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1.
Chemosphere ; 310: 136871, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36244420

RESUMO

Evidence concerning the associations of ambient air pollution exposure with bone mineral density and osteoporosis has been mixed. We conducted cross-sectional and prospective analysis of the associations between air pollution exposure and osteoporosis using data from UK Biobank study. Estimated bone mineral density (eBMD) of each participant at baseline survey was calculated using quantitative ultrasound data, and incident osteoporosis cases were identified during the follow-up period according to health-related records. Air pollution concentrations were assessed using land use regression models. We fitted multivariable linear and logistic regression models to estimate the associations of air pollution with eBMD and osteoporosis prevalence at baseline. We applied cox proportional hazard regression models to assess the relationships between air pollution and osteoporosis incidence. Among the 341,311 participants at baseline, higher air pollution exposure was associated with lower eBMD levels and increased odds of osteoporosis prevalence. For example, an IQR increase in PM2.5, PM2.5 absorbance, PM10, NO2 and NOx levels were associated with 0.0018 (95% CI: 0.0012, 0.0023) to 0.0052 (95% CI: 0.0046, 0.0058) g/cm2 decrease in eBMD. A total of 330,988 participants without osteoporosis were followed up for an average of 12.0 years. We identified 8105 incident osteoporosis cases (456 cases with pathological fracture and 7634 cases without pathological fracture) during the follow-up. The hazard ratios for an interquartile range increase in PM2.5, PM2.5 absorbance, PM10, NO2 and NOx were 1.09 (95% CI: 1.06, 1.12), 1.04 (95% CI: 1.02, 1.07), 1.04 (95% CI: 1.01, 1.07), 1.07 (95% CI: 1.04, 1.10), and 1.06 (95% CI: 1.03, 1.09), respectively. Our study suggests that ambient air pollution might be a risk factor of decreased bone mineral density and osteoporosis incidence.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Fraturas Espontâneas , Osteoporose , Humanos , Dióxido de Nitrogênio/análise , Estudos de Coortes , Material Particulado/análise , Poluentes Atmosféricos/análise , Densidade Óssea , Estudos Transversais , Exposição Ambiental/análise , Poluição do Ar/análise , Osteoporose/epidemiologia
2.
Sci Total Environ ; 858(Pt 2): 159890, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36334679

RESUMO

BACKGROUND: Fine particulate matter (PM2.5), smoking, and genetic factors are associated with lung cancer. However, the relationship between PM2.5, smoking and subtypes of lung cancer remains unclear. Moreover, it is unclear whether genetic risk modifies the impact of PM2.5 and smoking on incident lung cancer. METHODS: A total of 298,069 participants from the UK Biobank study without lung cancer at baseline were included in this study. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were estimated using multivariable Cox proportional models for the association of lung cancer and its subtypes with PM2.5, smoking, and genetic risk. Potential gene-smoking or gene-PM2.5 interactions were also estimated. We further estimated population attributable fractions for incident lung cancer. RESULTS: During 10.4 years of follow-up, 1683 incident lung cancer cases were identified. Our analysis found that genetic variants, smoking, and PM2.5 were significantly associated with incident lung cancer. For different histological types of lung cancer, the HRs for squamous cell lung carcinoma associated with PM2.5 (per 5 µg/m3 increment) and current smoking were 2.76 (95 % CI: 1.72, 4.42, p < 0.001) and 48.64 (95 % CI: 27.96, 84.61, p < 0.001), while the HRs for lung adenocarcinoma were 1.59 (95 % CI: 1.13, 2.23, p < 0.001) and 9.89 (95 % CI: 7.91, 12.36, p < 0.001), respectively. We further found that participants with high levels of PM2.5 pollution and high genetic risk had the highest risk of incident lung cancer (HR = 1.81, 95 % CI: 1.39, 2.35, p < 0.001), while the interaction between PM2.5 and genetic risk was not statistically significant. We observed that the population attributable fractions of lung cancer attributable to current smoking and high PM2.5 exposure were estimated to be 67.45 % and 17.59 %. CONCLUSION: Genetic susceptibility, smoking, and PM2.5 are important risk factors for lung cancer. Both smoking and PM2.5 are more closely associated with an elevated risk of squamous cell lung cancer.

3.
J Ethnopharmacol ; 302(Pt A): 115878, 2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36341814

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qian Yang Yu Yin granules (QYYYG) have a long history in the treatment of hypertensive renal damage (HRD) in China. Clinical studies have found that QYYYG stabilizes blood pressure and prevents early renal damage. However, the exact mechanism is not entirely clear. AIM OF THE STUDY: To evaluate the therapeutic effect and further explore the therapeutic mechanism of QYYYG against HRD. MATERIALS AND METHODS: The efficacy of QYYYG in treating HRD was assessed in spontaneous hypertension rats (SHR). Renal autophagy and the TRPC6-CaMKKß-AMPK pathway in rats were evaluated. The regulatory role of QYYYG in angiotensin II (Ang II) induced abnormal autophagy in rat podocytes was determined by detecting autophagy-related proteins, intracellular Ca2+ content, and the TRPC6-CaMKKß-AMPK-mTOR pathway expressions. Finally, we established a stable rat podocyte cell line overexpressing TRPC6 and used the cells to verify the regulatory effects of QYYYG. RESULTS: QYYYG alleviated HRD and reversed the abnormal expression of autophagy-related genes in the SHR. In vitro, QYYYG protected against Ang II-induced podocyte damage. Furthermore, treatment of podocytes with QYYYG reversed Ang II-induced autophagy and inhibited Ang II-stimulated TRPC6 activation, Ca2+ influx and activation CaMKKß-AMPK pathway. Overexpression of TRPC6 resulted in pronounced activation of CaMKKß, AMPK, and autophagy induction in rat podocytes, which were significantly attenuated by QYYYG. CONCLUSIONS: The present study suggested that QYYYG may exert its HRD protective effects in part by regulating the abnormal autophagy of podocytes through the TRPC6-CaMKKß-AMPK-mTOR pathway.

4.
Poult Sci ; 102(1): 102286, 2022 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-36436372

RESUMO

Aflatoxin B1 (AFB1) is the most toxic subtype of aflatoxin in feed. Poultry is sensitive to AFB1, and the liver is the main target organ of AFB1. Our previous studies have shown that taraxasterol isolated from the traditional Chinese medicinal herb Taraxacum has protective effects against immune-mediated and alcoholic-induced liver injuries. This study aimed to investigate whether taraxasterol has the protective effect and its mechanism against AFB1-induced injury in chicken primary hepatocytes in vitro. The chicken primary hepatocytes were induced with AFB1 (0.05 µg/mL), and treated with taraxasterol (5, 10, and 20 µg/mL). The results showed that taraxasterol increased superoxide dismutase (SOD) and glutathione (GSH) activity and decreased malondialdehyde (MDA) and reactive oxygen species (ROS) production in AFB1-induced hepatocytes. Moreover, taraxasterol up-regulated the mRNA and protein expression of antioxidant-related factors heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase 1 (NQO1) and nuclear factor erythroid E2-related factor 2 (Nrf2), while down-regulated the expression of oxidant-related factor Kelch-like ECH-associated protein 1 (Keap1) in Nrf2/Keap1 signaling pathway. In addition, taraxasterol effectively reduced AFB1-induced hepatocyte autophagy and inhibited the mRNA expression of autophagy-related genes Beclin-2, LC3-I, LC3-II, and ATG-5. Taraxasterol also inhibited AFB1-induced hepatocyte apoptosis and decreased the mRNA expression of apoptosis-related genes Caspase3 and Caspase9. These findings indicates taraxasterol alleviates oxidative stress in AFB1-induced chicken hepatocytes by activating Nrf2/Keap1 signaling pathway, and regulating the cell autophagy and apoptosis.

5.
J Card Surg ; 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36423241

RESUMO

OBJECTIVE: To observe fat tissue and the expression of adipokines in rheumatic heart valves and explore the possible role of fat tissue and adipokines in the pathology of rheumatic heart disease (RHD). METHODS: In this retrospective study, a total of 29 patients who received mitral valve replacement surgery were included. The study group consisted of 25 patients with RHD while the control group consisted of 4 patients with secondary mitral insufficiency caused by coronary heart disease (CAD). The clinical data of the patients including medical history, age, body mass index (BMI), fasting blood glucose (FBG), total triglycerides (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), apolipoprotein(a) [apo(a)], apolipoprotein(b) [apo(b)] were collected and compared. Cardiac ultrasonography was used to assess valve conditions before surgery. The removed valves were collected. The hematoxylin-eosin (HE) staining, oil-red O staining, and Masson's trichrome staining were adopted to evaluate the histological changes in the mitral valve. Immunohistochemical (IMC) staining was performed to evaluate the expression of adiponectin, leptin, and chemerin. RESULTS: There was no significant difference in general information and blood lipid levels between the two groups (all p > .05). Preoperative ultrasonography showed adipose tissue in the mitral valve of RHD patients. In the study group, rheumatic mitral valve samples showed thickening, adherence at the junction of the leaflets, calcification, and yellowish or fat mass by naked observation. The HE staining showed that there was calcification, inflammatory cell infiltration, fibrous tissue arranged disorder, and neovascularization. The oil-red O staining suggested fatty infiltration. Masson's trichrome staining suggested disorderly arrangement of collagen fiber and elastic fiber in rheumatic lesions, and the lesions were dominated by collagen fiber hyperplasia and less elastic fiber hyperplasia. The results of IMC indicated that chemerin was not expressed in valves of the control group. Most of the valve samples from the study group also did not show leptin and the leptin was seen in only a few rheumatic mitral valves with vascular hyperplasia. Adiponectin was not found in the valves of the study group and the control group. CONCLUSION: Adipose tissue in the rheumatic mitral valve could be observed by ultrasound. The fat mass and adipokines existed in rheumatic mitral valves, the adipocytokine chemerin is involved in the progression of the pathology in RHD.

6.
Polymers (Basel) ; 14(19)2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36235890

RESUMO

Wood-plastic composite (WPC) is a kind of composite material that is made of plastic and wood fiber or wood powder. Because it is mothproof, is resistant to corrosion, and has plasticity, among other advantages, it has been researched and used increasingly in building materials. The flexural property of WPC is an important subject in evaluating its mechanical properties. In this paper, wood-plastic raw materials and processing technology are introduced; the internal and external factors of WPC which affect the flexural properties are analyzed; the different ways of enhancing the bending capacity, including the surface pretreatment, addition of different modifiers (compatibility agent and coupling agent) etc. are summarized; and the methods of operation and strengthening effect are analyzed. This work provides a reference for further research in related fields.

7.
Front Mol Neurosci ; 15: 979483, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277498

RESUMO

Objective: Trigeminal neuralgia (TN), one of the most severe and debilitating chronic pain conditions, is often accompanied by mood disorders, such as anxiety and depression. Electroacupuncture (EA) is a characteristic therapy of Traditional Chinese Medicine with analgesic and anxiolytic effects. This study aimed to investigate whether EA ameliorates abnormal TN orofacial pain and anxiety-like behavior by altering synaptic plasticity in the hippocampus CA1. Materials and methods: A mouse infraorbital nerve transection model (pT-ION) of neuropathic pain was established, and EA or sham EA was used to treat ipsilateral acupuncture points (GV20-Baihui and ST7-Xiaguan). Golgi-Cox staining and transmission electron microscopy (TEM) were administrated to observe the changes of synaptic plasticity in the hippocampus CA1. Results: Stable and persistent orofacial allodynia and anxiety-like behaviors induced by pT-ION were related to changes in hippocampal synaptic plasticity. Golgi stainings showed a decrease in the density of dendritic spines, especially mushroom-type dendritic spines, in hippocampal CA1 neurons of pT-ION mice. TEM results showed that the density of synapses, membrane thickness of the postsynaptic density, and length of the synaptic active zone were decreased, whereas the width of the synaptic cleft was increased in pT-ION mice. EA attenuated pT-ION-induced orofacial allodynia and anxiety-like behaviors and effectively reversed the abnormal changes in dendritic spines and synapse of the hippocampal CA1 region. Conclusion: EA modulates synaptic plasticity of hippocampal CA1 neurons, thereby reducing abnormal orofacial pain and anxiety-like behavior. This provides evidence for a TN treatment strategy.

8.
Ecotoxicol Environ Saf ; 246: 114182, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36270037

RESUMO

INTRODUCTION: It remains unknown whether higher dietary intake of antioxidant vitamins could reduce the harmful effects of air pollution on incident diabetes mellitus. METHODS: A total of 156,490 participants free of diabetes mellitus in the UK Biobank data were included in this analysis. Antioxidant vitamin intake was measured using a 24-h food intake questionnaire, and results were categorized as sufficient or insufficient according to the British Recommended Nutrient Intake. Exposure to fine particles (PM2.5), thoracic particles (PM10), nitrogen dioxide (NO2), and nitrogen oxide (NOx) was estimated using land use regression models at participants' residences. Incident diabetes mellitus was identified using health administrative datasets. Cox regression models were used to assess the associations. RESULTS: A total of 4271 incident diabetes mellitus cases were identified during a median follow-up of 11.7 years. Compared with participants with insufficient intake of antioxidant vitamins, those with sufficient consumption had a weaker association between air pollution (PM2.5, PM10 and NO2) and diabetes mellitus [sufficient vs. insufficient: HR = 1.12 (95 % CI: 0.87, 1.45) vs. 1.69 (95 % CI: 1.42, 2.02) for PM2.5, 1.00 (95 % CI: 0.88, 1.14) vs. 1.21 (95 % CI: 1.10, 1.34) for PM10, and 1.01 (95 % CI: 0.98, 1.04) vs. 1.05 (95 % CI: 1.03, 1.07) for NO2 (all p for comparison < 0.05)]. Among different antioxidant vitamins, we observed stronger effects for vitamin C and E. CONCLUSION: Our study suggests that ambient air pollution is one important risk factor of diabetes mellitus, and sufficient intake of antioxidant vitamins may reduce such adverse effects of air pollution on diabetes mellitus.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Diabetes Mellitus , Humanos , Dióxido de Nitrogênio/toxicidade , Antioxidantes , Estudos de Coortes , Material Particulado/toxicidade , Poluentes Atmosféricos/análise , Vitaminas , Exposição Ambiental , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Diabetes Mellitus/epidemiologia , Vitamina A , Vitamina K , Ingestão de Alimentos
9.
Mol Cell ; 82(21): 4080-4098.e12, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36272410

RESUMO

Growing evidence suggests prevalence of transcriptional condensates on chromatin, yet their mechanisms of formation and functional significance remain largely unclear. In human cancer, a series of mutations in the histone acetylation reader ENL create gain-of-function mutants with increased transcriptional activation ability. Here, we show that these mutations, clustered in ENL's structured acetyl-reading YEATS domain, trigger aberrant condensates at native genomic targets through multivalent homotypic and heterotypic interactions. Mechanistically, mutation-induced structural changes in the YEATS domain, ENL's two disordered regions of opposing charges, and the incorporation of extrinsic elongation factors are all required for ENL condensate formation. Extensive mutagenesis establishes condensate formation as a driver of oncogenic gene activation. Furthermore, expression of ENL mutants beyond the endogenous level leads to non-functional condensates. Our findings provide new mechanistic and functional insights into cancer-associated condensates and support condensate dysregulation as an oncogenic mechanism.


Assuntos
Neoplasias , Corpos Nucleares , Humanos , Domínios Proteicos , Cromatina/genética , Mutação , Neoplasias/genética
10.
Anal Chem ; 94(42): 14642-14651, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36218121

RESUMO

In this work, near-infrared fluorescent silver nanoclusters (Ag NCs) were prepared based on the in situ formed poly methacrylic acid (PMAA) as the template and stabilizer, which is synthesized by methacrylic acid (MAA) and hydroxyl radical (·OH) that is generated by the cascade nanoenzyme reaction of cupric oxide nanoparticles (CuO NPs). CuO NPs possess the intrinsic glutathione-like (GPx-like) and peroxidase-like (POD-like) activities, which can catalyze glutathione (GSH) and O2 to produce hydrogen peroxide (H2O2), and then transform into ·OH. The fluorescence intensity of Ag NCs decreases with the addition of GSH, because the -SH can easily anchor on the surface, resulting in the PMAA leaving the Ag NCs, and the coeffect of GSH and PMAA results in the aggregation to form larger Ag NPs. A good linear relationship between the fluorescence quenching rate and the GSH concentration was found in the range 0.01-40 µM with the detection limit 8.0 nM. The Ag NCs can be applied in the detection of GSH in the serum, as well as bioimaging of endogenous and exogenous GSH in cells with high sensitivity. Moreover, the normal and cancer cells can be distinguished through bioimaging because of the different GSH levels. The new method for the preparation of biocompatible nanoprobe based on the nanozyme tandem catalysis and the in situ formed template can avoid the direct usage of polymers or protein templates that hinder preparation and separation, providing a reliable approach for the synthesis, biosensing, and bioimaging of nanoclusters.


Assuntos
Nanopartículas Metálicas , Prata , Polieletrólitos , Peróxido de Hidrogênio , Radical Hidroxila , Glutationa , Catálise , Peroxidases
11.
Adv Sci (Weinh) ; : e2204949, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36285692

RESUMO

The development of low-cost, high-efficiency, and stable electrocatalysts for hydrogen evolution reaction (HER) under alkaline conditions is a key challenge in water electrolysis. Here, an interfacial engineering strategy that is capable of simultaneously regulating nanoscale structure, electronic structure, and interfacial structure of Mo2 N quantum dots decorated on conductive N-doped graphene via codoping single-atom Al and O (denoted as AlO@Mo2 N-NrGO) is reported. The conversion of Anderson polyoxometalates anion cluster ([AlMo6 O24 H6 ]3- , denoted as AlMo6) to Mo2 N quantum dots not only result in the generation of more exposed active sites but also in situ codoping atomically dispersed Al and O, that can fine-tune the electronic structure of Mo2 N. It is also identified that the surface reconstruction of AlOH hydrates in AlO@Mo2 N quantum dots plays an essential role in enhancing hydrophilicity and lowering the energy barriers for water dissociation and hydrogen desorption, resulting in a remarkable alkaline HER performance, even better than the commercial 20% Pt/C. Moreover, the strong interfacial interaction (MoN bonds) between AlO@Mo2 N and N-doped graphene can significantly improve electron transfer efficiency and interfacial stability. As a result, outstanding stability over 300 h at a current density higher than 100 mA cm-2 is achieved, demonstrating great potential for the practical application of this catalyst.

12.
BMC Genomics ; 23(1): 717, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36266635

RESUMO

BACKGROUND: It is important to understand the functional impact of somatic mutation and methylation aberration at an individual level to implement precision medicine. Recent studies have demonstrated that the perturbation of gene interaction networks can provide a fundamental link between genotype (or epigenotype) and phenotype. However, it is unclear how individual mutations affect the function of biological networks, especially for individual methylation aberration. To solve this, we provided a sample-specific driver module construction method using the 2-order network theory and hub-gene theory to identify individual perturbation networks driven by mutations or methylation aberrations. RESULTS: Our method integrated multi-omics of breast cancer, including genomics, transcriptomics, epigenomics and interactomics, and provided new insight into the synergistic collaboration between methylation and mutation at an individual level. A common driver pattern of breast cancer was identified from a novel perspective of a driver module, which is correlated to the occurrence and development of breast cancer. The constructed driver module reflects the survival prognosis and degree of malignancy among different subtypes of breast cancer. Additionally, subtype-specific driver modules were identified. CONCLUSIONS: This study explores the driver module of individual cancer, and contributes to a better understanding of the mechanism of breast cancer driven by the mutations and methylation variations from the point of view of the driver network. This work will help identify new therapeutic combinations of gene mutations and drugs in humans.


Assuntos
Redes Reguladoras de Genes , Neoplasias , Humanos , Genômica/métodos , Epigenômica , Mutação , Prognóstico , Neoplasias/genética
13.
Mol Nutr Food Res ; : e2200196, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36239154

RESUMO

SCOPE: Given the d-lactate dehydrogenase (D-LDH) deficiency, L- but not d-lactate is assumed to be the physiological isomer in mammals. Paradoxically, many fermented foods (e.g., yogurt, sauerkraut, cheeses) often contain substantial amounts of d-lactate. In the present study, dietary d-lactate may be a previously unrecognized nutrient aiding in inflammatory resolution is hypothesized. METHODS AND RESULTS: The anti-inflammatory properties of d-lactate are evaluated in experimental colitis and endotoxemia. Oral administration of d-lactate favorably affects acute inflammation in two different mouse models. Analysis of lactate-the lactate receptor (the hydroxycarboxylic acid receptor 1 HCA1, formerly GPR81) signal axis in inflammation is performed in primary peritoneal macrophages and wild-type (WT) or GPR81 knockout (KO) mice. GPR81 KO mice are susceptible to endotoxic shock than WT mice, while d-lactate exerts its anti-inflammatory activities in a GPR81-dependent manner. Mechanistically, the activation of lactate-GPR81 axis may suppress LPS-TLR4 signaling to modulate M1 macrophage polarization. Although D-LDH deficiency in mammals impairs d-lactate clearance, it might prolong its plasma terminal half-life, and thus provide a pharmacokinetic advantage of d-lactate over l-lactate. CONCLUSION: This study highlights housekeeping function of the lactate-GPR81 axis in inflammation control, and suggests that dietary intake of d-lactate may underlie Metchnikoff's probiotic yogurt theory of life prolongation.

14.
BMC Med ; 20(1): 375, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36310158

RESUMO

BACKGROUND: Though the association between air pollution and incident type 2 diabetes (T2D) has been well documented, evidence on the association with development of subsequent diabetes complications and post-diabetes mortality is scarce. We investigate whether air pollution is associated with different progressions and outcomes of T2D. METHODS: Based on the UK Biobank, 398,993 participants free of diabetes and diabetes-related events at recruitment were included in this analysis. Exposures to particulate matter with a diameter ≤ 10 µm (PM10), PM2.5, nitrogen oxides (NOx), and NO2 for each transition stage were estimated at each participant's residential addresses using data from the UK's Department for Environment, Food and Rural Affairs. The outcomes were incident T2D, diabetes complications (diabetic kidney disease, diabetic eye disease, diabetic neuropathy disease, peripheral vascular disease, cardiovascular events, and metabolic events), all-cause mortality, and cause-specific mortality. Multi-state model was used to analyze the impact of air pollution on different progressions of T2D. Cumulative transition probabilities of different stages of T2D under different air pollution levels were estimated. RESULTS: During the 12-year follow-up, 13,393 incident T2D patients were identified, of whom, 3791 developed diabetes complications and 1335 died. We observed that air pollution was associated with different progression stages of T2D with different magnitudes. In a multivariate model, the hazard ratios [95% confidence interval (CI)] per interquartile range elevation in PM2.5 were 1.63 (1.59, 1.67) and 1.08 (1.03, 1.13) for transitions from healthy to T2D and from T2D to complications, and 1.50 (1.47, 1.53), 1.49 (1.36, 1.64), and 1.54 (1.35, 1.76) for mortality risk from baseline, T2D, and diabetes complications, respectively. Generally, we observed stronger estimates of four air pollutants on transition from baseline to incident T2D than those on other transitions. Moreover, we found significant associations between four air pollutants and mortality risk due to cancer and cardiovascular diseases from T2D or diabetes complications. The cumulative transition probability was generally higher among those with higher levels of air pollution exposure. CONCLUSIONS: This study indicates that ambient air pollution exposure may contribute to increased risk of incidence and progressions of T2D, but to diverse extents for different progressions.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Diabetes Mellitus Tipo 2 , Humanos , Incidência , Diabetes Mellitus Tipo 2/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluição do Ar/efeitos adversos , Material Particulado/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise
15.
Plant Commun ; 3(6): 100456, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36196059

RESUMO

Dracaena, a remarkably long-lived and slowly maturing species of plant, is world famous for its ability to produce dragon's blood, a precious traditional medicine used by different cultures since ancient times. However, there is no detailed and high-quality genome available for this species at present; thus, the molecular mechanisms that underlie its important traits are largely unknown. These factors seriously limit the protection and regeneration of this rare and endangered plant resource. Here, we sequenced and assembled the genome of Dracaena cochinchinensis at the chromosome level. The D. cochinchinensis genome covers 1.21 Gb with a scaffold N50 of 50.06 Mb and encodes 31 619 predicted protein-coding genes. Analysis showed that D. cochinchinensis has undergone two whole-genome duplications and two bursts of long terminal repeat insertions. The expansion of two gene classes, cis-zeatin O-glucosyltransferase and small auxin upregulated RNA, were found to account for its longevity and slow growth. Two transcription factors (bHLH and MYB) were found to be core regulators of the flavonoid biosynthesis pathway, and reactive oxygen species were identified as the specific signaling molecules responsible for the injury-induced formation of dragon's blood. Our study provides high-quality genomic information relating to D. cochinchinensis and significant insight into the molecular mechanisms responsible for its longevity and formation of dragon's blood. These findings will facilitate resource protection and sustainable utilization of Dracaena.


Assuntos
Croton , Dracaena , Dracaena/genética , Dracaena/metabolismo , Longevidade , Resinas Vegetais/metabolismo , Croton/genética , Croton/metabolismo , Cromossomos/metabolismo
16.
Am J Epidemiol ; 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36269005

RESUMO

Evidence on the association between air pollution and dementia is accumulating but still inconclusive, and the potential effect modification by genetics is unclear. We investigated the joint effects of air pollution exposure and genetic risk on incident dementia in a prospective cohort, the UK Biobank study. Land use regression models were used to estimate exposure to ambient particulate matter (fraction size: < 2.5 µm, PM2.5; 2.5-10 µm, PMc; and >10 µm, PM10), PM2.5 absorbance, nitrogen dioxide (NO2) and nitrogen oxides (NOx) at each individual's baseline residence. A polygenic risk score (PRS) was calculated as a quantitative measure of genetic dementia risk. Incident cases of dementia were ascertained through linkage to health administrative datasets. Among the 227,840 participants included in analysis, 3,774 incident dementia cases (including 1,238 Alzheimer's disease and 563 vascular dementia) were identified. After adjustment for a variety of covariates including genetics, positive associations were found between exposure to air pollution, particularly PM10, PM2.5 absorbance and NO2, and incident all-cause dementia and Alzheimer's disease, but not vascular dementia. No significant air pollution-genetics interaction was found either on multiplicative or additive scales. Exposure to air pollution was associated with a higher risk of developing dementia regardless of genetic risk.

17.
Nat Cell Biol ; 24(11): 1655-1665, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36266488

RESUMO

Tumour cells exhibit greater metabolic plasticity than normal cells and possess selective advantages for survival and proliferation with unclearly defined mechanisms. Here we demonstrate that glucose deprivation in normal hepatocytes induces PERK-mediated fructose-1,6-bisphosphatase 1 (FBP1) S170 phosphorylation, which converts the FBP1 tetramer to monomers and exposes its nuclear localization signal for nuclear translocation. Importantly, nuclear FBP1 binds PPARα and functions as a protein phosphatase that dephosphorylates histone H3T11 and suppresses PPARα-mediated ß-oxidation gene expression. In contrast, FBP1 S124 is O-GlcNAcylated by overexpressed O-linked N-acetylglucosamine transferase in hepatocellular carcinoma cells, leading to inhibition of FBP1 S170 phosphorylation and enhancement of ß-oxidation for tumour growth. In addition, FBP1 S170 phosphorylation inversely correlates with ß-oxidation gene expression in hepatocellular carcinoma specimens and patient survival duration. These findings highlight the differential role of FBP1 in gene regulation in normal and tumour cells through direct chromatin modulation and underscore the inactivation of its protein phosphatase function in tumour growth.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , Histonas/genética , Histonas/metabolismo , Frutose-Bifosfatase/genética , PPAR alfa/genética , PPAR alfa/metabolismo , Frutose , Neoplasias Hepáticas/patologia , Transcrição Genética , Fosfoproteínas Fosfatases/metabolismo
18.
Neurology ; 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36171142

RESUMO

BACKGROUND: Ambient air pollution has been widely linked with morbidity and mortality of stroke. However, its effects on dynamic progression trajectory of stroke remain unknown. OBJECTIVE: To investigate the effects of ambient air pollution on progression trajectory from healthy to incident stroke, post-stroke cardiovascular diseases, and subsequent death. METHODS: We retrieved 318,752 participants from the UK Biobank. The annual concentrations of air pollution [particulate matter (PM2.5, PMcoarse, PM10 and PM2.5 absorbance), nitrogen dioxide (NO2), and nitrogen oxides (NOx)] were estimated through land-use regressions. A multi-state regression model was employed to investigate the effects of air pollution on each stage of the progression of stroke. RESULTS: During 3,765,630 person-years of follow-up, we identified 5,967 incident stroke patients, 2,985 post-stroke cardiovascular patients, and 1,020 deaths afterward. Each 5 µg/m3 increase in PM2.5, NO2, and NOx was associated with the transition from healthy to incident stroke [Hazard Ratios (HRs) (95% confidence intervals (CI)) = 1.24 (1.10, 1.40); 1.02 (1.00, 1.03); 1.01 (1.00, 1.02)] and transitions from healthy to death directly [1.30 (1.21, 1.40); 1.03 (1.02, 1.04); 1.02 (1.01, 1.02)]. We also observed positive associations for post-stroke CVDs, especially for NO2 [1.04 (95% CI: 1.02, 1.06)], but these effects gradually declined for mortality outcome. CONCLUSION: This study provides the first evidence that ambient air pollution is one important factor associated with the progression of stroke, and the effects differed across different clinical stages. A better understanding of the differential effects of air pollutants on different stroke transition stages could provide valuable insight toward targets for health management and clinical prevention.

19.
Nanoscale ; 14(36): 13248-13260, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36052817

RESUMO

In conventional thermocatalytic reactions under a reducing atmosphere, stabilization of the active Cu+ component and inhibition of over-reduction into metallic Cu0 are extremely challenging. In this study, Au@Cu2O core-shell nano-catalysts with different Cu2O shell thicknesses were synthesized, and the effect of the Au nano-core on Cu+ stability under a reducing atmosphere and the catalytic performance of Cu+ in the ethynylation of formaldehyde were investigated. The Au nano-core facilitates Cu2O dispersion and leads to an increase of 0.2-0.5 eV in electron binding energies of Cu2O and Cu2C2 in the range of 27-55 nm, attributed to the long-range electromagnetic effect of Au NPs. Specifically, active Cu+ centers exhibit high stability under a reducing atmosphere due to the long-range electromagnetic effect of the Au nano-core. In the ethynylation of formaldehyde as a probe reaction, Cu+/(Cu0 + Cu+) on Au@Cu2O catalysts remained at 88-91%. The catalytic performance in the ethynylation of formaldehyde revealed that the introduction of an Au nano-core into Cu-based catalysts increased the TOF from 0.37 to 0.7 h-1, and decreased the activation energy from 42.6 to 38.1 kJ mol-1. Additionally, the Cu+/(Cu0 + Cu+) ratios and the catalytic performance in the ethynylation of formaldehyde (BD yield = 65%, BD selectivity = 95%) on Au@Cu2O catalysts remained constant after nine cycles, while pure Cu2O readily deactivated due to the dramatically reduced Cu+/(Cu0 + Cu+) ratios and carbyne deposition. In summary, Cu+ in Cu-based catalysts showed high catalytic activity and stability during the ethynylation of formaldehyde due to the long-range electromagnetic effect of the Au nano-core.

20.
ACS Appl Mater Interfaces ; 14(39): 45005-45012, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36162132

RESUMO

A liquid-liquid interfacial reaction combines reactants with large polarity disparity to achieve greener and more efficient chemistry that is otherwise challenging in traditional single-phase systems. However, current interfacial approaches suffer from the need for a large amount of solvent/reactant/emulsifier and poor reaction performance arising from intrinsic thermodynamic constraints. Herein, we achieve an efficient interfacial reaction by creating a magnetic-responsive, microscale liquid-liquid interface and exploit its dynamic spinning motion to generate vortex-like hydrodynamic flows that rapidly converge biphasic reactants to the point-of-reaction. Notably, the spinning of this functional interface at 800 rpm boosts the reaction efficiency and its apparent equilibrium constant by > 500-fold and 105-fold, respectively, higher than conventional methods that utilize bulk and/or non-dynamic liquid interfaces, even with external mechanical stirring. By driving reaction equilibrium toward favorable product formation, our unique design offers enormous opportunities to realize efficient multiphasic reactions crucial for diverse applications in chemical synthesis, environmental remediation, and even molecular recycling.

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