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Xianlinggubao formula (XLGB), is a traditional Chinese compound Medicine that has been extensively used in osteoarthritis and aseptic osteonecrosis, but its curative effect on diabetic osteoporosis (DOP) and its pharmacological mechanisms remains not clear. The aim of the present study was to investigate the possible mechanism of drug repurposing of XLGB in DOP therapy. We acquired XLGB active compounds from the traditional Chinese medicine systems pharmacology and traditional Chinese medicines integrated databases and discovered potential targets for these compounds by conducting target fishing using the traditional Chinese medicine systems pharmacology and Swiss Target Prediction databases. Gene Cards and Online Mendelian Inheritance in Man® database were used to identify the DOP targets. Overlapping related targets between XLGB and DOP was selected to build a protein-protein interaction network. Next, the Metascape database was utilized to enrich the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. In addition, Auto-Dock Vina software was used to verify drug and target binding. In total, 48 hub targets were obtained as the candidate targets responsible for DOP therapy. The anti-DOP effect mediated by XLGB was primarily centralized on the advanced glycation end products (AGEs)-receptor for AGE signaling pathway in diabetic complications and osteoclast differentiation. In addition, AKT serine/threonine kinase 1, tumor necrosis factor, Interleukin-6, vascular endothelial growth factor A and peroxisome proliferator activated receptor gamma, which were considered as potential therapeutic targets. Furthermore, molecular docking results confirm the credibility of the predicted therapeutic targets. This study elucidates that XLGB may through regulating AGEs formation and osteoclast differentiation as well as angiogenesis and adipogenesis against DOP. And this study provides new promising points to find the exact regulatory mechanisms of XLGB mediated anti-DOP effect.
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Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Farmacología en Red , Osteoporosis , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Osteoporosis/tratamiento farmacológico , Humanos , Farmacología en Red/métodos , Mapas de Interacción de Proteínas/efectos de los fármacos , Medicina Tradicional China/métodos , Transducción de Señal/efectos de los fármacos , Complicaciones de la Diabetes/tratamiento farmacológicoRESUMEN
BACKGROUND: Since most infants are usually discharged before age 48-72 hours, peak bilirubin levels will almost always occur after discharge. Parents may be the first to observe the onset of jaundice after discharge, but visual assessment is unreliable. The jaundice colour card (JCard) is a low-cost icterometer designed for the assessment of neonatal jaundice. The objective of this study was to evaluate parental use of JCard to detect jaundice in neonates. METHODS: We conducted a multicentre, prospective, observational cohort study in nine sites across China. A total of 1161 newborns ≥35 weeks of gestation were enrolled in the study. Measurements of total serum bilirubin (TSB) levels were based on clinical indications. The JCard measurements by parents and paediatricians were compared with the TSB. RESULTS: JCard values of parents and paediatricians were correlated with TSB (r=0.754 and 0.788, respectively). The parents' and paediatricians' JCard values 9 had sensitivities of 95.2% vs 97.6% and specificities of 84.5% vs 71.7% for identifying neonates with TSB ≥153.9 µmol/L. The parents' and paediatricians' JCard values 15 had sensitivities of 79.9% vs 89.0% and specificities of 66.7% vs 64.9% for identifying neonates with TSB ≥256.5 µmol/L. Areas under the receiver operating characteristic curves of parents for identifying TSB ≥119.7, ≥153.9, ≥205.2, and ≥256.5 µmol/L were 0.967, 0.960, 0.915, and 0.813, respectively, and those of paediatricians were 0.966, 0.961, 0.926 and 0.840, respectively. The intraclass correlation coefficient was 0.933 between parents and paediatricians. CONCLUSION: The JCard can be used to classify different levels of bilirubin, but it is less accurate with high bilirubin levels. The JCard diagnostic performance of parents was slightly lower than that of paediatricians.
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Ictericia Neonatal , Anciano , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Bilirrubina , Ictericia Neonatal/diagnóstico , Padres , Estudios ProspectivosRESUMEN
The influence of environmental quality on the quality of urban life and on migration decisions is an important research issue in urban economics and environmental economics. Using the 2012-2014 China Labor Dynamics Survey data (CLDS), this paper uses a conditional logit model (CLM) and Instrumental Variable (IV) estimation to examine the impact of air pollution on the migrant migration decision. We find that air pollution significantly negatively impacts the migration decisions of migrants. Specifically, if the PM2.5 level of a city increases by 10 µg/m3, the probability of migrants flowing into the city will be significantly reduced by 21.2%. It shows that migrants choose to flow into cities with better spatial quality to reduce the risk of exposure to air pollution. After controlling for the characteristics of the outflow and the reasons for the flow, the impact of air pollution on migrants' migration decisions remains robust. Heterogeneity analysis shows that middle-aged, male, married, and highly educated migrants are more sensitive to air pollution. This paper enriches the research on air pollution and labor mobility at the micro level and provides empirical evidence for policymaking related to environmental governance and labor mobility in a low-carbon society.
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Contaminación del Aire , Migrantes , Humanos , Persona de Mediana Edad , Masculino , Conservación de los Recursos Naturales , Política Ambiental , Empleo , ChinaRESUMEN
Rapid global industrialization has resulted in widespread cadmium contamination in agricultural soils and products. A considerable proportion of rice consumers are exposed to Cd levels above the provisional safe intake limit, raising widespread environmental concerns on risk management. Therefore, a generalized approach is urgently needed to enable correct evaluation and early warning of cadmium contaminants in rice products. Combining big data and computer science together, this study developed a system named "SMART Cd Early Warning", which integrated 4 modules including genotype-to-phenotype (G2P) modelling, high-throughput sequencing, G2P prediction and rice Cd contamination risk assessment, for rice cadmium accumulation early warning. This system can rapidly assess the risk of rice cadmium accumulation by genotyping leaves at seeding stage. The parameters including statistical methods, population size, training population-testing population ratio, SNP density were assessed to ensure G2P model exhibited superior performance in terms of prediction precision (up to 0.76 ± 0.003) and computing efficiency (within 2 h). In field trials of cadmium-contaminated farmlands in Wenling and Fuyang city, Zhejiang Province, "SMART Cd Early Warning" exhibited superior capability for identification risk rice varieties, suggesting a potential of "SMART Cd Early-Warning system" in OsGCd risk assessment and early warning in the age of smart.
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Oryza , Contaminantes del Suelo , Cadmio/análisis , Contaminantes del Suelo/análisis , Suelo , Medición de RiesgoRESUMEN
Cerebral cavernous malformation (CCM) is caused by loss-of-function mutations in CCM1, CCM2, or CCM3 genes of endothelial cells. It is characterized by pericyte deficiency. However, the role of pericytes in CCMs is not yet clarified. We found pericytes in Cdh5Cre ERT2 ;Ccm1 fl/fl (Ccm1 ECKO ) mice had a high expression of PDGFRß. The inhibition of pericyte function by CP-673451 aggravated the CCM lesion development. RNA-sequencing analysis revealed the molecular traits of pericytes, such as highly expressed ECM-related genes, especially Fn1. Furthermore, KLF4 coupled with phosphorylated SMAD3 (pSMAD3) promoted the transcription of fibronectin in the pericytes of CCM lesions. RGDS peptide, an inhibitor of fibronectin, decreased the lesion area in the cerebella and retinas of Ccm1 ECKO mice. Also, human CCM lesions had abundant fibronectin deposition, and pSMAD3- and KLF4-positive pericytes. These findings indicate that pericytes are essential for CCM lesion development, and fibronectin intervention may provide a novel target for therapeutic intervention in such patients.
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Mercury (Hg) is a toxic and nonessential element for organisms, and its contamination in the environment is a global concern. Previous research has shown that Hg stress may cause severe damage to rice roots; however, the transcriptomic changes in roots and physio-biochemical responses in leaves to different levels of Hg stress are not fully understood. In the present study, rice seedlings were exposed to 20, 80, and 160 µM HgCl2 for three days in hydroponic experiments. The results showed that the majority of Hg was accumulated in rice roots after Hg exposure, and the 80- and 160-µM Hg stresses significantly increased the root-to-shoot translocation factors relative to 20-µM Hg stress, resulting in elevated Hg concentrations in rice shoots. Only the 160-µM Hg stress significantly inhibited root growth compared with the control, while photosynthesis capacity in leaves was significantly reduced under Hg stress. RNA transcriptome sequencing analyses of the roots showed that common responsive differentially expressed genes were strongly associated with glutathione metabolism, amino acid biosynthesis, and secondary metabolite metabolism, which may play significant roles in Hg accumulation by rice plants. Nine crucial genes identified by protein-protein interaction network analysis may be used as candidate target genes for further investigation of the detoxification mechanism, encoding proteins involved in jasmonic acid synthesis, sugar metabolism, allene oxide synthase, glutathione peroxidase, dismutase, and catalase. Furthermore, physio-biochemical analyses of the leaves indicated that higher production of reactive oxygen species was induced by Hg stress, while glutathione and antioxidant enzymes may play crucial roles in Hg detoxification. Our findings provide transcriptomic and physio-biochemical features of rice roots and shoots, which advance our understanding of the responsive and detoxification mechanisms in rice under different levels of Hg stress.
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Mercurio , Oryza , Oryza/metabolismo , Catalasa/metabolismo , Mercurio/análisis , Transcriptoma , Antioxidantes/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Glutatión Peroxidasa/metabolismo , Raíces de Plantas/metabolismo , Plantones/metabolismo , Glutatión/metabolismo , Aminoácidos/metabolismo , Azúcares/metabolismo , ARN/metabolismoRESUMEN
BACKGROUND & AIMS: The liver has complex interconnecting blood vessel and biliary networks; however, how the vascular and biliary network form and regulate each other and liver function are not well-understood. We aimed to examine the role of Heg in mammalian liver development and functional maintenance. METHODS: Global (Heg-/-) or liver endothelial cell (EC)-specific deletion of Heg (Lyve1-Cre;Hegfl/fl ) mice were used to study the in vivo function of Heg in the liver. Carbon-ink anterograde and retrograde injection were used to visualize the 3-dimensional patterning of liver portal and biliary networks, respectively. RNA sequencing, histology, and molecular and biochemical assays were used to assess liver gene expression, protein distribution, liver injury response, and function. RESULTS: Heg deficiency in liver ECs led to a sparse liver vascular and biliary network. This network paucity does not compromise liver function under baseline conditions but did alter liver zonation. Molecular analysis revealed that endothelial Heg deficiency decreased expression of Wnt ligands/agonists including Wnt2, Wnt9b, and Rspo3 in ECs, which limits Axin2 mediated canonical Wnt signaling and the expression of cytochrome P450 enzymes in hepatocytes. Under chemical-induced stressed conditions, Heg-deficiency in liver ECs protected mice from drug-induced liver injuries. CONCLUSION: Our study found that endothelial Heg is essential for the 3-D patterning of the liver vascular and indirectly regulates biliary networks and proper liver zonation via its regulation of Wnt ligand production in liver endothelial cells. The endothelial Heg-initiated changes of the liver metabolic zonation and metabolic enzyme expression in hepatocytes was functionally relevant to xenobiotic metabolism and drug induced liver toxicity.
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Proteínas Wnt , Vía de Señalización Wnt , Animales , Células Endoteliales , Hígado/patología , Mamíferos/metabolismo , Ratones , Proteínas Wnt/genética , Vía de Señalización Wnt/genética , beta Catenina/metabolismoRESUMEN
Pteris vittata is an arsenic (As) hyperaccumulator that can accumulate several thousand mg As kg-1 DW in aboveground biomass. A key factor for its hyperaccumulation ability is its highly efficient As long-distance translocation system. However, the underlying molecular mechanisms remain unknown. We isolated PvAsE1 through the full-length cDNA over-expression library of P. vittata and characterized it through a yeast system, RNAi gametophytes and sporophytes, subcellular-location and in situ hybridization. Phylogenomic analysis was conducted to estimate the appearance time of PvAsE1. PvAsE1 was a plasma membrane-oriented arsenite (AsIII) effluxer. The silencing of PvAsE1 reduced AsIII long-distance translocation in P. vittata sporophytes. PvAsE1 was structurally similar to solute carrier (SLC)13 proteins. Its transcripts could be observed in parenchyma cells surrounding the xylem of roots. The appearance time was estimated at c. 52.7 Ma. PvAsE1 was a previously uncharacterized SLC13-like AsIII effluxer, which may contribute to AsIII long-distance translocation via xylem loading. PvAsE1 appeared late in fern evolution and might be an adaptive subject to the selection pressure at the Cretaceaou-Paleogene boundary. The identification of PvAsE1 provides clues for revealing the special As hyperaccumulation characteristics of P. vittata.
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Arsénico , Arsenitos , Helechos , Pteris , Contaminantes del Suelo , Arsénico/metabolismo , Arsenitos/metabolismo , Biodegradación Ambiental , Helechos/metabolismo , Raíces de Plantas/metabolismo , Pteris/genética , Contaminantes del Suelo/análisis , Contaminantes del Suelo/metabolismoRESUMEN
PURPOSE: The neonatal mouse possesses a transient capacity for cardiac regeneration during the first few days of life. The regenerative response of neonatal mouse is primarily mediated by pre-existing cardiomyocyte (CM) proliferation, which has been identified as the primary source of myocardial regeneration. Postnatal 4-day-old (P4) mouse CMs appear to undergo a rapid transition from hyperplastic to hypertrophic growth and binucleation. By 7 days following birth this regenerative potential is lost which coincidently correspond with CM cell cycle arrest and binucleation. CCM2-like (Ccm2l) plays pivotal roles in cardiovascular development and cardiac growth, indicating a potential function in heart regeneration postnatally. The aim of this study was to determine the cardiac regeneration ability of P4 neonatal mouse using a novel and more reproducible injury model and to determine whether Ccm2l has any functional roles in heart repair following ischemic injury. METHODS: We performed a modified left anterior descending artery (LAD) ligation procedure on P4 mice to examine cardiac regenerative responses at different time points. Additionally, we generated an endothelial-specific Ccm2l gain-of-function transgenic mouse to determine the role of Ccm2l in neonatal cardiac regeneration. RESULTS: We found that the P4 mouse heart harbor a robust regenerative response after injury that was through the proliferation of pre-existing CMs but cardiac hypertrophy and subsequent remodeling was still evident 60 days after LAD ligation. Furthermore, we show that endothelial-specific overexpression of Ccm2l does not promote CM proliferation and heart repair after LAD ligation. CONCLUSION: The neonatal heart at P4 harbors a robust but incomplete capacity for cardiac regeneration. Endothelial overexpression of Ccm2l has no effect on cardiac regeneration.
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Infarto del Miocardio , Miocitos Cardíacos , Animales , Animales Recién Nacidos , Ciclo Celular , Corazón , Ratones , RegeneraciónRESUMEN
Post-translational modifications (PTMs) have been confirmed to be involved in multiple female reproductive events, but their role in physiological ovarian aging is far from elucidated. In this study, mice aged 3, 12 or 17 months (3M, 12M, 17M) were selected as physiological ovarian aging models. The expression of female reproductive function-related genes, the global profiles of PTMs, and the level of histone modifications and related regulatory enzymes were examined during physiological ovarian aging in the mice by quantitative real-time PCR and western blot, respectively. The results showed that the global protein expression of Kbhb (lysineß-hydroxybutyryllysine), Khib (lysine 2-hydroxyisobutyryllysine), Kglu (lysineglutaryllysine), Kmal (lysinemalonyllysine), Ksucc (lysinesuccinyllysine), Kcr (lysinecrotonyllysine), Kbu (lysinebutyryllysine), Kpr (lysinepropionyllysine), SUMO1 (SUMO1 modification), ub (ubiquitination), P-Typ (phosphorylation), and 3-nitro-Tyr (nitro-tyrosine) increased significantly as mice aged. Moreover, the modification level of Kme2 (lysinedi-methyllysine) and Kac (lysineacetyllysine) was the highest in the 3M mice and the lowest in 12M mice. In addition, only trimethylation of histone lysine was up-regulated progressively and significantly with increasing age (p < 0.001), H4 ubiquitination was obviously higher in the 12M and 17M mice than 3M (p < 0.001), whereas the modification of Kpr (lysinepropionylation) and O-GlcNA in 17M was significantly decreased compared with the level in 3M mice (p < 0.05, p < 0.01). Furthermore, the expression levels of the TIP60, P300, PRDM9, KMT5B, and KMT5C genes encoding PTM regulators were up-regulated in 17M compared to 3M female mice (p < 0.05). These findings indicate that altered related regulatory enzymes and PTMs are associated with physiological ovarian aging in mice, which is expected to provide useful insights for the delay of ovarian aging and the diagnosis and treatment of female infertility.
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Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Ovario/fisiología , Proteómica/métodos , Acetilación , Animales , Senescencia Celular , Femenino , Regulación de la Expresión Génica , Código de Histonas , Histonas/metabolismo , Ratones , Modelos Animales , Fosforilación , Procesamiento Proteico-Postraduccional , UbiquitinaciónRESUMEN
To understand the effects of A- and B-type wheat starch on noodle quality, two noodle models with (Model 1) and without (Model 2) gluten were constructed with five different ratios of A- to B-granules (100A-0B, 75A-25B, 50A-50B, 25A-75B, and 0A-100B). With increasing proportions of B-granules, the noodle structures of Models 1 and 2 became increasingly dense. The cooking loss, water absorption, proportion of free water, chewiness, cohesiveness and resilience decreased from 35.64 to 15.49%, 240.92 to 228.58%, 88.89 to 85.98%, 21.93 to 13.24 N, 0.77 to 0.56, and 0.61 to 0.36, respectively, with the increased proportion of B-granules in Model 2, while those parameters normally presented "V" or inverted "V" trends in Model 1. Compared to their counterparts in Model 2, gluten networks with 25-50% B-granules had an outstanding ability to increase the percentage of tightly bound water, hardness, chewiness and springiness by 4.50%, 24.07 N, 25.05 N, and 0.17 at most and reduce the proportion of free water and water absorption by 5.56 and 73.70% at most, respectively. The results indicated that the effect of the gluten network on noodle qualities may partially depend on its structure, which is shaped by the granule size distribution. Compared to the other characteristics of noodles, the springiness was influenced by a more complicated mechanism involving A- and B-granules in Model 2, while it was strongly affected by the gluten network under the given experimental conditions in Model 1.
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Glútenes/química , Almidón/química , Triticum/química , Culinaria , Harina/análisis , Manipulación de Alimentos , Dureza , Tamaño de la Partícula , AguaRESUMEN
Cadmium is a toxic element with a half-life of more than a few decades that can be absorbed by crops and threaten human health. The problem of food security caused by cadmium through soil-crop systems has received great attention in China. Maize is a staple food widely cultivated throughout the world. However, the lack of systematic study makes it difficult to draw an accurate conclusion on its exact characteristics of cadmium accumulation and the corresponding health risk assessment. The availability of cadmium increased with the decrease of soil pH in acidic soil, enhancing the uptake of cadmium by crops and thus posing a major threat to food safety. In this study, the performance of kernel cadmium accumulation in abundant maize inbred and important hybrid lines were analyzed on acidic fields with different pollution levels in China. It was found that the kernel cadmium concentration both in inbred and hybrid lines showed left skewed distribution and concentrated significantly in a low interval under different soil cadmium gradients with good correlation. The classification of cadmium risk level in maize germplasm and cultivars and the analysis of soil cadmium threshold for maize safe planting can provide references to utilize the crop more feasibly and effectively. Maize may be an important staple crop to reduce human exposure to cadmium in agricultural soil.
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Suelo , Zea mays , Cadmio , China , Contaminantes del SueloRESUMEN
Arsenic is a toxic metalloid. Arsenic pollution in soils affects food safety and threatens human health. Pteris vittata L. has enormous application value in phytoremediation of arsenic-contaminated soil for its high arsenic hyperaccumulation ability. Understanding the arsenic hyperaccumulation molecular mechanism of P. vittata is the core theoretical basis of phytoremediation technology. This review introduces the omics study on arsenic hyperaccumulation mechanisms, as well as important molecular component that is involved in arsenic hyperaccumulation of P. vittata. Further research directions and trends are also discussed.
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Arsénico , Biodegradación Ambiental , Pteris , Contaminantes del Suelo , Arsénico/metabolismo , Pteris/metabolismo , Contaminantes del Suelo/metabolismoRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
Cadmium (Cd) accumulation in rice grain poses a serious threat to human health. While several transport systems have been reported, the complicity of rice Cd transport and accumulation indicates the necessity of identifying additional genes, especially those that are responsible for Cd accumulation divergence between indica and japonica rice subspecies. Here, we show that a gene, OsCd1, belonging to the major facilitator superfamily is involved in root Cd uptake and contributes to grain accumulation in rice. Natural variation in OsCd1 with a missense mutation Val449Asp is responsible for the divergence of rice grain Cd accumulation between indica and japonica. Near-isogenic line tests confirm that the indica variety carrying the japonica allele OsCd1V449 can reduce the grain Cd accumulation. Thus, the japonica allele OsCd1V449 may be useful for reducing grain Cd accumulation of indica rice cultivars through breeding.
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Cadmio/metabolismo , Grano Comestible/metabolismo , Proteínas de la Membrana/metabolismo , Oryza/metabolismo , Contaminantes del Suelo/metabolismo , Alelos , Asparagina/genética , Cadmio/análisis , Membrana Celular/metabolismo , Grano Comestible/química , Humanos , Proteínas de la Membrana/genética , Mutación Missense , Oryza/química , Oryza/genética , Filogenia , Fitomejoramiento/métodos , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Polimorfismo de Nucleótido Simple , Contaminantes del Suelo/análisis , Valina/genéticaRESUMEN
BACKGROUND: Patients with diabetes mellitus were often accompanied with hyperlipidemia. ATP-binding cassette sub-family A member1 (ABCA1) promotes the efflux of lipids and thereby mediates the metabolism of cholesterol. The aim of our study was to determine the associations of ABCA1 gene polymorphisms with the risks of diabetes mellitus and dyslipidemia in diabetic patients. METHODS: We retrieved literature about the relationship between ABCA1 gene polymorphisms (C69T and R230C) and the risk of diabetes through PubMed, Web of Science, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Cochrane database. Weighted mean difference (WMD) and odds ratio (OR) were used to compare continuous and dichotomous variables, respectively, accompanied by their 95% confidence interval (CI). RESULTS: A total of 1746 diabetic patients and 1292 non-diabetic controls were enrolled. All subjects were Caucasians. ABCA1 R230C T allele was significantly associated with reduced the risk of diabetes (OR = 0.75, 95% CI = 0.57-0.98, P = 0.04). There was no association of ABCA1 C69T gene polymorphisms with the risk of diabetes. However, subgroup analyses showed that the ABCA1 C69T gene mutation significantly reduced the risk of hypertriglyceridemia in diabetic patients as compared with that in non-diabetic subjects (dominant model: WMD =0.66, 95% CI = 0.52-0.8, P < 0.0001; recessive model: WMD = 0.47, 95%CI = 0.11-0.83, P = 0.01). CONCLUSIONS: ABCA1 R230C T allele gene mutation is a protective in decreasing the risk of diabetes in Caucasians and ABCA1 C69T gene mutation markedly influences the level of lipid metabolism in diabetic patients.
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Transportador 1 de Casete de Unión a ATP/genética , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Metabolismo de los Lípidos/genética , Mutación/genética , Genes Dominantes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Sesgo de Publicación , Factores de RiesgoRESUMEN
Arsenic accumulation in soil is a global problem typically addressed using phytoremediation methods. Pteris vittata, a model arsenic hyperaccumulator, has great potential as a genetically engineered plant for phytoremediation. However, the lack of omic information on this species has severely limited the identification and application of its arsenic hyperaccumulation and regulation components. In this study, we used an optimized single-molecular real-time (SMRT) strategy to create a de novo full-length transcriptomic-tonoplast proteomic database for this unsequenced fern and to determine the genetic components underlying its arsenic hyperaccumulation-regulation mechanisms. We established a comprehensive network consisting of six major transporter families, two novel resistance pathways, and a regulatory system by examining alternative splicing (AS) and long non-coding RNA (lncRNA) in different tissues following As(III) and As(V) treatment. The database and network established in this study will deepen our understanding of the unique hyperaccumulation and regulation mechanisms of P. vittata, ultimately providing a valuable resource for futher research on phytoremediation of arsenic-contaminated soil.
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Arsénico/toxicidad , Pteris/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Biodegradación Ambiental , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas de Transporte de Membrana/genética , Proteínas de Plantas/genética , Pteris/genética , Pteris/metabolismo , ARN Largo no Codificante , ARN de Planta , TranscriptomaRESUMEN
Menopause is associated with dyslipidemia and an increased risk of cardio-cerebrovascular disease. The classic view assumes that the underlying mechanism of dyslipidemia is attributed to an insufficiency of estrogen. In addition to a decrease in estrogen, circulating follicle-stimulating hormone (FSH) levels become elevated at menopause. In this study, we find that blocking FSH reduces serum cholesterol via inhibiting hepatic cholesterol biosynthesis. First, epidemiological results show that the serum FSH levels are positively correlated with the serum total cholesterol levels, even after adjustment by considering the effects of serum estrogen. In addition, the prevalence of hypercholesterolemia is significantly higher in peri-menopausal women than that in pre-menopausal women. Furthermore, we generated a mouse model of FSH elevation by intraperitoneally injecting exogenous FSH into ovariectomized (OVX) mice, in which a normal level of estrogen (E2) was maintained by exogenous supplementation. Consistently, the results indicate that FSH, independent of estrogen, increases the serum cholesterol level in this mouse model. Moreover, blocking FSH signaling by anti-FSHß antibody or ablating the FSH receptor (FSHR) gene could effectively prevent hypercholesterolemia induced by FSH injection or high-cholesterol diet feeding. Mechanistically, FSH, via binding to hepatic FSHRs, activates the Gi2α/ß-arrestin-2/Akt pathway and subsequently inhibits the binding of FoxO1 with the SREBP-2 promoter, thus preventing FoxO1 from repressing SREBP-2 gene transcription. This effect, in turn, results in the upregulation of SREBP-2, which drives HMGCR nascent transcription and de novo cholesterol biosynthesis, leading to the increase of cholesterol accumulation. This study uncovers that blocking FSH signaling might be a new strategy for treating hypercholesterolemia during menopause, particularly for women in peri-menopause characterized by FSH elevation only.
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Colesterol/biosíntesis , Hormona Folículo Estimulante Humana/antagonistas & inhibidores , Hormona Folículo Estimulante Humana/sangre , Hipercolesterolemia/epidemiología , Hígado/metabolismo , Menopausia/metabolismo , Adulto , Animales , Anticuerpos/farmacología , Anticolesterolemiantes/farmacología , Estudios Transversales , Modelos Animales de Enfermedad , Estrógenos/metabolismo , Femenino , Células Hep G2 , Humanos , Hipercolesterolemia/inducido químicamente , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Prevalencia , ARN Interferente Pequeño/genética , Receptores de HFE/genética , Receptores de HFE/metabolismoRESUMEN
Heavy metals may cause deleterious effects on human health through consumption of contaminated food crops. To assess the safety of soybean consumption, concentrations of heavy metals (Cu, Zn, Cr, Ni, Cd, As, Pb and Hg) in soybean grains sampled from the farmland in North Anhui (suitable for high-protein soybeans planting) were analyzed. The results showed that the concentrations of Ni, Cr, Cu and Pb in soybean gains exceeded the Chinese safety limits, with over-standard rate of 92.59%, 74.07%, 37.04% and 9.88% respectively. Spatial distribution of soybean pollution analysis showed that soybeans were severe polluted by Ni and concentrated in the west of North Anhui. SR-µXRF elemental maps of soybean gains indicated Cu, Cr, Ni, Pb and Hg specifically enriched at the embryo. In relation to health risks, there were no obvious non-carcinogenic risk and carcinogenic risk (CR) through ingesting soybeans from North Anhui. But it can induce a threat to people's health if the consumption of soybean exceeds the routine dose.
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Monitoreo del Ambiente , Glycine max/química , Metales Pesados/análisis , Contaminantes del Suelo/análisis , China , Humanos , Medición de Riesgo , SueloRESUMEN
Neutrophils, an important component of the innate immune system, release extracellular traps (NETs) to eliminate invading pathogens by trapping and killing microbes. Recent studies have shown that NETs play a multitude of additional roles in immunity and inflammatory diseases. Therefore, NETs may be involved in persistent hepatitis B virus (HBV) infection, and the objectives of the current study were to determine whether HBV influences NET release and to identify the underlying mechanisms. HBV-infected mice (C57BL/6) were used to detect the efficiency of bacterial eradication by neutrophils in vivo. Primary neutrophils and circulating blood samples were collected from 40 patients with chronic hepatitis B infection, as well as 40 healthy controls, to detect NET release using a Quant-iT Pico Green dsDNA assay, Western blotting, and live-cell imaging and to determine the levels of HBV-DNA and HBV markers. NET release was decreased in patients with chronic hepatitis B infection, and hepatitis B surface Ag, hepatitis B E Ag, and hepatitis B core Ab levels negatively correlated with NET release. We also examined the effect of HBV proteins (HBV X protein, HBV C protein, HBV E protein, and HBV S protein) on NET release in vitro. Based on flow cytometry, cytochrome c reduction assay, and Western blotting, HBV C protein and HBV E protein inhibited NET release by decreasing reactive oxygen species production and autophagy. Overall, HBV may inhibit NET release by modulating reactive oxygen species production and autophagy to escape the immune system and promote the establishment of chronic infection.