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The ovary is an important reproductive and endocrine organ for the continuation of the species and the homeostasis of the body's internal environment. Arsenic exposure is a global public health problem. However, the damage to the ovaries caused by exposure to arsenic-contaminated drinking water from neonatal mice period remains unclear. Here, we showed that arsenic exposure resulted in reduced granulosa cell proliferation, diminished ovarian reserve, decreased oogenesis, and endocrine disruption in mice. Mechanistically, arsenic exposure decreased the protein level of METTL3 in granulosa cells. The m6A modification levels of mitophagy regulated gene BNIP3 in 3’UTR region was decreased in arsenic exposed granulosa cells. Meanwhile, YTHDF2, which decays mRNA, bound to the 3′UTR region of BNIP3 was also decreased in arsenic exposed ovarian granulosa cells. Thus, BNIP3 mRNA becames more stable, and mitophagy was increased. The excessive mitophagy in granulosa cells led to endocrine disruption, follicular atresia and diminished ovarian reserve. In summary, our study reveals that METTL3-dependent m6A modification regulates granulosa cell mitophagy and follicular atresia by targeting BNIP3 which are induced by arsenic exposure.

Aiming at the problems of low processing efficiency, low groove shape accuracy and poor surface quality caused by grinding wheel wear in the grinding process of Cf/SiC composite grooves. In this paper, based on the motion mode of grinding wheel grinding, the wear volume formula of grinding wheels was analyzed, and the grinding wheel wear comparison experiment of different bond diamond grinding wheels grinding Cf/SiC composite grooves was carried out, and the more suitable kind of diamond grinding wheel for grinding Cf/SiC composite grooves was selected. From the experimental results, compared with the ceramic-bonded diamond wheel and resin-bonded diamond wheel, the grinding times of electroplated diamond wheel grinding Cf/SiC composites were increased by 20 and 104, respectively, and the surface roughness of the groove was most stable and the processing damage was smallest. Therefore, the best quality of grinding Cf/SiC composites groove was obtained by the electroplated diamond grinding wheel, and its life in grinding Cf/SiC composites was the longest. At the same time, the wear mechanism of the electroplated grinding wheel was explored, the wear on the bottom surface of the electroplated grinding wheel was more serious than that on the circumferential surface. The wear on the bottom surface was mainly wear and tear, and it gradually diffused along the inner diameter of the grinding wheel with the increasing grinding times.

In this paper, the Vickers indentation experiments were carried out under different loads on the polished surface of polycrystalline yttrium aluminum garnet (YAG) ceramics to investigate the surface fracture behavior and subsurface damage under quasi-static conditions. The surface of polycrystalline YAG ceramic was corroded for intuitively observing the surface fracture behavior under quasi-static load, and the method of section polishing combined with chemical corrosion was used to examine the subsurface damage. The Johnson-Holmquist (JH-2) material model of polycrystalline YAG ceramics was established and imported into Abaqus software to simulate the process of Vickers indentation, so as to predict surface fracture behavior and subsurface damage depth under quasi-static load. The results show that the surface fracture behavior was divided into two stages with the increase of loads, that is, the fracture toughness value increased gradually and the fracture behavior was mainly transgranular fracture in the loading range of 0.05–0.3kgf. The fracture toughness value decreased obviously and fracture behavior was mainly intergranular fracture when the load range was 0.3-1kgf. The simulation values of surface fracture length and subsurface damage depth under different loads are highly consistent with the experimental results of Vickers indentation, the accuracy of the established simulation model was verified, which has an important guiding value for predicting the surface fracture behavior and subsurface damage in ultra-precision grinding of polycrystalline YAG ceramics.

SET and MYND domain protein 2 (SMYD2) can methylate histone H3 at lysine36 (H3K36) and some non-histone substrates to play a role in tumorigenesis. However, It is unclear how SMYD2 contributes to chronic kidney disease (CKD). Here, AZ505 or LLY507, which could inhibit SMYD2, were used in cisplatin-induced CKD to investigate the effects and possible mechanisms by which they might act. We found that high expression of SMYD2 in cisplatin-induced CKD. However, AZ505 or LLY507 can significantly inhibit its expression, improve renal function injury and fibrosis induced by cisplatin, inhibit the transition of epithelial cells to a fibrogenic phenotype and fibrosis-related proteins, inhibit the expression of Inflammatory Cytokines (such as IL-6 and TNF-α), And inhibit the phosphorylation of pro-fibrosis molecule Smad3 and signal transduction and transcription activator-3 (STAT3) and up-regulated the expression of renal protective factor Smad7. In cultured tubular epithelial cells, AZ505 also can inhibit the expression of EMT, fibrosis-related proteins, and inflammatory cytokines in cisplatin-induced tubular epithelial cells. Based on these findings, SMYD2 may be a critical regulator of cisplatin-induced CKD and targeted pharmacological inhibition of SMYD2 may prevent cisplatin-induced CKD through Smad3 or STAT3-related signaling pathways.

Summary: Current diagnostic methods for diabetic nephropathy (DN) lack precision, especially in early stages and monitoring progression. This study aims to find potential biomarkers for DN progression and evaluate their accuracy. Using serum samples from healthy controls (NC), diabetic patients (DM), early-medium stage DN (DN-EM), and late-stage DN (DN-L), researchers employed quantitative proteomics and Mfuzz clustering analysis revealed 15 proteins showing increased expression during DN progression, hinting at their biomarker potential. Combining Mfuzz clustering with weighted gene co-expression network analysis (WGCNA) highlighted five candidates (HMGB1, CD44, FBLN1, PTPRG, and ADAMTSL4). HMGB1 emerged as a promising biomarker, closely correlated with renal function changes. Experimental validation supported HMGB1’s upregulation under high glucose conditions, reinforcing its potential as an early detection biomarker for DN. This research advances DN understanding and identifies five potential biomarkers, notably HMGB1, as a promising early monitoring target. These findings set the stage for future clinical diagnostic applications in DN.

Long-term high sugar accelerates skin ageing via glycosylation. In this study, microalgae-derived active compounds were investigated for their potentially beneficial effects on skin ageing. Two carotenoids, namely astaxanthin (in the form of either monoester or diester) and lutein, were separated from the green alga Haematococcus pluvialis. These carotenoid fractions significantly attenuated the high glucose (HG)-induced cell injury and oxidative stress. They also inhibited the formation of Nε-Carboxymethyllysine (CML), a typical product of glycosylation. The degradation of collagen I and III caused by HG was substantially recovered, in which astaxanthin monoester exhibited the most prominent effect. This was attributed to the down-regulation of matrix metalloproteinase (MMP)-2 mRNA expression. Through proteomics analyses, six hub proteins were identified, which work as highly connected nodes in the protective effects of astaxanthin monoester against HG stress. These findings strongly suggest the benefits of microalgae-derived carotenoids in alleviating HG-induced skin ageing.

Background: There is growing evidence indicating a connection between fine particulate matter (PM2.5) and depressive symptoms. Metabolic risk factors are critical determinants of depressive symptoms. However, the mediating role of these factors on the association between PM2.5 and depressive symptoms remains elusive. We aimed to investigate whether and to what extent metabolic risk factors mediated the link between long-term PM2.5 exposure and depressive symptoms. Methods: This study comprised 7794 individuals aged between 30 and 79 years who participated in two waves of the on-site surveys in the China Multi-Ethnic Cohort. Ambient PM2.5 concentrations were assessed utilizing a random forest method based on satellite data. We employed the Patient Health Questionnaire-9 to assess depressive symptoms at wave 2, and the overall as well as three sub-domain symptom scores (emotional, neurovegetative, and neurocognitive symptoms) were calculated. Three metabolic risk factors, including hypertension, diabetes, and dyslipidemia, were considered. Mediation analyses were conducted to assess the indirect effects of PM2.5 on depressive symptoms through metabolic risk factors. Results: We found a positive association between chronic exposure to ambient PM2.5 and overall depressive symptoms as well as the three sub-domains. In mediation analyses, metabolic risk factors partially mediated the associations of PM2.5 on depressive symptoms. The natural indirect effects (RR, 95% CI) of PM2.5 on overall, emotional, neurovegetative, and neurocognitive symptoms mediated through metabolic risk factors were 1.004(1.001, 1.007), 1.004 (1.001, 1.008), 1.004 (1.001, 1.007), and 1.003(0.999, 1.007), respectively. Larger indirect effects were found in elderly participants (mediated proportion, 29.3%), females (13.3%), and people who did not consume alcohol (19.6%). Conclusions: Metabolic risk factors may act as mediators in the relationship between chronic PM2.5 exposure and depression. Treatment of metabolic risk factors may be an opportunity to reduce the burden of depression caused by long-term exposure to PM2.5.

Background: Particulate matter (PM) exposure has been linked with cardiovascular disease (CVD) and metabolic syndrome (MetS), the latter characterized by concurrent multiple metabolic disorders. As a result, the mechanisms assumption from PM to CVD through MetS have emerged, thus requiring further epidemiological evidence. This cohort study aimed to assess whether MetS mediates the associations of PM with CVD risk. Methods: This study included 14,195 participants from the Chengdu cohort of the China Multi-Ethnic Cohort (CMEC) study in 2018. The primary outcome of incident CVD diagnoses was identified using matched hospital records from the Health Information Center of Sichuan Province. Residence-specific levels of PM with aerodynamic diameters of ≤ 1 µm (PM1), ≤ 2.5 µm (PM2.5), and ≤ 10 µm (PM10) were estimated by spatiotemporal models. Causal mediation analyses were applied to evaluate the indirect effect of MetS. Results: Increased exposure levels to PM were significantly associated with MetS and CVD. Mediation analyses indicated that the associations between PM exposure and CVD were mediated by MetS, with the proportion of multiple mediations being 19.3%, 12.1%, and 13.5% for PM1, PM2.5, and PM10, respectively. Further moderated mediation analyses suggested that male, overweight individuals, alcohol drinkers, and those suffering from indoor air pollution may experience more significant adverse effects from PM exposure on CVD via MetS than others. Conclusions: Our findings suggest that MetS partially mediates the association between long-term exposure to PM and CVD. These mediation effects appear to be amplified by demographic characteristics and unhealthy lifestyles.

Unprogrammed macrophage polarization, especially prolonged activation of proinflammatory macrophages, is associated with delayed wound healing in diabetic objectives. Macrophage-derived exosomes cargo a variety of microRNAs (miRNAs), participating in different stages in wound healing. Here, exosomes were isolated from naive bone marrow–derived macrophages (BMDMs) (M0-Exos), interferon-γ plus lipopolysaccharide-polarized BMDMs (M1-Exos), and interleukin-4-polarized BMDMs (M2-Exos). M1-Exos impaired migration and tube formation in human umbilical vein endothelial cells (HUVECs) compared to M0-Exos, whereas M2-Exos exhibited the opposite effects. High-throughput sequencing was performed to decipher the miRNA expression profiles in M0-Exos, M1-Exos, and M2-Exos. A total of 63 miRNAs were identified to be differentially expressed in exosomes derived from polarized BMDMs. Among them, miRNA-155-5p is highly expressed in M1-Exos, which interrupted angiogenesis in HUVECs. Furthermore, miRNA-155-5p directly binds to the 3′ UTR of growth differentiation factor 6 (GDF6) mRNA to suppress its protein expression. Lastly, local administration of a temperature-sensitive hydrogel Pluronic F-127 loading miRNA-155-5p antagomiR promoted angiogenesis and accelerated wound healing in diabetic db/db mice via enhancing GDF6. In summary, this study deciphered the miRNA expression profiles in exosomes from polarized macrophages. M2-like macrophage-derived exosomes and miRNA-155-5p inhibitors could be promising therapeutics against diabetic foot ulcers.

Background & Aims: Existing evidence suggests that long-term exposure to ambient fine particulate pollution (PM2.5) may increase metabolic dysfunction-associated fatty liver disease (MAFLD) risk. However, there is still limited evidence on the association of PM2.5 constituents with MAFLD. Therefore, this study explores the associations between the five main chemical constituents of PM2.5 and MAFLD to provide more explicit information on the liver exposome. Methods: A total of 76,727 participants derived from the China Multi-Ethnic Cohort, a large-scale epidemic survey in southwest China, were included in this study. Multiple linear regression models were used to estimate the pollutant-specific association with MAFLD. Weighted quantile sum regression was used to evaluate the joint effect of the pollutant-mixture on MAFLD and identify which constituents contribute most to it. Results: Three-year exposure to PM2.5 constituents was associated with a higher MAFLD risk and more severe liver fibrosis. Odds ratios for MAFLD were 1.480, 1.426, 1.294, 1.561, 1.618, and 1.368 per standard deviation increase in PM2.5, black carbon, organic matter, ammonium, sulfate, and nitrate, respectively. Joint exposure to the five major chemical constituents was also positively associated with MAFLD (odds ratio 1.490, 95% CI 1.360–1.632). Nitrate contributed most to the joint effect of the pollutant-mixture. Further stratified analyses indicate that males, current smokers, and individuals with a high-fat diet might be more susceptible to ambient PM2.5 exposure than others. Conclusions: Long-term exposure to PM2.5 and its five major chemical constituents may increase the risk of MAFLD. Nitrate might contribute most to MAFLD, which may provide new clues for liver health. Males, current smokers, and participants with high-fat diets were more susceptible to these associations. Impact and implications: This large-scale epidemiologic study explored the associations between constituents of fine particulate pollution (PM2.5) and metabolic dysfunction-associated fatty liver disease (MAFLD), and further revealed which constituents play a more important role in increasing the risk of MAFLD. In contrast to previous studies that examined the effects of PM2.5 as a whole substance, this study carefully explored the health effects of the individual constituents of PM2.5. These findings could (1) help researchers to identify the specific particles responsible for hepatotoxicity, and (2) indicate possible directions for policymakers to efficiently control ambient air pollution, such as targeting the sources of nitrate pollution.

Background: Exposure to particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5) may increase the risk of 10-year atherosclerotic cardiovascular disease (ASCVD) risk. While PM2.5 is comprised of various components, the evidence on the correlation of its components with 10-year ASCVD risk and which component contributes most remains limited. Methods: Data were derived from the baseline assessments of China Multi-Ethnic Cohort (CMEC). In total, 69,722 individuals aged 35–74 years were included into this study. The annual average concentration of PM2.5 and its components (black carbon, ammonium, nitrate, sulfate, organic matter, soil particles, and sea salt) were estimated by satellite remote sensing and chemical transport models. The ASCVD risk of individuals was calculated by the equations from the China-PAR Project (prediction for ASCVD risk in China). The relationship between single exposure to PM2.5 and its components and predicted 10-year ASCVD risk was assessed using the logistic regression model. The effect of joint exposure was estimated, and the most significant contributor was identified using the weighted quantile sum approach. Results: Totally 69,722 participants were included, of which 95.8 % and 4.2 % had low and high 10-year ASCVD risk, respectively. Per standard deviation increases in the 3-year average concentration of PM2.5 mass (odds ratio [OR] 1.23, 95 % confidence interval [CI]: 1.12–1.35), black carbon (1.21, 1.11–1.33), ammonium (1.21, 1.10–1.32), nitrate (1.25, 1.14–1.38), organic matter (1.29, 1.18–1.42), sulfate (1.17, 1.07–1.28), and soil particles (1.15, 1.04–1.26) were related to high 10-year ASCVD risk. The overall effect (1.19, 1.11–1.28) of the PM2.5 components was positively associated with 10-year ASCVD risk, and organic matter had the most contribution to this relationship. Female participants were more significantly impacted by PM2.5, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles compared to others. Conclusion: Long-term exposure to PM2.5 mass, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles were positively associated with high 10-year ASCVD risk, while sea salt exhibited a protective effect. Moreover, the organic matter might take primary responsibility for the relationship between PM2.5 and 10-year ASCVD risk. Females were more susceptible to the adverse effect.

Background: Ambient particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) consists of various toxic constituents. However, the health effect of PM2.5 may differ depending on its constituents, but the joint effect of PM2.5 constituents remains incompletely understood. Objective: Our goal was to evaluate the joint effect of long-term PM2.5 constituent exposures on dyslipidemia and identify the most hazardous chemical constituent. Methods: This study included 67,015 participants from the China Multi-Ethnic Cohort study. The average yearly levels of PM2.5 constituents for all individuals at their residences were assessed through satellite remote sensing and chemical transport modeling. Dyslipidemia was defined as one or more following abnormal blood lipid concentrations: total cholesterol (TC) ≥ 6.22 mmol/L, triglycerides (TG) ≥ 2.26 mmol/L, high-density lipoprotein cholesterol (HDL-C)

Nuclear fusion reactions which produce energies and most of the elements in the Universe are the keys to driving the process of the Big Bang nucleosynthesis, as well as the evolution of stars. For fusions in real astrophysical conditions, it is crucial to directly measure them in the plasma environments. However, it is challenging to obtain reaction cross sections quantitatively because of the high instabilities of plasma. Here, an innovative self-calibration method is proposed to eliminate the large uncertainties caused by the plasma instabilities. And for the first time, it is applied to investigating the deuteron-lithium nuclear-fusion reaction 7Li(D,n)8Be in the plasma, which is related to the Big Bang lithium abundance puzzle. Further, the reaction's astrophysical S-factor in the Gamow window around 173 keV in the plasma is measured to be S=(24±8) MeV⋅barn, which demonstrates from an experimental point of view that the coulomb screening effect does not play an essential role in this 7Li consuming reaction related to the Big Bang lithium abundance puzzle. This self-calibration method for nuclear reactions in the plasma can also be applied to exploring other nuclear-fusion reactions, such as 7Li(p,α)4He and 6Li(p,α)3He, as well as providing a new probe for detecting plasma dynamics.

Execution time, reliability, and energy consumption are the three main performance parameters of processor scheduling for real-time embedded systems. It is very meaningful to optimize the energy optimization of processor scheduling to satisfy the requirements on time limit and reliability. This paper tries to optimize the energy consumption of the processor under three constraints: the partial ordering relations between task modules, the time limit, and the reliability. Based on directed acrylic graph (DAG) and quantum particle swarm optimization (QPSO), two scheduling algorithms were developed for the problem, namely, DAG_QPSO_I and DAG_QPSO_II. The two algorithms were compared with each other, and with other intelligent algorithms. The results show that the proposed algorithms are superior in optimization effect and efficiency, DAG_QPSO_I makes energy consumption more efficient than DAG_QPSO_II, and DAG_QPSO_II meets stricter requirements on time limit and reliability than DAG_QPSO_I.

Background: Numerous studies have shown that residential greenness positively correlates with enhanced health. Metabolic dysfunction-associated fatty liver disease (MAFLD) affects about a quarter of the population while lacking specific treatments. Given that the association between green space and MAFLD is still unknown, we explored the association between residential greenness and MAFLD as well as the potential mechanisms based on the baseline survey of the China Multi-Ethnic Cohort (CMEC). Methods: Residential greenness was expressed as normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI). MAFLD was assessed through hepatic steatosis, the presence of overweight/obesity, type 2 diabetes mellitus, and evidence of metabolic dysregulation. We used logistic regression to examine the association between NDVI/EVI and the prevalence of MAFLD. Moreover, we utilized causal mediation analyses to explore the role of physical activity and ambient particulate matters (PM1, PM2.5, and PM10) on the association between residential greenness and MAFLD. Results: We included 72,368 participants from the CMEC and found that residential greenness was negatively associated with the prevalence of MAFLD. For an interquartile range (IQR) increase in NDVI500 m and EVI500 m, the odds ratio (OR) of MAFLD were 0.78 (95 %CI: 0.75, 0.81) and 0.81 (95 %CI: 0.78, 0.84), respectively. Greater association between residential greenness and MAFLD was observed among males. Air pollutants and physical activity could mediate a partial effect (8.5–22.9 %) of residential greenness on MAFLD. Conclusion: Higher residential greenness was associated with decreased risk of MAFLD. Moreover, the association was greater among males. The protective effects of residential greenness may be achieved by mitigating the hazardous effects of air pollutants and encouraging physical activity.

Laser truing has broad application prospects, but the problems of thermal damage and the metamorphic layer of diamond have not been well solved, which significantly affects the quality and precision of truing. To address these problems, we propose a novel laser truing method with a spray-mist assistant (SMA) for an electroplated diamond grinding wheel. First, the action mechanism of SMA laser truing is analysed. Subsequently, the effects of the truing parameters, including the spray pressure and laser truing iterations, on the SMA laser truing quality are studied. Next, a new analysis method is proposed to describe the SMA laser truing effect and thermal damage based on the fractal theory. Finally, the laser truing of an electroplated diamond grinding wheel based on SMA is described. The results show that the SMA laser truing effect is closely related to the spray pressure and truing iterations. The influence of the SMA laser truing iterations on the height of the abrasive grains on the surface of the grinding wheel can be divided into three key stages: rapid decrease stage, slow decrease stage, and stable stage. The inhibition of diamond graphitisation by SMA laser truing is remarkable, and the graphitisation phenomenon is completely eliminated.

Background: Limited studies have examined associations between air pollutants exposure and renal function, especially in China, with the most extensive chronic kidney disease (CKD) disease burden worldwide. Objectives: This study examines associations between long-term exposure to ambient PM2.5, NO2, CO, O3, SO2 and renal function. Methods: We included 80,225 participants aged 30–79 years from the baseline data of the China Multi-Ethnic Cohort (CMEC) study. Three-year average concentrations of PM2.5, NO2, CO, O3, and SO2 were estimated using satellite-based spatiotemporal models. Renal function is determined by the estimated glomerular filtration rate (eGFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. After adjusting for covariates, generalized propensity scores (GPS) weighting regression was used to estimate associations between ambient air pollutants and renal function. Results: An increase of 0.1 mg/m3 CO (OR [odds ratio] =1.20 95% CI [confidence interval], 1.05–1.37) was positively associated with CKD. An increase of 1 μg/m3 in SO2 (1.07, 1.00–1.14) concentration was positively associated with CKD. An increase of 10 μg/m3 in PM2.5 (1.17, 0.99–1.38), NO2 (1.12, 0.83–1.51) and O3 (1.10, 0.81–1.50) concentration was not associated with CKD. These effects are stronger in those younger than 65, smoking and with low BMI. Conclusions: In this study, we found that long-term exposure to ambient CO and SO2 were positively associated with CKD. Gaseous pollutants should also arouse the concern of relevant departments.

Background: A growing body of studies have reported the health benefits of greenness. However, less is known about the potential beneficial effects of residential greenness on gut microbiota, which is essential to human health. In this study, we aim to examine the association between residential greenness and gut microbiota in a population-based cohort study. Methods: We included 1758 participants based on the China Multi-Ethnic Cohort (CMEC) study and collected their stool samples for 16S sequencing to derive gut microbiota data. Residential greenness was estimated using the satellite-based data on enhanced vegetation index (EVI) and the normalized differential vegetation index (NDVI) in circular buffers of 250 m, 500 m, and 1000 m. The relationships between residential greenness levels and the composition of gut microbiota, measured by standardized α-diversity and taxonomic composition, were assessed using linear regression and Spearman correlation weighted by generalized propensity scores. Results: Higher greenness levels were significantly positively associated with standardized α-diversity. Per interquartile range (IQR) increase of EVI and NDVI in the circular buffer of 250 m were associated with the increments of 0.995(95% confidence interval (CI): 0.212–1.778) and 0.653(95% CI: 0.160–1.146) in the standardized Shannon index. For the taxonomic composition of gut microbiota, higher greenness levels were significantly correlated with 29 types of microbial taxonomic composition. NDVI in the circular buffer of 250 m was associated with increased Firmicutes (r = 0.102, adjusted p value = 0.004), which was the dominant composition in the gut microbiota. Conclusions: Increased amounts of residential greenness may support healthy gut microbiota by benignly altering their composition. These findings suggested that green spaces should be designed to support diverse gut microbiota and ultimately optimize health benefits.

The urbanization of coastal margins and the resulting deterioration of coastal water environment have been a major concern, due to their substantial threat to the health and sustainability of coastal marine ecosystems. However, the spatiotemporal information about these two aspects and their correlation analysis are still lacking in China. This study quantitatively investigated the urbanization and water quality dynamics from 54 statistical units of coastal margins with a width of 40 km in mainland China, and examined the response characteristics of different water quality indicators to the coastal margin urbanization (CMU). Our results revealed that CMU generally shifted from low to medium/high levels nationwide in 2000–2013, with a 75% increase in the average urbanization index, while the nearshore water quality did not vary significantly over time, maintaining a medium level in the sequence of water quality from good to bad during the study period. The spatial heterogeneity of CMU and water quality distribution was evident. Yangtze River Estuary, Pearl River Estuary, Hangzhou Bay, Bohai Bay and the coastal provinces located here, including Shanghai, Tianjin, Zhejiang, and Guangdong, should receive more attention due to their excessive CMU and the worst coastal water quality. The indicators that characterize the overall state and eutrophication of water quality were found to be sensitive to CMU. Compared with coastal cities, coastal margins were stronger in terms of urbanization intensity and impact on coastal water quality. The findings will provide basic scientific information for decision-making on urbanization control and ecological restoration in coastal margins, and will also promote the understanding of the CMU process and its environmental impact from a continental-scale perspective.

The machining difficulty has limited the further application of ultra-hard materials. For V-shaped coarse-grained electroplated cubic boron nitride (CBN) grinding wheel, a precise and efficient pulse laser truing method was proposed. Firstly, a theoretical model of the pulse laser truing process was established in order to optimize the laser truing energy distribution. Secondly, the effects of truing depth, grinding wheel speed, laser power and truing time were analyzed. Finally, the grinding performance of laser trued wheels were evaluated. The results showed that larger grinding wheel speed n would bring higher energy value and more stable energy distribution, truing depth h would not affect the value and stability of energy. CBN would not undergo phase transition and could bear more laser power Pavg. With the increase of truing time t, the geometric precision of V-shaped grinding wheel could be improved. The angle of V-shaped grinding wheel could reach 90.15° (deviation 0.02°), the bottom fillet radius was 53 μm (less than 100 μm). The surface roughness and grinding force corresponding to laser truing were less than that of mechanical truing, the truing time required was reduced by 72%∼83%, and the corresponding tooth profile angle and bottom fillet were basically the same.

The balancing between tumor suppression and cell viability is the key to balance aging and tumorigenesis, and reach tumor-free longevity, or healthy aging. We speculate that the balance of tumor suppression signaling and the cell growth sustaining mechanisms in molecular genetics might reflect the balance between Yin and Yang in Chinese medicine. Some Chinese medicine herbs are known to sustain longevity, and help to prevent aging related diseases, such as Panax Ginseng, Ganoderma Lucidum etc. Based on Chinese medicine databases and the molecular signature database, we try to apply in silico systems pharmacology to analyze the function of these herbs in modulating signaling pathways. We found that most of these herbs could enhance cellular mitochondrial function: oxidative phosphorylation. Surprisingly, the lipids metabolism pathways were found in all the herbs analyzed. Interestingly, the cell proliferation pathways, such as telomere maintenance pathway, Myc pathway, E2F pathway, as well as the cell quality control pathway (apoptosis pathway) were also found to be enhanced in most herbs, which added evidences to our balancing hypothesis. Thus, our data revealed the sustainable energy production, the sustainable cell proliferation, and the quality control build the life triangle for the mechanism of action of Chinese medicinal herbs with longevity sustaining property. This methodology might help to predict the molecular mechanism of Chinese medicine herbs, and further understand the formulation of Chinese medicine in preventing aging-related diseases. The limitations of this kind of analysis are also discussed.

Polyaniline (PANI) is a commonly used electrochromic material due to its tunable optical properties under an applied potential. In order to fabricate large-area electrochromic devices, PANI has to be deposited uniformly in large scale. Unfortunately, the existing deposition techniques can hardly meet the requirement. In this work, sequential solution polymerization (SSP) technique is introduced for in-situ deposition of large-area PANI films. This process involves synthesis of hydrated vanadium pentoxide (HVO), formation of V2O5 precursor film and in-situ polymerization in an aniline monomer solution. PANI films with a size of 16 × 10 cm2 are realized using bar coating in ambient. This method is facile and efficient, compatible with roll-to-roll printing technology. Electrochromic devices based on SSP PANI films exhibit high optical contract in the vis-NIR region and good cyclability. This study demonstrates that SSP shows great potential in in-situ deposition of large-area PANI films for the development of optoelectronic modules.

In this investigation, the novel fractional order simulations are performed in order to inspect the characteristics of mass and heat transfer over porous inclined surface subject to the magnetic force impact. The radiative phenomenon and slip wall constraints are utilized to make the model more comprehensive. The convective thermal mechanism of heat transfer is predicted with assumptions of ramped temperature. The recent definitions of fractional derivatives are followed. The famous technique of fractional approach namely Atangana-Baleanu (AB) and Caputo-time fractional derivative are employed for the solution procedure. Various relations expressing the mathematical functions for the fractional derivatives are encountered. The major outcomes are listed for parameters govern for the model. This obtained result reflects many engineering and industrial applications like thermal processes, processing industries, nuclear reactions, solar systems, energy production etc.

There were dramatic changes in the ecological vulnerability (EV) of the China-Pakistan Economic Corridor (CPEC) region due to the effects of climate change and human activity. Obtaining field observation and statistical data for the evaluation of the EV of the CPEC region is difficult due to its transnational status. This study proposes a novel remote sensing ecological vulnerability index (RSEVI) based on the Moderate Resolution Imaging Spectroradiometer (MODIS), STRM3, DMSP-OLS, and NPP-VIIRS products. The RSEVI index was applied to the CPEC region to investigate the spatiotemporal changes in EV and the influencing factors during 2000–2019. The results showed that: (1) the large-scale application of the RSEVI index showed good applicability to the CPEC region, with a precision of 89.75%; (2) the average RSEVI value for the CPEC region was 0.83, thereby falling into a category of “intensive vulnerability”; (3) a stable trend in RSEVI was observed for the entire CPEC region during the study period, except for the Indus Basin where there was a significant change; (4) the increasing rate of the RSEVI in the northeastern parts exceeded that of other parts during 2000–2019; (5) precipitation, temperature, and vegetation coverage showed negative relationships with RSEVI, whereas RSEVI showed a positive relationship with slope. The RSEVI results indicated that ice and bare land were the most vulnerable, whereas cropland was the least vulnerable; (6) there were differences in the dominant factor and dominant interactive factor among different sub-regions. The results of this study could provide important decision support for the protection of the ecological environment and for economic development.

Transparent polycrystalline magnesium aluminate spinel (PMAS), owing to its high optical transparency with acceptable mechanical properties and chemical stabilities, exhibits great potential for optical applications under extreme environments and operating conditions. The first stage of preparing highly transparent PMAS is attainable with the rapidly maturing sintering technology. However, the machining technologies aiming to achieve high shape accuracy and surface quality on PMAS are still restricted by its poor machinability and limited endeavours to survey. This paper provides a comprehensive collection of PMAS processing strategies. The state-of-the-art techniques for sintering PMAS are reviewed with a focus on the technical details and intimate relationship with the material properties. The fundamental material properties of PMAS including the crystal structure, mechanical properties and damage mechanisms are systematically discussed. These characteristics inherently govern the material removal mechanisms and the generation of surface damages in the subsequent machining processes. The surveyed fundamental studies signify that the combination of high brittleness, strong anisotropy within each single-crystal grain and polycrystalline structure is the major obstacle in achieving damage-free surface finish. In this regard, further explorations of improving machining performance with advanced machining technologies and enhancing the machinability through optimising sintering strategies are expected in the outlook.

Background: Transplant arteriosclerosis (TA) remains the major cause of chronic graft failure in solid organ transplantation. The phenotypic modulation of vascular smooth muscle cells (VSMCs) is a key event for the initiation and progression of neointimal formation and TA. This study aims to explore the role and underlying mechanism of phosphoinositide 3-kinases γ (PI3Kγ) in VSMC phenotypic modulation and TA. Methods: The rat model of aortic transplantation was established to detect PI3Kγ expression and its role in neointimal formation and vascular remodeling in vivo. PI3Kγ shRNA transfection was employed to knockdown PI3Kγ gene. Aortic VSMCs was cultured and treated with TNF-α to explore the role and molecular mechanism of PI3Kγ in VSMC phenotypic modulation. Findings: Activated PI3Kγ/p-Akt signaling was observed in aortic allografts and in TNF-α-treated VSMCs. Lentivirus-mediated shRNA transfection effectively inhibited PI3Kγ expression in medial VSMCs while restoring the expression of VSMC contractile genes, associated with impaired neointimal formation in aortic allografts. In cultured VSMCs, PI3Kγ blockade with pharmacological inhibitor or genetic knockdown markedly abrogated TNF-α-induced downregulation of VSMC contractile genes and increase in cellular proliferation and migration. Moreover, SOX9 located in nucleus competitively inhibited the interaction of Myocardin and SRF, while PI3Kγ inhibition robustly reduced SOX9 expression and its nuclear translocation and repaired the Myocardin/SRF association. Interpretation: These results suggest that PI3Kγ plays a critical role in VSMC phenotypic modulation via a SOX9-dependent mechanism. Therefore, PI3Kγ in VSMCs may represent a promising therapeutic target for the treatment of TA. Fund: National Natural Science Foundation of China. Keywords: PI3Kγ, Vascular smooth muscle cells, Transplant arteriosclerosis, SOX9, Phenotypic modulation

Purpose: Microgravity is known to cause endothelium dysfunction in astronauts returning from spaceflight. We aimed to reveal the regulatory mechanism in alterations of human endothelial cells after simulated microgravity (SMG). Methods: We utilized the rotary cell culture system (RCCS-1) to explore the subsequent effects of SMG on human umbilical vein endothelial cells (HUVECs). Results: SMG-treated HUVECs appeared obvious growth inhibition after return to normal gravity, which might be attributed to a set of responses including alteration of cytoskeleton, decreased cell adhesion capacity and increased apoptosis. Expression levels of mTOR and its downstream Apaf-1 were increased during subsequent culturing after SMG. miR-22 was up-regulated and its target genes SRF and LAMC1 were down-regulated at mRNA levels. LAMC1 siRNAs reduced cell adhesion rate and inhibited stress fiber formation while SRF siRNAs caused apoptosis. Conclusion: SMG has the subsequent biological effects on HUVECs, resulting in growth inhibition through mTOR signaling and miR-22-mediated mechanism. Keywords: Simulated microgravity, Growth inhibition, miR-22, Serum response factor, LAMC1, mTOR

Objective: We report preliminary results of an ongoing study that assesses the efficacy of tacrolimus on Kimura's disease (KD)., Study Design: A patient with refractory KD after surgery and treatment with prednisone was treated with tacrolimus. Tacrolimus (FK-506) was administered at an initial dosage of 1 mg every 12 hours, and FK-506 concentration in the blood was monitored monthly. FK-506 blood concentration was controlled within 5 to 15 μg/L. After 6 months, the dosage of tacrolimus was reduced to 0.5 mg daily for another 2 months and then treatment was stopped., Results: Swelling of the bilateral salivary glands disappeared within the first week. No serious side effects were noted and the disease has not recurred in the 2 years of follow-up., Conclusions: Tacrolimus may be an effective treatment for patients with KD, but more research is needed to determine its long-term efficacy and safety as well as its mechanism of action., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Foreign bodies located at the base of the skull pose a surgical challenge. Here, a customized computer-designed surgical guide bar was designed to facilitate removal of a skull base foreign body., Methods: Within 24h of the patient's presentation, a guide bar and mounting platform were designed to remove a foreign body located adjacent to the transverse process of the atlas and pressing against the internal carotid artery., Results: The foreign body was successfully located and removed using the custom designed guide bar and computer operative planning. Ten months postoperatively the patient was free of complaints and lacked any complications such as restricted opening of the mouth or false aneurysm. The inferior alveolar nerve damage noted immediately postoperatively (a consequence of mandibular osteotomy) was slightly reduced at follow-up, but labial numbness persisted., Conclusions: The navigation tools described herein were successfully employed to aid foreign body removal from the skull base., (Copyright (c) 2009 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

We and others reported previously that IGF-I inhibits dexamethasone-induced proteolysis in cultured L6 myotubes. Recent evidence suggests that this effect of IGF-I at least in part reflects PI3K/Akt-mediated inhibition of Foxo transcription factors. The potential role of other mechanisms, downstream of PI3K/Akt, is not well understood. Here we tested the hypothesis that PI3K/Akt-mediated inactivation of GSK-3beta and activation of mTOR contribute to the anabolic effects of IGF-I in dexamethasone-treated myotubes. Cultured L6 myotubes were treated with 1 microM dexamethasone in the absence or presence of 0.1 microg/ml of IGF-I and inhibitors of GSK-3beta and mTOR. Protein degradation was measured by determining the release of trichloroacetic acid soluble radioactivity from myotubes that had been prelabeled with (3)H-tyrosine for 48 h. IGF-I reduced basal protein breakdown rates and completely abolished the dexamethasone-induced increase in myotube proteolysis. These effects of IGF-I were associated with increased phosphorylation of Akt, GSK-3beta, and the mTOR downstream targets p70(S6K) and 4E-BP1. The PI3K inhibitor LY294002 and the mTOR inhibitor rapamycin reversed the anabolic effect of IGF-I in dexamethasone-treated myotubes. In addition, the GSK-3beta inhibitors LiCl and TDZD-8 reduced protein degradation in a similar fashion as IGF-I. Our results suggest that PI3K/Akt-mediated inactivation of GSK-3beta and activation of mTOR contribute to the anabolic effects of IGF-I in dexamethasone-treated myotubes.