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1.
J Hazard Mater ; 476: 135048, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964041

RESUMO

While the cardiovascular system is a primary target of organophosphorus flame retardants (OPFRs), particularly aryl-OPFRs, it is still exclusive whether the diisodecyl phenyl phosphate (DIDPP), widely used and broadly present in the environment at high concentrations, elicits atherosclerosis effects. Liver X receptors (LXRs) play a direct role in regulating the formation of atherosclerotic lesions. This study was the first to demonstrate that DIDPP acts as an LXRα ligand and functions as an LXRα antagonist with a half-maximal inhibitory concentration of 16.2 µM. We showed that treatment of an in vitro macrophage model with 1 to 10 µM of DIDPP resulted in the downregulation of direct targets of LXRα, namely ABCA1, ABCG1 and SR-B1, thereby leading to a 7.9-13.2 % reduction in cholesterol efflux. This caused dose-dependent, 24.1-43.1 % increases in the staining intensity of foam cells in the macrophage model. This atherosclerotic effect of DIDPP was proposed to be due to its antagonism of LXRα activity, as DIDPP treatment did not alter cholesterol influx. In conclusion, the findings of this study demonstrate that exposure to DIDPP may be a risk factor for atherosclerosis due to the LXRα-antagonistic activity of DIDPP and its ubiquity in the environment.

2.
Polymers (Basel) ; 16(12)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38931993

RESUMO

Carbon fiber resin-based composite materials are widely employed in the manufacturing of composite shells. During the curing process, the temperature gradients and cure degree gradients make it easy to generate thermal strains in both carbon fibers and resin, with the resin experiencing cure shrinkage strain due to the curing reaction, ultimately leading to residual stresses and strains. In this paper, a three-dimensional thermo-chemo-mechanical coupled curing model of the composite shell was established based on a resin test, and the changes of temperature, curing degree, residual stress, and strain during the solidification of the composite shell were investigated. First, the curing property parameters and elastic modulus of HCM-2184 resin were obtained through a curing dynamic test and a tensile test. Then, considering the heat release and shrinkage reaction of solidification, a coupled thermo-chemo-mechanical curing model was developed with the CHILE (α) elastic model, and the curing process of the composite shell was simulated numerically. The results show that the resin used in the test belongs to the autocatalytic reaction. For thin composite shells, the heat accumulation inside the shell during curing is not obvious. During the curing process, the curing shrinkage behavior of the resin is an important factor for the generation of residual stress and residual strain.

3.
Cell Rep Med ; 5(2): 101379, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38382465

RESUMO

The high failure rate of clinical trials in Alzheimer's disease (AD) and AD-related dementia (ADRD) is due to a lack of understanding of the pathophysiology of disease, and this deficit may be addressed by applying artificial intelligence (AI) to "big data" to rapidly and effectively expand therapeutic development efforts. Recent accelerations in computing power and availability of big data, including electronic health records and multi-omics profiles, have converged to provide opportunities for scientific discovery and treatment development. Here, we review the potential utility of applying AI approaches to big data for discovery of disease-modifying medicines for AD/ADRD. We illustrate how AI tools can be applied to the AD/ADRD drug development pipeline through collaborative efforts among neurologists, gerontologists, geneticists, pharmacologists, medicinal chemists, and computational scientists. AI and open data science expedite drug discovery and development of disease-modifying therapeutics for AD/ADRD and other neurodegenerative diseases.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Inteligência Artificial , Desenvolvimento de Medicamentos , Descoberta de Drogas , Registros Eletrônicos de Saúde
4.
Front Aging Neurosci ; 16: 1320755, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38414632

RESUMO

Background: Understanding the sensitivity and utility of clinical assessments across different HD stages is important for study/trial endpoint selection and clinical assessment development. The Integrated HD Progression Model (IHDPM) characterizes the complex symptom progression of HD and separates the disease into nine ordered disease states. Objective: To generate a temporal map of discriminatory clinical measures across the IHDPM states. Methods: We applied the IHDPM to all HD individuals in an integrated longitudinal HD dataset derived from four observational studies, obtaining disease state assignment for each study visit. Using large-scale screening, we estimated Cohen's effect sizes to rank the discriminative power of 2,472 clinical measures for separating observations in disease state pairs. Individual trajectories through IHDPM states were examined. Discriminative analyses were limited to individuals with observations in both states of the pairs compared (N = 3,790). Results: Discriminative clinical measures were heterogeneous across the HD life course. UHDRS items were frequently identified as the best state pair discriminators, with UHDRS Motor items - most notably TMS - showing the highest discriminatory power between the early-disease states and early post-transition period states. UHDRS functional items emerged as strong discriminators from the transition period and on. Cognitive assessments showed good discriminative power between all state pairs examined, excepting state 1 vs. 2. Several non-UHDRS assessments were also flagged as excellent state discriminators for specific disease phases (e.g., SF-12). For certain state pairs, single assessment items other than total/summary scores were highlighted as having excellent discriminative power. Conclusion: By providing ranked quantitative scores indicating discriminatory ability of thousands of clinical measures between specific pairs of IHDPM states, our results will aid clinical trial designers select the most effective outcome measures tailored to their study cohort. Our observations may also assist in the development of end points targeting specific phases in the disease life course, through providing specific conceptual foci.

5.
Environ Sci Technol ; 57(50): 21327-21336, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38059695

RESUMO

Exposure to environmental endocrine-disrupting chemicals (EDCs) can cause extensive health issues. However, specific EDCs remain elusive. This work aimed at performing nontargeted identification of estrogen receptor α (ERα)-active compounds using an ERα protein affinity assay combined with high-resolution mass spectrometry in the source and drinking water sampled from major rivers in China. Fifty-one potential ERα-active compounds across 13 categories were identified. For the first time, diisodecyl phenyl phosphate was found to have antiestrogenic activity, and three chemicals (galaxolidone, bensulfuron methyl, and UV234) were plausible ERα ligands. Among the 51 identified compounds, 12 were detected in the aquatic environment for the first time, and the concentration of N-phenyl-2-naphthylamine, a widely used antioxidant in rubber products, was up to 1469 and 1190 ng/L in source and drinking water, respectively. This study demonstrated the widespread presence of known and unknown ERα estrogenic and antiestrogenic pollutants in the major rivers that serve as key sources of drinking water in China and the low removal efficiency of these chemicals in drinking water treatment plants.


Assuntos
Água Potável , Disruptores Endócrinos , Poluentes Ambientais , Poluentes Químicos da Água , Receptor alfa de Estrogênio/química , Receptor alfa de Estrogênio/metabolismo , Poluentes Ambientais/análise , Água Potável/análise , Receptores de Estrogênio , Espectrometria de Massas , Disruptores Endócrinos/análise , Disruptores Endócrinos/química , Poluentes Químicos da Água/análise , Rios , Monitoramento Ambiental/métodos
6.
Environ Sci Technol ; 57(49): 20551-20558, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38037888

RESUMO

Hexaphenoxycyclotriphosphazene (HPCTP), an unregistered chemical, has been used as a substitute for triphenyl phosphate in flame retardants and plasticizers. Here, we identified its metabolite, pentaphenoxycyclotriphosphazene (PPCTP) in the liver of Japanese medaka exposed to HPCTP. When sexually mature female medaka were exposed to HPCTP at 37.0, 90.4, and 465.4 ng/L for 35 days, the HPCTP concentration (642.1-2531.9 ng/g lipid weight [lw]) in the embryos considerably exceeded that (34.7-298.1 ng/g lw) in the maternal muscle, indicating remarkable maternal transfer. During 0-9 days postfertilization, the HPCTP concentration in the embryos decreased continuously, while the PPCTP concentration increased. HPCTP and PPCTP antagonized the retinoic X receptor with 50% inhibitory concentrations (IC50) of 34.8 and 21.2 µM, respectively, and PPCTP also antagonized the retinoic acid receptor with IC50 of 2.79 µM. Such antagonistic activities may contribute to eye deformity (4.7% at 465.4 ng/L), body malformation (2.1% at 90.4 ng/L and 6.8% at 465.4 ng/L), and early developmental mortality (11.6-21.7% in all exposure groups) of the embryos. HPCTP was detected in a main tributary of the Yangtze River Basin. Thus, HPCTP poses a risk to wild fish populations, given the developmental toxicities associated with this chemical and its metabolite.


Assuntos
Retardadores de Chama , Oryzias , Poluentes Químicos da Água , Animais , Feminino , Tretinoína , Fígado , Oryzias/fisiologia , Retardadores de Chama/toxicidade , Poluentes Químicos da Água/análise
7.
Environ Sci Technol ; 57(48): 19374-19382, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37948298

RESUMO

While environmental factors have been considered contributors to atherosclerosis, it remains unclear whether drinking water promotes foam cell formation, the initial event of atherosclerosis. This study revealed that drinking water from six major cities in China, namely, Harbin, Jinan, Shanghai, Wuhan, Chongqing, and Zhuhai, significantly promoted foam cell formation in an in vitro macrophage model at a minimum concentration fold of 2. Moreover, cholesterol efflux was significantly impeded by all samples at 2-16-fold, while cholesterol influx was induced only by samples from Jinan and Chongqing at 16-fold, suggesting the dominant role of efflux in foam cell formation. Interestingly, except for the sample from Jinan, the samples exhibited complete inhibition of liver X receptor α (LXRα) activities at 160-fold, indicating the potential role of chemicals in drinking water in promoting foam cell formation by antagonizing LXRα. Through LXRα protein affinity selection-mass spectrometry, we identified ten LXRα-binding compounds, with efavirenz being revealed for the first time as a significant inducer of foam cell formation through LXRα antagonism. Overall, this study clarifies the atherosclerotic risks posed by drinking water and demonstrates the efavirenz-related atherosclerotic effects.


Assuntos
Aterosclerose , Água Potável , Receptores X do Fígado , Humanos , Aterosclerose/induzido quimicamente , Aterosclerose/metabolismo , China , Colesterol/metabolismo , Cidades , Receptores X do Fígado/antagonistas & inibidores
8.
ACS Appl Mater Interfaces ; 15(48): 56275-56284, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37982453

RESUMO

Hydrogels have attracted significant attention in various fields, such as smart sensing, human-machine interaction, and biomedicines, due to their excellent flexibility and versatility. However, current hydrogel electronic skins are still limited in stretchability, and their sensing functionality is often single-purpose, making it difficult to meet the requirements of complex environments and multitasking. In this study, we developed an MXene nanoplatelet and phytic acid-coreinforced poly(vinyl alcohol) (PVA) composite, denoted as MXene-PA-PVA. The strong hydrogen bonds formed by the interaction of the different components and the enhancement of chain entanglement result in a significant improvement in the mechanical properties of the PVA/PA/MXene composite hydrogel. This improvement is reflected in an increase of 271.43% in the maximum tensile strain and 35.29% in the maximum fracture stress. Moreover, the composite hydrogel exhibits excellent adhesion, water retention, heat resistance, and conductivity properties. The PVA/PA composite material combined with MXene demonstrates great potential for use as multifunctional sensors for strain and temperature detection with a strain-sensing sensitivity of 3.23 and a resistance temperature coefficient of 8.67. By leveraging the multifunctional characteristics of this composite hydrogel, electronic skin can accurately monitor human behavior and physiological reactions. This advancement opens up new possibilities for flexible electronic devices and human-machine interactions in the future.


Assuntos
Hidrogéis , Pele , Humanos , Condutividade Elétrica , Eletrônica
9.
J Environ Sci (China) ; 131: 26-36, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37225378

RESUMO

The high-speed rail (HSR) network in China has experienced rapid development since the 2000s. In 2016, the State Council of the People's Republic of China issued a revised version of the "Mid- and Long-term Railway Network Plan", detailing the expansion of the railway network and construction of an HSR system. In the future, the HSR construction efforts in China will further increase, which is considered to impact regional development and air pollutant emissions. Therefore, in this paper, we apply a transportation network-multiregional computable general equilibrium (CGE) model to estimate the dynamic effects of HSR projects on economic growth, regional disparities, and air pollutant emissions in China. The results indicate that HSR system improvement could generate a positive economic impact but could also increase emissions. The gross domestic product (GDP) growth per unit investment cost stimulated by HSR investment is found to be the largest in eastern China but the smallest in the northwest regions. Conversely, HSR investment in Northwest China contributes to a substantial reduction in regional disparities in terms of the GDP per capita. In regard to air pollution emissions, HSR construction in South-Central China results in the largest increase in CO2 and NOX emissions, while for CO, SO2, and fine particulate matter (PM2.5) emissions, the largest increase occurs due to HSR construction in Northwest China. At the regional level, the provinces with large changes in accessibility also experience large changes in their air pollutant emissions.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Humanos , Produto Interno Bruto , Desenvolvimento Econômico , China
10.
Environ Sci Technol ; 57(18): 7254-7262, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37092689

RESUMO

Records of the environmental occurrence of organothiophosphate esters (OTPEs), which are used as flame retardants and food and industrial additives, are unavailable. In this study, we discovered three OTPEs, namely O,O,O-tris(2,4-di-tert-butylphenyl) phosphorothioate (AO168═S), O-butyl O-(butyl-methylphenyl) O-(di-butylphenyl) phosphorothioate (BBMDBPt)/O,O-bis(dibutylphenyl) O-methyl phosphorothioate (BDBPMPt), and O-butyl O-ethyl O-hydrogen phosphorothioate (BEHPt), in the surface water of the Yangtze River Basin by applying a characteristic phosphorothioate fragment-directed high-resolution mass spectrometry method. Among the 17 water samples tested, the detection frequencies of AO168═S and BEHPt were 100% and that of BBMDBPt/BDBPMPt was 29%. The mean concentration of AO168═S was 56.9 ng/L (30.5-148 ng/L), and semi-quantitative analysis revealed that the mean concentrations of BEHPt and BBMDBPt/BDBPMPt were 17.2 ng/L (5.5-65.4 ng/L) and 0.8 ng/L (

Assuntos
Retardadores de Chama , Rios , Rios/química , Ésteres/análise , Organofosfatos/análise , Espectrometria de Massas , Retardadores de Chama/análise , Água , Organotiofosfatos , Monitoramento Ambiental , China
11.
Environ Health Perspect ; 131(4): 47007, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37027338

RESUMO

BACKGROUND: Amniogenesis is a key event in biochemical pregnancy, and its failure may result in human embryonic death. However, whether and how environmental chemicals affect amniogenesis remain largely unknown. OBJECTIVES: The objective of the present study was to screen chemicals that may disrupt amniogenesis in an amniotic sac embryoid model and to investigate the potential mechanism of amniogenesis failure, with a focus on organophosphate flame retardants (OPFRs). METHODS: This study developed a high-throughput toxicity screening assay based on transcriptional activity of octamer-binding transcription factor 4 (Oct4). For the two positive OPFR hits with the strongest inhibitory activity, we used time-lapse and phase-contrast imaging to assess their effects on amniogenesis. Associated pathways were explored by RNA-sequencing and western blotting, and potential binding target protein was identified through a competitive binding experiment. RESULTS: Eight positive hits exhibiting Oct4 expression were identified, with 2-ethylhexyl-diphenyl phosphate (EHDPP) and isodecyl diphenyl phosphate (IDDPP) showing the strongest inhibitory activity. EHDPP and IDDPP were found to disrupt the rosette-like structure of the amniotic sac or inhibit its development. Functional markers of squamous amniotic ectoderm and inner cell mass were also found disrupted in the EHDPP- and IDDPP-exposed embryoids. Mechanistically, embryoids exposed to each chemical exhibited abnormal accumulation of phosphorylated nonmuscle myosin (p-MLC-II) and were able to bind to integrin ß1 (ITGß1). CONCLUSION: The amniotic sac embryoid models suggested that OPFRs disrupted amniogenesis likely by inhibiting the ITGß1 pathway, thus providing direct in vitro evidence associating OPFRs with biochemical miscarriage. https://doi.org/10.1289/EHP11958.


Assuntos
Retardadores de Chama , Organofosfatos , Gravidez , Feminino , Humanos , Organofosfatos/toxicidade , Retardadores de Chama/toxicidade , Compostos de Bifenilo , Fosfatos
12.
Environ Sci Technol ; 57(17): 6844-6853, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-37080910

RESUMO

Environmental pollutants can disrupt the homeostasis of endogenous metabolites in organisms, leading to metabolic disorders and syndromes. However, it remains highly challenging to efficiently screen for critical biological molecules affected by environmental pollutants. Herein, we found that enzyme could catalyze hydrogen-deuterium (H-D) exchange between a deuterium-labeled environmental pollutant [D38-bis(2-ethylhexyl) phthalate (D38-DEHP)] and several groups of enzyme-regulated metabolites [cardiolipins (CLs), monolysocardiolipins (MLCLs), phospholipids (PLs), and lysophospholipids (LPLs)]. A high-throughput scanning identified the D-labeled endogenous metabolites in a simple enzyme [phospholipase A2 (PLA2)], enzyme mixtures (liver microsomes), and living organisms (zebrafish embryos) exposed to D38-DEHP. Mass fragmentation and structural analyses showed that similar positions were D-labeled in the CLs, MLCLs, PLs, and LPLs, and this labeling was not attributable to natural metabolic transformations of D38-DEHP or incorporation of its D-labeled side chains. Molecular docking and competitive binding analyses revealed that DEHP competed with D-labeled lipids for binding to the active site of PLA2, and this process mediated H-D exchange. Moreover, competitive binding of DEHP against biotransformation enzymes could interfere with catabolic or anabolic lipid metabolism and thereby affect the concentrations of endogenous metabolites. Our findings provide a tool for discovering more molecular targets that complement the known toxic endpoints of metabolic disruptors.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Animais , Dietilexilftalato/metabolismo , Dietilexilftalato/toxicidade , Poluentes Ambientais/toxicidade , Deutério , Hidrogênio , Simulação de Acoplamento Molecular , Medição da Troca de Deutério , Peixe-Zebra
13.
Ecotoxicol Environ Saf ; 255: 114719, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37032573

RESUMO

The combination of glyphosate (Gly) and hard water (Hwt) is a suspected risk factor for chronic interstitial nephritis in agricultural communities (CINAC). Accumulated mitochondrial damage and proximal tubular epithelial (PTE) cell senescence have been implicated in CINAC pathogenesis. Melatonin (Mel) has potential mitochondrial function and renoprotective properties, but its role and mechanism in CINAC are unknown. Here, we detected PTE cell senescence and PTEN-induced putative protein kinase 1 (PINK1)-parkin RBR E3 ubiquitin protein ligase (Parkin)-dependent mitophagy in mice orally administered with different doses of Gly combined with Hwt (Gly: 100 mg/kg·bw and 0.7 mg/L; Hwt: 2,500 mg/L CaCO3 and 250 mg/L Ca2+) for different durations (12 and 36 w) using histological examination, transmission electron microscopy (TEM), immunofluorescence (IF) analysis, and immunohistochemistry (IHC), immunoblotting, ELISA and biochemical assays with kits. The same assays were performed after combination treatment with Mdivi-1 (an inhibitor of mitophagy, i.p. 10 mg/kg·bw, twice a week for 12 w) or Mel (i.p. 10 mg/kg·bw, once a day for 12 w) under high-level exposure. Gly combined with Hwt (Gly-Hwt) significantly increased P16-P21-dependent PTE cell senescence, mitochondrial fission and oxidative stress, and activated PINK1-Parkin-mediated mitophagy, accompanied by defective autophagic flux at high doses but unaltered autophagic flux at low doses. Improved senescence occurred after Mdivi-1 administration, suggesting that mitophagy is involved in cellular senescence. Mel significantly decreased senescence induced by Gly-Hwt. Furthermore, PINK1-Parkin-dependent mitophagy and autophagic flux were markedly enhanced, and mitochondrial function was improved, as evidenced by reductions in mitochondrial fission and subsequent oxidative damage. Thus, Gly and Hwt synergistically promote PTE cell senescence through PINK1-Parkin-mediated mitophagy, and Mel exerts renoprotective effects by modulating mitophagy, suggesting therapeutic applications in ageing-related CINAC.


Assuntos
Melatonina , Mitofagia , Camundongos , Animais , Proteínas Quinases/metabolismo , Melatonina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Senescência Celular , Ubiquitina-Proteína Ligases/metabolismo , Glifosato
14.
Clin J Am Soc Nephrol ; 18(3): 394-396, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36723176
15.
Adv Sci (Weinh) ; 10(10): e2205289, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36683149

RESUMO

Though gut microbiome disturbance may be involved in the etiology of gestational diabetes mellitus (GDM), data on the gut microbiome's dynamic change during pregnancy and associations with gestational glucose metabolism are still inadequate. In this prospective study comprising 120 pairs of GDM patients and matched pregnant controls, a decrease in the diversity of gut microbial species and changes in the microbial community composition with advancing gestation are found in controls, while no such trends are observed in GDM patients. Multivariable analysis identifies 10 GDM-related species (e.g., Alistipes putredinis), and the integrated associations of these species with glycemic traits are modified by habitual intake of fiber-rich plant foods. In addition, the microbial metabolic potentials related to fiber fermentation (e.g., mannan degradation pathways) and their key enzymes consistently emerge as associated with both GDM status and glycemic traits. Microbial features especially those involved in fiber fermentation, provide an incremental predictive value in a prediction model with established risk factors of GDM. These data suggest that the gut microbiome remodeling with advancing gestation is different in GDM patients compared with controls, and dietary fiber fermentation contributes to the influence of gut microbiome on gestational glycemic regulation.


Assuntos
Diabetes Gestacional , Microbioma Gastrointestinal , Gravidez , Feminino , Humanos , Estudos Prospectivos , Estudos de Casos e Controles , Glucose
16.
J Hazard Mater ; 445: 130461, 2023 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-36436451

RESUMO

Low doses of bisphenol A (BPA), a typical endocrine-disrupting chemical (EDC), have been reported to exhibit estrogenic action in animals; however, the effects have not been fully clarified because of their non-reproducibility. Here, we developed a novel, short-term screening test for estrogen-like chemicals using in vivo bioluminescence imaging of estrogen-responsive reporter (E-Rep) mice. Comparative studies using 17α-ethinylestradiol and selective estrogen receptor modulators demonstrated that the method provides higher detection sensitivity and requires less time than the uterotrophic bioassay, a well-established, in vivo screening method for estrogen-like chemicals. Our method could detect the estrogenic effects of BPA at doses below tolerable daily intakes, whereas the uterotrophic bioassay could not. Our results indicated that in vivo bioluminescence imaging using E-Rep mice was extremely useful for screening estrogenic chemicals and detecting estrogenic effects at low doses of EDCs, including BPA. Our method should help resolve the controversy about low-dose effects of EDCs.


Assuntos
Disruptores Endócrinos , Estrogênios , Camundongos , Animais , Estrogênios/toxicidade , Fenóis/toxicidade , Compostos Benzidrílicos/toxicidade , Estrona , Disruptores Endócrinos/toxicidade
17.
Environ Pollut ; 318: 120914, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36563994

RESUMO

Freight transport has become increasingly important regarding CO2 and air pollutant emissions in China but has rarely been assessed using consumption-based methods. Based on the multi-regional input-output tables of China, in this work, we use structural path analysis (SPA) to link interprovincial trade-related freight turnover to responsible sectors of final consumption. We find that from 2007 to 2012, the interprovincial trade turnover in China increased by 39% and reached 3.87 × 1012 ton-km in 2012, associated with emissions of approximately 370 Mt CO2, 6.1 Mt CO and 2.5 Mt NOx. We also find that each 10 thousand CNY final consumption on interprovincial traded goods in China may drive 2000 ton-km of freight turnover and generate 200 kg CO2 emissions. This environmental burden will decrease by a factor of five if only locally produced goods are consumed. Final consumption in equipment, construction, service and food caused the most significant freight turnover; they drive a large quantity of low-value-added but heavy-weight semifinished products, such as mining and metal products, to be shipped across the provinces at the very upstream of the supply chain. Policymakers should aim to optimize China's industrial geographical layout and trade structure to facilitate deep CO2 reductions associated with the freight transport system.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Dióxido de Carbono/análise , Poluentes Atmosféricos/análise , China , Indústrias
18.
Environ Pollut ; 316(Pt 1): 120560, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36328287

RESUMO

Benzotriazole ultraviolet stabilizers (BUVSs) have been reported to induce inflammatory responses which may promote cholesterol accumulation and to downregulate the expression of genes involved in cholesterol biosynthesis; hence, we speculated whether BUVSs promote foam cell formation, which plays a key role in all stages of atherosclerosis. Herein, we used high-content imaging to screen all available BUVSs; of all the 17 candidates, 6 of them could promote foam cell formation at 10 µM. Further analyses showed that one BUVS UV-234 markedly increased the foam cell staining intensity by 15.0%-55.9% in the 0.5-10 µM exposure groups in a dose-dependent manner. Cholesterol influx was markedly enhanced by 21.0%-24.5% in the 5-10 µM exposure groups and cholesterol efflux was downregulated by 21.2%-59.3% in the 0.5-10 µM exposure groups, indicating that cholesterol efflux may play a major role in foam formation considering cholesterol efflux was downregulated at a relatively low concentration. Gene expression of ABCA1 and ABCG1 which regulate the cholesterol efflux were also decreased at 0.5-10 µM. The degradation of hypoxia-inducible factor 1α (HIF1α) via the ubiquitin-proteasome system was observed at 0.5-10 µM, probably contributing to the downregulated expression of the genes encoding liver X receptors (LXR) α/ß and their targets, ABCA1 and ABCG1. Thus, our study revealed that BUVSs frequently detected in the environment can promote foam cell formation in macrophages, contributing to the risk of atherosclerosis in humans.


Assuntos
Aterosclerose , Células Espumosas , Humanos , Macrófagos/metabolismo , Colesterol
19.
AMIA Annu Symp Proc ; 2023: 426-435, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38222374

RESUMO

Chronic gastrointestinal (GI) conditions, such as inflammatory bowel diseases (IBD), offer a promising opportunity to create classification systems that can enhance the accuracy of predicting the most effective therapies and prognosis for each patient. Here, we present a novel methodology to explore disease subtypes using our open-sourced BiomedSciAI toolkit. Applying methods available in this toolkit on the UK Biobank, including subpopulation-based feature selection and multi-dimensional subset scanning, we aimed to discover unique subgroups from GI surgery cohorts. Of a 12,073-patient cohort, a subgroup of 440 IBD patients was discovered with an increased risk of a subsequent GI surgery (OR: 2.21, 95% CI [1.81-2.69]). We iteratively demonstrate the discovery process using an additional cohort (with a narrower definition of GI surgery). Our results show that the iterative process can refine the subgroup discovery process and generate novel hypotheses to investigate determinants of treatment response.


Assuntos
Doenças Inflamatórias Intestinais , Biobanco do Reino Unido , Humanos , Bancos de Espécimes Biológicos , Doenças Inflamatórias Intestinais/cirurgia , Prognóstico , Doença Crônica , Resultado do Tratamento
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