following up on our recent discoveries that GRP78 haploinsufficiency suppresses both KRASG12D-driven pancreatic and lung tumorigenesis, we seek to determine the underlying mechanisms. Here, we report that knockdown of GRP78 via siRNA reduced oncogenic KRAS protein level in human lung, colon, and pancreatic cancer cells bearing various KRAS mutations. This effect was at the post-transcriptional level and is independent of proteasomal degradation or autophagy. Moreover, targeting GRP78 via small molecule inhibitors such as HA15 and YUM70 with anti-cancer activities while sparing normal cells significantly suppressed oncogenic KRAS expression in vitro and in vivo, associating with onset of apoptosis and loss of viability in cancer cells bearing various KRAS mutations. Collectively, our studies reveal that GRP78 is a previously unidentified regulator of oncogenic KRAS expression, and, as such, augments the other anti-cancer activities of GRP78 small molecule inhibitors to potentially achieve general, long-term suppression of mutant KRAS-driven tumorigenesis.

Priestley-Taylor equation (PT) and the Penman-Monteith equation (PM) are commonly used methods for regional evapotranspiration monitoring, using the PT coefficient (αa) and PM crop/ vegetation coefficient (Kc). This paper investigates the seasonal changes in αa and Kc at five sites in Australia and China, to understand the relationship between environmental conditions and evapotranspiration when applying different evaporation estimation methods. The research shows that higher actual evapotranspiration does not lead to higher αa and Kc values. αa and Kc perform similarly in cropland and forest environments in both China and Australia. Both αa and Kc continuously increase to a peak during the growing season and then decrease to their lowest values during the winter season. Considering Kc’s similar performance to αa and its greater data processing requirements, Kc has few advantages for estimating regional evapotranspiration. Applying the Priestley-Taylor equation with a regional α indicator will enhance the accuracy and reduce the workload when estimating regional evapotranspiration for similar landcover types based on remote sensing.

The COVID-19 pandemic continues to threaten global public health. Reliable assessment of community vulnerability is therefore essential to fighting and mitigating the pandemic. This study presents a framework that considers the roles of internal and external factors, including the components of social vulnerability, exposure, and sensitivity, to comprehensively and accurately assess community vulnerability to the pandemic. With respect to internal factors, we summarized the inherent social characteristics of people groups using census data and explored the roles of both overall and four major thematic social vulnerabilities in shaping community infection by COVID-19. We then designed two external factors to characterize exposure and sensitivity and implemented an aggregation by multiplying them with the internal social vulnerability to achieve a comprehensive vulnerability assessment. The role of the estimated vulnerability in shaping community infection was evaluated by statistical and spatial analysis as well as by risk factor classification using defined rules. This case study of Hong Kong demonstrated the value of our framework in vulnerability assessment and revealed the role of vulnerability in shaping community infection by COVID-19.

Cluster of differentiation 47 (CD47)/signal regulatory protein alpha (SIRPα) is a negative innate immune checkpoint signaling pathway that restrains immunosurveillance and immune clearance, and thus has aroused wide interest in cancer immunotherapy. Blockade of the CD47/SIRPα signaling pathway shows remarkable antitumor effects in clinical trials. Currently, all inhibitors targeting CD47/SIRPα in clinical trials are biomacromolecules. The poor permeability and undesirable oral bioavailability of biomacromolecules have caused researchers to develop small-molecule CD47/SIRPα pathway inhibitors. This review will summarize the recent advances in CD47/SIRPα interactions, including crystal structures, peptides and small molecule inhibitors. In particular, we have employed computer-aided drug discovery (CADD) approaches to analyze all the published crystal structures and docking results of small molecule inhibitors of CD47/SIRPα, providing insight into the key interaction information to facilitate future development of small molecule CD47/SIRPα inhibitors.

RNA sequencing (RNA-seq)-based whole transcriptome analysis (WTA) using ever-evolving next-generation sequencing technologies has become a primary tool for coding and/or noncoding transcriptome profiling. As WTA requires RNA-seq data for both coding and noncoding RNAs, one key step for obtaining high-quality RNA-seq data is to remove ribosomal RNAs, which can be accomplished by using various commercial kits. Nonetheless, an ideal rRNA removal method should be efficient, user-friendly and cost-effective so it can be adapted for homemade RNA-seq library construction. Here, we developed a novel reverse transcriptase-mediated ribosomal RNA depletion (RTR2D) method. We demonstrated that RTR2D was simple and efficient, and depleted human or mouse rRNAs with high specificity without affecting coding and noncoding transcripts. RNA-seq data analysis indicated that RTR2D yielded highly correlative transcriptome landscape with that of NEBNext rRNA Depletion Kit at both mRNA and lncRNA levels. In a proof-of-principle study, we found that RNA-seq dataset from RTR2D-depleted rRNA samples identified more differentially expressed mRNAs and lncRNAs regulated by Nutlin3A in human osteosarcoma cells than that from NEBNext rRNA Depletion samples, suggesting that RTR2D may have lower off-target depletion of non-rRNA transcripts. Collectively, our results have demonstrated that the RTR2D methodology should be a valuable tool for rRNA depletion.

Chronic myeloid leukemia (CML) is a malignancy that evolves through a multi-step process. Alternative splicing of several genes has been linked to the progression of the disease, but involvement of alternations in splicing profiles has not been reported. RNA-seq of peripheral blood mononuclear cell (PBMC) samples characterized the differentially expressed and spliced transcripts in five CML chronic phase (CP) and five blast phase (BP) patients, and five healthy controls. Global splicing alteration analysis detected 6474 altered splicing events altered between CML and healthy samples, including many of the previously reported splicing variants and showing a more profound altered splicing deregulation in BP samples. Functional clustering of differentially spliced genes in CP revealed a preferred enrichment relating to cell signaling, while the spliceosome pathway was most overrepresented in BP samples. One differentially spliced spliceosome gene hnRNPA1 showed two splice isoforms; the longer isoform contained exon 8 was preferentially expressed in the BP patients, and the short one excluding exon 8 was specific to healthy controls. Our findings suggested that alternative splicing deregulation played a central role during the progression of CML from CP to BP, and the longer isoform of hnRNPA1 might represent a diagnostic marker and therapeutic target for CML.

Abstract: Thrombocytopenia is associated with life-threatening bleeding and is common in myelodysplastic syndromes (MDS). Robust molecular prognostic biomarkers need to be developed to improve clinical decision making for patients with MDS with thrombocytopenia. Wilms tumor 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) are promising immunogenic antigen candidates for immunotherapy, and their clinical effects on patients with MDS with thrombocytopenia are still not well understood. We performed a multicenter observational study of adult patients with MDS with thrombocytopenia from 7 different tertiary medical centers in China. We examined bone marrow samples collected at diagnosis for WT1 and PRAME transcript levels and then analyzed their prognostic effect for patients with MDS with thrombocytopenia. In total, we enrolled 1110 patients diagnosed with MDS with thrombocytopenia. Overexpression of WT1 and PRAME was associated with elevated blast percentage, worse cytogenetics, and higher Revised International Prognostic Scoring System (IPSS-R) risk. Further, both WT1 and PRAME overexpression were independent poor prognostic factors for acute myeloid leukemia evolution, overall survival, and progression-free survival. Together, the 2 genes overexpression identified a population of patients with MDS with substantially worse survival. On the basis of WT1 and PRAME transcript levels, patients with MDS with IPSS-R low risk were classified into 2 significantly divergent prognostic risk groups: a low-favorable group and a low-adverse group. The low-adverse group had survival similar to that of patients in the intermediate-risk group. Our study demonstrates that the evaluation of WT1/PRAME transcript analysis may improve the prognostication precision and better risk-stratify the patients.

Good-quality emission data are essential to validate national climate commitments and implement domestic policies. However, conventional bottom-up data collection is costly and subject to potential manipulation by stakeholders when data pass through their hands, which could pose challenges on the efficiency and effectiveness of compliance monitoring especially in developing countries. Satellite observations, specifically OCO-2 XCO2 measurements, are utilized in this study to develop a relatively independent and timely dataset for screening the attainment statuses of national and subnational CO2 mitigation goals in China’s 13th Five-Year Plan (FYP, 2016–2020). We establish CO2 emission estimation models at both pixel and provincial levels. As interpolated with the pixel-level model, CO2 emissions of prefecture-level municipalities indicate that approximately three fifth of them had accomplished their individualized FYP mitigation goals by 2019, while our provincial-level estimation suggests that three quarters of provinces had attained theirs. More resources for compliance monitoring could thus be directed to other presumably-unattaining local governments. National aggregate absolute emissions showed 8.0–18.3% reduction in 2019 across three provincial models from the 2015 level, while national CO2 intensity dropped by 28.8–36.8% to imply attaining the 18% reduction goals.

The burrowing activity of plateau pikas (Ochotona curzoniae; hereafter, pikas) may profoundly influence vegetation species composition on the Qinghai-Tibetan Plateau (QTP). Although significant efforts have been made to examine the relationship between vegetation species composition and pikas disturbance, our knowledge regarding the direct influence of pikas activity on vegetation species diversity is still limited. We conducted field observations on pikas burrows and surrounding vegetation patches at 23 alpine grassland sites to investigate this effect. When compared to vegetation patches, pikas burrowing activity decreased soil hardness, thus improving water infiltration, while caused the less reduction of soil nutrition and soil moisture when compared to adjacent vegetation patches. Vegetation species composition on pikas burrows significantly differed from that on vegetation patches. Common plant species between pikas burrows and vegetation patches were fewer than three in all types of grasslands, and ten species were found exclusively on pikas burrows. The total species richness, including both pikas burrows and vegetation patches, was approximately 1.3–2.5 times higher than that on each single patch type (pikas burrows or vegetation patches). A conceptual framework was proposed to synthesize the evolution of vegetation species composition under a disturbance regime resulting from pika’s burrowing. Overall, we concluded that pika’s burrowing activity enhanced vegetation species richness by loosening the soil, creating safe sites for seed settling and germination, which provided a novel habitat for vegetation invasion.

Background: Since the first report in 2008 of cases of anaplastic lymphoma kinase (ALK)-positive histiocytosis, originally described as a systemic, self-limiting disease in infants, the range of ALK-positive histiocytosis has been expanded to include localized diseases in older children and adults. Case presentation: We present the case of an 18-year-old woman with a periumbilical painless mass for 5 months who underwent resection of the mass. Pathological examination showed that the tumour consisted predominantly of fascicular to storiform growth of nonatypical spindle cells admixed with lymphocytic infiltrates. The tumour spindle cells were diffusely positive for CD68, CD163 and ALK. Further molecular tests revealed an ALK gene fusion with Kinesin Family Member 5B (KIF5B) (E24)-ALK (E20), confirming ALK-positive histiocytosis. Follow-up at one and a half years after resection showed no tumour recurrence. Conclusion: Remission of ALK-positive histiocytosis in local lesions can be achieved by complete resection, and clinical follow-up shows a favourable prognosis.

Recurrent hydatidiform mole (RHM) is characterized by the occurrence of at least twice hydatidiform mole. Unlike sporadic complete hydatidiform moles (CHMs), which are androgenetic with 2 paternal chromosomes, CHMs associated with familial recurrence are genetically biparental with a maternal and a paternal chromosome. NLRP7 mutations have been reported in 55% of RHM cases. Here, we generated induced pluripotent stem cells (iPSCs) from a patent with NLRP7 gene mutation c.1261C > T by reprogramming peripheral blood mononuclear cells by non-integrated method. The resulting iPSCs carrying NLRP7 mutation, had normal karyotype, expressed pluripotency markers, and could differentiate into three germ layers in vivo.

W-K-TiC alloys with different titanium carbide concentrations (0.05, 0.1, 0.25, 0.5, 1, 2) wt.% were fabricated through Mechanical Alloying and Spark Plasma Sintering. The effects of the addition of nano-scaled TiC particles on the relative density, Vickers micro-hardness, microstructure, crystal information, thermal shock resistance, and tensile strength were investigated. It is revealed that the doped TiC nano-particles located at the grain boundaries. The relative density and Vickers micro-hardness of W-K-TiC alloys was enhanced with TiC addition and the highest Vickers micro-hardness is 731.55. As the TiC addition increased from 0.05 to 2 wt%, the room-temperature tensile strength raised from 141 to 353 MPa. The grain size of the W-K-TiC alloys decreased sharply from 2.56 μm to 330 nm with the enhanced TiC doping. The resistance to thermal shock damage of W-K-TiC alloys was improved slightly with the increased TiC addition. Keywords: Potassium-doped tungsten, Titanium carbide, Spark plasma sintering, Tensile strength, Thermal shock

Background: Cardiac hypertrophy is a key pathological process in the context of diabetic cardiomyopathy. Naringenin exhibits multiple pharmacological activities, but the effect of naringenin on cardiomyocyte hypertrophy under diabetic conditions is still far from clear. Methods: Cardiomyocyte hypertrophy was induced by high glucose (HG, glucose at 25.5 mmol/L) in H9c2 cells, which was determined by cell surface area, protein content and atrial natriuretic factor (ANF) mRNA expression. The effect of naringenin on cardiomyocyte hypertrophy was observed and its mechanisms were investigated by administration with various inhibitors on epoxyeicosatrienoic acids (EETs)/peroxisome proliferator-activated receptors (PPARs). The level of 14,15-EET was measured by ELISA. The mRNA and protein expressions were detected by qRT-PCR or Western blot, respectively. Results: Naringenin (0.1, 1, 10 μmol/L) inhibited cardiomyocyte hypertrophy in a concentration-dependent manner (P

MicroRNAs (miRNAs) are an evolutionarily conserved class of small regulatory noncoding RNAs, binding to complementary target mRNAs and resulting in mRNA translational inhibition or degradation, and they play an important role in regulating many aspects of physiologic and pathologic processes in mammalian cells. Thus, efficient manipulations of miRNA functions may be exploited as promising therapeutics for human diseases. Two commonly used strategies to inhibit miRNA functions include direct transfection of chemically synthesized miRNA inhibitors and delivery of a gene vector that instructs intracellular transcription of miRNA inhibitors. While most miRNA inhibitors are based on antisense molecules to bind and sequester miRNAs from their natural targets, it is challenging to achieve effective and stable miRNA inhibition. Here we develop a user-friendly system to express circular inhibitors of miRNA (CimiRs) by exploiting the noncanonical head-to-tail backsplicing mechanism for generating endogenous circular RNA sponges. In our proof-of-principle experiments, we demonstrate that the circular forms of the hsa-miR223-binding site of human β-arrestin1 (ARRB1) 3′ UTR sponge RNA (BUTR), the bulged anti-miR223 (cirBulg223) and bulged anti-miR21 (cirBulg21), exhibit more potent suppression of miRNA functions than their linear counterparts. Therefore, the engineered CimiR expression system should be a valuable tool to target miRNAs for basic and translational research. Keywords: microRNA, miRNA, miRNA sponge, circular RNA, miRNA inhibitor, competing endogenous RNA, miRNA decoy, noncoding RNA, oncomiR

Objective: A growing evidence demonstrates that inflammation is a major contributor to the pathogenesis of pulmonary arterial hypertension (PAH). However, blocking inflammation has only been shown to be of minor clinical benefit due to a lack of understanding of the precise inflammation present in PAH. Thus, the present study aimed to investigate characteristics of inflammatory process in PAH induced by monocrotaline (MCT) in rats. Methods: Adult male Sprague-Dawley rats received a single dose of MCT (50 mg/kg, ip), and the occurrence of PAH and inflammation biomarkers were measured at 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30 days after MCT injection. Results: From the 6th day after the injection of MCT, the mean pulmonary artery pressure gradually increased and doubled on the 30th day, accompanied by right ventricular hypertrophy and pulmonary arterial remodeling in a time-dependent manner. In the first 6 days after MCT treatment, only pro-inflammatory cytokines TNF-α, IL-1β increased, which was defined as acute inflammatory phase, after that, both pro-inflammatory factors TNF-α, IL-1β, IL-6, IL-12 and anti-inflammatory factors Arg1, IL-10, TGF-β increased, which was defined as chronic inflammatory phase. The M1/M2 macrophage ratios in lung and alveolar lavage fluid were elevated on the 6th and 30th day, moreover, which were higher on the 6th than 30th day, and the PI3K/Akt signaling pathway increased along with the progression of PAH and correlated with pro-inflammatory proteins, which revealed also to some extent the characteristics of inflammation of PAH induced by MCT. Conclusion: The course of PAH induced by MCT injection is progressive with persistent inflammation, which is defined as acute inflammatory phase within 6 days after MCT treatment, after that, is defined as chronic inflammatory phase.

Synthetic dyes have caused serious ecological and environmental threats in our daily lives. Effective and inexpensive dye-degradation methods are desperately perused for decades. In this work, ultrasonic-vibration treatment is found as an effective approach that can dramatically improve the degradation performance of industrial Fe78Si9B13 amorphous powders towards methylene blue. As demonstrated by synchrotron X-ray nano-computed tomography and scanning electron microscope combined with X-ray photoelectron spectroscopy, the micro-channels on the surface or inside of Fe78Si9B13 particles offer a shortcut for fast mass transfer and supply plenty of reactive sites with low density and high energy due to the structural rejuvenation after ultrasonic vibration. It leads to the reduction of the reaction activation energy of degradation under the pseudo-first-order kinetic model and an exceptional decomposition capacity. Our work not only extremely drives down the current costs of wastewater treatments, but also provides a promising approach for tuning the effectivity of alloying catalysts via manipulating the potential energy state of metallic glasses based on the high-frequency mechanical vibration technique.

Satellite-based human settlement extraction methods have limited practical applications, due to merely studying the difference between human settlements and other land cover/use types in physical attributes (e.g., spectral signature and land surface temperature) instead of considering basic anthropogenic attributes (e.g., human distribution and human activities). To deal with this challenge, we proposed a novel method to accurately extract human settlements by integrating mobile phone locating-request (MPL) data and remotely sensed data. In this study, human settlements for selected cities were mapped at a medium resolution (30 ​m) by redistributing the MPL data using Landsat Normalized Difference Vegetation Index (NDVI) adjusted weights, with an overall accuracy of above 90.0%. Additionally, by extending the proposed method to the MPL and Moderate Resolution Imaging Spectroradiometer (MODIS) data, a coarse-resolution (250 ​m) map of human settlements in China was created with an overall accuracy of 95.2%. Compared with the widely used nighttime light based methods, the proposed method could solve the long-existing problems such as data saturation and blooming effects, as well as characterizing human settlements with fine spatial details. Our study provides an alternative approach to human settlement extraction by combining its physical and anthropogenic attributes, and it can be easily adjusted with multi-scale remotely sensed data and applied to human settlement extraction at different scales.

Nine hundred data were collected from rigorously simulated EHIDiC for propylene/propane separation using the Aspen Plus-Matlab communication platform. Statistical analysis was performed to give a further understanding of EHIDiC, a highly coupled system. The input variables, integrated stages, and the corresponding heat of two couples of external exchangers were generated stochastically in a wide range to cover the completely reasonable operation window. The results of blocks and streams in the flowsheet were calculated as the output data, including the flow rate, the temperature, and the pressure, as well as Total Annualized Cost (TAC). The data can be reused to design and optimize both the steady and dynamic schemes of EHIDiC, especially with machine learning methods. This manuscript gave a full description of collecting and analyzing of the data used in the research article “Data-driven analysis and optimization of externally heat-integrated distillation columns (EHIDiC)” [1].

Summary: Embryonic stem cells (ESCs) exhibit high levels of ribosomal RNA (rRNA) transcription and ribosome biogenesis. Here, we reveal an unexpected role for an essential DEAD-box helicase, DDX18, in antagonizing the polycomb repressive complex 2 (PRC2) to prevent deposition of the repressive H3K27me3 mark onto rDNA in pluripotent cells. DDX18 binds and sequesters PRC2 in the outer layer of the nucleolus and counteracts PRC2 complex formation in vivo and in vitro. DDX18 knockdown leads to increased occupancy of PRC2 and H3K27me3 at rDNA loci, accompanied by drastically decreased rRNA transcription and reduced ribosomal protein expression and translation. Auxin-induced rapid degradation of DDX18 enhances PRC2 binding at rDNA. The inhibition of PRC2 partially rescues the effects of DDX18 depletion on rRNA transcription and ESC self-renewal. These results demonstrate a critical role for DDX18 in safeguarding the chromatin and transcriptional integrity of rDNA by counteracting the epigenetic silencing machinery to promote pluripotency. : Zhang et al. report an interplay between the DEAD-box helicase DDX18 and the polycomb repressive complex 2 (PRC2) in governing the hyperactive state of ribosomal DNA in pluripotency regulation. DDX18 counteracts PRC2 complex formation and prevents PRC2 binding and aberrant histone methylation at rDNA loci. Keywords: stem cell pluripotency, DDX18, RNA-binding protein, PRC2, rRNA transcription, rDNA loci, nucleolus

Polydatin has a wide range of pharmacological activities, yet the underlying effects on diabetic hepatopathy remain unclear. Diabetic model was established by feeding mice a high-energy diet for 4 weeks combined with streptozotocin, then hepatopathy model was confirmed by histopathological observation after another 4 weeks. Polydatin supplementation (50 or 100 mg/kg/day, i.g.) for an additional 4 weeks improved signs of liver damage compared to untreated mice. The protein and mRNA expressions of PPARs were down-regulated, while of NF-κB, iNOS and COX-2 were up-regulated following diabetic hepatic injury, and TNF-α and IL-1β were increased in serum. Polydatin supplementation up-regulated PPAR-β expression, but elevated PPAR-α only at 100 mg/kg/day, while had no influence on PPAR-γ. Polydatin also corrected the above abnormal proinflammatory cytokines levels. In conclusion, polydatin can improve hepatic injury in diabetic mice, which may be due to a reduction of proinflammatory cytokines through the promoted expressions of PPAR-β and -α.

Dual Functional Lithium Lead (DFLL) blanket was proposed for its advantages of high energy exchange efficiency and on-line tritium extraction, and it was selected as the candidate test blanket module (TBM) for China Fusion Engineering Test Reactor (CFETR) and the blanket for Fusion Design Study (FDS) series fusion reactors. Considering the influence of high energy fusion neutron irradiation and high heat flux thermal load on the blanket, China Low Activation Martensitic (CLAM) steel was selected as the structural material for DFLL blanket. The structure of the blanket and the cooling internal components were pretty complicated. Meanwhile, high precision and reliability were required in the blanket fabrication. Therefore, several welding techniques, such as hot isostatic pressing diffusion bonding, tungsten inner gas welding, electron beam welding and laser beam welding were developed for the fabrication of cooling internals and the assembly of the blanket. In this work, the weldability on CLAM steel by different welding methods and the properties of as-welded and post-weld heat-treated joints were investigated. Meanwhile, the welding schemes and the assembly strategy for TBM fabrication were raised. Many tests and research efforts on scheme feasibility, process standardization, component qualification and blanket assembly were reviewed.

Background: Air pollution undermines people's physical health. So why wouldn't people take actions to reduce air pollution? We argue that social preferences might play a part. Specifically, we examined the links between air pollution, interpersonal trust, and preferences to buy so-called sin stocks (companies that polluted the environment). Because previous research has shown that high pollution induces a belief in immorality as a social norm (akin to “broken-window” effect), we predicted that pollution is linked to lower trusting and trustworthy behaviours, and higher likelihood to buy sin stocks. Second, we examined the moderating role of participants' subjective socioeconomic status (SSES). Specifically, previous studies have shown that low SSES induces a feeling of deprivation and higher vulnerability. Therefore, we predicted an interaction between pollution and SSES, such that low SSES participants in highly polluted environment should display the lowest levels of trusting and trustworthy behaviours, and highest likelihood to buy sin stock. Methods: We recruited 4177 participants residing in 31 provinces of mainland China during January, 2018. Participants were asked to play three incentivised behavioural games measuring their likelihood to buy sin stocks, trusting behaviour, and trustworthiness, respectively. We disseminated our survey via a mobile phone application, making it possible to pay the participants according to their performance on the games, and estimate the instantaneous, real-time air pollution (PM2·5) from dynamic monitoring station data based on each participant's GPS information. Findings: We found a robust main effect of pollution and an interaction effect between SSES and real-time PM2·5 levels, as we had predicted. Interpretation: Our findings counter the common wisdom that people are motivated to take actions to improve their own environment. Instead, a polluted environment could create a bad norm that undermines trust and environmental protection. Funding: Partial funding came from a seed grant for the Chinese University of Hong Kong (CUHK)—Chinese Academy of Social Sciences (CASS) Research Collaboration on Social Psychology offered by the Research Committee of CUHK.

Degenerative cartilage endplate (CEP) shows decreased chondrification and increased ossification. Cartilage endplate stem cells (CESCs), with the capacity for chondro-osteogenic differentiation, are responsible for CEP restoration. CEP is avascular and hypoxic, while the physiological hypoxia is disrupted in the degenerated CEP. Hypoxia promoted chondrogenesis but inhibited osteogenesis in CESCs. This tissue-specific differentiation fate of CESCs in response to hypoxia was physiologically significant with regard to CEP maintaining chondrification and refusing ossification. MIF, a downstream target of HIF1A, is involved in cartilage and bone metabolisms, although little is known about its regulatory role in differentiation. In CESCs, MIF was identified as a key point through which HIF1A regulated the chondro-osteogenic differentiation. Unexpectedly, unlike the traditionally recognized mode, increased nuclear-expressed MIF under hypoxia was identified to act as a transcriptional regulator by interacting with the promoter of SOX9 and RUNX2. This mode of HIF1A/MIF function may represent a target for CEP degeneration therapy.