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1.
Life Sci Alliance ; 6(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36414381

RESUMO

Enhanced fatty acid synthesis is a hallmark of tumors, including glioblastoma. SREBF1/2 regulate the expression of enzymes involved in fatty acid and cholesterol synthesis. Yet, little is known about the precise mechanism regulating SREBP gene expression in glioblastoma. Here, we show that a novel interaction between the co-activator/co-repressor CTBP and the tumor suppressor ZBTB18 regulates the expression of SREBP genes. In line with our findings, metabolic assays and glucose tracing analysis confirm the reduction in several phospholipid species upon ZBTB18 expression. Our study identifies CTBP1/2 and LSD1 as co-activators of SREBP genes and indicates that the functional activity of the CTBP-LSD1 complex is altered by ZBTB18. ZBTB18 binding to the SREBP gene promoters is associated with reduced LSD1 demethylase activity of H3K4me2 and H3K9me2 marks. Concomitantly, the interaction between LSD1, CTBP, and ZNF217 is increased, suggesting that ZBTB18 promotes LSD1 scaffolding function. Our results outline a new epigenetic mechanism enrolled by ZBTB18 and its co-factors to regulate fatty acid synthesis that could be targeted to treat glioblastoma patients.


Assuntos
Glioblastoma , Humanos , Ácidos Graxos , Glioblastoma/genética , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Lipídeos , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
2.
Sci Total Environ ; 856(Pt 2): 159292, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36208731

RESUMO

Numerous studies have highlighted the physical and mental health benefits of contact with nature, typically in landscapes characterized by plants (i.e., "greenspace") and water (i.e., "bluespace"). However, natural landscapes are not always green or blue, and the effects of other landscapes are worth attention. This narrative review attempts to overcome this limitation of past research. Rather than focusing on colors, we propose that natural landscapes are composed of at least one of three components: (1) plants (e.g., trees, flowering plants, grasses, sedges, mosses, ferns, and algae), (2) water (e.g., rivers, canals, lakes, and oceans), and/or (3) rocks and minerals, including soil. Landscapes not dominated by plants or liquid-state water include those with abundant solid-state water (e.g., polar spaces) and rocks or minerals (e.g., deserts and caves). Possible health benefits of solid-state water or rock/mineral dominated landscapes include both shorter-term (e.g., viewing images) and longer-term (e.g., living in these landscapes) exposure durations. Reported benefits span improved emotional and mental states and medical treatment resources for respiratory conditions and allergies. Mechanisms underlying the health benefits of exposure consist of commonly discussed theories in the "greenspace" and "bluespace" literature (i.e., instoration and restoration) as well as less discussed pathways in that literature (i.e., post-traumatic growth, self-determination, supportive environment theory, and place attachment). This is the first review to draw attention to the potential salutogenic value of natural landscapes beyond "greenspace" and "bluespace." It is also among the first to highlight the limitations and confusion that result from classifying natural landscapes using color. Since the extant literature on natural landscapes - beyond those with abundant plants or liquid-state water - is limited in regard to quantity and quality, additional research is needed to understand their restorative potential and therapeutic possibilities.


Assuntos
Meio Ambiente , Saúde Mental , Plantas , Água
3.
Nutrition ; 106: 111910, 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36459845

RESUMO

OBJECTIVES: The role of plasma phospholipid arachidonic acid (AA) in the development of non-alcoholic fatty liver disease (NALFD), cirrhosis, and liver cancer remains unclear. This study aimed to determine the causality of the associations of plasma phospholipid AA with NALFD, cirrhosis, and liver cancer using Mendelian randomization analysis. METHODS: Nine independent single-nucleotide polymorphisms associated with plasma phospholipid AA at the genome-wide significance were used as instrumental variables. Summary-level data for three outcomes were obtained from 1) a genome-wide association study for NAFLD, 2) the UK Biobank study, and 3) the FinnGen study. The sensitivity analysis excluding the pleiotropic variant rs174547 in the FADS1 gene was performed. Estimates from different sources were combined using the fixed-effects meta-analysis method. RESULTS: Per standard deviation increase in AA levels, the combined odds ratio was 1.06 (95% confidence interval, 1.02-1.11; P = 0.008) for NAFLD, 1.05 (95% confidence interval, 1.01-1.09; P = 0.009) for cirrhosis, and 0.99 (95% confidence interval, 0.94-1.05; P = 0.765) for liver cancer. The associations remained stable in the sensitivity analysis excluding rs174547. CONCLUSIONS: This study suggests potential causal associations of high levels of plasma phospholipid AA with the risk of NAFLD and cirrhosis.

4.
Ecotoxicol Environ Saf ; 248: 114344, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36455349

RESUMO

Considering that research has mainly focussed on how excessive iron supplementation leads to reproductive cytotoxicity, there is a lack of in-depth research on reproductive system disorders caused by iron deficiency. To gain a better understanding of the effects of iron deficiency on the reproductive system, especially spermatogenesis, we first constructed a mouse model of iron deficiency. We employed multi-omic analysis, including transcriptomics, metabolomics, and microbiomics, to comprehensively dissect the impact of iron deficiency on spermatogenesis. Moreover, we verified our findings in detail using western blot, immunofluorescence, immunohistochemistry, qRT-PCR and other techniques. Microbiomic analysis revealed altered gut microbiota in iron-deficient mice, and functional predictive analysis showed that gut microbiota can regulate spermatogenesis. The transcriptomic data indicated that iron deficiency directly alters expression of meiosis-related genes. Transcriptome data also revealed that iron deficiency indirectly regulates spermatogenesis by affecting hormone synthesis, findings confirmed by metabolomic data, western blot and immunofluorescence. Interestingly, competing endogenous RNA networks also play a vital role in regulating spermatogenesis after iron deficiency. Taken together, the data elucidate that iron deficiency impairs spermatogenesis and increases the risk of male infertility by affecting hormone synthesis and promoting gut microbiota imbalance.


Assuntos
Deficiências de Ferro , Masculino , Camundongos , Animais , Espermatogênese , Metabolômica , Ferro , Hormônios
5.
Front Cardiovasc Med ; 9: 1025063, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465459

RESUMO

Objective: This Mendelian randomization (MR) study aimed to investigate the causal relationship between osteoarthritis (OA) and cardiovascular disease (CVD). Methods: From a genome-wide association study of European ancestry, we selected single nucleotide polymorphisms for two types of OA, knee osteoarthritis (KOA) and hip osteoarthritis (HOA), as instrumental variables. We evaluated three types of CVD: coronary heart disease (CHD), heart failure (HF), and stroke. We used the traditional inverse variance weighting (IVW) method and other methods to estimate causality. Heterogeneity and sensitivity tests were also applied. Finally, we conducted a MR analysis in the opposite direction to investigate reverse causality. Results: IVW analysis showed that HOA significantly affected the incidence of HF [odds ratio (OR): 1.0675; 95% confidence interval (CI): 0.0182-0.1125, P = 0.0066]. HOA significantly affected the incidence of stroke (OR: 1.1368; 95% CI: 1.0739-1.2033, P = 9.9488e-06). CHD could dramatically affect the incidence of KOA (OR: 0.9011; 95% CI: 0.8442-0.9619, P = 0.0018). The rest of the results were negative. Conclusions: Our results revealed a potential causal relationship between HOA and risk of HF, and a potential causal relationship between HOA and risk of stroke. Our findings also suggested that CHD has a significant causal relationship with the risk of KOA. This paper may provide new ideas for the treatment of OA and CVD.

6.
Zhongguo Zhong Yao Za Zhi ; 47(20): 5610-5616, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36471979

RESUMO

This study aims to investigate the effect of Chaihu Shugan Powder(CHSG) on liver injury in rats with intrahepatic cholestasis by regulating farnesoid X receptor(FXR)/nuclear factor erythroid-2-related factor(Nrf2)/antioxidant response element(ARE) pathway. Eighty-four SD rats were classified into normal group, model group, CHSG-L group(0.5 g·kg~(-1)), CHSG-H group(2.5 g·kg~(-1)), ursodeoxycholic acid group(UDCA group, 100 mg·kg~(-1)), CHSG-H+sh-NC group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-NC lentivirus), CHSG-H+sh-FXR group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-FXR lentivirus), with 12 rats in each group. Rats were treated with corresponding drugs except for the normal group and the model group, once a day, for 7 days. On 5 th day, rats, except the normal group, were given α-naphthalene isothiocyanate(ANIT) at a dose of 100 mg·kg~(-1), once a day for 3 days to induce intrahepatic cholestasis, and the normal group was given the same amount of normal saline. Rats were anesthetized 1 h after the last administration and the 2 h bile flow was measured. Aeroset chemistry analyzer was employed to detect the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), and total bile acid(TBA) in rat serum. Based on hematoxylin and eosin(HE) staining, the pathological changes of rat liver tissue were observed. Glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in rat liver tissue homogenate were monitored with corresponding kits. Western blot was used to detect the expression of FXR, Nrf2, and heme oxygenase-1(HO-1) proteins in rat liver tissue. Compared with the normal group, the model group showed many spots or concentrated necrotic areas in the liver tissue, infiltration of a large number of inflammatory cells, swelling liver cells with nuclear shrinkage. The 2 h bile flow, levels of GSH-Px and SOD, and relative expression of FXR, Nrf2, and HO-1 proteins were significantly lower, and the levels of ALT, AST, TBIL, TBA and MDA were significantly higher in the model group than in the normal group. Compared with the model group, CHSG-L group, CHSG-H group, and UDCA group demonstrated significant alleviation of pathological damage of the liver tissue, significantly high 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2 and HO-1 proteins, and significantly low levels of ALT, AST, TBIL, TBA and MDA. Compared with the CHSG-H group, the CHSG-H+sh-FXR group had worse liver pathological damage, significantly low levels of 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2, and HO-1 proteins, and significantly high levels of ALT, AST, TBIL, TBA, and MDA. CHSG may protect against liver injury in rats with intrahepatic cholestasis by activating the FXR/Nrf2/ARE pathway.

7.
J Biol Chem ; 298(12): 102654, 2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36441026

RESUMO

The cytochrome-b5 reductase (CYB5R) family of flavoproteins is known to regulate reduction-oxidation (redox) balance in cells. The five enzyme members are highly compartmentalized at the subcellular level and function as "redox switches" enabling the reduction of several substrates, such as heme and coenzyme Q. Critical insight into the physiological and pathophysiological significance of CYB5R enzymes has been gleaned from several human genetic variants that cause congenital disease and a broad spectrum of chronic human diseases. Among the CYB5R genetic variants, CYB5R3 is well-characterized and deficiency in expression and activity is associated with type II methemoglobinemia, cancer, neurodegenerative disorders, diabetes, and cardiovascular disease. Importantly, pharmacological and genetic-based strategies are underway to target CYB5R3 to circumvent disease onset and mitigate severity. Despite our knowledge of CYB5R3 in human health and disease, the other reductases in the CYB5R family have been understudied, providing an opportunity to unravel critical function(s) for these enzymes in physiology and disease. In this review, we aim to provide the broad scientific community an up-to-date overview of the molecular, cellular, physiological, and pathophysiological roles of CYB5R proteins.

8.
Br J Psychol ; 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36330995

RESUMO

Moral character is widely expected to lead to moral judgements and practices. However, such expectations are often breached, especially when moral character is measured by self-report. We propose that because self-reported moral character partly reflects a desire to appear good, people who self-report a strong moral character will show moral harshness towards others and downplay their own transgressions-that is, they will show greater moral hypocrisy. This self-other discrepancy in moral judgements should be pronounced among individuals who are particularly motivated by reputation. Employing diverse methods including large-scale multination panel data (N = 34,323), and vignette and behavioural experiments (N = 700), four studies supported our proposition, showing that various indicators of moral character (Benevolence and Universalism values, justice sensitivity, and moral identity) predicted harsher judgements of others' more than own transgressions. Moreover, these double standards emerged particularly among individuals possessing strong reputation management motives. The findings highlight how reputational concerns moderate the link between moral character and moral judgement.

9.
BMC Med ; 20(1): 455, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36424608

RESUMO

BACKGROUND: We performed phenome-wide Mendelian randomization analysis (MR-PheWAS), two-sample MR analysis, and systemic review to comprehensively explore the health effects of milk consumption in the European population. METHODS: Rs4988235 located upstream of the LCT gene was used as the instrumental variable for milk consumption. MR-PheWAS analysis was conducted to map the association of genetically predicted milk consumption with 1081 phenotypes in the UK Biobank study (n=339,197). The associations identified in MR-PheWAS were examined by two-sample MR analysis using data from the FinnGen study (n=260,405) and international consortia. A systematic review of MR studies on milk consumption was further performed. RESULTS: PheWAS and two-sample MR analyses found robust evidence in support of inverse associations of genetically predicted milk consumption with risk of cataract (odds ratio (OR) per 50 g/day increase in milk consumption, 0.89, 95% confidence interval (CI), 0.84-0.94; p=3.81×10-5), hypercholesterolemia (OR, 0.91, 95% CI 0.86-0.96; p=2.97×10-4), and anal and rectal polyps (OR, 0.85, 95% CI, 0.77-0.94; p=0.001). An inverse association for type 2 diabetes risk (OR, 0.92, 95% CI, 0.86-0.97; p=0.003) was observed in MR analysis based on genetic data with body mass index adjustment but not in the corresponding data without body mass index adjustment. The systematic review additionally found evidence that genetically predicted milk consumption was inversely associated with asthma, hay fever, multiple sclerosis, colorectal cancer, and Alzheimer's disease, and positively associated with Parkinson's disease, renal cell carcinoma, metabolic syndrome, overweight, and obesity. CONCLUSIONS: This study suggests several health effects of milk consumption in the European population.


Assuntos
Diabetes Mellitus Tipo 2 , Neoplasias Renais , Humanos , Animais , Análise da Randomização Mendeliana , Leite , Diabetes Mellitus Tipo 2/epidemiologia , Polimorfismo de Nucleotídeo Único
10.
Artigo em Inglês | MEDLINE | ID: mdl-36352835

RESUMO

BACKGROUND: Sleep dysregulation has been linked to gastrointestinal dysfunction and inflammation. AIMS: To explore the associations between sleep duration, daytime napping and inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Exposure information was obtained from the baseline questionnaire. Sleep duration was coded as continuous and categorical (≤5, 6, 7, 8, ≥9 h/day) variables. Daytime napping was defined as yes (sometimes/usually) and no (never/rarely). Incident IBD cases were defined from primary care and hospital inpatient records. Polygenic risk scores (PRS) for the outcomes were constructed and categorised into low, intermediate and high risk. Hazard ratio (HR) and confidence interval (CI) were estimated using Cox proportional hazard regression. RESULTS: The analysis included 2604 incident IBD cases (806 CD and 1798 UC) with a median follow-up of 12.0 years. Comparing sleep duration ≤5 with 7 h/day, the HR of IBD, CD and UC was 1.36 (95% CI, 1.17-1.59), 1.53 (95% CI, 1.17-2.00) and 1.29 (95% CI, 1.07-1.56), respectively. Comparing participants with and without daytime napping, the HR of IBD, CD and UC was 1.13 (95% CI, 1.05-1.23), 1.25 (95% CI, 1.08-1.44) and 1.09 (95% CI, 0.90-1.20), respectively. No interaction of sleep duration and daytime napping with PRS was detected.  However, the associations appeared stronger in individuals with high rather than low PRS. CONCLUSIONS: This study reveals positive associations between short sleep duration and daytime napping and IBD risk.

11.
Adv Sci (Weinh) ; : e2205069, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36354197

RESUMO

The sluggish ion-transport in electrodes and low utilization of active materials are critical limitations of organic cathodes, which lead to the slow reaction dynamics and low specific capacity. In this study, the hierarchical tube is constructed by iron-hexaazatrinaphthalene tricarboxylic acid coordination polymer (Fe-HATNTA), using HATNTA as the self-engaged template to coordinate with Fe2+ ions. This Fe-HATNTA tube with hierarchical porous structure ensures the sufficient contact between electrolyte and active materials, shortens the diffusion distance, and provides more favorable transport pathways for ions. When employed as the cathode for rechargeable Li-ion batteries, Fe-HATNTA delivers a high specific capacity (244 mAh g-1 at 50 mA g-1 , 91% of theoretical capacity), excellent rate capability (128 mAh g-1 at 9 A g-1 ), and a long-term cycle life (73.9% retention over 3000 cycles at 5 A g-1 ). Moreover, the Li+ ions storage and conduction mechanisms are further disclosed by the ex situ and in situ characterizations, kinetic analyses, and theoretical calculations. This work is expected to boost further enthusiasm for developing the hierarchical structured metal-organic coordination polymers with superb ionic storage and transport as high-performance organic cathodes.

12.
Genes (Basel) ; 13(11)2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36360247

RESUMO

BACKGROUND: Observational research has found a bidirectional relationship between major depressive disorder and gastroesophageal reflux disease; however, the causal association of this relationship is undetermined. AIMS: A bidirectional Mendelian randomization study was performed to explore the causal relationships between major depressive disorder and gastroesophageal reflux disease. METHODS: For the instrumental variables of major depressive disorder and gastroesophageal reflux disease, 31 and 24 single-nucleotide polymorphisms without linkage disequilibrium (r2 ≤ 0.001) were selected from relevant genome-wide association studies, respectively, at the genome-wide significance level (p ≤ 5 × 10-8). We sorted summary-level genetic data for major depressive disorder, gastroesophageal reflux disease, gastroesophageal reflux disease without esophagitis, and reflux esophagitis from meta-analysis study of genome-wide association studies involving 173,005 individuals (59,851 cases and 113,154 non-cases), 385,276 individuals (80,265 cases and 305,011 non-cases), 463,010 individuals (4360 cases and 458,650 non-cases), and 383,916 individuals (12,567 cases and 371,349 non-cases), respectively. RESULTS: Genetic liability to major depressive disorder was positively associated with gastroesophageal reflux disease and its subtypes. Per one-unit increase in log-transformed odds ratio of major depressive disorder, the odds ratio was 1.31 (95% confidence interval [CI], 1.19-1.43; p = 1.64 × 10-8) for gastroesophageal reflux disease, 1.51 (95% CI, 1.15-1.98; p = 0.003) for gastroesophageal reflux disease without esophagitis, and 1.21 (95% CI, 1.05-1.40; p = 0.010) for reflux esophagitis. Reverse-direction analysis suggested that genetic liability to gastroesophageal reflux disease was causally related to increasing risk of major depressive disorder. Per one-unit increase in log-transformed odds ratio of gastroesophageal reflux disease, the odds ratio of major depressive disorder was 1.28 (95% confidence interval, 1.11-1.47; p = 1.0 × 10-3). CONCLUSIONS: This Mendelian randomization study suggests a bidirectional causal relationship between major depressive disorder and gastroesophageal reflux disease.


Assuntos
Transtorno Depressivo Maior , Esofagite Péptica , Refluxo Gastroesofágico , Humanos , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/genética
13.
J Chromatogr A ; 1685: 463587, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36323102

RESUMO

The measurement of illicit drugs in wastewater is increasingly being adopted as a method for objective monitoring of population-level illicit drug use. This work describes the first small-volume direct-injection ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of 11 illicit drugs and metabolites in wastewater. The method required an injection volume of only 30 µL of wastewater sample, the limits of detection (LOD) ranged from 0.4 ng/L to 2 ng/L and the lower limits of quantitation (LLOQ) ranged from 1 ng/L to 5 ng/L. Application of the method to real wastewater samples collected from wastewater treatment plants revealed morphine in all samples, together with other illicit drugs (methamphetamine, codeine, ketamine, and nor-ketamine) in some samples. Small-volume direct injection showed great potential as an efficient method for the high-throughput determination of illicit drugs in wastewater.


Assuntos
Drogas Ilícitas , Ketamina , Poluentes Químicos da Água , Águas Residuárias/química , Cromatografia Líquida/métodos , Drogas Ilícitas/análise , Espectrometria de Massas em Tandem/métodos , Poluentes Químicos da Água/análise , Cromatografia Líquida de Alta Pressão/métodos
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(11): 1252-1256, 2022 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-36317213

RESUMO

OBJECTIVE: To analyze the clinical features and genetic basis for a Chinese pedigree affected with familial adenomatous polyposis (FAP). METHODS: Clinical information of the patient was collected. Genomic DNA was extracted from peripheral blood sample of the patient and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: The proband, a 33-year-old female, was found to have multiple adenomatous polyps in the intestine. WES revealed that she has harbored a heterozygous variant of the APC gene, namely c.1922dupA (p.N641fs*10), which was unreported previously. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic. CONCLUSION: The c.1922dupA (p.N641fs*10) variant of the APC gene probably underlay the FAP in this pedigree. Above finding has enabled genetic counseling for this family.


Assuntos
Proteína da Polipose Adenomatosa do Colo , Polipose Adenomatosa do Colo , Feminino , Humanos , Adulto , Linhagem , Proteína da Polipose Adenomatosa do Colo/genética , Mutação em Linhagem Germinativa , Polipose Adenomatosa do Colo/genética , China , Mutação
16.
Am J Clin Nutr ; 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36205540

RESUMO

BACKGROUND: Circulating levels of homocysteine and folate are inconsistently associated with the risk of non-alcoholic fatty liver disease (NAFLD) in observational studies. OBJECTIVE: We conducted a meta-analysis and Mendelian randomization (MR) analyses to examine these associations. METHODS: We performed a meta-analysis of observational studies identified from three databases to evaluate the associations of serum homocysteine and folate levels with NAFLD from inception to 07 April 2022. We conducted MR analyses to strengthen the causal inference in these associations. Independent single-nucleotide polymorphisms without linkage disequilibrium (r2 <0.01) and strongly (P < 5×10-8) associated with serum homocysteine (n=13) and folate (n=2) concentrations were selected as instrumental variables from two meta-analyses of genome-wide association studies (GWAS) of 44,147 and 37,645 individuals of European ancestry, respectively. Data on NAFLD were obtained from a GWAS of 8,434 NAFLD cases and 770,180 controls of European ancestry. We further included four liver enzymes as secondary outcomes from GWAS of 361,194 individuals with European descent. RESULTS: Twenty-two observational studies comprising 30,368 participants were included in the meta-analysis. There was a positive association between serum homocysteine and NAFLD risk (n=20, odds ratio [OR] 1.96, 95% confidence interval [CI] 1.57, 2.45) and an inverse association between serum folate and NAFLD risk (n=12, OR 0.75, 95% CI 0.58, 0.99). In MR analysis, the OR of NAFLD was 1.17 (95% CI 1.01, 1.36) and 0.75 (95% CI 0.55, 1.02) per 1-SD increment of genetically predicted circulating levels of homocysteine and folate, respectively. Each 1-SD increase of genetically predicted circulating homocysteine and folate conferred a change in alanine aminotransferase levels of 0.62 (95% CI 0.20, 1.04) and -0.84 (95% CI -0.14, -1.54) U/L, respectively. CONCLUSIONS: This study suggests a potential role of circulating homocysteine and possibly folate in NAFLD, which calls for future clinical exploration of the possibility of lowering homocysteine levels to prevent NAFLD. Systematic review registration: registered at https://www.crd.york.ac.uk/prospero/ as CRD42021296434.

17.
Nat Protoc ; 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36307543

RESUMO

Metal-organic frameworks (MOFs) demonstrate promise for a multitude of applications owing to their high porosity and surface area. However, the majority of conventional MOFs possess only micropores with very limited accessibility to substances larger than 2 nm-especially functional biomacromolecules like some proteins. It is challenging to create an appropriately large pore size while avoiding framework collapse in MOFs. Herein, we present the generation of mesopores in microporous MOFs through three facile and effective techniques, namely Soxhlet washing, linker hydrolysis and linker thermolysis. These postsynthetic elimination approaches have been applied in selected MOFs, including PCN-250, PCN-160 and UiO-66, and controllably generate MOFs with hierarchical pores and high stability. Our work demonstrates reproducible and straightforward methods resulting in hierarchically porous materials that possess the benefits of mesoporosity while borrowing the robustness of a micropore framework. All the procedures can be conducted reliably at a multigram scale and operation time less than 6 h, representing a significant effort in the field of MOF synthesis. These hierarchically porous MOFs show great promise in a wide range of applications as efficient adsorbents, catalysts and drug carriers.

18.
New Phytol ; 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36239093

RESUMO

Heterostyly, a plant sexual polymorphism controlled by the S-locus supergene, has evolved numerous times among angiosperm lineages and represents a classic example of convergent evolution in form and function. Determining whether underlying molecular convergence occurs could provide insights on constraints to floral evolution. Here, we investigated S-locus genes in distylous Gelsemium (Gelsemiaceae) to determine whether there is evidence of molecular convergence with unrelated distylous species. We used several approaches, including anatomical measurements of sex-organ development and transcriptome and whole-genome sequencing, to identify components of the S-locus supergene. We also performed evolutionary analysis with candidate S-locus genes and compared them with those reported in Primula and Turnera. The candidate S-locus supergene of Gelsemium contained four genes, of which three appear to have originated from gene duplication events within Gelsemiaceae. The style-length genes GeCYP in Gelsemium and CYP734A50 in Primula likely arose from duplication of the same gene, CYP734A1. Three out of four S-locus genes in Gelsemium elegans were hemizygous, as previously reported in Primula and Turnera. We provide genomic evidence on the genetic convergence of the supergene underlying distyly among distantly related angiosperm lineages and help to illuminate the genetic architecture involved in the evolution of heterostyly.

19.
Appl Opt ; 61(28): 8527-8532, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36256170

RESUMO

Bound states in the continuum (BICs) are perfectly confined resonances within the radiation continuum. The novel characteristics of single BICs have been studied in great detail in various wave systems, including electromagnetic waves, acoustic waves, water waves, and elastic waves in solids. In practice, the performance of BICs is limited by the finite size of the structure, while the combination of multiple BICs can further improve the localization of resonances. In this study, we experimentally demonstrate the combination of Fabry-Perot and symmetry-protected BICs at near infrared wavelengths by employing a compound photonic crystal system composed of a photonic crystal slab and a distributed Bragg reflector, resulting in an enhanced high quality factor.

20.
Elife ; 112022 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-36250974

RESUMO

Background: Epidemiological studies observed gender differences in COVID-19 outcomes, however, whether sex hormone plays a causal in COVID-19 risk remains unclear. This study aimed to examine associations of sex hormone, sex hormones-binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), and COVID-19 risk. Methods: Two-sample Mendelian randomization (TSMR) study was performed to explore the causal associations between testosterone, estrogen, SHBG, IGF-1, and the risk of COVID-19 (susceptibility, hospitalization, and severity) using genome-wide association study (GWAS) summary level data from the COVID-19 Host Genetics Initiative (N=1,348,701). Random-effects inverse variance weighted (IVW) MR approach was used as the primary MR method and the weighted median, MR-Egger, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test were conducted as sensitivity analyses. Results: Higher genetically predicted IGF-1 levels have nominally significant association with reduced risk of COVID-19 susceptibility and hospitalization. For one standard deviation increase in genetically predicted IGF-1 levels, the odds ratio was 0.77 (95% confidence interval [CI], 0.61-0.97, p=0.027) for COVID-19 susceptibility, 0.62 (95% CI: 0.25-0.51, p=0.018) for COVID-19 hospitalization, and 0.85 (95% CI: 0.52-1.38, p=0.513) for COVID-19 severity. There was no evidence that testosterone, estrogen, and SHBG are associated with the risk of COVID-19 susceptibility, hospitalization, and severity in either overall or sex-stratified TSMR analysis. Conclusions: Our study indicated that genetically predicted high IGF-1 levels were associated with decrease the risk of COVID-19 susceptibility and hospitalization, but these associations did not survive the Bonferroni correction of multiple testing. Further studies are needed to validate the findings and explore whether IGF-1 could be a potential intervention target to reduce COVID-19 risk. Funding: We acknowledge support from NSFC (LR22H260001), CRUK (C31250/A22804), SHLF (Hjärt-Lungfonden, 20210351), VR (Vetenskapsrådet, 2019-00977), and SCI (Cancerfonden).


Assuntos
COVID-19 , Estudo de Associação Genômica Ampla , COVID-19/epidemiologia , COVID-19/genética , Estrogênios , Hormônios Esteroides Gonadais , Hospitalização , Humanos , Fator de Crescimento Insulin-Like I/genética , Polimorfismo de Nucleotídeo Único , Testosterona
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