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BackgroundThe repeated outbreaks of COVID-19 and the rapid increase in uncertainty have had many negative effects on the public’s mental health, especially on emotional aspects such as anxiety and depression. However, in previous studies, there are few studies exploring the positive factors between uncertainty and anxiety. The innovation of this study is the first to explore the mechanism of coping style and resilience as people’s psychological protective factors between uncertainty and anxiety caused by the COVID-19 pandemic.MethodsThis study explored the relationship between intolerance of uncertainty and anxiety of freshmen with coping style as mediating variable and resilience as moderating variable. A total of 1049 freshmen participated in the study and completed the Intolerance of Uncertainty Scale (IUS-12), Self-rating Anxiety Scale (SAS), Simplified Coping Style Questionnaire (SCSQ), and Connor-Davidson Resilience Scale (CD-RISC).ResultsSAS score of the surveyed students (39.56 ± 10.195) was significantly higher than that of the Normal Chinese score (29.78 ± 10.07, p < 0.001). Intolerance of uncertainty was significantly positively correlated with anxiety (β = 0.493, p < 0.001). Positive coping style has a significant negative impact on anxiety (β = −0.610, p < 0.001), negative coping style has a significant positive impact on anxiety (β = 0.951, p < 0.001). Resilience moderates the second half of the influence of negative coping style on anxiety (β = 0.011, t = 3.701, p < 0.01).ConclusionThe findings suggest that high levels of intolerance of uncertainty had negative effects mental burden during the COVID-19 pandemic. The knowledge of the mediating role of coping style and the moderating role of resilience may be used by health care workers when consulting freshmen with physical health complaints and psychosomatic disorders.

Climate change has made disastrous heatwaves more frequent. Heatwave-related health impacts are much more devastating for more intense heatwaves. In the summer of 2017, exceptional heatwaves occurred in many regions, including China. This study aims to evaluate the cardiovascular mortality risk associated with the 2017 exceptional heatwaves and compare the mortality risk of the severe heatwaves with those in other years. Using daily data for a spectrum of cardiovascular mortality and temperature for 102 Chinese counties (2014–2017), we estimated the association between heatwave and mortality by generalized linear mixed-effects models. Compared with matched non-heatwave days, mortality risks on heatwaves days in 2017 increased 27.8% (95% CI, 14.8–42.3%), 26.7% (8.0–48.5%), 30.1% (10.2–53.7%), 27.3% (1.4–59.9%), 32.2% (3.4–68.4%), and 25.2% (1.0–57.7%) for total circulatory diseases, cerebrovascular disease, ischemic heart disease (IHD), acute IHD, chronic IHD, and myocardial infarction. The 2017 exceptional heatwaves impacted ischemic heart disease mortality and myocardial infarction mortality more than heatwaves in 2014–2016. Here we show that the severe heatwaves in 2017 posed catastrophic death threats for those under-studied cardiovascular diseases.

High-resolution observations of typhoon boundary layer above 100 m are rare as traditional wind towers are generally below 100 m, which limits the study of typhoon boundary layer and engineering applications such as wind-resistant design of tall buildings and wind turbines in typhoon-prone regions. In this study, boundary layer winds of super typhoon Lekima (2019) are observed, simulated and analyzed. Together with traditional wind tower, Doppler wind lidar is utilized for observations of typhoon boundary layer in order to obtain measured data above 100 m. Besides, Computational Fluid Dynamics (CFD) simulation based on Large Eddy Simulation (LES) method is conducted to further investigate the impact of complex terrain on the near-surface wind characteristics. The results show that the power law fits the mean wind speed profile well below 100 m. However, before and after the typhoon lands, a local reverse or low-level jet occurs in the mean wind speed profile at the height of 100–300 m, which cannot be depicted by the power law. Meanwhile, the turbulence intensity increases with height and experiences larger fluctuations. In addition, there is a significant negative correlation between the ground elevation and power exponents of the fitted mean wind speed profiles. This study provides useful information to better understand wind characteristics of the typhoon boundary layer.

Background: Ambient ozone pollution is steadily increasing and becoming a major environmental risk factor contributing to the global disease burden. Although the association between short-term ozone exposure and mortality has been widely studied, results are mostly reported on deaths from non-accidental or total cardiopulmonary disease rather than a spectrum of causes. In particular, a knowledge gap still exists for the potential thresholds in mortality risks. Methods: This nationwide time-series study in China included 323 counties totaling 230,266,168 residents. Daily maximum 8-hour average was calculated as the ozone exposure metric. A two-stage statistical approach was adopted to assess ozone effects on 21 cause-specific deaths for 2013–2018. The subset approach and threshold approach were utilized to explore potential thresholds, and stratification analysis was used to evaluate population susceptibility. Results: On average, the annual mean ozone concentration was 93.4 μg/m3 across 323 counties. A 10-μg/m3 increase in lag 0–1 day of ozone was associated with increases of 0.12 % in mortality risk from non-accidental disease, 0.11 % from circulatory disease, 0.09 % from respiratory disease, 0.29 % from urinary system disease, and 0.20 % from nervous system disease. There may be a “safe” threshold in the ozone-mortality association, which may be between 60 and 100 μg/m3, and vary by cause of death. Women and older adults (especially those over 75) are more affected by short-term ozone exposure. Populations in North China had a higher risk of ozone-related circulatory mortality, while populations in South China had a higher risk of ozone-related respiratory mortality. Conclusions: National findings link short-term ozone exposure to premature death from circulatory, respiratory, neurological, and urinary diseases, and provide evidence for a potential “safe” threshold in the association of ozone and mortality. These findings have important implications for helping policymakers tighten the relevant air quality standards and developing early warning systems for public health protection in China.

Ambient fine particulate matter (PM2.5) pollution is a major environmental and public health challenge in China. In the recent decade, the PM2.5 level has decreased mainly driven by reductions in particulate sulfate as a result of large-scale desulfurization efforts in coal-fired power plants and industrial facilities. Emerging evidence also points to the differential toxicity of particulate sulfate affecting human health. However, estimating the long-term spatiotemporal trend of sulfate is difficult because a ground monitoring network of PM2.5 constituents has not been established in China. Spaceborne sensors such as the Multi-angle Imaging SpectroRadiometer (MISR) instrument can provide complementary information on aerosol size and type. With the help of state-of-the-art machine learning techniques, we developed a sulfate prediction model under support from available ground measurements, MISR-retrieved aerosol microphysical properties, and atmospheric reanalysis data at a spatial resolution of 0.1°. Our sulfate model performed well with an out-of-bag cross-validation R2 of 0.68 at the daily level and 0.93 at the monthly level. We found that the national mean population-weighted sulfate concentration was relatively stable before the Air Pollution Prevention and Control Action Plan was enforced in 2013, ranging from 10.4 to 11.5 µg m−3. But the sulfate level dramatically decreased to 7.7 µg m−3 in 2018, with a change rate of −28.7 % from 2013 to 2018. Correspondingly, the annual mean total non-accidental and cardiopulmonary deaths attributed to sulfate decreased by 40.7 % and 42.3 %, respectively. The long-term, full-coverage sulfate level estimates will support future studies on evaluating air quality policies and understanding the adverse health effect of particulate sulfate.

Abstract While the facilitated transport of heavy metals by colloids such as clay particles has been widely recognized, the influence of heavy metals on transport of the colloids has received much less attention. This study conducted saturated column experiments to systematically examine influence of multivalent heavy metal cations on transport of natural clay colloids and fullerene nC60 nanoparticles in glass bead porous media. Results showed that the presence of Cd2+ in the solution can cause more deposition of clay colloids in glass beads compared to Ca2+ at a given ionic strength (IS), and the subsequent release by IS reduction was less, demonstrating that the presence of Cd2+ increased the irreversibility of attachment. When the glass beads were initially adsorbed with Ca2+ and Cd2+, the release of clay colloids was significantly reduced due to strong cation bridge between the clay colloids and collector surfaces via the heavy metal cations. The release of clay colloids was significantly increased upon reduction of solution IS if the Na+ was used to exchange for the Ca2+ or Cd2+ before the IS reduction. Additional experiments showed that the nC60 nanoparticles that were deposited in the presence of Fe3+ and Cu2+ cannot be released by reduction of solution IS. However, the nanoparticle release occurred when the Ca2+ was used to exchange for the Fe3+ and Cu2+. Our work was the first to reveal the influence of heavy metal cations on the irreversibility of colloid attachment, and the findings have important implication to fabrication of functional nanomaterials for stabilization of heavy metals in soil and development of mathematic models for accurate prediction of cotransport of heavy metals and colloids in subsurface environments.

Although exposure to fine particulate matter (PM2.5) has been associated with cognitive decline, little is known about which PM2.5 constituents are more harmful. Recent study on the association between PM2.5 and sleep quality prompted us to propose that sleep quality may mediate the adverse effects of PM2.5 components on cognitive decline. Understanding the association between PM2.5 constituents and cognitive function, as well as the mediating role of sleep quality provides a future intervention target for improving cognitive function. Using data involving 1834 participants from a multicenter cross-sectional study in nine cities of the Beijing-Tianjin-Hebei (BTH) region in China, we undertook multivariable linear regression analyses to quantify the association of annual moving-average PM2.5 and its chemical constituents with cognitive function and to assess the modifying role of exposure characteristic in this association. Besides, we examined the extent to which this association of PM2.5 constituents with cognitive function was mediated via sleep quality by a mediation analysis. We observed significantly negative associations between an increase of one interquartile range increase in PM2.5 [−0.876 (95 % CI: −1.205, −0.548)], organic carbon [−0.481 (95 % CI: −0.744, −0.219)], potassium [−0.344 (95 % CI: −0.530, −0.157)], iron [−0.468 (95 % CI: −0.646, −0.291)], and ammonium ion [−0.125 (95 % CI: −0.197, −0.052)] and cognitive decline. However, we didn’t find any individual components more harmful than PM2.5. Poor sleep quality partially mediated the estimated associations, which were explained ranging from 2.28 % to 11.99 %. Stratification analyses showed that people living in areas with lower greenspace were more susceptible to specific PM2.5 components. Our study suggests that the adverse effect of suffering from PM2.5 components is more pronounced among individuals with poor sleep quality, amplifying environmental inequalities in health. Besides reducing environmental pollution, improving sleep quality may be another measure worth considering to improve cognition if our research is confirmed in the future.

Background: Air pollution is associated with accelerated biological ages determined by DNA methylation (DNAm) patterns, imposing further risks of age-related adverse effects. However, little is known about the independent and joint effects of exposure to gaseous organic chemicals that may share a common source. Methods: We conducted a panel study with the 3-day exposure assessment monthly among 73 Chinese healthy elderly people aged 60 to 69 years in Jinan, Shandong province during September 2018 to January 2019. Exposure to 26 ambient organic chemical contaminants were measured by wearable passive samplers, including volatile organic compounds, polycyclic aromatic hydrocarbons (PAHs), phthalates (PAEs), nitroaromatics (NIs), polybrominated diphenyl ethers, chlorinated hydrocarbons, and organophosphate esters. The Illumina MethylationEPIC BeadChip was used to measure DNA methylation levels in blood samples, and based on which, epigenetic ageing biomarkers, including Hannum clock, Horvath clock, DNAm PhenoAge, DNAm GrimAge, and DNAm estimator of telomere length (DNAmTL) were calculated. Linear mixed effect models were used to estimate the linear associations between 3-day personal chemical exposure and the epigenetic biomarkers, Weighted quantile sum (WQS) regression and the Bayesian kernel machine regression (BKMR) model were further used to evaluate the effect of chemical mixtures. Results: Multiple linear mixed effects regression models showed that DNAmPhenoAge acceleration was significantly and positively associated with exposure to PAEs, NIs, and PAHs in healthy elderly individuals. Both WQS regression and BKMR models showed a significant positive association with DNAmPhenoAge acceleration with chemical exposures, in which the effect of di-n-butyl phthalate exposure showed the greatest importance. Conclusion: These findings suggest that exposure to a mixture of airborne chemicals significantly increase the acceleration of the epigenetic biomarker of phenotypic age. These findings serve to identify toxic chemicals in the air and facilitate the evaluation of their potentially severe health effects.

Background: Short-term fine particulate matter (PM2.5) exposure and increased circulatory mortality have been well documented. However, there are inconsistent findings on mortality effects of traffic-related pollutants from the perspective of sources or constituents. Few studies have examined such associations using source and constituents simultaneously, and even less are based on large-scale, nationally representative data. We aimed to conduct a comprehensive analysis to investigate source- and constituent-specific mortality effects due to traffic-related PM2.5 pollution in China. Methods: We extracted daily mortality data in 280 counties from the China Disease Surveillance Points system (DSPs) from January 2013 to December 2018. Daily concentrations of traffic-related PM2.5 and specific constituents were simulated using the Community Multiscale Air Quality (CMAQ) model. The downscaling and adjustment methods were carried out to generate a refined exposure assessment. We estimated the circulatory mortality risk using a standard two-stage approach, combining generalized linear model (GLM) with a quasi-Poisson distribution and random-effects meta-analysis. Results: We observed that traffic-related PM2.5 and specific constituents were significantly associated with increased circulatory mortality. An increase of interquartile range of traffic-related PM2.5, elemental carbon (EC), organic carbon (OC), and nitrate (NO3−) were associated with elevated circulatory mortality risks of 1.80 % (95 % confidence interval, CI: 1.27, 2.33), 1.85 % (1.33, 2.37), 1.42 % (0.90, 1.94), and 1.10 % (0.55, 1.66) at 3-day moving average (lag 0-2 days), respectively. We also found relatively high associations between traffic-related PM2.5 and EC exposures and cardiovascular mortality, and OC exposure and cerebrovascular mortality. Moreover, our stratified analysis demonstrated such mortality risks tended to be stronger in males, individuals age 65 years or older, and during the cold season. Conclusion: Our findings provided robust evidence on significant associations of traffic-related PM2.5 and specific constituents with circulatory mortality. Further emissions abatement from the transportation sector and corresponding pollutants should merit a particular focus in China.

The Yili goose is the only indigenous goose breed that originates from Anser anser in China, known for its adaptability, strong flying ability, and tender meat with a low body lipid content. The liver plays a crucial role in lipid and glucose metabolism, including the intake, secretion, transportation, and storage of fatty acids (FAs). In this study, RNA-sequencing (RNA-seq) technology was performed to analyze the liver differentially expressed genes of Yili geese and their hybrid geese to investigate differences in liver lipid and glucose metabolism. A total of 452 differentially expressed genes (Q-value < 0.05) were identified. Notably, in KEGG enrichment analysis, four pathways (Q-value < 0.05) were enriched to be associated with lipid and glucose metabolism, including the metabolic pathway, PI3K–Akt signaling pathway, glycolysis/gluconeogenesis, and steroid biosynthesis. This study provides insights into potential candidate genes and metabolic pathways that affect the liver lipid metabolism of Yili goose. These findings provide a better understanding of animal liver lipid deposition and metabolism.

Objectives: Infectious bursal disease virus (IBDV) is a highly contagious, acutely infectious agent that causes immunosuppression in chickens. We expressed IBDV VP2 proteins in Escherichia coli (E. coli) to develop an effective virus-like-particles (VLPs) vaccine and evaluated its immunogenicity. Methods: The VLPs produced in E. coli were used as an immunogen mixed with a water-in-mineral-oil adjuvant (MontanideTM ISA 71 VG, ISA 71 RVG) or a white oil (7#) adjuvant. VLPs without an adjuvant, commercial subunit vaccine, inactivated vaccine, and attenuated vaccine were used as controls. These test vaccines were intramuscularly injected into 19-day-old SPF chickens, which were challenged with the IBDV virulent strain at 30 days after vaccination. Results: The adjuvants boosted antibody production, and the adjuvant groups (except white oil) produced higher antibody levels than the non-adjuvanted controls and the commercial vaccine groups. In terms of cellular immunity, the VLPs plus adjuvant combinations produced higher levels of cytokines, IL-2, IL-4, and IFN-γ than the controls. Conclusion: IBDV VLPs plus the ISA 71 RVG adjuvant can be used as an optimal vaccine combination for improving the immune efficacy of IBD subunit vaccines, which can protect against the virulent strain.

Abstract Background The incidence and mortality of invasive breast cancer (IBC) are increasing annually. Hence, it is urgently needed to determine reliable biomarkers for not only monitoring curative effects, but evaluating prognosis. In present study, we aim to determine the potential role of Carboxypeptidase N1 (CPN1) in IBC tissues on chemotherapeutic efficacy and poor prognosis. Methods The expression level of CPN1 in IBC tissue samples (n = 123) was quantified by tissue microarray technique and immunohistochemical staining. Moreover, sera of IBC patients (n = 34) that underwent three to five consecutive chemotherapy sessions were collected. The patients were randomly stratified into a training (n = 15) as well as a validation group (n = 19). The expression of serum CA153 and CPN1 was quantified by electrochemiluminescence and ELISA assay, respectively. Results By univariate and multivariate Cox regression analysis, we show that CPN1 expression in IBC tissues, as an independent risk factor, is related to a poor overall survival (OS) and progression-free survival (PFS) (P

The chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) is shown to promote the progression of breast cancer. We previously identified cancer cell-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) as a potential regulator of MCP-1 production in the murine 4T1 breast cancer, but it played a minimum role in overall MCP-1 production. Here, we evaluated the crosstalk between 4T1 cells and fibroblasts. When fibroblasts were co-cultured with 4T1 cells or stimulated with the culture supernatants of 4T1 cells (4T1-sup), MCP-1 production by fibroblasts markedly increased. 4T1 cells expressed mRNA for platelet-derived growth factor (PDGF)-a, b and c, and the PDGF receptor inhibitor crenolanib almost completely inhibited 4T1-sup-induced MCP-1 production by fibroblasts. However, PDGF receptor antagonists failed to reduce MCP-1 production in tumor-bearing mice. Histologically, 4T1 tumors contained a small number of αSMA-positive fibroblasts, and Mcp-1 mRNA was mainly associated with macrophages, especially those surrounding necrotic lesions on day 14, by in situ hybridization. Thus, although cancer cells have the capacity to crosstalk with fibroblasts via PDGFs, this crosstalk does not play a major role in MCP-1 production or cancer progression in this model. Unraveling complex crosstalk between cancer cells and stromal cells will help us identify new targets to help treat breast cancer patients.

Abstract Background Alteration of the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBD alleviation. However, it is unclear whether the gut microbiota exerts an effect when EGCG attenuates IBD. Results We first explored the effect of oral or rectal EGCG delivery on the DSS-induced murine colitis. Our results revealed that anti-inflammatory effect and colonic barrier integrity were enhanced by oral, but not rectal, EGCG. We observed a distinct EGCG-mediated alteration in the gut microbiome by increasing Akkermansia abundance and butyrate production. Next, we demonstrated that the EGCG pre-supplementation induced similar beneficial outcomes to oral EGCG administration. Prophylactic EGCG attenuated colitis and significantly enriched short-chain fatty acids (SCFAs)-producing bacteria such as Akkermansia and SCFAs production in DSS-induced mice. To validate these discoveries, we performed fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) to inoculate DSS-treated mice. Microbiota from EGCG-dosed mice alleviated the colitis over microbiota from control mice and SFF shown by superiorly anti-inflammatory effect and colonic barrier integrity, and also enriched bacteria such as Akkermansia and SCFAs. Collectively, the attenuation of colitis by oral EGCG suggests an intimate involvement of SCFAs-producing bacteria Akkermansia, and SCFAs, which was further demonstrated by prophylaxis and FMT. Conclusions This study provides the first data indicating that oral EGCG ameliorated the colonic inflammation in a gut microbiota-dependent manner. Our findings provide novel insights into EGCG-mediated remission of IBD and EGCG as a potential modulator for gut microbiota to prevent and treat IBD. Video Abstract

Abstract The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has placed a global public burden on health authorities. Although the virological characteristics and pathogenesis of COVID-19 has been largely clarified, there is currently no specific therapeutic measure. In severe cases, acute SARS-CoV-2 infection leads to immune disorders and damage to both the adaptive and innate immune responses. Having roles in immune regulation and regeneration, mesenchymal stem cells (MSCs) serving as a therapeutic option may regulate the over-activated inflammatory response and promote recovery of lung damage. Since the outbreak of the COVID-19 pandemic, a series of MSC-therapy clinical trials has been conducted. The findings indicate that MSC treatment not only significantly reduces lung damage, but also improves patient recovery with safety and good immune tolerance. Herein, we summarize the recent progress in MSC therapy for COVID-19 and highlight the challenges in the field.

Projecting future air pollution and related health burdens remains challenging because of the complex interactions among future emissions, population, and climate change. In this study, we estimated the premature deaths attributed to ambient fine particulate matter (PM2.5) and ozone (O3) from 2015 to 2100 under four socioeconomic climate scenarios based on an age-stratified assessment method. We found that PM2.5 will decrease in all shared socioeconomic pathway (SSP) scenarios and O3 will decrease in the SSP1-2.6 and SSP2-4.5 scenarios, contributing to a decrease in premature mortality together with the declining total population in China. However, the benefits of a decline in population size and PM2.5 and O3 concentrations over time will be largely offset by population aging, and premature death caused by PM2.5 and O3 will continue to rise till 2060–2080. This impact was greater for the O3-related deaths than those for PM2.5. Our study highlights the importance of future prevention strategies that must jointly improve air quality and susceptibility to aging.

Previous studies showed different risk effects on exposure of fine particulate matter (PM2.5) mass for cardiovascular disease (CVD) globally, which is likely due to different constituents of PM2.5. This study aimed to investigate the association between short-term exposure of PM2.5 constituents and hospital admissions of CVD. Daily counts of city-specific hospital admissions for CVD in 18 cities in China between 2014 and 2017 were extracted from the national Urban Employee Basic Medical Insurance database and the Beijing Municipal Commission of Health and Family Planning Information Center database. Directly measured PM2.5 constituents, including ions and polycyclic aromatic hydrocarbons, were collected by the Chinese Environmental Public Health Tracking system. We used the time-stratified case-crossover design to estimate the association between PM2.5 constituents and hospital admissions of CVD. Concentrations of ions accounted for the majority of the detected constituents. Excess risk (ER) of average ions concentrations for CVD was highest as 2.30% (95% CI: 1.62–2.99%) for NH4+, whose major sources are residential and agricultural emissions. This was followed by 1.85% (1.30–2.41%) for NO3- (generally from vehicles), 0.95% (0.28–1.63%) for SO42- (often from fossil fuel burning) respectively. The association for ions were generally consistent with ischemic heart disease (IHD) and ischemic stroke, e.g., NH4+ was associated with IHD (2.50%; 1.52–3.48%) and ischemic stroke (1.77%; 0.65–2.9%). For polycyclic aromatic hydrocarbons (PAHs), mainly from coal and vehicle-related oil combustion, the constituents were all associated with ischemic stroke but not for IHD. The ER for ischemic stroke was highest at 1.69% (0.99–2.39%) for indeno (123-cd) pyrene. Thus, in terms of the subtypes of CVD, the risks of hospital admissions varied with exposure to different PM2.5 constituents. Exposed to NH4+ had the highest risk to IHD and ischemic stroke, whereas PAHs were predominately associated with ischemic stroke only.

BackgroundDietary fatty acids have been shown to be associated with the development of cognition. However, research on the role of fatty acid intake in dietary patterns and fatty acid patterns (FAPs) in the development of cognitive function is limited. The aim of this study was to explore the correlation between dietary patterns and FAPs and to provide available evidence for preventing mild cognitive impairment (MCI) through these patterns.Materials and methodsThe 973 participants aged between 65 and 85 were recruited from 2020 to 2021 for this multicenter research in Beijing. Neuropsychological tests were used for cognitive evaluation, and data of dietary intake in the past 12 months were collected with semi-quantitative food frequency questionnaire. The erythrocyte membrane fatty acid profile was tested by chromatography and mass spectrometry lipid profiling. Factor analysis was used to derive the main dietary patterns and FAPs. Pearson’s correlation or Spearman’s correlation was used to explore the association between dietary patterns and FAPs. Binary logistic regression was applied to examine the relationship between patterns and cognitive function.ResultsSix dietary patterns and six FAPs were identified, explaining 53.4 and 80.9% of the total variance separately. After adjusting all potential confounders, T3 of the pattern 1 and FAP2 were the independent protect factors for MCI, respectively (OR 0.601, 95% CI [0.395, 0.914]; OR 0.108, 95% CI [0.019, 0.623]). Rich of SM (26:0), SM (24:1), and SM (26:1) is the characteristic of FAP2. A positive correlation was found between component scores of dietary pattern1 and FAP2 (r = 0.441, p = 0.001). People who adhered to a reasonable intake of animal flesh consumed more various long-chain fatty acids as well.ConclusionThe erythrocyte membrane metabolites, SM (26:0), SM (24:1), and SM (26:1), might function as early biomarkers for predicting or monitoring of cognitive aging in the elderly. The dietary pattern with recommended animal flesh consumption was significantly associated with FAP characterized by very long-chain SMs. This dietary pattern affected FAP, which might achieve the ultimate goal of neuroprotection through the very long-chain SMs. A rational intake of dietary fatty acids might be an effective way on preventing MCI in the elderly.

BackgroundThe outbreak of COVID-19 had a widely negative effect on adolescents’ academics, stress, and mental health. At a critical period of cortical development, adolescents’ cognition levels are highly developed, while the ability of emotion control is not developed at the same pace. Faced with negative emotions such as stress and social loneliness caused by COVID-19, adolescents’ “hot” executive function encounters severer emotional regulation challenges than ever before.ObjectiveThe present study established a moderated mediation model to investigate the impact of rumination on “hot” execution function among Chinese middle school students during the COVID-19 pandemic, and the specific role of depression and mindfulness in the association.Materials and methodsThis cross-sectional study was conducted on 650 students recruited from a province in central China. The participants completed questionnaires and experiment between July 2021 and August 2021. Rumination Responses Scales, Self-rating Depression Scale, and Mindful Attention Awareness Scale were used to measure the level of rumination, depression, and mindfulness. The reaction time and accuracy of the emotional conflict experiment were recorded to reflect the “hot” executive function.ResultsThe results of the moderated mediation model indicated that rumination of middle school students significantly and positively predicted depression in adolescents (β = 0.26, p < 0.001). Meanwhile, the indirect effect of depression on the relationship between rumination and “hot” executive function was significant; depression partially mediated this relationship (word-face congruent condition: β = −0.09, p < 0.01; word-face incongruent condition: β = −0.07, p < 0.05). Furthermore, mindfulness buffered the association between rumination and depression, according to moderated mediation analysis (β = −0.11, p < 0.001). For adolescents with low levels of mindfulness, the relationship was substantially stronger.ConclusionIn the context of the COVID-19 pandemic, middle school students’ rumination would lead to depression, which can negatively impact their “hot” executive function. Besides, mindfulness could resist the adverse effect of rumination on depression. The educators should pay more attention to students’ mental health, provide targeted strategies that boost mindfulness to promote their cognitive flexibility, and thus protect the normal development of their executive function during crisis events.

With the rapid economic development in recent years, China has increased its investment in infrastructure construction, and the construction industry has become a significant contributor to China’s carbon dioxide (CO2) emissions. Therefore, carbon emission reduction in the construction industry is crucial to achieving the goal of “carbon peaking and carbon neutrality” as soon as possible. However, few studies have investigated the factors influencing CO2 emissions from the construction industry in terms of spatial and temporal differences. To address this gap, we first improve the calculation method for the construction industry’s life-cycle assessment (LCA). The geographically and temporally weighted regression (GTWR) model is then utilized to provide insight into the spatio-temporal heterogeneity of the various factors influencing CO2 emissions across other regions and times. The results show that: 1) CO2 emissions from the construction industry in China increased rapidly from 576.5 million tons (Mt) in 2004–3,230 Mt in 2012 and then gradually decreased to 1998.51 Mt in 2020; indirect CO2 emissions accounted for more than 90% of the total CO2 emissions after 2008. 2) There is a solid global positive correlation between CO2 emissions from the construction industry in China during most of the time, and the spatial distribution of CO2 emissions shows a northeast-southwest pattern, with the center of gravity gradually shifting from central China to the southwest. 3) Economic output and industrial agglomeration are positive factors for the increase of CO2 emissions from the construction industry; and urbanization level, production efficiency, and energy efficiency are inhibiting factors for the increase of CO2 emissions from the construction industry. But the contribution and trend of each influencing factor differed significantly across time and regions, showing substantial spatial and temporal heterogeneity. Our findings provide a scientific basis for the Chinese government to implement a regional carbon reduction strategy for the construction industry.

To confront the growing threat of climate change and achieve carbon neutrality, green governance has come under the spotlight globally. This paper investigates the effect of stock market liberalization on corporate green innovation, aiming to explore whether foreign investor engagement contributes to the green development of Chinese enterprises. Employing a staggered DID estimation, we find that firms generate a higher level of green innovation output after they experience the liberalization, and this effect is more pronounced when foreign investors become the focal firms’ top ten shareholders. Meanwhile, foreign investors who enter China’s A-share market with the implementation of this policy are value investors, indicating that stock market liberalization can help lead firms’ investment decision more future-oriented. We also find that financing constraints play a significant role in the association between stock market liberalization and corporate green innovation. The results of heterogeneity analyses show that the positive implication of liberalization on corporate green innovation is stronger for non state-owned enterprises, firms in high-tech industries and firms in less polluting industries. Our paper provides new insights into the economic effect of foreign investor engagement in emerging capital market and the factors affecting corporate green innovation in China.

Summary: Air pollution is a major environmental and public health challenge in China and the Chinese government has implemented a series of strict air quality policies. However, particulate nitrate (NO3−) concentration remains high or even increases at monitoring sites despite the total PM2.5 concentration has decreased. Unfortunately, it has been difficult to estimate NO3− concentration across China due to the lack of a PM2.5 speciation monitoring network. Here, we use a machine learning model incorporating ground measurements and satellite data to characterize the spatiotemporal patterns of NO3−, thereby understanding the disease burden associated with long-term NO3− exposure in China. Our results show that existing air pollution control policies are effective, but increased NO3− of traffic emissions offset reduced NO3− of industrial emissions. In 2018, the national mean mortality burden attributable to NO3− was as high as 0.68 million, indicating that targeted regulations are needed to control NO3− pollution in China.

The high variability and unpredictability of the plasma concentration of voriconazole (VRC) pose a major challenge for clinical administration. The aim of this study was to develop a population pharmacokinetics (PPK) model of VRC and identify the factors influencing VRC PPK in patients with talaromycosis. Medical records and VRC medication history of patients with talaromycosis who were treated with VRC as initial therapy were collected. A total of 233 blood samples from 69 patients were included in the study. A PPK model was developed using the nonlinear mixed-effects models (NONMEM). Monte Carlo simulation was applied to optimize the initial dosage regimens with a therapeutic range of 1.0–5.5 mg/L as the target plasma trough concentration. A one-compartment model with first-order absorption and elimination adequately described the data. The typical voriconazole clearance was 4.34 L/h, the volume of distribution was 97.4 L, the absorption rate constant was set at 1.1 h-1, and the bioavailability was 95.1%. Clearance was found to be significantly associated with C-reactive protein (CRP). CYP2C19 polymorphisms had no effect on voriconazole pharmacokinetic parameters. ‏Monte Carlo simulation based on CRP levels showed that a loading dose of 250 mg/12 h and a maintenance dose of 100 mg/12 h are recommended for patients with CRP ≤ 96 mg/L, whereas a loading dose of 200 mg/12 h and a maintenance dose of 75 mg/12 h are recommended for patients with CRP > 96 mg/L. The average probability of target attainment of the optimal dosage regimen in CRP ≤ 96 mg/L and CRP > 96 mg/L groups were 61.3% and 13.6% higher than with empirical medication, and the proportion of Cmin > 5.5 mg/L decreased by 28.9%. In conclusion, the VRC PPK model for talaromycosis patients shows good robustness and predictive performance, which can provide a reference for the clinical individualization of VRC. Adjusting initial dosage regimens based on CRP may promote the rational use of VRC.

Abstract The electrochemical conversion of carbon dioxide (CO2) to carbon monoxide (CO) is a favorable approach to reduce CO2 emission while converting excess sustainable energy to important chemical feedstocks. At high current density (>100 mA cm−2), low energy efficiency (EE) and unaffordable cell cost limit the industrial application of conventional CO2 electrolyzers. Thus, a crucial and urgent task is to design a new type of CO2 electrolyzer that can work efficiently at high current density. Here we report a polymer‐supported liquid layer (PSL) electrolyzer using polypropylene non‐woven fabric as a separator between anode and cathode. Ag based cathode was fed with humid CO2 and potassium hydroxide was fed to earth‐abundant NiFe‐based anode. In this configuration, the PSL provided high‐pH condition for the cathode reaction and reduced the cell resistance, achieving a high full cell EE over 66 % at 100 mA cm−2.

In order to solve the vibration and reliability problems of timing belt transmission system of a 2.0L VVT engine，the mechanical model of timing drive system is simplified from the point of view of force balance，and the external excitation factors affecting the vibration of timing drive system are quickly found. Through the methods of reducing the fluctuation of camshafts loads，reducing VVT adjusting shock，optimizing belt tensioner internal structure，reducing the vibration of timing belt transmission system and timing tensioner swing，the issues of wear failure of timing tensioner and belt are solved. The key index of the vibration of the timing transmission system is determined，and the reliability test of the engine is verified.

Ecological protection and high-quality development of the Yellow River Basin (YRB), China, aroused remarkable concerns from China’s Central Government, and has been a major national strategy. The Inner Mongolia reach of the Yellow River Basin (IM-YRB) is a typical dryland with pervasive vegetation restoration through the actions of the ecological projects that have been conducted in recent years. However, how climate changes and human activities, such as land use and land cover (LULC) changes, jointly impact vegetation variations in this region remains poorly understood. Here, using an explainable machine learning technique, we evaluated linkages between the kernel normalized difference vegetation index (kNDVI) and air temperature, precipitation, soil moisture, and LULC changes, and relevant marginal contributions of these four drivers to the observed vegetation changes. The grassland fraction on a pixel level was selected as the quantitative LULC variable due to its key role in regional LULC. We found that interannual kNDVI changes in most areas of this study region were negatively sensitive to temperature, but positively sensitive to precipitation and soil moisture, with area fractions of 71.74%, 96.93%, and 89.33%, respectively. The area fraction of negative kNDVI sensitivity to LULC was roughly equivalent to that of positive kNDVI sensitivity. The contributions of air temperature, precipitation, soil moisture, and LULC to overall kNDVI changes were 21.54%, 33.32%, 32.19%, and 12.95%, respectively. Moisture conditions also play a critical role in vegetation changes, which was reflected by the fluctuating growth of kNDVI as interannual changes in precipitation. Nonetheless, kNDVI changes are also affected by LULC, and LULC became the dominant factor behind the kNDVI anomalies over the grassland restoration regions from barren over the IM-YRB. This research provides theoretical support for dryland vegetation restoration under the influence of climate change.

In response to the sustainable development goal of agriculture put forward by the United Nations, countries have introduced a series of agricultural environmental protection policies. However, the effectiveness of these policies has been hindered by insufficient responses from farmers. This study begins with the fundamental logic of farmers’ production behavior and first introduces family and place identities into the theoretical analysis framework of farmers’ environment-friendly production behavior (EPB). Using primary survey data for farmers from the northwestern Chinese province of Gansu, a hierarchical regression and simple slope analysis models were developed to verify how family and place identities affect farmers’ EPB. The potential moderating effect of place identity on the relationship between family identity and farmers’ EPB is further investigated. The results show that improving family identity has a significantly negative effect on farmers’ EPB, while improving place identity can significantly promote farmers’ EPB. Compared with respondents who have a low place identity, the inhibitory effect of family identity on farmers’ EPB is significantly weakened for those who have a high place identity, which suggests that farmers with a high place identity are more likely to engage in EPBs in agricultural production. This study highlights the importance of considering the economic logic toward maximizing family economic interests and the social logic oriented toward collective interests in the decision-making process of agricultural environmental policies.

Abstract Background Endometriosis is a refractory and recurrent disease and it affects nearly 10% of reproductive-aged women and 40% of infertile patients. The commonly accepted theory for endometriosis is retrograde menstruation where endometrial tissues invade into peritoneal cavity and fail to be cleared due to immune dysfunction. Therefore, the comprehensive understanding of immunologic microenvironment of peritoneal cavity deserves further investigation for the previous studies mainly focus on one or several immune cells. Results High-quality transcriptomes were from peritoneal fluid samples of patients with endometriosis and control, and firstly subjected to 10 × genomics single-cell RNA-sequencing. We acquired the single-cell transcriptomes of 10,280 cells from endometriosis sample and 7250 cells from control sample with an average of approximately 63,000 reads per cell. A comprehensive map of overall cells in peritoneal fluid was first exhibited. We unveiled the heterogeneity of immune cells and discovered new cell subtypes including T cell receptor positive (TCR+) macrophages, proliferating macrophages and natural killer dendritic cells in peritoneal fluid, which was further verified by double immunofluorescence staining and flow cytometry. Pseudo-time analysis showed that the response of macrophages to the menstrual debris might follow the certain differentiation trajectory after endometrial tissues invaded into the peritoneal cavity, that is, from antigen presentation to pro-inflammation, then to chemotaxis and phagocytosis. Our analyses also mirrored the dysfunctions of immune cells including decreased phagocytosis and cytotoxic activity and elevated pro-inflammatory and chemotactic effects in endometriosis. Conclusion TCR+ macrophages, proliferating macrophages and natural killer dendritic cells are firstly reported in human peritoneal fluid. Our results also revealed that immune dysfunction happens in peritoneal fluid of endometriosis, which may be responsible for the residues of invaded menstrual debris. It provided a large-scale and high-dimensional characterization of peritoneal microenvironment and offered a useful resource for future development of immunotherapy.

Abstract SDG711 is a histone H3K27me2/3 transmethylase in rice, a homolog of CLF in Arabidopsis, and plays key roles in regulating flowering time and panicle development. In this work, we investigated the role of SDG711 in rice seed development. Overexpression and downregulation of SDG711 lead to a decrease and increase in the expression level of genes related to starch accumulation, resulting in smaller seeds or even seed abortion. ChIP assay showed that SDG711-mediated H3K27me3 changed significantly in genes related to endosperm development, and SDG711 can directly bind to the gene body region of several starch synthesis genes and amylase genes. In addition, H3K4me3 and H3K9ac modifications also cooperate with H3K27me3 to regulate the development of the endosperm. Our results suggest that the crosstalk between SDG711-mediated H3K27me3 and H3K4me3, and H3K9ac are involved in starch accumulation to control normal seed development.

PurposeIn this study, we examined the changes to the composition and function of the gut microbiota from patients with metabolic dysfunction-associated fatty liver disease (MAFLD).We compared patients in a case group (liver stiffness (LSM) ≥ 7.4 kPa) with a matched control group (LSM < 7.4 kPa) and investigated the correlation between characteristics of the microbiota and other biochemical indicators. MethodsThe study looked at a total of 85 men with MAFLD, 17 of whom were in the case group and 68 of whom were in the control group. We measured waist circumference, blood pressure, and body mass index, as well as clinical parameters including liver stiffness, enzyme levels, cholesterol levels, and fat attenuation. Whole-genome shotgun sequencing technology and the MetaCyc database were then used to detect the composition and major pathways of the gut microbiota for each patient. Statistical analyses were performed, including the chi-square test, the student’s t-test, the Wilcoxon rank-sum test, and the Mann–Whitney test. ResultsWhole-genome sequencing showed that the composition of the gut microbiota in patients with an LSM of above 7.4 kPa was significantly different to that of the control group. There were seven bacterial species that were different between the two groups. Prevotella copri, Phascolarctobacterium succinatutens, Eubacterium biforme, and Collinsella aerofaciens were enriched in the case group (P < 0.05). Conversely, Bacteroides coprocola, Bacteroides stercoris and Clostridiales bacterium 1_7_47FAA were decreased in the case group (P < 0.05). Furthermore, after removing low abundance pathways, a total of 32 microbial pathways were found to be significantly different between the two groups. Most pathways enriched in the case group over the control were related to biosynthesis of metabolites including amino acids, vitamins, nucleosides, and nucleotides. Conclusion. The composition and function of the gut microbiota in patients with increased liver stiffness are significantly altered. This observation may provide new avenues to better understand the mechanism of liver fibrosis.

Background: Evidence for the association between long-term exposure to ozone (O3) and cause-specific cardiovascular disease (CVD) mortality is inconclusive, and this association has rarely been evaluated at high O3 concentrations. Objectives: We aim to evaluate the associations between long-term O3 exposure and cause-specific CVD mortality in a Chinese population. Methods: From 2009 to 2018, 744,882 subjects (median follow-up of 7.72 years) were included in the CHinese Electronic health Records Research in Yinzhou (CHERRY) study. The annual average concentrations of O3 and fine particulate matter (PM2.5), which were estimated using grids with a resolution up to 1 × 1 km, were assigned to the community address for each subject. The outcomes were deaths from CVD, ischemic heart disease (IHD), myocardial infarction (MI), stroke, and hemorrhagic/ischemic stroke. Time-varying Cox model adjusted for PM2.5 and individual-level covariates was used. Results: The mean of annual average O3 concentrations was 68.05 μg/m3. The adjusted hazard ratio per 10 μg/m3 O3 increase was 1.22 (95% confidence interval [CI]: 1.13–1.33) for overall CVD mortality, 1.08 (0.91–1.29) for IHD, 1.21 (0.90–1.63) for MI, 1.28 (1.15–1.43) for overall stroke, 1.39 (1.16–1.67) for hemorrhagic stroke and 1.22 (1.00–1.49) for ischemic stroke, respectively. The study showed that subjects without hypertension had a higher risk for CVD mortality associated with long-term O3 exposure (1.66 vs. 1.15, p = 0.01). Conclusions: We observed the association between long-term exposure to high O3 concentrations and cause-specific CVD mortality in China, independent of PM2.5 and other CVD risk factors. This suggested an urgent need to control O3 pollution, especially in developing countries.

This investigation probed endometriosis treatment using targeted nanoparticles (NPs) to modulate autophagic activity. To that end, a novel form of polymer-based NP gene delivery platform consisting of polyethyleneimine (PEI) conjugated to stearic acid (SA) and nucleotides (DNA/siRNAs) and enclosed by hyaluronic acid (HA) was prepared. CD44 is highly upregulated in cystic lesions, and HA–CD44 binding in this specific nanoplatform was used to achieve targeted drug delivery to CD44-expression endometriotic tissues. The expression of autophagy-related genes was modulated to explore the importance of this process in the development of endometriosis. By inducing autophagic activity, we were able to reduce the size of endometriotic cysts and suppress the development of ectopic endometrium. To further confirm the relationship between autophagic activity and this disease in humans and animals, numbers of autophagic vesicles and autophagic protein expression were assessed in lesion tissue samples from patients, revealing there may be consistency between animal and human data. Overall, these data revealed the ability of this (PEI–SA/DNA) HA gene delivery system to regulate autophagic activity and, thereby, aid in the treatment of endometriosis.

It is predicted that by 2035, metabolic syndrome (MS) will be found in nearly more than half of our adult population, seriously affecting the health of our body. MS is usually accompanied by the occurrence of abnormal liver enzymes, such as elevated gamma-glutamyl transpeptidase (GGT). More and more studies have shown that the gut microbiota is involved in MS; however, the correlation between gut microbiota and MS with elevated GGT has not been studied comprehensively. Especially, there are few reports about its role in the physical examination of the population of men with MS and elevated GGT. By using the whole-genome shotgun sequencing technology, we conducted a genome-wide association study of the gut microbiome in 66 participants diagnosed as having MS accompanied by high levels of GGT (case group) and 66 participants with only MS and normal GGT level (control group). We found that the number of gut microbial species was reduced in participants in the case group compared to that of the control group. The overall microbial composition between the two groups is of significant difference. The gut microbiota in the case group is characterized by increased levels of “harmful bacteria” such as Megamonas hypermegale, Megamonas funiformis, Megamonas unclassified, Klebsiella pneumoniae, and Fusobacterium mortiferum and decreased levels of “beneficial bacteria” such as Faecalibacterium prausnitzii, Eubacterium eligens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides dorei, and Alistipes putredinis. Moreover, the pathways of POLYAMSYN-PWY, ARG+POLYAMINE-SYN, PWY-6305, and GOLPDLCAT-PWY were also increased in the case group, which may play a role in the elevation of GGT by producing amine, polyamine, putrescine, and endogenous alcohol. Taken together, there are apparent changes in the composition of the gut microbiome in men with MS and abnormal GGT levels, and it is high time to discover specific gut microbiome as a potential therapeutic target in that population. More in-depth studies of relevant mechanism could offer some new methods for the treatment of MS with elevated GGT.

Ecological conservation and high-quality development of the YRB (Yellow River Basin) has been adopted as a national strategy. However, the ecological environment of the YRB is fragile and it has degraded in recent years. Here we proposed an ecological degradation index system based on the Pressure-State-Response (PSR) model and evaluated trends in ecological degradation of the YRB using the Mann-Kendall trend test. We found an upward-downward-upward trend in the ecological degradation index (EDI) during the period of 2000–2019. We also observed an intensifying degradation of eco-environment from the upper to the lower YRB. Meanwhile, 69.9% of the YRB is under degraded eco-environment, while 29.5% of the YRB is dominated by improved eco-environment. Specifically, the ecological degradation intensity of Henan and Shandong Province with dense population and rapid economic development is the highest. Due to active and effective improvement measures taken by the government, the degradation intensity has been having a decreasing tendency. However, higher degradation intensity of eco-environment of the YRB should arouse human concerns. As to the driving factors, human activities can be regarded as the major driving factors for degraded eco-environment, and water stress and economic development exert increasing impacts on the eco-environment of the YRB. Our finding can provide a decision-making basis for the ecological management and high-quality development of the YRB.

Aging is now the most profound risk factor for almost all non-communicable diseases. Studies have shown that probiotics play a specific role in fighting aging. We used metagenomic sequencing to study the changes in gut microbes in different age groups and found that aging had the most significant effect on subjects’ gut microbe structure. Our study divided the subjects (n=614) into two groups by using 50 years as the age cut-off point for the grouping. Compared with the younger group, several species with altered abundance and specific functional pathways were found in the older group. At the species level, the abundance of Bacteroides fragilis, Bifidobacterium longum, Clostridium bolteae, Escherichia coli, Klebsiella pneumoniae, and Parabacteroides merdae were increased in older individuals. They were positively correlated to the pathways responsible for lipopolysaccharide (LPS) biosynthesis and the degradation of short-chain fatty acids (SCFAs). On the contrary, the levels of Barnesiella intestinihominis, Megamonas funiformis, and Subdoligranulum unclassified were decreased in the older group, which negatively correlated with the above pathways (p-value

ObjectiveInflammatory bowel disease (IBD) often occurs along with extraintestinal manifestations, including hepatic injury. Milk fat globule membrane (MFGM) is an active substance with a potential anti-inflammation activity. However, its alleviated effect and mechanisms in IBD as well as the IBD-induced secondary liver injury are still unclear.MethodsC57BL/6J mice were administered with a 21-day oral gavage of MFGM, followed by 7 days of drinking water with 4% dextran sulfate sodium (DSS). Disease activity index (DAI), histological features, and cytokines of the colon and liver were evaluated. Then, RNA-seq of the colon and liver was conducted. The gut microbiota was assessed by analyzing 16S rRNA gene sequences, and finally the integrity and the function of the mucus barrier were evaluated by Alcian blue staining, real-time quantitative PCR, and ELISA.ResultsProphylactic MFGM treatment was effective against colitis to include effects in body weight loss, DAI score, colonic length, intestinal pathology, and histological score. Additionally, prophylactic MFGM decreased the levels of interleukin (IL)-1β, IL-6, and myeloperoxidase in colonic tissue, while it increased the IL-10 level. Moreover, the gene expressions of MUC2, MUC4, Reg3b, and Reg3g associated with the production of the molecular mediator of immune response, membrane invagination, and response to protozoan were strikingly upregulated when administered with MFGM. On the other hand, the beneficial effects of MFGM were related to the enriched abundance of genera such as Faccalibacumum and Roseburia in feces samples. Consistently, the administration of MFGM was also found to alleviate DSS-induced hepatic injury. Furthermore, the glutathione transferase activity pathway was enriched in the liver of MFGM-treated mice after DSS administration. Mechanistically, prophylactic MFGM enhanced the mucosal barrier by increasing the gene levels of Reg3b and Reg3g. Meanwhile, the alleviation of MFGM on liver injury was dependent on the reduced hepatic oxidative stress.ConclusionsMFGM attenuated colitis and hepatic injury by maintaining the mucosal barrier and bacterial community while inhibiting oxidative stress, which might be an effective therapy of hepatic injury secondary to IBD.

Abstract Background Intrauterine growth restriction (IUGR) has negative impacts on the postnatal survival, growth and development of humans and animals, with not only on newborns but also adulthood. However, the characteristics for nutrient digestion and absorption in IUGR offspring are still largely unknown. Therefore, the normal birth weight (NBW) and IUGR growing pigs were used in this study to investigate their differences in nutrient utilization, with an expectition for further nutritional optimization of the IUGR offspring during their later life. Methods Twelve IUGR and 12 NBW growing pigs were fitted with catheters in their portal vein to measure blood flow rate as well as nutrients and metabolites in plasma. The digestibilities of nutrients in different intestinal segments, and bacterial fermentation in the large intestine were examined to reveal the characteristics of nutrients utilization in IUGR versus NBW pigs. Results The rate of portal venous blood flow did not differ beween IUGR and NBW pigs. Plasma concentrations of total cholesterol, triglycerides and glucose were much lower but those of urea were higher in the portal vein of IUGR pigs, compared with the NBW pigs. The ileal digestibility of dry matter, gross energy and starch were lower in IUGR pigs than in NBW pigs. IUGR increased hindgut microbial diversity and bacterial fermentation activity in the caecum. In vitro cross-fermentation of ileal digesta by caecal microbes of NBW and IUGR pigs showed that gas production was much higher for IUGR ileal digesta regardless of the source of caecal inocula. Conclusion IUGR impairs the nutrient digestion and absorption in small intestine, reduces caecal microbial diversity and promotes bacterial fermentation in the large intestine during the growing phase. These findings aid in our understanding of nutrient metabolism in IUGR pigs and provide the basis for future nutritional interventions.

Abstract Background The diagnosis of immunoglobulin G serum antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) associated inflammatory demyelinating disorders can be confirmed by the presence of MOG-IgG, yet its general cut-off concentration had not yet to be defined. Whether it is significant that a seropositive lower titer level for MOG-IgG could cause disease is still unknown. Case presentation A 55-year-old Chinese woman presented with acute optic neuritis manifestations in the left eye. MRI showed a left optic nerve demyelination image and a T2 hyperintensity at C7 vertebral segment without any extra specific lesions. AQP4-IgG was tested seronegative, while the MOG-IgG was positive, titer 1:10, by indirect immunofluorescence. Considering the lower concentration, we retested serum MOG-IgG after 6 months of steroid therapy, using cell-based assay, then we still got the same result which was also barely above the negative cut-off value. So, the clinical diagnose was “possible MOG-IgG-associated encephalomyelitis”. The woman’s condition improved by steroid therapy without relapse. Conclusions Seropositive MOG-IgG, even at a lower level, could lead to an autoimmune inflammatory demyelination. In adults, it commonly presents as ON and myelitis. Although the patient had a considerable reaction, steroid therapy could not make MOG-IgG seronegative, instead, the antibody may persist even during remission and flare-ups can recur after steroid withdrawal. Therefore, a long-term follow-up is necessary to monitor the patient’s prognosis.

Deep learning classifiers require a large number of labeled samples to train the model. Active learning reduces the dependence of classification model on labeled samples by gradually selecting high-quality samples for iterative training. In this article, an active learning method for pattern classification is proposed, which can use fewer labeled samples to achieve higher classification accuracy. The algorithm uses PEDCC-Loss to train the network model according to the predefined evenly-distributed class centroids (PEDCC) of the classification task, maximizing the distance between classes. Then, the maximum value of the cosine distance is selected to measure the sample uncertainty according to the PEDCC output characteristics. In the active learning algorithm iteration, samples with high uncertainty are selected for manual labeling, and samples with low uncertainty are given pseudo labels. At the same time, manual label samples and pseudo label samples are used to train the classification network to continuously optimize the classification boundary. Compared with CRL, LLAL and other methods, the experimental results on CIFAR100, CIFAR10, SVHN, and Animals-10 data sets show the effectiveness of this algorithm.

With the increasing requirements for computing in modern society, Multi-access Edge Computing (MEC) has received widespread attention for meeting low-latency. In MEC network, mobile devices can offload computing-intensive tasks to edge servers for computing. Wireless Power Transmission (WPT) provides initial energy for mobile devices, and the tasks of mobile devices consume energy when they are locally calculated or completely offloaded. The combination of the two technologies forms the Wireless Powered Mobile Edge Computing (WP-MEC) network. In this article, considering the impact of WPT transmission time $\tau _{0}$ , we study the offloading and scheduling of tasks for multiple mobile devices in the WP-MEC network, which is an NP-hard problem. We formulate this scheduling problem to minimize the time delay under the constraint of WPT transmission energy. We regard our problem studied in this paper as a multidimensional knapsack problem (MKP). The difference is that the knapsack capacity in MKP is limited, while in our problem, the knapsack that one item can choose is limited. Therefore, we improve the Artificial Fish Swarm Algorithm (AFSA) and propose Computation Scheduling Based on the Artificial Fish Swarm Algorithm (CS-AFSA) to find the optimal scheduling. We encode a scheduling scheme as an artificial fish and regard the delay corresponding to the scheduling as the optimization object. The optimal artificial fish can be gradually approached and determined through the swarm, follow and prey behavior of artificial fish. The optimal artificial fish is the optimal scheduling scheme. More importantly, based on the original behavior of AFSA, we also improve the scheme that does not meet the WPT energy constraint, including the modification of infeasible artificial fish and insufficient artificial fish. Besides, we also consider how to find the best WPT transmission time $\tau _{0}$ . Finally, we perform data simulation on the proposed algorithm.

Abstract Background The microbiota presents a compartmentalized distribution across different gut segments. Hence, the exogenous microbiota from a particular gut segment might only invade its homologous gut location during microbiota transplantation. Feces as the excreted residue contain most of the large-intestinal microbes but lack small-intestinal microbes. We speculated that whole-intestinal microbiota transplantation (WIMT), comprising jejunal, ileal, cecal, and colonic microbiota, would be more effective for reshaping the entire intestinal microbiota than conventional fecal microbiota transplantation fecal microbiota transplantation (FMT). Results We modeled the compartmentalized colonization of the gut microbiota via transplanting the microbiota from jejunum, ileum, cecum, and colon, respectively, into the germ-free mice. Transplanting jejunal or ileal microbiota induced more exogenous microbes’ colonization in the small intestine (SI) of germ-free mice rather than the large intestine (LI), primarily containing Proteobacteria, Lactobacillaceae, and Cyanobacteria. Conversely, more saccharolytic anaerobes from exogenous cecal or colonic microbiota, such as Bacteroidetes, Prevotellaceae, Lachnospiraceae, and Ruminococcaceae, established in the LI of germ-free mice that received corresponding intestinal segmented microbiota transplantation. Consistent compartmentalized colonization patterns of microbial functions in the intestine of germ-free mice were also observed. Genes related to nucleotide metabolism, genetic information processing, and replication and repair were primarily enriched in small-intestinal communities, whereas genes associated with the metabolism of essential nutrients such as carbohydrates, amino acids, cofactors, and vitamins were mainly enriched in large-intestinal communities of germ-free mice. Subsequently, we compared the difference in reshaping the community structure of germ-free mice between FMT and WIMT. FMT mainly transferred LI-derived microorganisms and gene functions into the recipient intestine with sparse SI-derived microbes successfully transplanted. However, WIMT introduced more SI-derived microbes and associated microbial functions to the recipient intestine than FMT. Besides, WIMT also improved intestinal morphological development as well as reduced systematic inflammation responses of recipients compared with FMT. Conclusions Segmented exogenous microbiota transplantation proved the spatial heterogeneity of bacterial colonization along the gastrointestinal tract, i.e., the microbiota from one specific location selectively colonizes its homologous gut region. Given the lack of exogenous small-intestinal microbes during FMT, WIMT may be a promising alternative for conventional FMT to reconstitute the microbiota across the entire intestinal tract. Video Abstract

Abstract Background Pancreatic neuroendocrine tumors (PANETs) are rare, slow growing cancers that often present with local and distant metastasis upon detection. PANETS contain distinct karyotypes, epigenetic dysregulation, and recurrent mutations in MEN1, ATRX, and DAXX (MAD+); however, the molecular basis of disease progression remains uncharacterized. Methods We evaluated associations between aneuploidy and the MAD+ mutational state of 532 PANETs from 11 published genomic studies and 19 new cases using a combination of exome, targeted panel, shallow WGS, or RNA-seq. We mapped the molecular timing of MAD+ PANET progression using cellular fractions corrected for inferred tumor content. Results In 287 PANETs with mutational data, MAD+ tumors always exhibited a highly recurrent signature of loss of heterozygosity (LOH) and copy-number alterations affecting 11 chromosomes, typically followed by genome doubling upon metastasis. These LOH chromosomes substantially overlap with those that undergo non-random mis-segregation due to ectopic CENP-A localization to flanking centromeric regions in DAXX-depleted cell lines. Using expression data from 122 PANETs, we found decreased gene expression in the regions immediately adjacent to the centromere in MAD+ PANETs. Using 43 PANETs from AACR GENIE, we inferred this signature to be preceded by mutations in MEN1, ATRX, and DAXX. We conducted a meta-analysis on 226 PANETs from 8 CGH studies to show an association of this signature with metastatic incidence. Our study shows that MAD+ tumors are a genetically diverse and aggressive subtype of PANETs that display extensive chromosomal loss after MAD+ mutation, which is followed by genome doubling. Conclusions We propose an evolutionary model for a subset of aggressive PANETs that is initiated by mutation of MEN1, ATRX, and DAXX, resulting in defects in centromere cohesion from ectopic CENP-A deposition that leads to selective loss of chromosomes and the LOH phenotype seen in late-stage metastatic PANETs. These insights aid in disease risk stratification and nominate potential therapeutic vulnerabilities to treat this disease.

Dynamic surface patterns are widely used in information security and anticounterfeiting technologies. Here, the authors demonstrated a dynamic wrinkled and fluorescent pattern using a supramolecular network in which both the wrinkle morphology and fluorescence color can be regulated by pH or light.

Vascular calcification (VC) is a complex ectopic calcification process and an important indicator of increased risk for diabetes, atherosclerosis, chronic kidney disease, and other diseases. Therefore, clarifying the pathogenesis of VC is of great clinical significance. Numerous studies have shown that the onset and progression of VC are similar to bone formation. Members of the bone morphogenetic protein (BMP) family of proteins are considered key molecules in the progression of vascular calcification. BMP type I receptor A (BMPR1A) is a key receptor of BMP factors acting on the cell membrane, is widely expressed in various tissues and cells, and is an important “portal” for BMP to enter cells and exert their biological effect. In recent years, many discoveries have been made regarding the occurrence and treatment of ectopic ossification-related diseases involving BMP signaling targets. Studies have confirmed that BMPR1A is involved in osteogenic differentiation and that its high expression in vascular endothelial cells and smooth muscle cells can lead to vascular calcification. This article reviews the role of BMPR1A in vascular calcification and the possible underlying molecular mechanisms to provide clues for the clinical treatment of such diseases.

ObjectiveHealth dietary pattern is related with reduced risk of chronic metabolic disease, but the benefits were not fully clear in the Chinese population. The aim of this study was to explore the association between dietary patterns and multiple chronic metabolic diseases in middle-aged and elderly Chinese.MethodsA total of 718 Chinese adults aged ≥ 45 who lived in the Huairou regions of Beijing were included in the present cross-sectional analysis from 2019 to 2020. Dietary data were obtained by food frequency questionnaires (FFQs). Dietary patterns were identified by principal components analysis (PCA). Logistic regression analysis and hierarchical analysis were used to examine the relationship among dietary patterns, health management, and chronic diseases.ResultsFive dietary patterns were discovered in the subjects. The pattern with the higher percentage of energy supply by lipid was a risk factor for hypertension [odds ratio (OR) = 2.067, p = 0.013]. Lower energy intake (OR = 0.512, p = 0.012) and a reasonable ratio of dietary energy supply (OR = 0.506, p = 0.011) were beneficial to diabetes. The substitution of potato for grain might be an effective way of reducing diabetes (OR = 0.372, p < 0.001). The higher intake of high-quality protein was the protective factor for coronary heart disease (CHD; OR = 0.438, p = 0.008). Moderate intervention (OR = 0.185, p = 0.033) and appropriate health education (OR = 0.432, p = 0.016) could greatly subserve the prevention of chronic diseases, especially for hyperlipidemia. Men were more likely to be affected by health education, intervention, and follow-up than women. The prevalence of multimorbidity was higher in women (43.2%) than men (41.5%). The staple food intake and health management were also important factors to prevent multimorbidity.ConclusionDietary pattern with appropriate energy intake, a reasonable source of energy supply, high quality of macronutrients, and moderate management was associated with decreased risk of chronic metabolic diseases. Further studies are needed to clarify the cause–effect relationship between dietary patterns, health management, and chronic diseases and give suggestions to chronic metabolic disease prevention in middle-aged and elderly people in a rural area.

Although long non coding RNAs (lncRNAs) and circular RNAs (circRNAs) play important roles in the pathogenesis of diseases, endometriosis related lncRNAs and circRNAs are still rarely reported. This study focused on the potential molecular mechanism of endometriosis related competitive endogenous RNA (ceRNA) composed of lncRNAs and circRNAs. We performed high-throughout sequencing of six normal endometria, six eutopic endometria and six ectopic endometria for the first time to describe and analyze the expression profile of lncRNA, circRNA and mRNA. Our results showed that 140 lncRNAs, 107 circRNAs and 1,206 mRNAs were differentially expressed in the ectopic group, compared with the normal and eutopic groups. We established an lncRNA/circRNA-mRNA co-expression network using pearson correlation test. Meanwhile, the results of Gene set enrichment analysis analysis showed that the 569 up-regulated differentially expressed mRNA (DEmRNA) were mainly related to the epithelial-mesenchymal transition, regulation of immune system process and immune effector process. Subsequently, we established a DElncRNA-miRNA and DEcircRNA-miRNA network using the starbase database, identified the common miRNAs and constructed DElncRNA/DEcircRNA-miRNA pairs. miRDB, Targetscan, miRwalk and circRNA/lncRNA-mRNA pairs jointly determined the miRNA-mRNA portion of the circRNA/lncRNA-miRNA-mRNA co-expression network. RT-qPCR results of 15 control samples and 25 ectopic samples confirmed that circGLIS2, circFN1, LINC02381, IGFL2-AS1, CD84, LYPD1 and FAM163A were significantly overexpressed in ectopic tissues. In conclusion, this is the first study to illustrate ceRNA composed of differentially expressed circRNA, lncRNA and mRNA in endometriosis. We also found that lncRNA and circRNA exerted a pivotal function on the pathogenesis of endometriosis, which can provide new insights for further exploring the pathogenesis of endometriosis and identifying new targets.

Summary: Recent studies have shown that PM2.5 may activate the hypothalamus-pituitary-adrenal (HPA) axis by inducing hormonal changes, potentially explaining the increase in neurological and cardiovascular risks. In addition, an association between PM2.5 and gut microbiota and metabolites was established. The above evidence represents crucial parts of the gut-brain axis (GBA). In view of this evidence, we proposed a hypothesis that PM2.5 exposure may affect the HPA axis through the gastrointestinal tract microbiota pathway (GBA mechanism), leading to an increased risk of neurological and cardiovascular diseases. We conducted a real-world prospective repeated panel study in Jinan, China. At each visit, we measured real-time personal PM2.5 and collected fecal and blood samples. A linear mixed-effects model was used to analyze the association between PM2.5 and serum biomarkers, gut microbiota, and metabolites. We found that PM2.5 was associated with increased serum levels of hormones, especially the adrenocorticotropic hormone (ACTH) and cortisol, which are reliable hormones of the HPA axis. Gut microbiota and tryptophan metabolites and inflammation, which are important components of the GBA, were significantly associated with PM2.5. We also found links between PM2.5 and changes in the nervous and cardiovascular outcomes, e.g., increases of 19.77% (95% CI: −36.44, 125.69) in anxiety, 1.19% (95% CI: 0.65, 1.74) in fasting blood glucose (FBG), 2.09% (95% CI: 1.48, 2.70) in total cholesterol (TCHOL), and 0.93% (95% CI: 0.14, 1.72) in triglycerides (TG), were associated with 10 μg/m3 increase in PM2.5 at the lag 0–72 h, which represent the main effects of GBA. This study indicated the link between PM2.5 and the microbiota GBA for the first time, providing evidence of the potential mechanism for PM2.5 with neurological and cardiovascular system dysfunction.

Electroencephalogram (EEG) has been widely utilized in emotion recognition. Psychologists have found that emotions can be divided into conscious emotion and unconscious emotion. In this article, we explore to classify subliminal emotions (happiness and anger) with EEG signals elicited by subliminal face stimulation, that is to select appropriate features to classify subliminal emotions. First, multi-scale sample entropy (MSpEn), wavelet packet energy (Ei), and wavelet packet entropy (WpEn) of EEG signals are extracted. Then, these features are fed into the decision tree and improved random forest, respectively. The classification accuracy with Ei and WpEn is higher than MSpEn, which shows that Ei and WpEn can be used as effective features to classify subliminal emotions. We compared the classification results of different features combined with the decision tree algorithm and the improved random forest algorithm. The experimental results indicate that the improved random forest algorithm attains the best classification accuracy for subliminal emotions. Finally, subliminal emotions and physiological proof of subliminal affective priming effect are discussed.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry has been widely used as an emerging technology for the rapid identification of microorganisms. Cronobacter sakazakii (C. sakazakii) is a food-borne pathogen of particular importance to the powdered infant formula (PIF) processing environment due to its high lethality in infants. However, the traditional solid spotting detection method of pretreating samples for MALDI-TOF MS leads only to qualitative detection of C. sakazakii. We developed a new, low-cost, robust liquid spotting pretreatment method and used a response surface methodology to optimize its parameters. The applicability, accuracy, and quantitative potential were measured for different types of samples. The optimal parameters of this method were as follows: a volume of 70% formic acid of 25 μL, treatment with ultrasound at 350 W for 3 min, and a volume of acetonitrile added of 75 μL. These conditions led to the highest identification score for C. sakazakii (1926.42 ± 48.497). This method was found to detect bacteria accurately and reproducibly. When 70 strains of C. sakazakii isolates were analyzed with this method, the identification accuracy was 100%. The detection limit of C. sakazakii in environmental and PIF samples was 4.1 × 101 cfu/mL and 2.72 × 103 cfu/mL, respectively.