Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.722
Filtrar
1.
Nanotechnology ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38772350

RESUMO

Single-molecule detection technology is a technique capable of detecting molecules at the single-molecule level, characterized by high sensitivity, high resolution, and high specificity. Nanopore technology, as one of the single-molecule detection tools, is widely used to study the structure and function of biomolecules. In this study, we constructed a small-sized nanopore with a pore-cavity-pore structure, which can achieve a higher reverse capture rate. Through simulation, we investigated the electrical potential distribution of the nanopore with a pore-cavity-pore structure and analyzed the influence of pore size on the potential distribution. Accordingly, different pore sizes can be designed based on the radius of gyration of the target biomolecules, restricting their escape paths inside the chamber. In the future, nanopores with a pore-cavity-pore structure based on two-dimensional (2D) thin film materials are expected to be applied in single-molecule detection research, which provides new insights for various detection needs.

3.
Inflammation ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773023

RESUMO

Cancer therapy has entered a new era with the use of programmed cell death protein 1 (PD-1) immune checkpoint inhibitors. When combined with thoracic radiotherapy, it demonstrates synergistic anti-tumor effects and potentially worsens radiation-induced myocardial fibrosis (RIMF). RIMF is the final stage of radiation-induced heart disease (RIHD) and a potentially fatal clinical complication of chest radiotherapy. It is characterized by decreased ventricular elasticity and distensibility, which can result in decreased ejection fraction, heart failure, and even sudden cardiac death. Pyroptosis, a type of programmed cell death, is mediated by members of the gasdermin (GSDM) family and has been associated with numerous cardiac disorders. The effect of pyroptosis on myocardial fibrosis caused by a combination of radiotherapy and PD-1 inhibitors remains uncertain. In this study, a 6MV X-ray of 20 Gy for local heart irradiation was used in the RIHD mouse model. We noticed that PD-1 inhibitors aggravated radiation-induced cardiac dysfunction and RIMF, concurrently enhancing the presence of CD8+ T lymphocytes in the cardiac tissue. Additionally, our findings indicated that the combination of PD-1 inhibitor and thoracic radiation can stimulate caspase-1 to cleave GSDMD, thereby regulating pyroptosis and liberating interleukin-8 (IL-18). In the myocardium of mice, the manifestation of pyroptosis mediated by GSDMD is accompanied by the buildup of proteins associated with fibrosis, such as collagen I, transforming growth factor ß1 (TGF-ß1), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor α (TNF-α). Moreover, it was discovered that TFG-ß1 induced the phosphorylation of Smad2/Smad3 when the cardiac underwent PD-1 inhibitor in conjunction with thoracic irradiation (IR). The findings of this research indicate that PD-1 inhibitor worsen RIMF in mice by triggering GSDMD-induced pyroptosis and influencing the TGF-ß1/Smads pathway. While using the caspase-1 inhibitor Z-YVAD-FMK, RIMF can be alleviated. Blocking GSDMD may be a viable strategy for managing myocardial fibrosis caused by the combination of PD-1 inhibitors and radiotherapy.

6.
Nat Biotechnol ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724668

RESUMO

Single-cell chromatin accessibility sequencing (scATAC-seq) reconstructs developmental trajectory by phenotypic similarity. However, inferring the exact developmental trajectory is challenging. Previous studies showed age-associated DNA methylation (DNAm) changes in specific genomic regions, termed clock-like differential methylation loci (ClockDML). Age-associated DNAm could either result from or result in chromatin accessibility changes at ClockDML. As cells undergo mitosis, the heterogeneity of chromatin accessibility on clock-like loci is reduced, providing a measure of mitotic age. In this study, we developed a method, called EpiTrace, that counts the fraction of opened clock-like loci from scATAC-seq data to determine cell age and perform lineage tracing in various cell lineages and animal species. It shows concordance with known developmental hierarchies, correlates well with DNAm-based clocks and is complementary with mutation-based lineage tracing, RNA velocity and stemness predictions. Applying EpiTrace to scATAC-seq data reveals biological insights with clinically relevant implications, ranging from hematopoiesis, organ development, tumor biology and immunity to cortical gyrification.

7.
Front Endocrinol (Lausanne) ; 15: 1362085, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38752174

RESUMO

Background: Previous studies have identified several genetic and environmental risk factors for chronic kidney disease (CKD). However, little is known about the relationship between serum metals and CKD risk. Methods: We investigated associations between serum metals levels and CKD risk among 100 medical examiners and 443 CKD patients in the medical center of the First Hospital Affiliated to China Medical University. Serum metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). We analyzed factors influencing CKD, including abnormalities in Creatine and Cystatin C, using univariate and multiple analysis such as Lasso and Logistic regression. Metal levels among CKD patients at different stages were also explored. The study utilized machine learning and Bayesian Kernel Machine Regression (BKMR) to assess associations and predict CKD risk based on serum metals. A chained mediation model was applied to investigate how interventions with different heavy metals influence renal function indicators (creatinine and cystatin C) and their impact on diagnosing and treating renal impairment. Results: Serum potassium (K), sodium (Na), and calcium (Ca) showed positive trends with CKD, while selenium (Se) and molybdenum (Mo) showed negative trends. Metal mixtures had a significant negative effect on CKD when concentrations were all from 30th to 45th percentiles compared to the median, but the opposite was observed for the 55th to 60th percentiles. For example, a change in serum K concentration from the 25th to the 75th percentile was associated with a significant increase in CKD risk of 5.15(1.77,8.53), 13.62(8.91,18.33) and 31.81(14.03,49.58) when other metals were fixed at the 25th, 50th and 75th percentiles, respectively. Conclusions: Cumulative metal exposures, especially double-exposure to serum K and Se may impact CKD risk. Machine learning methods validated the external relevance of the metal factors. Our study highlights the importance of employing diverse methodologies to evaluate health effects of metal mixtures.


Assuntos
Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/induzido quimicamente , Feminino , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Adulto , Selênio/sangue , Fatores de Risco , China/epidemiologia , Metais Pesados/sangue , Metais Pesados/efeitos adversos , Idoso , Exposição Ambiental/efeitos adversos , Metais/sangue , Metais/efeitos adversos , Aprendizado de Máquina , Cistatina C/sangue , Teorema de Bayes , Potássio/sangue
8.
Front Vet Sci ; 11: 1353439, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737459

RESUMO

Porcine circoviruses disease (PCVD), caused by porcine circovirus (PCVs), is an important swine disease characterized by porcine dermatitis, nephrotic syndrome and reproductive disorders in sows. However, diseases caused by PCV2, PCV3, or PCV4 are difficult to distinguish, so a simple, rapid, accurate and high-throughput diagnostic and identification method is urgently needed to differentiate these three types. In this study, specific primers and probes were designed based on the conserved region sequences of the Rep gene of PCV2, and the Cap gene of PCV3 and PCV4. A multiplex qPCR assay was developed and optimized that the limit of detection concentration could reach as low as 3.8 copies/µL, with all correlation coefficients (R2) exceeding 0.999. Furthermore, the method showed no cross-reaction with other crucial porcine viral pathogens, and both intra-repeatability and inter-reproducibility coefficients of variation were below 2%. The assay was applied to the detection of 738 pig samples collected from 2020 to 2021 in Guangdong Province, China. This revealed positive infection rates of 65.18% for PCV2, 29.27% for PCV3, and 0% for PCV4, with a PCV2/PCV3 co-infection rate of 23.17%. Subsequently, complete genome sequences of 17 PCV2 and 4 PCV3 strains were obtained from the above positive samples and pre-preserved positive circovirus samples. Nucleotide sequence analysis revealed that the 17 PCV2 strains shared 96.7-100% complete nucleotide identity, with 6 strains being PCV2b and 11 strains being PCV2d; the 4 PCV3 strains shared 98.9-99.4% complete nucleotide identity, with 2 strains being PCV3a-1 and 2 strains being PCV3b. This research provides a reliable tool for rapid PCVs identification and detection. Molecular epidemiological investigation of PCVs in pigs in Guangdong Province will help us to understand PCV2 and PCV3 epidemiological characteristics and evolutionary trends.

9.
Chin Med J (Engl) ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710539

RESUMO

BACKGROUND: Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection. METHODS: A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with COVID-19-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2. RESULTS: Among the infected group, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685-11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068-2.343), traditional systemic (adjusted OR = 1.887, 95% CI = 1.263-2.818), and nonsystemic treatment (adjusted OR = 1.602, 95% CI = 1.117-2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680-1.274, compared to no treatment), according to multivariable logistic regression analysis. CONCLUSIONS: A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension. TRIAL REGISTRATION: ClinicalTrials.gov (No. NCT05961605).

10.
Nature ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750355

RESUMO

Plant pattern-recognition receptors perceive microorganism-associated molecular patterns to activate immune signalling1,2. Activation of the pattern-recognition receptor kinase CERK1 is essential for immunity, but tight inhibition of receptor kinases in the absence of pathogen is crucial to prevent autoimmunity3,4. Here we find that the U-box ubiquitin E3 ligase OsCIE1 acts as a molecular brake to inhibit OsCERK1 in rice. During homeostasis, OsCIE1 ubiquitinates OsCERK1, reducing its kinase activity. In the presence of the microorganism-associated molecular pattern chitin, active OsCERK1 phosphorylates OsCIE1 and blocks its E3 ligase activity, thus releasing the brake and promoting immunity. Phosphorylation of a serine within the U-box of OsCIE1 prevents its interaction with E2 ubiquitin-conjugating enzymes and serves as a phosphorylation switch. This phosphorylation site is conserved in E3 ligases from plants to animals. Our work identifies a ligand-released brake that enables dynamic immune regulation.

11.
J Am Chem Soc ; 146(19): 12883-12888, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38709642

RESUMO

Polyamides represent one class of materials that is important in modern society. Because of the numerous potential applications of polyamides in various fields, there is a high demand for new polyamide structures, which necessitates the development of new polymerization methods. Herein, we report a novel and efficient palladium-catalyzed hydroaminocarbonylative polymerization of dienes and diamines for the synthesis of cycloaliphatic polyamides. The method employs readily available starting materials, proceeds in an atom-economic manner, and creates a series of new functional polyamides in high yields and high molecular weights. In contrast with the traditional polyamides based on adipic acid, the cycloaliphatic polyamides have superior thermal resistance, higher glass-transition temperature, and better solubility in common organic solvents, thus probably featuring the merits of high-performance and good processability.

12.
Front Psychiatry ; 15: 1349989, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742128

RESUMO

Objective: Although extensive structural and functional abnormalities have been reported in schizophrenia, the gray matter volume (GMV) covariance of the amygdala remain unknown. The amygdala contains several subregions with different connection patterns and functions, but it is unclear whether the GMV covariance of these subregions are selectively affected in schizophrenia. Methods: To address this issue, we compared the GMV covariance of each amygdala subregion between 807 schizophrenia patients and 845 healthy controls from 11 centers. The amygdala was segmented into nine subregions using FreeSurfer (v7.1.1), including the lateral (La), basal (Ba), accessory-basal (AB), anterior-amygdaloid-area (AAA), central (Ce), medial (Me), cortical (Co), corticoamygdaloid-transition (CAT), and paralaminar (PL) nucleus. We developed an operational combat harmonization model for 11 centers, subsequently employing a voxel-wise general linear model to investigate the differences in GMV covariance between schizophrenia patients and healthy controls across these subregions and the entire brain, while adjusting for age, sex and TIV. Results: Our findings revealed that five amygdala subregions of schizophrenia patients, including bilateral AAA, CAT, and right Ba, demonstrated significantly increased GMV covariance with the hippocampus, striatum, orbitofrontal cortex, and so on (permutation test, P< 0.05, corrected). These findings could be replicated in most centers. Rigorous correlation analysis failed to identify relationships between the altered GMV covariance with positive and negative symptom scale, duration of illness, and antipsychotic medication measure. Conclusion: Our research is the first to discover selectively impaired GMV covariance patterns of amygdala subregion in a large multicenter sample size of patients with schizophrenia.

13.
Drug Dev Res ; 85(3): e22200, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38747107

RESUMO

In this study, we analyzed and verified differentially expressed genes (DEGs) in ROS and KEAP1 crosstalk in oncogenic signatures using GEO data sets (GSE4107 and GSE41328). Multiple pathway enrichment analyses were finished based on DEGs. The genetic signature for colorectal adenocarcinoma (COAD) was identified by using the Cox regression analysis. Kaplan-Meier survival and receiver operating characteristic curve analysis were used to explore the prognosis value of specific genes in COAD. The potential immune signatures and drug sensitivity prediction were also analyzed. Promising small-molecule agents were identified and predicted targets of α-hederin in SuperPred were validated by molecular docking. Also, expression levels of genes and Western blot analysis were conducted. In total, 48 genes were identified as DEGs, and the hub genes such as COL1A1, CXCL12, COL1A2, FN1, CAV1, TIMP3, and IGFBP7 were identified. The ROS and KEAP1-associated gene signatures comprised of hub key genes were developed for predicting the prognosis and evaluating the immune cell responses and immune infiltration in COAD. α-hederin, a potential anti-colorectal cancer (CRC) agent, was found to enhance the sensitivity of HCT116 cells, regulate CAV1 and COL1A1, and decrease KEAP1, Nrf2, and HO-1 expression significantly. KEAP1-related genes could be an essential mediator of ROS in CRC, and KEAP1-associated genes were effective in predicting prognosis and evaluating individualized CRC treatment. Therefore, α-hederin may be an effective chemosensitizer for CRC treatments in clinical settings.


Assuntos
Neoplasias Colorretais , Proteína 1 Associada a ECH Semelhante a Kelch , Espécies Reativas de Oxigênio , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Ácido Oleanólico/farmacologia , Ácido Oleanólico/análogos & derivados , Simulação de Acoplamento Molecular , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Prognóstico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
14.
Nat Commun ; 15(1): 4005, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740786

RESUMO

The neocortex comprises six cortical layers that play a crucial role in information processing; however, it remains unclear whether laminar processing is consistent across all regions within a single cortex. In this study, we demonstrate diverse laminar response patterns in the primary visual cortex (V1) of three male macaque monkeys when exposed to visual stimuli at different spatial frequencies (SFs). These response patterns can be categorized into two groups. One group exhibit suppressed responses in the output layers for all SFs, while the other type shows amplified responses specifically at high SFs. Further analysis suggests that both magnocellular (M) and parvocellular (P) pathways contribute to the suppressive effect through feedforward mechanisms, whereas amplification is specific to local recurrent mechanisms within the parvocellular pathway. These findings highlight the non-uniform distribution of neural mechanisms involved in laminar processing and emphasize how pathway-specific amplification selectively enhances representations of high-SF information in primate V1.


Assuntos
Estimulação Luminosa , Córtex Visual Primário , Vias Visuais , Animais , Masculino , Córtex Visual Primário/fisiologia , Vias Visuais/fisiologia , Percepção Visual/fisiologia , Córtex Visual/fisiologia , Macaca mulatta
15.
Front Cardiovasc Med ; 11: 1381222, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711793

RESUMO

Right aortic arch with isolation of left brachiocephalic artery is a rare congenital aortic arch anomaly. Herein, we reported a case of this rare anomaly with ventricular septal defect in a 9-month-old infant. We successfully reconstructed the islolated left brachiocephalic artery and repaired the ventricular septal defect in one stage.

16.
J Affect Disord ; 358: 270-282, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38723681

RESUMO

OBJECTIVE: Ganoderic Acid A (GAA), a primary bioactive component in Ganoderma, has demonstrated ameliorative effects on depressive-like behaviors in a Chronic Social Defeat Stress (CSDS) mouse model. This study aims to elucidate the underlying molecular mechanisms through proteomic analysis. METHODS: C57BL/6 J mice were allocated into control (CON), chronic social defeat stress (CSDS), GAA, and imipramine (IMI) groups. Post-depression induction via CSDS, the GAA and IMI groups received respective treatments of GAA (2.5 mg/kg) and imipramine (10 mg/kg) for five days. Behavioral assessments utilized standardized tests. Proteins from the prefrontal cortex were analyzed using LC-MS, with further examination via bioinformatics and PRM for differential expression. Western blot analysis confirmed protein expression levels. RESULTS: Chronic social defeat stress (CSDS) induced depressive-like behaviors in mice, which were significantly alleviated by GAA treatment, comparably to imipramine (IMI). Proteomic analysis identified distinct proteins in control (305), GAA-treated (949), and IMI-treated (289) groups. Enrichment in mitochondrial and synaptic proteins was evident from GO and PPI analyses. PRM analysis revealed significant expression changes in proteins crucial for mitochondrial and synaptic functions (namely, Naa30, Bnip1, Tubgcp4, Atxn3, Carmil1, Nup37, Apoh, Mrpl42, Tprkb, Acbd5, Dcx, Erbb4, Ppp1r2, Fam3c, Rnf112, and Cep41). Western blot validation in the prefrontal cortex showed increased levels of Mrpl42, Dcx, Fam3c, Ppp1r2, Rnf112, and Naa30 following GAA treatment. CONCLUSION: GAA exhibits potential antidepressant properties, with its action potentially tied to the modulation of synaptic functions and mitochondrial activities.

17.
J Hazard Mater ; 472: 134548, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38728866

RESUMO

The complex of heavy metals and organic acids leads to high difficulty in heavy metals separation by traditional technologies. Meanwhile, alkaline precipitation commonly used in industry causes the great consumption of resources and extra pollution. Herein, the effective decomplexation of Cu(Ⅱ)-EDTA and synchronous recycling of Cu2+ were realized by contact-electro-catalysis (CEC) coupled with capacitive deionization (CDI) innovatively. In particular, fluorinated ethylene propylene (FEP) as dielectric powders could generate reactive oxygen species under ultrasonic stimulation, realizing continuous deaminization and decarboxylation of Cu(Ⅱ)-EDTA and accelerating the totally breakage of Cu-O and Cu-N bonds. Additionally, the degradation pathway and intermediates evolution of Cu(Ⅱ)-EDTA were investigated using various characterization methods. It was confirmed that decarboxylation predominantly governed the degradation process of Cu(Ⅱ)-EDTA in CEC. During the course of treatment, the degradation ratio of Cu(Ⅱ)-EDTA reached 86.4 % within 150 min. Impressively, this strategy had satisfactory applicability to other metal combinations and excellent cycle stability. Subsequently, the released Cu ions were captured by CuSe cathode electrode through CDI. This research elucidated the degradation mechanism of persistent organic pollutant during CEC, and provided a novel approach for efficiently treating industrial wastewater containing metal complexes and advancing the exploitation and utilization of new technologies for metal recovery.

18.
Lab Invest ; : 102076, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729353

RESUMO

New therapies are being developed for breast cancer and in this process some "old" biomarkers are re-utilized and given a new purpose. It is not always recognized that, by changing a biomarker's intended use, a new biomarker assay is created. The Ki-67 biomarker is typically assessed by immunohistochemistry (IHC) to provide a proliferative index in breast cancer. Canadian laboratories assessed the analytical performance and diagnostic accuracy of their Ki-67 IHC laboratory developed tests (LDTs), of relevance for the LDTs' clinical utility. Canadian clinical IHC laboratories enrolled in the Canadian Biomarker Quality Assurance (CBQA) Pilot Run for Ki-67 in breast cancer by invitation. The Dako Ki-67 IHC pharmDx assay was employed as a study reference assay. The Dako central laboratory (USA) was the reference laboratory. Participants received unstained slides of breast cancer tissue microarrays (TMAs) with 32 cases and performed their in-house Ki-67 assay. The results were assessed using QuPath, an open-source software for bio-image analysis. Positive percent agreement (PPA, sensitivity) and negative percent agreement (NPA, specificity) were calculated against the Dako Ki-67 IHC pharmDx assay for 5%, 10%, 20% and 30% cut-offs. Overall, PPA and NPA varied depending on the selected cut-off; participants were more successful with 5% and 10%, than with 20% and 30% cut-offs. Only four out of 16 laboratories had robust IHC protocols with acceptable PPA for all cut-offs. The lowest PPA for the 5% cut-off was 85%, for 10% was 63%, for 20% was 14%, and for 30% was 13%. The lowest NPA for the 5% cut-off was 50%, for 10% was 33%, for 20% was 50%, and for 30% was 57%. Despite many years of international efforts to standardize IHC testing for Ki-67 in breast cancer, our results indicate that Canadian clinical LDTs have a wide analytical sensitivity range and poor agreement for 20% and 30% cut-offs. The poor agreement was not due to the readout, but rather due to IHC protocol conditions. IKWG recommendations related to Ki-67 IHC standardization cannot take full effect without reliable fit-for-purpose reference materials that are required for the initial assay calibration, assay performance monitoring, and proficiency testing.

19.
Gene ; : 148596, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38782219

RESUMO

Major depressive disorder (MDD) is a common psychological condition, the consequences of which, such as suicide, can be severe. Escitalopram, a selective serotonin reuptake inhibitor, is a commonly used antidepressant in clinics. However, more than one-third of patients with MDD do not respond to this drug. Gene polymorphism may affect the efficacy of escitalopram, but the genetic architecture of the antidepressant response in patients with MDD remains unclear. We perform a genome-wide association study (GWAS) of the genetic effect on the outcome of escitalopram in patients with MDD. A total of 203 patients with MDD and 176 healthy control (HC) adults were recruited from Beijing Anding Hospital. Patients received 12 weeks of antidepressant treatment with escitalopram. The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) or Hamilton depression scale (HAMD) were used to evaluate the severity of depression symptoms at the baseline and the end of 2 and 12 weeks of treatment. A total of 140 variants in MDD patients were identified by GWAS to have genome-wide significance (p < 5e - 8) compared with HCs. Similarly, 189 and 18 variants were identified to be associated with QIDS-SR and HAMD score changes in patients after antidepressant treatment (p < 1e - 5), including rs12602361, rs72799048, rs16842235, and rs2518256. In the two weeks QIDS-SR score study, the gene-level association for these variants and gene set enrichment analyses implicate the enrichment of genes involved in the synaptic plasticity process and nervous system development that may be impaired. Our results implicate the predictive capacity of the effect of escitalopram treatment, supporting a link between genetic basis and remission of depression disease.

20.
Gene ; : 148598, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38782224

RESUMO

Genes are the basic units of protein synthesis in organisms, and accurately identifying the translation initiation site (TIS) of genes is crucial for understanding the regulation, transcription, and translation processes of genes. However, the existing models cannot adequately extract the feature information in TIS sequences, and they also inadequately capture the complex hierarchical relationships among features. Therefore, a novel predictor named CapsNet-TIS is proposed in this paper. CapsNet-TIS first fully extracts the TIS sequence information using four encoding methods, including One-hot encoding, physical structure property (PSP) encoding, nucleotide chemical property (NCP) encoding, and nucleotide density (ND) encoding. Next, multi-scale convolutional neural networks are used to perform feature fusion of the encoded features to enhance the comprehensiveness of the feature representation. Finally, the fused features are classified using capsule network as the main network of the classification model to capture the complex hierarchical relationships among the features. Moreover, we improve the capsule network by introducing residual block, channel attention, and BiLSTM to enhance the model's feature extraction and sequence data modeling capabilities. In this paper, the performance of CapsNet-TIS is evaluated using TIS datasets from four species: human, mouse, bovine, and fruit fly, and the effectiveness of each part is demonstrated by performing ablation experiments. By comparing the experimental results with models proposed by other researchers, the results demonstrate the superior performance of CapsNet-TIS.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...