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1.
Proc Natl Acad Sci U S A ; 121(11): e2312596121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38437555

RESUMO

Self-assembled DNA crystals offer a precise chemical platform at the ångström-scale for DNA nanotechnology, holding enormous potential in material separation, catalysis, and DNA data storage. However, accurately controlling the crystallization kinetics of such DNA crystals remains challenging. Herein, we found that atomic-level 5-methylcytosine (5mC) modification can regulate the crystallization kinetics of DNA crystal by tuning the hybridization rates of DNA motifs. We discovered that by manipulating the axial and combination of 5mC modification on the sticky ends of DNA tensegrity triangle motifs, we can obtain a series of DNA crystals with controllable morphological features. Through DNA-PAINT and FRET-labeled DNA strand displacement experiments, we elucidate that atomic-level 5mC modification enhances the affinity constant of DNA hybridization at both the single-molecule and macroscopic scales. This enhancement can be harnessed for kinetic-driven control of the preferential growth direction of DNA crystals. The 5mC modification strategy can overcome the limitations of DNA sequence design imposed by limited nucleobase numbers in various DNA hybridization reactions. This strategy provides a new avenue for the manipulation of DNA crystal structure, valuable for the advancement of DNA and biomacromolecular crystallography.


Assuntos
5-Metilcitosina , DNA , Cristalização , Catálise , Cristalografia
2.
J Am Chem Soc ; 146(8): 5461-5469, 2024 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-38355136

RESUMO

Two-dimensional (2D) DNA origami assembly represents a powerful approach to the programmable design and construction of advanced 2D materials. Within the context of hybridization-mediated 2D DNA origami assembly, DNA spacers play a pivotal role as essential connectors between sticky-end regions and DNA origami units. Here, we demonstrated that programming the spacer length, which determines the binding radius of DNA origami units, could effectively tune sticky-end hybridization reactions to produce distinct 2D DNA origami arrays. Using DNA-PAINT super-resolution imaging, we unveiled the significant impact of spacer length on the hybridization efficiency of sticky ends for assembling square DNA origami (SDO) units. We also found that the assembly efficiency and pattern diversity of 2D DNA origami assemblies were critically dependent on the spacer length. Remarkably, we realized a near-unity yield of ∼98% for the assembly of SDO trimers and tetramers via this spacer-programmed strategy. At last, we revealed that spacer lengths and thermodynamic fluctuations of SDO are positively correlated, using molecular dynamics simulations. Our study thus paves the way for the precision assembly of DNA nanostructures toward higher complexity.


Assuntos
DNA , Nanoestruturas , DNA Intergênico , Conformação de Ácido Nucleico , DNA/química , Nanoestruturas/química , Hibridização de Ácido Nucleico , Nanotecnologia
3.
J Am Chem Soc ; 146(28): 18948-18957, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38959409

RESUMO

Single-molecule localization methods have been popularly exploited to obtain super-resolved images of biological structures. However, the low blinking frequency of randomly switching emission states of individual fluorophores greatly limits the imaging speed of single-molecule localization microscopy (SMLM). Here we present an ultrafast SMLM technique exploiting spontaneous fluorescence blinking of cyanine dye aggregates confined to DNA framework nanostructures. The DNA template guides the formation of static excimer aggregates as a "light-harvesting nanoantenna", whereas intermolecular excitation energy transfer (EET) between static excimers causes collective ultrafast fluorescence blinking of fluorophore aggregates. This DNA framework-based strategy enables the imaging of DNA nanostructures with 12.5-fold improvement in speed compared to conventional SMLM. Further, we demonstrate the use of this strategy to track the movement of super-resolved DNA nanostructures for over 20 min in a microfluidic system. Thus, this ultrafast SMLM holds great potential for revealing the dynamic processes of biomacromolecules in living cells.


Assuntos
DNA , Corantes Fluorescentes , Nanoestruturas , DNA/química , Corantes Fluorescentes/química , Nanoestruturas/química , Imagem Individual de Molécula/métodos , Carbocianinas/química , Microscopia de Fluorescência/métodos
4.
Small ; : e2407046, 2024 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-39469735

RESUMO

Diabetic wound healing is a formidable challenge, often complicated by biofilms, immune dysregulation, and hindered vascularization within the wound environments. The intricate interplay of these microenvironmental factors has been a significant oversight in the evolution of therapeutic strategies. Herein, the design of an efficient and versatile oxygen-bonded amorphous transition metal dichalcogenide biocatalyst (aRuS-Or) with pH-responsive reactive oxygen biocatalysis for combined antibacterial and anti-inflammatory therapies in promoting diabetic wound healing is reported. Leveraging the incorporation of Ru─O bonds, aRuS-Or exhibits optimized adsorption/desorption behavior of oxygen intermediates, thereby enhancing both the reactive oxygen species (ROS) generation activity in acidic conditions and ROS scavenging performance in neutral environments. Remarkably, aRuS-Or demonstrates exceptional bactericidal potency within infected milieus through biocatalytic ROS generation. Beyond its antimicrobial capability, post-eradication, aRuS-Or serves a dual role in mitigating oxidative stress in inflammatory wounds, providing robust cellular protection and fostering an M2-phenotype polarization of macrophages, which is pivotal for accelerating the wound repair process. The findings underscore the multifaceted efficacy of aRuS-Or, which harmoniously integrates high antibacterial action with anti-inflammatory and pro-angiogenic properties. This triad of functionalities positions aRuS-Or as a promising candidate for the comprehensive management of complex diabetic ulcers, addressing the unmet needs in the current therapeutics.

5.
Chembiochem ; : e202400363, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39166897

RESUMO

Mapping the endocytic vesicular acidification process is of prior importance to better understand the health and pathological processes of cells. Herein, by integrating a pH-sensitive i-motif and a pair of fluorescence resonance energy transfer (FRET) into a tetrahedral DNA framework (TDF), we develop a pH-responsive DNA nanomachine, allowing for efficient sensing of pH from 7.0 to 5.5 via the pH-triggered spatial proximity modulation of FRET. The inheriting endo-lysosome-targeting ability of TDF enables spatiotemporal tracking of endocytic vesicle acidification during the endosomal maturation process. Analysis of pH-dependent FRET response at single fluorescent spot level reveals the significant difference of endocytic vesicular acidification between normal and cancer cells. The performance of pH-responsive DNA nanomachine underlines its potential for studies on vesicle acidification-related pathologies as a universal platform.

6.
Drug Metab Dispos ; 52(5): 432-441, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38485279

RESUMO

Drug-induced liver injury (DILI) is a frequent cause of clinical trial failures during drug development. While inhibiting bile salt export pump (BSEP) is a well-documented DILI mechanism, interference with genes related to bile acid (BA) metabolism and transport can further complicate DILI development. Here, the effects of twenty-eight compounds on genes associated with BA metabolism and transport were evaluated, including those with discontinued development or use, boxed warnings, and clean labels for DILI. The study also included rifampicin and omeprazole, pregnane X receptor and aryl hydrocarbon receptor ligands, and four mitogen-activated protein kinase kinase (MEK1/2) inhibitors. BSEP inhibitors with more severe DILI, notably pazopanib and CP-724714, significantly upregulated the expression of 7 alpha-hydroxylase (CYP7A1), independent of small heterodimer partner (SHP) expression. CYP7A1 expression was marginally induced by omeprazole. In contrast, its expression was suppressed by mometasone (10-fold), vinblastine (18-fold), hexachlorophene (2-fold), bosentan (2.1-fold), and rifampin (2-fold). All four MEK1/2 inhibitors that show clinical DILI were not potent BSEP inhibitors but significantly induced CYP7A1 expression, accompanied by a significant SHP gene suppression. Sulfotransferase 2A1 and BSEP were marginally upregulated, but no other genes were altered by the drugs tested. Protein levels of CYP7A1 were increased with the treatment of CYP7A1 inducers and decreased with obeticholic acid, an farnesoid X receptor ligand. CYP7A1 inducers significantly increased bile acid (BA) production in hepatocytes, indicating the overall regulatory effects of BA metabolism. This study demonstrates that CYP7A1 induction via various mechanisms can pose a risk for DILI, independently or in synergy with BSEP inhibition, and it should be evaluated early in drug discovery. SIGNIFICANCE STATEMENT: Kinase inhibitors, pazopanib and CP-724714, inhibit BSEP and induce CYP7A1 expression independent of small heterodimer partner (SHP) expression, leading to increased bile acid (BA) production and demonstrating clinically elevated drug-induced liver toxicity. MEK1/2 inhibitors that show BSEP-independent drug-induced liver injury (DILI) induced the CYP7A1 gene accompanied by SHP suppression. CYP7A1 induction via SHP-dependent or independent mechanisms can pose a risk for DILI, independently or in synergy with BSEP inhibition. Monitoring BA production in hepatocytes can reliably detect the total effects of BA-related gene regulation for de-risking.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Indazóis , Pirimidinas , Sulfonamidas , Humanos , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/genética , Doença Hepática Induzida por Substâncias e Drogas/genética , Omeprazol/efeitos adversos , Ácidos e Sais Biliares , Colesterol 7-alfa-Hidroxilase/metabolismo
7.
Cerebrovasc Dis ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38253035

RESUMO

OBJECTIVE: Aim of the present article was the demonstration of the institutional experience with the endovascular management of the anterior inferior cerebellar artery (AICA) aneurysms in order to propose a treatment algorithm. METHODS: Clinical data were obtained from 33 patients with 37 AICA aneurysms who had been surgically treated at the authors' hospital between 2010 and 2022. The patients' medical records, imaging data, and follow-up outcomes were retrospectively analyzed. RESULTS: All 33 patients (10 males, 23 females; mean age 54.88±12.49 years) underwent endovascular therapy for AICA aneurysms. The most common chief complaints were headache (87.9%), nausea and vomiting (57.6%), and alteration of consciousness (27.3%). 31 patients experienced subarachnoid hemorrhage (SAH). Regarding the AICA aneurysm location, 23 aneurysms were found at the right side of AICA in DSA images, and there were 6, 9, 16, 6 aneurysms in segments A1-A4, respectively. Coiling (59.5%), Onyx embolization (29.7%), coiling-combined Onyx embolization (5.4%), non-intervention (5.4%) were chosen in the surgical strategy. The length of follow-up was 8.09±5.05 months, and 84.8% of the patients had favorable modified Rankin Scale (mRS) scores. The complete occlusion rates were 94.6%. Postoperative complications occurred in 4 cases (12.1 %), including new neurological deficit in 3 cases and cerebral infarction in 1 case. 1 patient died after follow-up because of the severe pneumonia. Poor initial Hunt and Hess grade (HHG) (p=0.007) was the risk factor for unfavorable clinical outcome. The rupture status (p=0.025) and the location (p=0.021) of the AICA aneurysms are statistically significant in determining which operation strategy to be chosen. Coiling had an advantage over Onyx embolization (P=0.001) in parent artery preservation (PAP). CONCLUSIONS: In this study, an algorithm for the treatment of AICA aneurysms was proposed based on the clinical status of the patients before treatment, the anatomical factors of AICA and the technical conditions of EVT. To our knowledge, this is the first study to report more than 30 cases of AICA aneurysms that had been treated by EVT and to advocate a treatment algorithm. EVT of AICA aneurysms is an optional strategy, but decisions are made based on the specific condition, anatomical location and other factors.

8.
Environ Sci Technol ; 58(20): 8685-8695, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38709795

RESUMO

Forecasting alterations in ambient air pollution and the consequent health implications is crucial for safeguarding public health, advancing environmental sustainability, informing economic decision making, and promoting appropriate policy and regulatory action. However, predicting such changes poses a substantial challenge, requiring accurate data, sophisticated modeling methodologies, and a meticulous evaluation of multiple drivers. In this study, we calculate premature deaths due to ambient fine particulate matter (PM2.5) exposure in India from the 2020s (2016-2020) to the 2100s (2095-2100) under four different socioeconomic and climate scenarios (SSPs) based on four CMIP6 models. PM2.5 concentrations decreased in all SSP scenarios except for SSP3-7.0, with the lowest concentration observed in SSP1-2.6. The results indicate an upward trend in the five-year average number of deaths across all scenarios, ranging from 1.01 million in the 2020s to 4.12-5.44 million in the 2100s. Further analysis revealed that the benefits of reducing PM2.5 concentrations under all scenarios are largely mitigated by population aging and growth. These findings underscore the importance of proactive measures and an integrated approach in India to improve atmospheric quality and reduce vulnerability to aging under changing climate conditions.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Material Particulado , Índia , Humanos , Poluentes Atmosféricos/análise , Exposição Ambiental , Clima
9.
Nucleic Acids Res ; 50(D1): D1448-D1455, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34718712

RESUMO

The advent of single-cell sequencing opened a new era in transcriptomic and genomic research. To understand cell composition using single-cell studies, a variety of cell markers have been widely used to label individual cell types. However, the specific database of cell markers for use by the plant research community remains very limited. To overcome this problem, we developed the Plant Cell Marker DataBase (PCMDB, http://www.tobaccodb.org/pcmdb/), which is based on a uniform annotation pipeline. By manually curating over 130 000 research publications, we collected a total of 81 117 cell marker genes of 263 cell types in 22 tissues across six plant species. Tissue- and cell-specific expression patterns can be visualized using multiple tools: eFP Browser, Bar, and UMAP/TSNE graph. The PCMDB also supports several analysis tools, including SCSA and SingleR, which allows for user annotation of cell types. To provide information about plant species currently unsupported in PCMDB, potential marker genes for other plant species can be searched based on homology with the supported species. PCMDB is a user-friendly hierarchical platform that contains five built-in search engines. We believe PCMDB will constitute a useful resource for researchers working on cell type annotation and the prediction of the biological function of individual cells.


Assuntos
Bases de Dados Genéticas , Marcadores Genéticos/genética , Plantas/genética , Software , Biologia Computacional , Genômica , Células Vegetais/classificação , Plantas/classificação , Transcriptoma/genética , Interface Usuário-Computador
10.
BMC Oral Health ; 24(1): 993, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39182077

RESUMO

BACKGROUND: Periodontitis is the sixth-most common disease worldwide. The oral microbiome composition and its association with Periodontal disease (PD) have been largely explored; however, limited studies have explored the microbial profiles of both oral and toothbrushes in patients with PD. Thus, this study aimed to ascertain the oral and toothbrushes microbial composition in high-altitude populations, hypothesizing that their correlation with periodontal health would differ from those at lower altitudes, potentially indicating links between environmental factors, microbial colonization patterns, and periodontal health in distinct geographic contexts. METHODS: In the present study, we enrolled 35 individuals including 21 healthy and 14 diagnosed with PD from the Lhasa region of Tibet, China. Saliva and toothbrush samples were collected from each participant to assess the association between toothbrush usage and oral microbiome with PD using 16 S rRNA gene-specific V3-V4 regions sequencing. To assess the oral and toothbrush microbiome composition and diversity and its possible link to PD. RESULTS: Significantly higher Alpha diversity (Shannon index) was observed between the PD group and PD toothbrushes (p = 0.00021) and between the PD group and Healthy toothbrushes (p = 0.00041). The predominant species were Proteobacteria, Bacteroidota, Firmicutes, Actinobacteria, and Fusobacteria, with genera Pseudomonas, Veillonella, Neisseria, Acinetobacter, and Haemophilus. In addition, PICRUST2 analysis unveiled 44 significant pathways differentiating the disease and healthy groups, along with 29 pathways showing significant differences between their respective toothbrush microbial profiles. The distinct oral and toothbrush microbial composition among high-altitude populations suggests potential adaptations to the challenges of high-altitude environments. CONCLUSION: This study emphasizes the importance of tailored dental care strategies, accounting for altitude and racial factors, to effectively manage periodontal health in these communities. Further research is warranted to investigate the specific microbial mechanisms and develop targeted interventions for optimizing oral health in populations across varying altitudes.


Assuntos
Altitude , Doenças Periodontais , Escovação Dentária , Humanos , Masculino , Estudos de Casos e Controles , Feminino , Escovação Dentária/instrumentação , Adulto , Doenças Periodontais/microbiologia , Pessoa de Meia-Idade , Microbiota , Tibet , Saliva/microbiologia , Boca/microbiologia
11.
J Cell Mol Med ; 27(7): 991-1005, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36915230

RESUMO

Cyclin D1 (CCND1), a mediator of cell cycle control, has a G870A polymorphism which results in the formation of two splicing variants: full-length CCND1 (CCND1a) and C-terminally truncated CCND1 species (CCND1b). However, the role of CCND1a and CCND1b variants in cancer chemoresistance remains unknown. Therefore, this study aimed to explore the molecular mechanism of alternative splicing of CCND1 in breast cancer (BC) chemoresistance. To address the contribution of G870A polymorphism to the production of CCND1 variants in BC chemoresistance, we sequenced the G870A polymorphism and analysed the expressions of CCND1a and CCND1b in MCF-7 and MCF-7/ADM cells. In comparison with MCF-7 cells, MCF-7/ADM cells with the A allele could enhance alternative splicing with the increase of SC-35, upregulate the ratio of CCND1b/a at both mRNA and protein levels, and activate the CDK4/CyclinD1-pRB-E2F1 pathway. Furthermore, CCND1b expression and the downstream signalling pathway were analysed through Western blotting and cell cycle in MCF-7/ADM cells with knockdown of CCND1b. Knockdown of CCND1b downregulated the ratio of CCND1b/a, demoted cell proliferation, decelerated cell cycle progression, inhibited the CDK4/CyclinD1-pRB-E2F1 pathway and thereby decreased the chemoresistance of MCF-7/ADM cells. Finally, CCND1 G870A polymorphism, the alternative splicing of CCDN1 was detected through Sequenom Mass ARRAY platform, Sanger sequencing, semi-quantitative RT-PCR, Western blotting and immunohistochemistry in clinical BC specimens. The increase of the ratio of CCND1b/a caused by G870A polymorphism was involved in BC chemoresistance. Thus, these findings revealed that CCND1b/a ratio caused by the polymorphism is involved in BC chemoresistance via CDK4/CyclinD1-pRB-E2F1 pathway.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Processamento Alternativo/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Ciclina D1/genética , Quinase 4 Dependente de Ciclina/genética , Resistencia a Medicamentos Antineoplásicos/genética , Fator de Transcrição E2F1/genética , Polimorfismo Genético , Proteína do Retinoblastoma/metabolismo
12.
BMC Genomics ; 24(1): 194, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37046216

RESUMO

BACKGROUND: Maize has many kernel colors, from white to dark black. However, research on the color and nutritional quality of the different varieties is limited. The color of the maize grain is an important characteristic. Colored maize is rich in nutrients, which have received attention for their role in diet-related chronic diseases and have different degrees of anti-stress protection for animal and human health. METHODS: A comprehensive metabolome (LC-MS/MS) and transcriptome analysis was performed in this study to compare different colored maize varieties from the perspective of multiple recombination in order to study the nutritional value of maize with different colors and the molecular mechanism of color formation. RESULTS: Maize kernels with diverse colors contain different types of health-promoting compounds, highlighting that different maize varieties can be used as functional foods according to human needs. Among them, red-purple and purple-black maize contain more flavonoids than white and yellow kernels. Purple-black kernels have a high content of amino acids and nucleotides, while red-purple kernels significantly accumulate sugar alcohols and lipids. CONCLUSION: Our study can provide insights for improving people's diets and provide a theoretical basis for the study of food structure for chronic diseases.


Assuntos
Transcriptoma , Zea mays , Animais , Humanos , Zea mays/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Perfilação da Expressão Gênica , Cor
13.
Curr Issues Mol Biol ; 45(7): 6067-6084, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37504299

RESUMO

(1) Background: Sophora subprostrate, is the dried root and rhizome of Sophora tonkinensis Gagnep. Sophora subprostrate polysaccharide (SSP1) was extracted from Sophora subprostrate, which has shown good anti-inflammatory and antioxidant effects. Previous studies showed SSP1 could modulate inflammatory damage induced by porcine circovirus type 2 (PCV2) in murine splenic lymphocytes, but the specific regulatory mechanism is unclear. (2) Methods: Whole transcriptome analysis was used to characterize the differentially expressed mRNA, lncRNA, and miRNA in PCV2-infected cells and SSP1-treated infected cells. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and other analyses were used to screen for key inflammation-related differentially expressed genes. The sequencing results were verified by RT-qPCR, and western blot was used to verify the key protein in main enriched signal pathways. (3) Results: SSP1 can regulate inflammation-related gene changes induced by PCV2, and its interventional mechanism is mainly involved in the key differential miRNA including miR-7032-y, miR-328-y, and miR-484-z. These inflammation-related genes were mainly enriched in the TNF signal pathway and NF-κB signal pathway, and SSP1 could significantly inhibit the protein expression levels of p-IκB, p-p65, TNF-α, IRF1, GBP2 and p-SAMHD1 to alleviate inflammatory damage. (4) Conclusions: The mechanism of SSP1 regulating PCV2-induced murine splenic lymphocyte inflammation was explored from a whole transcriptome perspective, which provides a theoretical basis for the practical application of SSP1.

14.
New Phytol ; 238(4): 1420-1430, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36843251

RESUMO

The basal levels of salicylic acid (SA) vary dramatically among plant species. In the shoot, for example, rice contains almost 100 times higher SA levels than Arabidopsis. Despite its high basal levels, neither the biosynthetic pathway nor the biological functions of SA are well understood in rice. Combining with metabolite analysis, physiological, and genetic approaches, we found that the synthesis of basal SA in rice shoot is dependent on OsAIM1, which encodes a beta-oxidation enzyme in the phenylalanine ammonia-lyase (PAL) pathway. Compromised SA accumulation in the Osaim1 mutant led to a lower shoot temperature than wild-type plants. However, this shoot temperature defect resulted from increased transpiration due to elevated steady-state stomatal aperture in the mutant. Furthermore, the high basal SA level is required for sustained expression of OsWRKY45 to modulate the steady-state stomatal aperture and shoot temperature in rice. Taken together, these results provide the direct genetic evidence for the critical role of the PAL pathway in the biosynthesis of high basal level SA in rice, which plays an important role in the regulation of steady-state stomatal aperture to promote fitness under stress conditions.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Oryza , Oryza/metabolismo , Ácido Salicílico/metabolismo , Plantas/metabolismo , Arabidopsis/genética , Fenilalanina Amônia-Liase/genética , Fenilalanina Amônia-Liase/metabolismo , Regulação da Expressão Gênica de Plantas , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/metabolismo , Proteínas de Arabidopsis/metabolismo
15.
BMC Cardiovasc Disord ; 23(1): 523, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891491

RESUMO

BACKGROUND: Metabolic disorders were a health problem for many adults with congenital heart disease, however, the differences in metabolic syndrome-related metabolite levels in adults with congenital heart disease compared to the healthy population were unknown. METHODS: We collected 18 studies reporting metabolic syndrome-associated metabolite levels in patients with congenital heart disease. Data from different studies were combined under a random-effects model using Cohen's d values. RESULTS: The results found that the levels of total cholesterol (Cohen's d -0.68, 95% CI: -0.91 to -0.45), high-density lipoprotein cholesterol (Cohen's d -0.63, 95% CI: -0.89 to -0.37), and low-density lipoprotein cholesterol (Cohen's d -0.32, 95% CI: -0.54 to -0.10) were significantly lower in congenital heart disease patients compared with controls. Congenital heart disease patients also had a lower body mass index (Cohen's d -0.27, 95% CI: -0.42 to -0.12) compared with controls. On the contrary, congenital heart disease patients had higher levels of hemoglobin A1c (Cohen's d 0.93, 95% CI: 0.17 to 1.70) than controls. Meanwhile, there were no significant differences in triglyceride (Cohen's d 0.07, 95% CI: -0.09 to 0.23), blood glucose (Cohen's d -0.12, 95% CI: -0.94 to 0.70) levels, systolic (Cohen's d 0.07, 95% CI: -0.30 to 0.45) and diastolic blood pressure (Cohen's d -0.10, 95% CI: -0.39 to 0.19) between congenital heart disease patients and controls. CONCLUSIONS: The lipid levels in patients with congenital heart disease were significantly lower than those in the control group. These data will help in the health management of patients with congenital heart disease and guide clinicians. PROSPERO REGISTRATION NUMBER: CRD42022228156.


Assuntos
Cardiopatias Congênitas , Síndrome Metabólica , Humanos , Adulto , Triglicerídeos , Cardiopatias Congênitas/diagnóstico , HDL-Colesterol , LDL-Colesterol
16.
Zhongguo Zhong Yao Za Zhi ; 48(14): 3765-3773, 2023 Jul.
Artigo em Zh | MEDLINE | ID: mdl-37475068

RESUMO

Small-molecule compounds with rich sources have diverse structures and activities. The active ingredients in traditional Chinese medicine(TCM) provide new sources for the discovery of new antitumor drugs. Aconitum plants as Chinese medicinal plants have the effects of dispelling wind, removing dampness, warming meridian, and relieving pain. They are mainly used to treat inflammation, pain, rheumatism, and tumors, improve heart function, and dilate blood vessels in clinical practice. Diterpenoid alkaloids are the main active components of Aconitum plants, including C20-, C19-, C18-diterpenoid alkaloids and bis-diterpenoid alkaloids. Stu-dies have demonstrated that diterpenoid alkaloids can effectively treat lung cancer, liver cancer, breast cancer, colon cancer and other cancers. Diterpenoid alkaloids are considered as the most promising natural compounds against cancers. In this review, we summarized the chemical structures and antitumor activities of C20-, C19-, C18-diterpenoid alkaloids and bis-diterpenoid alkaloids extracted from plants of Aconitum, aiming to provide reference for further development of diterpenoid alkaloids from Aconitum as antitumor drugs.


Assuntos
Aconitum , Alcaloides , Antineoplásicos , Diterpenos , Humanos , Aconitum/química , Estrutura Molecular , Alcaloides/análise , Diterpenos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Raízes de Plantas/química
17.
Angew Chem Int Ed Engl ; 62(35): e202305896, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37438325

RESUMO

Membrane curvature reflects physical forces operating on the lipid membrane, which plays important roles in cellular processes. Here, we design a mechanosensitive DNA (MSD) nanomachine that mimics natural mechanosensitive PIEZO channels to convert the membrane tension changes of lipid vesicles with different sizes into fluorescence signals in real time. The MSD nanomachine consists of an archetypical six-helix-bundle DNA nanopore, cholesterol-based membrane anchors, and a solvatochromic fluorophore, spiropyran (SP). We find that the DNA nanopore effectively amplifies subtle variations of the membrane tension, which effectively induces the isomerization of weakly emissive SP into highly emissive merocyanine isomers for visualizing membrane tension changes. By measuring the membrane tension via the fluorescence of MSD nanomachine, we establish the correlation between the membrane tension and the curvature that follows the Young-Laplace equation. This DNA nanotechnology-enabled strategy opens new routes to studying membrane mechanics in physiological and pathological settings.


Assuntos
Nanoporos , Nanotecnologia , Fluorescência , DNA , Lipídeos , Membrana Celular
18.
Funct Integr Genomics ; 22(4): 537-552, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35404023

RESUMO

Starch is an important primary metabolite in plants, which can provide bioenergy for fuel ethanol production. There are many studies focusing on starch metabolism in Arabidopsis, maize, and rice, but few reports have been made on the starch content of tobacco leaves. Hence, to identify the marker-trait associations and isolate the candidate genes related to starch content of tobacco leaf, the genome-wide association study (GWAS) was performed using a multiparent advanced generation intercross (MAGIC) population consisting of 276 accessions genotyped by a 430 K SNP array. In this study, we detected the leaf starch content of tobacco plants cultivated in two places (Zhucheng and Chenzhou), which showed a wide variation of starch content in the population. A total of 28 and 45 significant single-nucleotide polymorphism (SNP) loci associated with leaf starch content were identified by single-locus and multi-locus GWAS models, respectively, and the phenotypic variance explained by these loci varied from 1.80 to - 14.73%. Furthermore, among these quantitative trait loci (QTLs), one SNP, AX-106011713 located on chromosome 19, was detected repeatedly in multiple models and two environments, which was selected for linkage disequilibrium (LD) analysis to obtain the target candidate region. Through gene annotation, haplotype, and gene expression analysis, two candidate genes encoding E3 ubiquitin-protein ligase (Ntab0823160) and fructose-bisphosphate aldolase (Ntab0375050) were obtained. Results showed that the variety carrying the beneficial alleles of the two candidate genes had higher gene expression level and leaf starch content, suggesting the potential role of candidate genes in enhancing the level of tobacco leaf starch content. Furthermore, silencing of Ntab0823160 in tobacco leaves reduced the content of total starch to 39.41-69.75% of that in the wide type plants. Taken together, our results provide useful resources for further investigation of the starch metabolic pathway and are also beneficial for the creation of eco-friendly cultivars with increased accumulation of leaf starch content.


Assuntos
Estudo de Associação Genômica Ampla , Nicotiana , Mapeamento Cromossômico , Estudo de Associação Genômica Ampla/métodos , Desequilíbrio de Ligação , Fenótipo , Folhas de Planta/genética , Polimorfismo de Nucleotídeo Único , Amido/genética , Nicotiana/genética
19.
Neural Comput ; 34(8): 1812-1839, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35798326

RESUMO

Ultra-high-speed object detection and tracking are crucial in fields such as fault detection and scientific observation. Existing solutions to this task have deficiencies in processing speeds. To deal with this difficulty, we propose a neural-inspired ultra-high-speed moving object filtering, detection, and tracking scheme, as well as a corresponding accelerator based on a high-speed spike camera. We parallelize the filtering module and divide the detection module to accelerate the algorithm and balance latency among modules for the benefit of the task-level pipeline. To be specific, a block-based parallel computation model is proposed to accelerate the filtering module, and the detection module is accelerated by a parallel connected component labeling algorithm modeling spike sparsity and spatial connectivity of moving objects with a searching tree. The hardware optimizations include processing the LIF layer with a group of multiplexers to reduce ADD operations and replacing expensive exponential operations with multiplications of preprocessed fixed-point values to increase processing speed and minimize resource consumption. We design an accelerator with the above techniques, achieving 19 times acceleration over the serial version after 25-way parallelization. A processing system for the accelerator is also implemented on the Xilinx ZCU-102 board to validate its functionality and performance. Our accelerator can process more than 20,000 spike images with 250 × 400 resolution per second with 1.618 W dynamic power consumption.

20.
Environ Sci Technol ; 56(16): 11212-11224, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35925776

RESUMO

The Community Multiscale Air Quality model (CMAQv5.2) was implemented to investigate the sources and sinks of oxygenated volatile organic compounds (OVOCs) during a high O3 and high PM2.5 season in the Yangtze River Delta (YRD) region, based on constraints from observations. The model tends to overpredict non-oxygenated VOCs and underpredict OVOCs, which has been improved with adjusted emissions of all VOCs. The OVOCs in the YRD are dominated by ketones, aldehydes, and alcohols. Ketones and aldehydes mainly originate from direct emissions and secondary formation in the northern YRD, and primarily originate from secondary formation in the southern part influenced by biogenic emissions. The concentration of secondary organic aerosols (SOA) produced by OVOCs is 0.5-1.5 µg/m3, with 40-80% originated from organic nitrates, 20-70% originated from dicarbonyls, and 0-20% originated from isoprene epoxydiols. The influences of OVOCs on the atmospheric oxidation capacity are dominated by the OH• pathway during the day (∼350%) and by the NO3• pathway at night (∼150%). Consequently, O3 is enhanced by 30-70% in the YRD. Aerosols are also enhanced by 50-140%, 20-80%, and ∼20% for SOA, nitrate, and sulfate, respectively.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Aerossóis/análise , Poluentes Atmosféricos/análise , Aldeídos , China , Monitoramento Ambiental , Cetonas , Ozônio/análise
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