Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 173
Filtrar
1.
Trends Genet ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38734482

RESUMO

Genome-wide association studies (GWASs) have identified numerous genetic loci associated with human traits and diseases. However, pinpointing the causal genes remains a challenge, which impedes the translation of GWAS findings into biological insights and medical applications. In this review, we provide an in-depth overview of the methods and technologies used for prioritizing genes from GWAS loci, including gene-based association tests, integrative analysis of GWAS and molecular quantitative trait loci (xQTL) data, linking GWAS variants to target genes through enhancer-gene connection maps, and network-based prioritization. We also outline strategies for generating context-dependent xQTL data and their applications in gene prioritization. We further highlight the potential of gene prioritization in drug repurposing. Lastly, we discuss future challenges and opportunities in this field.

2.
Psychoradiology ; 4: kkae005, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694267

RESUMO

Background: Schizophrenia is a polygenic disorder associated with changes in brain structure and function. Integrating macroscale brain features with microscale genetic data may provide a more complete overview of the disease etiology and may serve as potential diagnostic markers for schizophrenia. Objective: We aim to systematically evaluate the impact of multi-scale neuroimaging and transcriptomic data fusion in schizophrenia classification models. Methods: We collected brain imaging data and blood RNA sequencing data from 43 patients with schizophrenia and 60 age- and gender-matched healthy controls, and we extracted multi-omics features of macroscale brain morphology, brain structural and functional connectivity, and gene transcription of schizophrenia risk genes. Multi-scale data fusion was performed using a machine learning integration framework, together with several conventional machine learning methods and neural networks for patient classification. Results: We found that multi-omics data fusion in conventional machine learning models achieved the highest accuracy (AUC ~0.76-0.92) in contrast to the single-modality models, with AUC improvements of 8.88 to 22.64%. Similar findings were observed for the neural network, showing an increase of 16.57% for the multimodal classification model (accuracy 71.43%) compared to the single-modal average. In addition, we identified several brain regions in the left posterior cingulate and right frontal pole that made a major contribution to disease classification. Conclusion: We provide empirical evidence for the increased accuracy achieved by imaging genetic data integration in schizophrenia classification. Multi-scale data fusion holds promise for enhancing diagnostic precision, facilitating early detection and personalizing treatment regimens in schizophrenia.

3.
Front Pharmacol ; 15: 1288964, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38327986

RESUMO

Objective: Based on real-world research, we aimed to evaluate the effectiveness and economy of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin 11 (rhIL-11) in the treatment of cancer therapy induced thrombocytopenia (CTIT). Methods: We retrospectively collected clinical data of patients with CTIT who were treated with rhTPO or rhIL-11 in a single cancer hospital from January 2020 to December 2021. Propensity score matching (PSM) was applied to eliminate confounding factors. The measurements of effectiveness analysis were the platelet compliance rate, days of medication, days of compliance, highest platelet count after medication, platelet count elevation before and after medication, and the lowest platelet count after next-cycle cancer therapy. The economic evaluation was performed according to the results of the effectiveness evaluation. At the same time, patients were stratified according to type of tumor and grade of thrombocytopenia for subgroup analysis. Results: A total of 262 patients were collected and 174 patients were enrolled after PSM, 87 in the rhTPO group and 87 in the rhIL-11 group. In all patients, there were no significant differences in the platelet compliance rate, mean days of medication, median days of compliance, median highest platelet count after medication, and the median platelet count elevation before and after medication between the two groups (p > 0.05), but the median lowest platelet count after next-cycle cancer therapy in the rhTPO group was lower than that in the rhIL-11 group (p = 0.014). The subgroup analysis showed that the rhTPO group had longer mean days of medication than the rhIL-11 group in patients with hematological malignancies (p = 0.042), and a lower median lowest platelet count after next-cycle cancer therapy in patients with grade I/II thrombocytopenia than rhIL-11 group (p = 0.022), with no significant difference in other outcome indicators (p > 0.05). As there was no statistically significant difference in platelet compliance rate between the two groups, the cost-minimization analysis showed that the rhIL-11 group had lower treatment costs than the rhTPO group. Conclusion: RhTPO and rhIL-11 showed similar effectiveness in the treatment of CTIT, but rhIL-11 was more advantageous in economic cost.

4.
Anal Chim Acta ; 1296: 342331, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38401939

RESUMO

BACKGROUND: The cell-free RNA (cf-RNA) of spent embryo medium (SEM) has aroused a concern of academic and clinical researchers for its potential use in non-invasive embryo screening. However, comprehensive characterization of cf-RNA from SEM still presents significant technical challenges, primarily due to the limited volume of SEM. Hence, there is urgently need to a small input liquid volume and ultralow amount of cf-RNA library preparation method to unbiased cf-RNA sequencing from SEM. (75) RESULT: Here, we report a high sensitivity agarose amplification-based cf-RNA sequencing method (SEM-Acf) for human preimplantation SEM cf-RNA analysis. It is a cf-RNA sequencing library preparation method by adding agarose amplification. The agarose amplification sensitivity (0.005 pg) and efficiency (105.35 %) were increased than that of without agarose addition (0.45 pg and 96.06 %) by âˆ¼ 90 fold and 9.29 %, respectively. Compared with SMART sequencing (SMART-seq), the correlation of gene expression was stronger in different SEM samples by using SEM-Acf. The cf-RNA number of detected and coverage uniformity of 3' end were significantly increased. The proportion of 5' end adenine, alternative splicing events and short fragments (<400 bp) were increased. It is also found that 4-mer end motifs of cf-RNA fragments was significantly differences between different embryonic stage by day3 spent cleavage medium and day5/6 spent blastocyst medium. (141) SIGNIFICANCE: This study established an efficient SEM amplification and library preparation method. Additionally, we successfully described the characterizations of SEM cf-RNA in preimplantation embryo using SEM-Acf, including expression features and fragment lengths. SEM-Acf facilitates the exploration of cf-RNA as a noninvasive embryo screening biomarker, and opens up potential clinical utilities of small input liquid volume and ultralow amount cf-RNA sequencing. (59).


Assuntos
Ácidos Nucleicos Livres , Diagnóstico Pré-Implantação , Gravidez , Feminino , Humanos , Diagnóstico Pré-Implantação/métodos , Sefarose , Blastocisto/metabolismo , RNA/genética , RNA/metabolismo
5.
Sci Adv ; 10(5): eadj4163, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38295177

RESUMO

Species-specific differences in acidic nuclear phosphoprotein 32 family member A (ANP32A) determine the restriction of avian-signature polymerase in mammalian cells. Mutations that evade this restriction, such as PB2-E627K, are frequently acquired when avian influenza A viruses jump from avian hosts to mammalian hosts. However, the mechanism underlying this adaptation process is still unclear. Here, we report that host factor ANP32 proteins can be incorporated into influenza viral particles through combination with the viral RNA polymerase (vPol) and then transferred into targeted cells where they support virus replication. The packaging of the ANP32 proteins into influenza viruses is dependent on their affinity with the vPol. Avian ANP32A (avANP32A) delivered by avian influenza A virions primes early viral replication in mammalian cells, thereby favoring the downstream interspecies transmission event by increasing the total amount of virus carrying adaptive mutations. Our study clarifies one role of avANP32A where it is used by avian influenza virus to help counteract the restriction barrier in mammals.


Assuntos
Vírus da Influenza A , Influenza Aviária , Animais , Galinhas , Mamíferos , Replicação Viral , Vírion
6.
J Genet Genomics ; 51(3): 313-325, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37225086

RESUMO

Mitogen-activated protein kinase (MAPK) cascades play important roles in disease resistance in model plant species. However, the functions of MAPK signaling pathways in crop disease resistance are largely unknown. Here we report the function of HvMKK1-HvMPK4-HvWRKY1 module in barley immune system. HvMPK4 is identified to play a negative role in barley immune response against Bgh, as virus-induced gene silencing of HvMPK4 results in enhanced disease resistance whilst stably overexpressing HvMPK4 leads to super-susceptibility to Bgh infection. Furthermore, the barley MAPK kinase HvMKK1 is found to specifically interact with HvMPK4, and the activated HvMKK1DD variant specifically phosphorylates HvMPK4 in vitro. Moreover, the transcription factor HvWRKY1 is identified to be a downstream target of HvMPK4 and phosphorylated by HvMPK4 in vitro in the presence of HvMKK1DD. Phosphorylation assay coupled with mutagenesis analyses identifies S122, T284, and S347 in HvWRKY1 as the major residues phosphorylated by HvMPK4. HvWRKY1 is phosphorylated in barley at the early stages of Bgh infection, which enhances its suppression on barley immunity likely due to enhanced DNA-binding and transcriptional repression activity. Our data suggest that the HvMKK1-HvMPK4 kinase pair acts upstream of HvWRKY1 to negatively regulate barley immunity against powdery mildew.


Assuntos
Ascomicetos , Hordeum , Ascomicetos/genética , Ascomicetos/metabolismo , Hordeum/genética , Hordeum/metabolismo , Hordeum/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Resistência à Doença/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Regulação da Expressão Gênica de Plantas/genética
7.
J Chem Inf Model ; 64(7): 2302-2310, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37682833

RESUMO

Presently, the field of analyzing differentially expressed genes (DEGs) of RNA-seq data is still in its infancy, with new approaches constantly being proposed. Taking advantage of deep neural networks to explore gene expression information on RNA-seq data can provide a novel possibility in the biomedical field. In this study, a novel approach based on a deep learning algorithm and cloud model was developed, named Deep-Cloud. Its main advantage is not only using a convolutional neural network and long short-term memory to extract original data features and estimate gene expression of RNA-seq data but also combining the statistical method of the cloud model to quantify the uncertainty and carry out in-depth analysis of the DEGs between the disease groups and the control groups. Compared with traditional analysis software of DEGs, the Deep-cloud model further improves the sensitivity and accuracy of obtaining DEGs from RNA-seq data. Overall, the proposed new approach Deep-cloud paves a new pathway for mining RNA-seq data in the biomedical field.


Assuntos
Algoritmos , Redes Neurais de Computação , RNA-Seq , Software
8.
J Cogn Neurosci ; 36(2): 239-260, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38010312

RESUMO

Reading comprehension is a vital cognitive skill that individuals use throughout their lives. The neurodevelopment of reading comprehension across the lifespan, however, remains underresearched. Furthermore, factors such as maturation and experience significantly influence functional brain development. Given the complexity of reading comprehension, which incorporates lower-level word reading process and higher-level semantic integration process, our study aims to investigate how age and reading experience influence the neurobiology underpinning these two processes across the lifespan. fMRI data of 158 participants aged from 7 to 77 years were collected during a passive word viewing task and a sentence comprehension task to engage the lower- and higher-level processes, respectively. We found that the neurodevelopment of the lower-level process was primarily influenced by age, showing increased activation and connectivity with age in parieto-occipital and middle/inferior frontal lobes related to morphological-semantic mapping while decreased activation in the temporoparietal regions linked to phonological processing. However, the brain function of the higher-level process was primarily influenced by reading experience, exhibiting a greater reliance on the frontotemporal semantic network with enhanced sentence-level reading performance. Furthermore, reading experience did not significantly affect the brain function of children, but had a positive effect on young adults in the lower-level process and on middle-aged and older adults in the higher-level process. These findings indicate that the brain function for lower- and higher-level processes of reading comprehension is differently affected by maturation and reading experience, and the experience effect is contingent on age regarding the two processes.


Assuntos
Compreensão , Leitura , Idoso , Criança , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Mapeamento Encefálico , Compreensão/fisiologia , Idioma , Longevidade , Imageamento por Ressonância Magnética , Semântica , Adolescente , Adulto
9.
BMJ Case Rep ; 16(11)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38035683

RESUMO

We present the case of a vulval superficial myofibroblastoma with a lymphocytic and eosinophilic rim in a woman in her late 20s. The tumour presented in pregnancy as a cystic lesion with pain and increasing size. While the histopathology of superficial myofibroblastomas has been well defined in the literature, to our knowledge, there has been no documentation of the presence of an inflammatory infiltrate of lymphocytes and eosinophils surrounding and within the tumour. This may potentially act as a diagnostic or prognostic reference.


Assuntos
Eosinofilia , Neoplasias de Tecido Muscular , Neoplasias Vulvares , Feminino , Humanos , Eosinofilia/patologia , Eosinófilos/patologia , Linfócitos/patologia , Neoplasias de Tecido Muscular/diagnóstico , Neoplasias de Tecido Muscular/cirurgia , Neoplasias de Tecido Muscular/patologia , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/cirurgia , Neoplasias Vulvares/patologia , Adulto
10.
Folia Neuropathol ; 61(3): 266-272, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818687

RESUMO

INTRODUCTION: The contribution of brain abnormalities in patients with Parkinson's disease (PD) to impaired functional status remains uncertain. Our study assessed whether global and regional brain structural abnormalities are associated with impaired performance of activities of daily living (ADL) in PD patients. MATERIAL AND METHODS: A retrospective analysis was conducted of 46 patients with PD, recruited prospectively from a movement disorder clinic. Motor impairment and disability were assessed using the Hoehn and Yahr (H-Y) scale and Unified Parkinson's Disease Rating Scale Part III (UPDRS-III). Cognitive status was evaluated with Montreal Cognitive Assessment (MoCA). The performance of ADL was indexed by the sum score of the Physical Self-Maintenance Scale (PSMS) and Lawton Instrumental ADL scale. Brain magnetic resonance imaging (MRI) was performed to assess white matter hyperintensities and medial temporal lobe atrophy (MTLA). Global brain atrophy, indexed by the relative grey matter volume (RGM), relative white matter volume (RWM) and average cortical thickness of the whole brain, was quantified by voxel-based morphometry (VBM). RESULTS: The ADL score (where higher scores indicate poorer performance) negatively correlated with RWM (where greater volume indicates less severe atrophy; r = -0.41, p = 0.004) and RGM (where greater volume indicates less severe atrophy; r = -0.43, p = 0.003) but not with the average cortical thickness ( r = -0.16, p = 0.29). With ADL score as the dependent variable in a linear regression model, H-Y stage and RWM significantly correlated with the ADL score after adjusting for age and MoCA score, and together accounted for 51% of the variance therein. RGM was not significantly correlated with the ADL score after adjusting for age and MoCA score. CONCLUSIONS: Cerebral white matter atrophy may be associated with the performance of ADL in patients with PD, indicating an important role of white matter impairment in their functional status.


Assuntos
Doença de Parkinson , Substância Branca , Humanos , Atividades Cotidianas , Doença de Parkinson/patologia , Substância Branca/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Atrofia/complicações , Atrofia/patologia , Substância Cinzenta/patologia
11.
Cell Genom ; 3(8): 100344, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37601976

RESUMO

Molecular quantitative trait loci (xQTLs) are often harnessed to prioritize genes or functional elements underpinning variant-trait associations identified from genome-wide association studies (GWASs). Here, we introduce OPERA, a method that jointly analyzes GWAS and multi-omics xQTL summary statistics to enhance the identification of molecular phenotypes associated with complex traits through shared causal variants. Applying OPERA to summary-level GWAS data for 50 complex traits (n = 20,833-766,345) and xQTL data from seven omics layers (n = 100-31,684) reveals that 50% of the GWAS signals are shared with at least one molecular phenotype. GWAS signals shared with multiple molecular phenotypes, such as those at the MSMB locus for prostate cancer, are particularly informative for understanding the genetic regulatory mechanisms underlying complex traits. Future studies with more molecular phenotypes, measured considering spatiotemporal effects in larger samples, are required to obtain a more saturated map linking molecular intermediates to GWAS signals.

12.
Cell Res ; 33(11): 821-834, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37500768

RESUMO

Maternal age at childbearing has continued to increase in recent decades. However, whether and how it influences offspring adult traits are largely unknown. Here, using adult body size as the primary readout, we reveal that maternal rather than paternal age has an evolutionarily conserved effect on offspring adult traits in humans, Drosophila, and Caenorhabditis elegans. Elucidating the mechanisms of such effects in humans and other long-lived animals remains challenging due to their long life course and difficulties in conducting in vivo studies. We thus employ the short-lived and genetically tractable nematode C. elegans to explore the mechanisms underlying the regulation of offspring adult trait by maternal aging. By microscopic analysis, we find that old worms transmit aged mitochondria with a donut-like shape to offspring. These mitochondria are rejuvenated in the offspring's early life, with their morphology fully restored before adulthood in an AMPK-dependent manner. Mechanistically, we demonstrate that early-life mitochondrial dysfunction activates AMPK, which in turn not only alleviates mitochondrial abnormalities but also activates TGFß signaling to increase offspring adult size. Together, our findings provide mechanistic insight into the ancient role of maternal aging in shaping the traits of adult offspring.


Assuntos
Proteínas Quinases Ativadas por AMP , Caenorhabditis elegans , Animais , Humanos , Adulto , Idoso , Envelhecimento/fisiologia , Tamanho Corporal , Mitocôndrias
13.
J Phys Chem A ; 127(31): 6400-6411, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37498222

RESUMO

Al-containing catalysts, e.g., Al(OTf)3, show good catalytic performance toward the conversion of cellulose to fructose in methanol solution. Here, we report the catalytic isomerization and alcoholysis mechanisms for the conversion of cellobiose to fructose at the PBE0/6-311++G(d,p), aug-cc-pVTZ theoretical level, combining the relevant experimental verifications of electrospray ionization mass spectrometry (ESI-MS), high-performance liquid chromatography (HPLC), and the attenuated total reflection-infrared (ATR-IR) spectra. From the alcoholysis of Al(OTf)3 in methanol solution, the catalytically active species involves both the [CH3OH2]+ Brønsted acid and the [Al(CH3O)(OTf)(CH3OH)4]+ Lewis acid. There are two reaction pathways, i.e., one through glucose (glycosidic bond cleavage followed by isomerization, w-G) and another through cellobiulose (isomerization followed by glycosidic bond cleavage, w-L). The Lewis acid ([Al(CH3O)(OTf)(CH3OH)4]+) is responsible for the aldose-ketose tautomerization, while the Brønsted acid ([CH3OH2]+) is in charge of ring-opening, ring-closure, and glycosidic bond cleavage. For both w-G and w-L, the rate-determining steps are related to the intramolecular [1,2]-H shift between C1-C2 for the aldose-ketose tautomerization catalyzed by the [Al(CH3O)(OTf)(CH3OH)4]+ species. The Lewis acid ([Al(CH3O)(OTf)(CH3OH)4]+) exhibits higher catalytic activity toward the aldose-ketose tautomerization of glycosyl-chain-glucose to glycosyl-chain-fructose than that of chain-glucose to chain-fructose. Besides, the Brønsted acid ([CH3OH2]+) shows higher catalytic activity toward the glycosidic bond cleavage of cellobiulose than that of cellobiose. Kinetically, the w-L pathway is predominant, whereas the w-G pathway is minor. The theoretically proposed mechanism has been experimentally testified. These insights may advance on the novel design of the catalytic system toward the conversion of cellulose to fructose.

15.
Se Pu ; 41(6): 513-519, 2023 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-37259876

RESUMO

Seven parabens are widely used in soy sauce, vinegar, jam, oyster sauce, stuffing, and other foods. The long-term intake of large amounts of parabens and similar substances may be harmful to the human body. Therefore, the addition of paraben preservatives to food should be strictly controlled. The current detection method is applicable to single target compound and several food categories, and the experimental pretreatment method involves extraction with anhydrous ethyl ether, which is a toxic reagent. Moreover, interferences in the analysis of parabens via gas chromatography limit the versatility and accuracy of the detection method. Herein, a novel method based on solid-phase extraction (SPE) coupled with high performance liquid chromatography (HPLC) was developed for the determination of seven paraben preservatives (methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, isopropyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate, and heptyl p-hydroxybenzoate) in oyster sauce, shrimp sauce, and fish sauce. Compared with the conventional method, the proposed work enables the determination of more compounds, thereby expanding its scope of application to different food types. This strategy also optimizes the pretreatment method and device parameters. The samples were extracted with methanol and 20% methanol aqueous solution by ultrasonication, respectively, and then centrifuged. The experimental pretreatment method was enriched, and sample clean-up was conducted using a MAX SPE column. The seven parabens were separated using a Chromcore 120 C18 column (150 mm×4.6 mm, 3.0 µm). Gradient elution was performed with acetonitrile-5 mmol/L ammonium acetate aqueous solution as the mobile phase (initial mobile phase volume ratio, 30∶70). The flow rate was 0.7 mL/min, and the column temperature was 35 ℃. A diode array detector with a detection wavelength of 254 nm was also used. The seven paraben preservatives showed good linearity in the range of 0.5-50.0 mg/L, with correlation coefficients greater than 0.9999. The limits of detection (LODs) and quantification (LOQs) for the seven paraben preservatives were 0.2-0.4 mg/kg and 0.5-1.3 mg/kg, respectively. A spiked recovery test was conducted using oyster sauce, shrimp sauce, and fish sauce at three spiked levels of 2, 40, and 200 mg/kg. Good recoveries for the seven paraben preservatives were obtained and the recoveries of the analytes in oyster sauce, shrimp sauce, and fish sauce were 91.0%-102%, 95.5%-106%, and 95.0%-105%, respectively, with relative standard deviations of ≤6.97%. Compared with the liquid-liquid extraction method, the proposed method demonstrated better purification effects. The recoveries of the seven paraben preservatives extracted using this method were also much higher than those obtained from liquid-liquid extraction. We determined the contents of these preservatives in 135 food products using the method established in this study and detected methyl p-hydroxybenzoate and ethyl p-hydroxybenzoate in soy sauce, vinegar, and pickles. Thus, the established method can be used for the effective determination of seven parabens in aquatic seasoning such as oyster sauce, shrimp sauce, and fish sauce.


Assuntos
Metanol , Parabenos , Animais , Humanos , Parabenos/análise , Cromatografia Líquida de Alta Pressão , Ácido Acético , Conservantes Farmacêuticos/análise , Extração em Fase Sólida/métodos , Água
16.
Nature ; 617(7962): 764-768, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37198478

RESUMO

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).


Assuntos
COVID-19 , Estado Terminal , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , COVID-19/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Genótipo , Técnicas de Genotipagem , Monócitos/metabolismo , Fenótipo , Proteínas rab de Ligação ao GTP/genética , Transcriptoma , Sequenciamento Completo do Genoma
17.
Open Life Sci ; 18(1): 20220581, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37250848

RESUMO

The treatment of preeclampsia is delivering women and extracting the placenta, but the Chinese Society of Obstetrics and Gynecology guidelines do not recommend the delivery of babies without severe features. The objectives of the study were to compare the effectiveness and safety of nifedipine and phytosterol in combination with nicardipine for the management of severe preeclampsia. Women (19-32 years; gestation age ≥ 30 weeks) with the complication of severe preeclampsia have received 10 mg of oral nifedipine (pregnant women received 10 mg of oralnifedipine, n = 112) or 1 mg/h intravenous nicardipine (pregnant women received 1 mg/h intravenous nicardipine (ND cohort), n = 115) or oral 10 mg nifedipine and 500 mg phytosterol (pregnant women received oral 10 mg nifedipine and 500 mg phytosterol (np cohort), n = 111) until 150/100 mmHg blood pressure was achieved. The time required to achieve the desired blood pressure control was 13 minutes shorter in the NP cohort compared to the NF (p < 0.0001, t = 11.605), and 3 minutes shorter compared to the ND (p < 0.0001, t = 2.79) cohorts. Stillbirths were reported in 14 (13%), 28 (24%), and 10 (9%) infants, and 13 (12%), 26 (23%), and 10 (9%) infants died from the NF, ND, and NP cohorts, respectively. The undesirable tocolytic effect was reported in 17 (15%) women of the ND cohort. Phytosterol with nifedipine has a synergistic or additive effect on the management of preeclampsia with fewer adverse outcomes.

18.
Chemosphere ; 331: 138842, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37142102

RESUMO

In this work, a kind of multifunctional magnetic plasmonic photocatalyst was prepared by a green and efficient process. Magnetic mesoporous anatase titanium dioxide (Fe3O4@mTiO2) was synthesized by microwave-assisted hydrothermal, and Ag NPs were simultaneously in-situ grown on Fe3O4@mTiO2 (Fe3O4@mTiO2@Ag), graphene oxide (GO) was then wrapped on Fe3O4@mTiO2@Ag (Fe3O4@mTiO2@Ag@GO) to increase its adsorption capacity for fluoroquinolone antibiotics (FQs). Owing to the localized surface plasmon resonance (LSPR) effect of Ag, as well as the photocatalytic capacity of TiO2, a multifunctional platform based on Fe3O4@mTiO2@Ag@GO was constructed for adsorption, surface-enhanced Raman spectroscopy (SERS) monitoring and photodegradation of FQs in water. The quantitative SERS detection of norfloxacin (NOR), ciprofloxacin (CIP), and enrofloxacin (ENR) was demonstrated with LOD of 0.1 µg mL-1, and the qualitative analysis was confirmed by density functional theory (DFT) calculation. The photocatalytic degradation rate of NOR over Fe3O4@mTiO2@Ag@GO was about 4.6 and 1.4 times faster than that of Fe3O4@mTiO2 and Fe3O4@mTiO2@Ag, indicating the synergetic effects of Ag NPs and GO, the used Fe3O4@mTiO2@Ag@GO can be easily recovered and recycled for at least 5 times. Thus, the eco-friendly magnetic plasmonic photocatalyst provided a potential solution for the removal and monitoring of residual FQs in environmental water.


Assuntos
Fluoroquinolonas , Água , Fotólise , Adsorção , Norfloxacino , Antibacterianos , Fenômenos Magnéticos
19.
bioRxiv ; 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37214875

RESUMO

Developmental dyslexia (DD) is typically associated with difficulties in manipulating speech sounds and, sometimes, in basic auditory processing. However, the neuroanatomical correlates of auditory difficulties in DD and their contribution to individual clinical phenotypes are still unknown. Recent intracranial electrocorticography (ECoG) findings associated processing of sound amplitude rises and speech sounds with posterior and middle superior temporal gyrus (STG), respectively. We hypothesize that regional STG anatomy will relate to specific auditory abilities in DD and that auditory processing abilities will relate to behavioral difficulties. One hundred and ten children (78 DD, 32 typically developing, age 7-15 years) completed amplitude rise time (ART) and speech in noise discrimination (SiN) tasks. They also underwent a battery of cognitive tests. Anatomical MRI scans were used to identify regions in which local cortical gyrification complexity correlated with auditory tasks in DD. Behaviorally, ART but not SiN performance was impaired in DD. Neurally, ART and SiN performance correlated with gyrification in posterior STG and middle STG, respectively. Furthermore, ART significantly contributed to reading impairments in DD, while SiN explained variance in phonological awareness only. Finally, ART and SiN performance was not correlated, and each task was correlated with distinct neuropsychological measures, such that distinct DD subgroups could be identified. Overall, we provide a direct link between the neurodevelopment of the left STG and individual variability in auditory processing abilities in DD. The dissociation between speech and non-speech deficits supports distinct DD phenotypes and implicates different approaches to interventions.

20.
Crit Rev Food Sci Nutr ; : 1-22, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37009832

RESUMO

Matcha, a powder processed from tea leaves, has a unique green tea flavor and appealing color, in addition to many other sought after functional properties for a wide range of formulated food applications (e.g., dairy products, bakery products, and beverage). The properties of matcha are influenced by cultivation method and processing post-harvest. The transition from drinking tea infusion to eating whole leaves provides a healthy option for the delivery of functional component and tea phenolics in various food matrix. The aim of this review is to describe the physico-chemical properties of matcha, the specific requirements for tea cultivation and industrial processing. The quality of matcha mainly depends on the quality of fresh tea leaves, which is affected by preharvest factors including tea cultivar, shading treatment, and fertilization. Shading is the key measure to increase greenness, reduce bitterness and astringency, and enhance umami taste of matcha. The potential health benefits of matcha and the gastrointestinal fate of main phenolics in matcha are covered. The chemical compositions and bioactivities of fiber-bound phenolics in matcha and other plant materials are discussed. The fiber-bound phenolics are considered promising components which endow matcha with boosted bioavailability of phenolics and health benefits through modulating gut microbiota.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA