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1.
Mol Psychiatry ; 29(6): 1857-1868, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38336841

RESUMO

Antipsychotic-induced weight gain (AIWG) is a common side effect of antipsychotic medication and may contribute to diabetes and coronary heart disease. To expand the unclear genetic mechanism underlying AIWG, we conducted a two-stage genome-wide association study in Han Chinese patients with schizophrenia. The study included a discovery cohort of 1936 patients and a validation cohort of 534 patients, with an additional 630 multi-ancestry patients from the CATIE study for external validation. We applied Mendelian randomization (MR) analysis to investigate the relationship between AIWG and antipsychotic-induced lipid changes. Our results identified two novel genome-wide significant loci associated with AIWG: rs10422861 in PEPD (P = 1.373 × 10-9) and rs3824417 in PTPRD (P = 3.348 × 10-9) in Chinese Han samples. The association of rs10422861 was validated in the European samples. Fine-mapping and functional annotation revealed that PEPD and PTPRD are potentially causal genes for AIWG, with their proteins being prospective therapeutic targets. Colocalization analysis suggested that AIWG and type 2 diabetes (T2D) shared a causal variant in PEPD. Polygenic risk scores (PRSs) for AIWG and T2D significantly predicted AIWG in multi-ancestry samples. Furthermore, MR revealed a risky causal effect of genetically predicted changes in low-density lipoprotein cholesterol (P = 7.58 × 10-4) and triglycerides (P = 2.06 × 10-3) caused by acute-phase of antipsychotic treatment on AIWG, which had not been previously reported. Our model, incorporating antipsychotic-induced lipid changes, PRSs, and clinical predictors, significantly predicted BMI percentage change after 6-month antipsychotic treatment (AUC = 0.79, R2 = 0.332). Our results highlight that the mechanism of AIWG involves lipid pathway dysfunction and may share a genetic basis with T2D through PEPD. Overall, this study provides new insights into the pathogenesis of AIWG and contributes to personalized treatment of schizophrenia.


Assuntos
Antipsicóticos , Diabetes Mellitus Tipo 2 , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores , Esquizofrenia , Aumento de Peso , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antipsicóticos/efeitos adversos , China , Estudos de Coortes , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Aumento de Peso/efeitos dos fármacos , Aumento de Peso/genética , População Branca/genética , População do Leste Asiático/genética
2.
BMC Med ; 22(1): 146, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38561734

RESUMO

BACKGROUND: Childhoods in urban or rural environments may differentially affect the risk of neuropsychiatric disorders, possibly through memory processing and neural response to emotional stimuli. Genetic factors may not only influence individuals' choices of residence but also modulate how the living environment affects responses to episodic memory. METHODS: We investigated the effects of childhood urbanicity on episodic memory in 410 adults (discovery sample) and 72 adults (replication sample) with comparable socioeconomic statuses in Beijing, China, distinguishing between those with rural backgrounds (resided in rural areas before age 12 and relocated to urban areas at or after age 12) and urban backgrounds (resided in cities before age 12). We examined the effect of childhood urbanicity on brain function across encoding and retrieval sessions using an fMRI episodic memory paradigm involving the processing of neutral or aversive pictures. Moreover, genetic association analyses were conducted to understand the potential genetic underpinnings that might contribute to memory processing and neural mechanisms influenced by early-life urban or rural environments. RESULTS: Episodic memory retrieval accuracy for more difficult neutral stimuli was similar between those with urban and rural childhoods, whereas aversive stimuli elicited higher retrieval accuracy in the urban group (P = 0.023). For aversive stimuli, subjects with urban childhood had relatively decreased engagement of the striatum at encoding and decreased engagement of the hippocampus at retrieval. This more efficient striatal encoding of aversive stimuli in those with urban childhoods was associated with common variation in neurotrophic tyrosine kinase receptor type 2 (NTRK2) (right striatum: P = 1.58×10-6). These findings were confirmed in the replication sample. CONCLUSIONS: We suggest that this differential striatal processing of aversive stimuli observed in individuals with urban or rural childhoods may represent mechanisms by which childhood urbanicity may affect brain circuits, heightening behavioral responses to negative stressors associated with urban environments. NTRK2-associated neural processes in the striatum may play a role in these processes.


Assuntos
Memória Episódica , Adulto , Criança , Humanos , Mapeamento Encefálico , Emoções/fisiologia , Hipocampo , Imageamento por Ressonância Magnética , Receptor trkB
3.
BMC Med ; 22(1): 392, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39272182

RESUMO

BACKGROUND: Air pollution, a reversible environmental factor, was significantly associated with the cognitive domains that are impaired in major depressive disorder (MDD), notably processing speed. Limited evidence explores the interactive effect of air pollution and the genetic risk of depression on cognition. This cross-sectional study aims to extend the research by specifically examining how this interaction influences depression-related cognitive impairment and resting-state brain function. METHODS: Eligible participants were 497 healthy adult volunteers (48.7% males, mean age 24.5) living in Beijing for at least 1 year and exposed to relatively high air pollution from the local community controlling for socioeconomic and genomic. Six months' ambient air pollution exposures were assessed based on residential addresses using monthly averages of fine particulate matter with a diameter of less than or equal to 2.5 µm (PM2.5). A cross-sectional analysis was conducted using functional magnetic resonance imaging (fMRI) and cognitive performance assessments. The polygenic risk score (PRS) of MDD was used to estimate genetic susceptibility. RESULTS: Using a general linear model and partial least square regression, we observed a negative association between resting-state local connectivity in precuneus and PRS-by-PM2.5 interactive effect (PFWE = 0.028), indicating that PM2.5 exposure reduced the spontaneous activity in precuneus in individuals at high genetic risk for MDD. DNA methylation and gene expression of the SLC30A3 gene, responsible for maintaining zinc-glutamate homeostasis, was suggestively associated with this local connectivity. For the global functional connectivity, the polygenic risk for MDD augmented the neural impact of PM2.5 exposure, especially in the frontal-parietal and frontal-limbic regions of the default mode network (PFDR < 0.05). In those genetically predisposed to MDD, increased PM2.5 exposure positively correlated with resting-state functional connectivity between the left angular gyrus and left cuneus gyrus. This connectivity was negatively associated with processing speed. CONCLUSIONS: Our cross-sectional study suggests that air pollution may be associated with an increased likelihood of cognitive impairment in individuals genetically predisposed to depression, potentially through alterations in the resting-state function of the occipitoparietal and default mode network.


Assuntos
Poluição do Ar , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Estudos Transversais , Poluição do Ar/efeitos adversos , Adulto , Adulto Jovem , Predisposição Genética para Doença , Material Particulado/efeitos adversos , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/fisiopatologia , Lobo Parietal/fisiopatologia , Lobo Parietal/diagnóstico por imagem , Pequim , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/fisiopatologia , Velocidade de Processamento
4.
Small ; 20(7): e2305658, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37798674

RESUMO

Defect engineering is promising to tailor the physical properties of 2D semiconductors for function-oriented electronics and optoelectronics. Compared with the extensively studied 2D binary materials, the origin of defects and their influence on physical properties of 2D ternary semiconductors are not clarified. Here, the effect of defects on the electronic structure and optical properties of few-layer hexagonal Znln2 S4 is thoroughly studied via versatile spectroscopic tools in combination with theoretical calculations. It is demonstrated that the Zn-In antistructural defects induce the formation of a series of donor and acceptor energy levels and sulfur vacancies induce donor energy levels, leading to rich recombination paths for defect emission and extrinsic absorption. Impressively, the emission of donor-acceptor pair in Znln2 S4 can be significantly tailored by electrostatic gating due to efficient tunability of Fermi level (Ef ). Furthermore, the layer-dependent dipole orientation of defect emission in Znln2 S4 is directly revealed by back focal plane imagining, where it presents obviously in-plane dipole orientation within a dozen-layer thickness of Znln2 S4 . These unique features of defects in Znln2 S4 including extrinsic absorption, rich recombination paths, gate tunability, and in-plane dipole orientation are definitely a benefit to the advanced orientation-functional optoelectronic applications.

5.
Brief Bioinform ; 23(6)2022 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-36305457

RESUMO

With the development of research on the complex aetiology of many diseases, computational drug repositioning methodology has proven to be a shortcut to costly and inefficient traditional methods. Therefore, developing more promising computational methods is indispensable for finding new candidate diseases to treat with existing drugs. In this paper, a model integrating a new variant of message passing neural network and a novel-gated fusion mechanism called GLGMPNN is proposed for drug-disease association prediction. First, a light-gated message passing neural network (LGMPNN), including message passing, aggregation and updating, is proposed to separately extract multiple pieces of information from the similarity networks and the association network. Then, a gated fusion mechanism consisting of a forget gate and an output gate is applied to integrate the multiple pieces of information to extent. The forget gate calculated by the multiple embeddings is built to integrate the association information into the similarity information. Furthermore, the final node representations are controlled by the output gate, which fuses the topology information of the networks and the initial similarity information. Finally, a bilinear decoder is adopted to reconstruct an adjacency matrix for drug-disease associations. Evaluated by 10-fold cross-validations, GLGMPNN achieves excellent performance compared with the current models. The following studies show that our model can effectively discover novel drug-disease associations.


Assuntos
Biologia Computacional , Redes Neurais de Computação , Biologia Computacional/métodos , Reposicionamento de Medicamentos/métodos , Algoritmos
6.
Br J Psychiatry ; : 1-7, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39391920

RESUMO

BACKGROUND: Observational studies have shown a controversial relationship between dietary fat intake and Alzheimer's disease, and the causal effects are unclear. AIMS: To assess the causal effects of total fat, saturated fat and polyunsaturated fat (PUF) intakes on the risk of Alzheimer's disease. METHOD: A two-sample Mendelian randomisation analysis was performed using genome-wide association study summary statistics on different types of fat intake from UK Biobank (n = 51 413) and on late-onset Alzheimer's disease (LOAD; 4282 cases, n = 307 112) and all forms of Alzheimer's disease (6281 cases, n = 309 154) from the FinnGen consortium. In addition, a multivariable Mendelian randomisation (MVMR) analysis was conducted to estimate the effects independent of carbohydrate and protein intakes. RESULTS: Genetically predicted per standard deviation increase in the total fat and saturated fat intakes were associated with 44 and 38% higher risks of LOAD (total fat: odds ratio = 1.44, 95% CI 1.03-2.02; saturated fat: odds ratio = 1.38, 95% CI 1.002-1.90; P = 0.049). The associations remained significant in the MVMR analysis (total fat: odds ratio = 3.31, 95% CI 1.74-6.29; saturated fat: odds ratio = 2.04, 95% CI 1.16-3.59). Total fat and saturated fat intakes were associated with a higher risk of all forms of Alzheimer's disease in the MVMR analysis (total fat: odds ratio = 2.09, 95% CI 1.22-3.57; saturated fat: odds ratio = 1.60, 95% CI 1.01-2.52). The PUF intake was not associated with LOAD or all forms of Alzheimer's disease. CONCLUSIONS: This study indicated that total dietary fat intake, especially saturated fat, contributed to the risk of Alzheimer's disease, and the effects were independent of other nutrients. These findings informed prevention strategies and management for Alzheimer's disease directly towards reducing dietary saturated fat intake.

7.
Cereb Cortex ; 33(3): 881-894, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-35254408

RESUMO

The approximate number system (ANS) is vital for survival and reproduction in animals and is crucial for constructing abstract mathematical abilities in humans. Most previous neuroimaging studies focused on identifying discrete brain regions responsible for the ANS and characterizing their functions in numerosity perception. However, a neuromarker to characterize an individual's ANS acuity is lacking, especially one based on whole-brain functional connectivity (FC). Here, based on the resting-state functional magnetic resonance imaging (rs-fMRI) data obtained from a large sample, we identified a distributed brain network (i.e. a numerosity network) using a connectome-based predictive modeling (CPM) analysis. The summed FC strength within the numerosity network reliably predicted individual differences in ANS acuity regarding behavior, as measured using a nonsymbolic number-comparison task. Furthermore, in an independent dataset of the Human Connectome Project (HCP), we found that the summed FC strength within the numerosity network also specifically predicted individual differences in arithmetic skills, but not domain-general cognitive abilities. Therefore, our findings revealed that the identified numerosity network could serve as an applicable neuroimaging-based biomarker of nonverbal number acuity and arithmetic skills.


Assuntos
Conectoma , Animais , Humanos , Conectoma/métodos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Cognição , Neuroimagem
8.
Cereb Cortex ; 33(6): 2761-2773, 2023 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35699600

RESUMO

Attention deficit hyperactivity disorder (ADHD) is a chronic neuropsychiatric disease that can markedly impair educational, social, and occupational function throughout life. Behavioral deficits may provide clues to the underlying neurological impairments. Children with ADHD exhibit a larger attentional blink (AB) deficit in rapid serial visual presentation (RSVP) tasks than typically developing children, so we examined whether brain connectivity in the neural network associated with AB can predict ADHD symptoms and thus serve as potential biomarkers of the underlying neuropathology. We first employed a connectome-based predictive model analysis of adult resting-state functional magnetic resonance imaging data to identify a distributed brain network for AB. The summed functional connectivity (FC) strength within the AB network reliably predicted individual differences in AB magnitude measured by a classical dual-target RSVP task. Furthermore, the summed FC strength within the AB network predicted individual differences in ADHD Rating Scale scores from an independent dataset of pediatric patients. Our findings suggest that the individual AB network could serve as an applicable neuroimaging-based biomarker of AB deficit and ADHD symptoms.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Intermitência na Atenção Visual , Conectoma , Adulto , Humanos , Criança , Imageamento por Ressonância Magnética/métodos , Encéfalo , Conectoma/métodos , Vias Neurais/diagnóstico por imagem
9.
Cereb Cortex ; 33(7): 3683-3700, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36005854

RESUMO

Difficulties in parsing the multiaspect heterogeneity of schizophrenia (SCZ) based on current nosology highlight the need to subtype SCZ using objective biomarkers. Here, utilizing a large-scale multisite SCZ dataset, we identified and validated 2 neuroanatomical subtypes with individual-level abnormal patterns of the tensor-based morphometric measurement. Remarkably, compared with subtype 1, which showed moderate deficits of some subcortical nuclei and an enlarged striatum and cerebellum, subtype 2, which showed cerebellar atrophy and more severe subcortical nuclei atrophy, had a higher subscale score of negative symptoms, which is considered to be a core aspect of SCZ and is associated with functional outcome. Moreover, with the neuroimaging-clinic association analysis, we explored the detailed relationship between the heterogeneity of clinical symptoms and the heterogeneous abnormal neuroanatomical patterns with respect to the 2 subtypes. And the neuroimaging-transcription association analysis highlighted several potential heterogeneous biological factors that may underlie the subtypes. Our work provided an effective framework for investigating the heterogeneity of SCZ from multilevel aspects and may provide new insights for precision psychiatry.


Assuntos
Imageamento por Ressonância Magnética , Esquizofrenia , Humanos , Imageamento por Ressonância Magnética/métodos , Esquizofrenia/diagnóstico por imagem , Neuroimagem , Cerebelo/diagnóstico por imagem , Atrofia
10.
BMC Psychiatry ; 24(1): 69, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263034

RESUMO

BACKGROUND: Alterations in surface area (SA) in specific regions of the cortex have been reported in many individuals with autism spectrum disorder (ASD), however, the genetic background between ASD and SA is still unclear. This study estimated the genetic correlation and causal effect of ASD and cortical SA. METHODS: Summarized data of genome-wide association studies (GWAS) were separately downloaded from the Psychiatric Genomics Consortium (18,381 cases of ASD, and 27,969 controls) and the Enhancing Neuroimaging Genetics through Meta-Analysis Consortium (33,992 participants of Europeans). We used Linkage disequilibrium score regression (LDSC) and Heritability Estimation from Summary Statistics (HESS) to calculate the heritability of each trait. As for the genetic correlation between ASD and SA, LDSC was used for global correlation and HESS was used to examine the local genetic covariance further. We used three Mendelian randomization (MR) methods, Inverse-variance weighted, MR-Egger, and weighted median to estimate the causal relationship. RESULTS: LDSC observed a nominal significant genetic correlation (rg = 0.1229, P-value = 0.0346) between ASD and SA of the rostral anterior cingulate gyrus whereas analysis through HESS did not reveal any significant loci having genetic covariance. Based on MR results, statistically meaningful estimations were found in the following areas, postcentral cortex (ß (SE) = 21.82 (7.84) mm, 95% CI: 6.46 to 37.19 mm, PIVW = 5.38 × 10- 3, PFDR = 3.09 × 10- 2), posterior cingulate gyrus (ß (SE) = 6.23 (2.69) mm, 95% CI: 0.96 to 11.49 mm, PIVW = 2.05 × 10- 2, PFDR = 4.26 × 10- 2), supramarginal gyrus (ß (SE) = 19.25 (8.43) mm, 95% CI: 29.29 to 35.77 mm, PIVW = 2.24 × 10- 2, PFDR = 4.31 × 10- 2). CONCLUSION: Our results provided genetic evidence to support the opinion that individuals with ASD tend to develop differences in cortical SA of special areas. The findings contributed to understanding the genetic relationship between ASD and cortical SA.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Giro do Cíngulo
11.
Ann Noninvasive Electrocardiol ; 29(4): e13130, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38932572

RESUMO

OBJECTIVE: To explore the influence of nutritional status on adverse clinical events in elderly patients with nonvalvular atrial fibrillation. METHODS: This retrospective observational cohort study included 196 patients, 75-102-years-old, with nonvalvular atrial fibrillation, hospitalized in our hospital. The nutritional status was assessed using Mini-Nutritional Assessment-Short Form (MNA-SF). Patients with MNA-SF scores of 0-11 and 12-14 were included in the malnutrition and nonmalnutrition groups, respectively. RESULTS: The average age of the malnutrition group was higher than that of the nonmalnutrition group, and the levels of body mass index (BMI), hemoglobin (HGB), and albumin (ALB) were significantly lower than those of the nonmalnutrition group, with statistical significance (p < .05). The incidence of all-cause death in the malnutrition group was higher than that in the nonmalnutrition group (p = .007). Kaplan-Meier curve indicated that malnutrition patients have a higher risk of all-cause death (log-rank test, p = .001) and major bleeding events (p = .017). Multivariate Cox proportional hazard regression analysis corrected for confounders showed that malnutrition was an independent risk factor of all-cause death (HR = 1.780, 95%CI:1.039-3.050, p = .036). The malnutrition group had a significantly high incidence of major bleeding than the nonmalnutrition group (p = .026), and there was no significant difference in the proportion of anticoagulation therapy (p = .082) and the incidence of ischemic stroke/systemic embolism (p = .310) between the two groups. CONCLUSIONS: Malnutrition is an independent risk factor of all-cause death in elderly patients with atrial fibrillation. The incidence of major bleeding in malnourished elderly patients with atrial fibrillation is high, and the benefit of anticoagulation therapy is not obvious.


Assuntos
Fibrilação Atrial , Desnutrição , Estado Nutricional , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Estudos Retrospectivos , Feminino , Masculino , Idoso , Idoso de 80 Anos ou mais , Desnutrição/complicações , Estudos de Coortes , Fatores de Risco , Avaliação Nutricional , Avaliação Geriátrica/métodos , Avaliação Geriátrica/estatística & dados numéricos
12.
Proc Natl Acad Sci U S A ; 118(46)2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34750260

RESUMO

Air pollution is a reversible cause of significant global mortality and morbidity. Epidemiological evidence suggests associations between air pollution exposure and impaired cognition and increased risk for major depressive disorders. However, the neural bases of these associations have been unclear. Here, in healthy human subjects exposed to relatively high air pollution and controlling for socioeconomic, genomic, and other confounders, we examine across multiple levels of brain network function the extent to which particulate matter (PM2.5) exposure influences putative genetic risk mechanisms associated with depression. Increased ambient PM2.5 exposure was associated with poorer reasoning and problem solving and higher-trait anxiety/depression. Working memory and stress-related information transfer (effective connectivity) across cortical and subcortical brain networks were influenced by PM2.5 exposure to differing extents depending on the polygenic risk for depression in gene-by-environment interactions. Effective connectivity patterns from individuals with higher polygenic risk for depression and higher exposures with PM2.5, but not from those with lower genetic risk or lower exposures, correlated spatially with the coexpression of depression-associated genes across corresponding brain regions in the Allen Brain Atlas. These converging data suggest that PM2.5 exposure affects brain network functions implicated in the genetic mechanisms of depression.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Encéfalo/efeitos dos fármacos , Depressão/induzido quimicamente , Adulto , Ansiedade/induzido quimicamente , Exposição Ambiental/efeitos adversos , Humanos , Material Particulado/efeitos adversos , Fatores de Risco
13.
Ecotoxicol Environ Saf ; 278: 116432, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38728947

RESUMO

Cadmium (Cd) pollution is a serious global environmental problem, which requires a global concern and practical solutions. Microbial remediation has received widespread attention owing to advantages, such as environmental friendliness and soil amelioration. However, Cd toxicity also severely deteriorates the remediation performance of functional microorganisms. Analyzing the mechanism of bacterial resistance to Cd stress will be beneficial for the application of Cd remediation. In this study, the bacteria strain, up to 1400 mg/L Cd resistance, was employed and identified as Proteus mirabilis Ch8 (Ch8) through whole genome sequence analyses. The results indicated that the multiple pathways of immobilizing and detoxifying Cd maintained the growth of Ch8 under Cd stress, which also possessed high Cd extracellular adsorption. Firstly, the changes in surface morphology and functional groups of Ch8 cells were observed under different Cd conditions through SEM-EDS and FTIR analyses. Under 100 mg/L Cd, Ch8 cells exhibited aggregation and less flagella; the Cd biosorption of Ch8 was predominately by secreting exopolysaccharides (EPS) and no significant change of functional groups. Under 500 mg/L Cd, Ch8 were present irregular polymers on the cell surface, some cells with wrapping around; the Cd biosorption capacity exhibited outstanding effects (38.80 mg/g), which was mainly immobilizing Cd by secreting and interacting with EPS. Then, Ch8 also significantly enhanced the antioxidant enzyme activity and the antioxidant substance content under different Cd conditions. The activities of SOD and CAT, GSH content of Ch8 under 500 mg/L Cd were significantly increased by 245.47%, 179.52%, and 241.81%, compared to normal condition. Additionally, Ch8 significantly induced the expression of Acr A and Tol C (the resistance-nodulation-division (RND) efflux pump), and some antioxidant genes (SodB, SodC, and Tpx) to reduce Cd damage. In particular, the markedly higher expression levels of SodB under Cd stress. The mechanism of Ch8 lays a foundation for its application in solving soil remediation.


Assuntos
Cádmio , Proteus mirabilis , Poluentes do Solo , Cádmio/toxicidade , Poluentes do Solo/toxicidade , Biodegradação Ambiental
14.
J Transl Med ; 21(1): 560, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37605207

RESUMO

BACKGROUND: Phosphodiesterases (PDEs) have been associated with psychiatric disorders in observational studies; however, the causality of associations remains unestablished. METHODS: Specifically, cyclic nucleotide PDEs were collected from genome-wide association studies (GWASs), including PDEs obtained by hydrolyzing both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) (PDE1A, PDE2A, and PDE3A), specific to cGMP (PDE5A, PDE6D, and PDE9A) and cAMP (PDE4D and PDE7A). We performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the relationship between PDEs and nine psychiatric disorders. The inverse-variance-weighted (IVW) method, MR-Egger, and weighted median were used to estimate causal effects. The Cochran's Q test, MR-Egger intercept test, MR Steiger test, leave-one-out analyses, funnel plot, and MR pleiotropy residual sum and outlier (MR-PRESSO) were used for sensitivity analyses. RESULTS: The PDEs specific to cAMP were associated with higher-odds psychiatric disorders. For example, PDE4D and schizophrenia (SCZ) (odds ratios (OR) = 1.0531, PIVW = 0.0414), as well as major depressive disorder (MDD) (OR = 1.0329, PIVW = 0.0011). Similarly, PDE7A was associated with higher odds of attention-deficit/hyperactivity disorder (ADHD) (OR = 1.0861, PIVW = 0.0038). Exploring specific PDE subtypes and increase intracellular cAMP levels can inform the development of targeted interventions. We also observed PDEs (which hydrolyzes both cAMP and cGMP) was associated with psychiatric disorders [OR of PDE1A was 1.0836 for autism spectrum disorder; OR of PDE2A was 0.8968 for Tourette syndrome (TS) and 0.9449 for SCZ; and OR of PDE3A was 0.9796 for MDD; P < 0.05]. Furthermore, psychiatric disorders also had some causal effects on PDEs [obsessive-compulsive disorder on increased PDE6D and decreased PDE2A and PDE4D; anorexia nervosa on decreased PDE9A]. The results of MR were found to be robust using multiple sensitivity analysis. CONCLUSIONS: In this study, potential causal relationships between plasma PDE proteins and psychiatric disorders were established. Exploring other PDE subtypes not included in this study could provide a more comprehensive understanding of the role of PDEs in psychiatric disorders. The development of specific medications targeting PDE subtypes may be a promising therapeutic approach for treating psychiatric disorders.


Assuntos
Transtorno do Espectro Autista , Transtorno Depressivo Maior , Transtornos Mentais , Humanos , Transtorno Depressivo Maior/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Transtornos Mentais/genética , 3',5'-AMP Cíclico Fosfodiesterases
15.
Rev Cardiovasc Med ; 24(1): 2, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39076873

RESUMO

Background: Estimated glucose disposal rate (eGDR) is highly associated with all-cause mortality in type 2 diabetes mellitus (T2DM) cases undergoing coronary artery bypass grafting (CABG). Nevertheless, eGDR's prognostic value in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) following percutaneous coronary intervention (PCI) remains unknown. Methods: The population of this retrospective cohort study comprised NSTE-ACS patients administered PCI in Beijing Anzhen Hospital between January and December 2015. The primary endpoint was major adverse cardiac and cerebral events (MACCEs). eGDR was calculated based on waist circumference (WC) ( eGDR WC ) or body mass index (BMI) ( eGDR BMI ). Results: Totally 2308 participants were included, and the mean follow-up time was 41.06 months. The incidence of MACCEs was markedly increased with decreasing eGDR. Multivariable analysis showed hazard ratios (HRs) for eGDR WC and eGDR BMI of 1.152 (95% confidence interval [CI] 1.088-1.219; p < 0.001) and 0.998 (95% CI 0.936-1.064; p = 0.957), respectively. Addition of eGDR WC to a model that included currently recognized cardiovascular risk factors markedly enhanced its predictive power compared with the baseline model (Harrell's C-index, eGDR WC versus Baseline model, 0.778 versus 0.768, p = 0.003; continuous net reclassification improvement (continuous-NRI) of 0.125, p < 0.001; integrated discrimination improvement (IDI) of 0.016, p < 0.001). Conclusions: Low eGDR independently predicts low survival of NSTE-ACS cases who underwent PCI.

16.
Mol Biol Rep ; 50(12): 10301-10313, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37971570

RESUMO

BACKGROUND: Brachyura crab is the largest branch of Decapoda crustacean. Phylogenetic relationships within Brachyura remain controversial to be investigated. The mitochondrial genome (mitogenome) is an important molecular marker for studying the phylogenetic relationships of Brachyura. METHODS AND RESULTS: To understand the phylogeny of Brachyura, the three complete mitogenomes from Charybdis annulata, Leptodius exaratus, and Spider crab were sequenced and annotated. Their full length was 15,747, 15,716, and 16,608 bp long, respectively. The first two crabs both contained 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes and a control region. However, Spider crab contained 13 PCGs, two rRNA genes, 25 tRNA genes and a control region. The mitogenomes of each of the three crabs exhibited high AT content (67.8%, 69.1%, and 70.8%), with negative AT skews (-0.014, - 0.028, and - 0.017) and GC skews (-0.269, - 0.286, and - 0.341). The gene order of C. annulata was identical to the ancestor of Brachyura. Compared with the ancestor of Brachyura, L. exaratus exhibited the gene rearrangements of Val (V)-rrnS-control region, and Spider crab had the four copies of Lys (K). Phylogenetic analyses indicated that C. annulata belonged to Portunidae family, Portunoidea superfamilies, L. exaratus belonged to Xanthidae family, Xanthoidea superfamilies, and Spider crab belonged to Mithracidae family, Majoidea superfamilies. Phylogenetic analyses showed that the two species (Somanniathelphusa boyangensis and Huananpotamon lichuanense) belonging to the Potamoidea were sister groups to the Thoracotremata, thus supporting the conclusion that Heterotremata is polyphyletic. CONCLUSION: The results of this study enriched the crab mitogenome database and enabled us to better understand the phylogenetic relationships of Brachyura.


Assuntos
Braquiúros , Genoma Mitocondrial , Animais , Filogenia , Genoma Mitocondrial/genética , Braquiúros/genética , Rearranjo Gênico/genética , RNA de Transferência/genética
17.
BMC Psychiatry ; 23(1): 598, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37592210

RESUMO

Urbanization is a trend lasting for more than one century worldwide. Four hundred ninety male and female adult Chinese Han participants with different urban and rural childhoods were included in this study. Early-life urban environment was found benefit for total grey matter volume (GMV), dorsolateral prefrontal cortex (DLPFC) GMV, temporal pole (TP) GMV and cognition function, and negatively correlated with medial prefrontal cortex (MPFC) GMV. Regression analysis showed that maternal education was a protective factor for total and DLPFC GMVs, while having siblings was better for MPFC GMV. Total, DLPFC and TP GMVs acts mediation effects between childhood urbanicity and different cognitive domains. These findings may suggest some pros and cons on brain structure associated with childhood urbanicity and related environmental factors.


Assuntos
Encéfalo , Cognição , Criança , Adulto , Feminino , Masculino , Humanos , Encéfalo/diagnóstico por imagem , Substância Cinzenta , Córtex Pré-Frontal , Córtex Cerebral
18.
BMC Womens Health ; 23(1): 579, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37940891

RESUMO

BACKGROUND: To investigate the prevalence of common sexually transmitted infections (STIs) and the association of STI/human papillomavirus co-infection in young and middle-aged women with previous abnormal cervical findings referred for colposcopy. METHODS: 719 cervical-swab cytobrush specimens were obtained from women aged ≤ 50 years who were referred for colposcopy at Peking University First Hospital due to previous abnormal cervical findings. HPV 21 typing and a panel of pathogenic STIs were tested for using the 21 HPV GenoArray Diagnostic Kit (HBGA-21PKG; HybriBio, Ltd., Chaozhou, China) and a nucleic acid STI detection kit (HybriBio Ltd. Guangzhou, China), after which colposcopy with multipoint positioning biopsy was performed. RESULTS: The overall prevalence of STIs among HPV positive women with previous abnormal cervical cancer screening results was 63.7% (458/719), with Ureaplasma parvum serovar 3, Ureaplasma parvum serovar 6 and herpes simplex virus type 2 having significantly higher prevalence among high-risk HPV positive patients (19.3%, Χ2 = 5.725, P = 0.018; 21.5%, Χ2 = 4.439, P = 0.035; 5.7%, Χ2 = 4.184, P = 0.048). Among patients positive for the high-risk human papillomavirus, the prevalence of Neisseria gonorrhoeae infection in human papillomavirus 16/18 positive patients was significantly higher than that in other patients (2.5%, Χ2 = 4.675; P = 0.043). Histopathologically, Chlamydia trachomatis infection was more frequently detected in lower than or equal to low-grade squamous intraepithelial lesion infection status (13.0%, Χ2 = 3.368; P = 0.041). CONCLUSIONS: The high prevalence of HPV coinfection with other sexually transmitted pathogens, particularly Ureaplasma parvum serovar 3, Ureaplasma parvum serovar 6, and herpes simplex virus type 2, calls for routine STI screening and effective STI prevention and management in patients with abnormal cervical cancer screening results.


Assuntos
Colposcopia , Infecções por Papillomavirus , Infecções Sexualmente Transmissíveis , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Detecção Precoce de Câncer , Papillomavirus Humano , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/diagnóstico , Ureaplasma , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia
19.
BMC Anesthesiol ; 23(1): 21, 2023 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635627

RESUMO

BACKGROUND: Transversus abdominis plane (TAP) block can provide effective analgesia for abdominal surgery. However, it was questionable whether TAP had additional effect in the context of multimodal analgesia (MMA). Therefore, this study aimed to assess the additional analgesic effect of preoperative TAP block when added to MMA protocol in open gynecological surgery. METHODS: In this prospective, randomized-controlled trial, 64 patients scheduled for open gynecological surgery were randomized to receive preoperative TAP block (Study group, n = 32) or placebo (Control group, n = 32) in addition to MMA protocol comprising dexamethasone, acetaminophen, flurbiprofen and celecoxib, and rescued morphine analgesia. The primary outcome was rescued morphine within 24 h after surgery. Secondary outcomes included pain scores, adverse effects, quality of recovery measured by 40-item quality of recovery questionnaire score (QoR-40) at 24 h, and quality of life measured with short-form health survey (SF - 36) on postoperative day (POD) 30. RESULTS: The Study group had less rescued morphine than the control group within 24 h [5 (2-9) vs. 8.5 (5-12.8) mg, P = 0.013]. The Study group had lower pain scores at 1 h [3 (2-4) vs. 4 (3-5), P = 0.007], 2 h [3 (2-4) vs. 3.5 (3-5), P = 0.010] and 6 h [3 (2-3) vs. 3 (2.3-4), P = 0.028], lower incidence of nausea at 48 h (25.8% vs. 50%, P = 0.039), and higher satisfaction score [10 (10-10) vs. 10 (8-10), P = 0.041]. The SF-36 bodily pain score on POD 30 was higher in the Study group (59 ± 13 vs. 49 ± 16, P = 0.023). CONCLUSIONS: Preoperative TAP block had additional analgesic effect for open gynecological surgery when used as part of multimodal analgesia. Rescued morphine within 24 h was significantly reduced and the SF-36 bodily pain dimension at 30 days after surgery was significantly improved. TRIAL REGISTRATION: www.chictr.org.cn (ChiCTR2000040343, on Nov 28 2020).


Assuntos
Analgesia , Analgésicos Opioides , Feminino , Humanos , Estudos Prospectivos , Qualidade de Vida , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/induzido quimicamente , Músculos Abdominais , Analgesia/métodos , Morfina , Procedimentos Cirúrgicos em Ginecologia , Anestésicos Locais , Método Duplo-Cego
20.
Psychiatry Clin Neurosci ; 77(9): 486-496, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37210704

RESUMO

AIM: This study identified discrepant therapeutic outcomes of antipsychotics. METHODS: A total of 5191 patients with schizophrenia were enrolled, 3030 as discovery cohort, 1395 as validation cohort, and 766 as multi-ancestry validation cohort. Therapeutic Outcomes Wide Association Scan was conducted. Types of antipsychotics (one antipsychotic vs other antipsychotics) were dependent variables, therapeutic outcomes including efficacy and safety were independent variables. RESULTS: In discovery cohort, olanzapine related to higher risk of weight gain (AIWG, OR: 2.21-2.86), liver dysfunction (OR: 1.75-2.33), sedation (OR: 1.76-2.86), increased lipid level (OR: 2.04-2.12), and lower risk of extrapyramidal syndrome (EPS, OR: 0.14-0.46); risperidone related to higher risk of hyperprolactinemia (OR: 12.45-20.53); quetiapine related to higher risk of sedation (OR = 1.73), palpitation (OR = 2.87), increased lipid level (OR = 1.69), lower risk of hyperprolactinemia (OR: 0.09-0.11), and EPS (OR: 0.15-0.44); aripiprazole related to lower risk of hyperprolactinemia (OR: 0.09-0.14), AIWG (OR = 0.44), sedation (OR: 0.33-0.47), and QTc prolongation (ß = -2.17); ziprasidone related to higher risk of increased QT interval (ß range: 3.11-3.22), nausea (OR: 3.22-3.91), lower risk of AIWG (OR: 0.27-0.46), liver dysfunction (OR: 0.41-0.38), and increased lipid level (OR: 0.41-0.55); haloperidol related to higher risk of EPS (OR: 2.64-6.29), hyperprolactinemia (OR: 5.45-9.44), and increased salivation (OR: 3.50-3.68). Perphenazine related to higher risk of EPS (OR: 1.89-2.54). Higher risk of liver dysfunction in olanzapine and lower risk of hyperprolactinemia in aripiprazole were confirmed in validation cohort, and higher risk of AIWG in olanzapine and hyperprolactinemia in risperidone were confirmed in multi-ancestry validation cohort. CONCLUSION: Future precision medicine should focus on personalized side-effects.


Assuntos
Antipsicóticos , Hiperprolactinemia , Esquizofrenia , Humanos , Antipsicóticos/efeitos adversos , Aripiprazol/efeitos adversos , Hiperprolactinemia/induzido quimicamente , Lipídeos , Olanzapina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Risperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico , Resultado do Tratamento
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