Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 62
Filtrar
Más filtros













Base de datos
Intervalo de año de publicación
1.
ACS Nano ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38876985

RESUMEN

Nonlead low-dimensional halide perovskites attract considerable attention as X-ray scintillators. However, most scintillation screens exhibit pronounced light scattering, which detrimentally reduces the quality of X-ray imaging. Herein, we employed a simple and straightforward solvent-free melt-quenching method to fabricate a large-area zero-dimension (0D) antimony-based perovskite transparent medium, namely (C20H20P)2SbCl5 (C20H20P+ = ethyltriphenylphosphine). The transparency is due to the large steric hindrance of C20H20P+, which hinders the formation of crystals during the quenching process, thus forming a glass with low refractive index and uniform structure. This medium exhibits a high transmittance exceeding 80% in the range of 450-800 nm and shows a large Stokes shift of 245 nm, thereby minimizing light scattering, mitigating self-absorption, and enhancing the clarity of X-ray imaging. Moreover, it exhibits a high radioluminescence light yield of ∼12,535 photons MeV-1 and displays a high X-ray spatial resolution of 30 lp mm-1 owing to its high transparency. This study presents an alternative candidate for achieving high-quality X-ray detection and extends the applicability of transparent perovskite scintillators.

2.
Cell Death Differ ; 31(3): 348-359, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38332048

RESUMEN

Hereditary spastic paraplegia (HSP) is a group of inherited neurodegenerative disorders characterized by progressive lower limb spasticity and weakness. One subtype of HSP, known as SPG54, is caused by biallelic mutations in the DDHD2 gene. The primary pathological feature observed in patients with SPG54 is the massive accumulation of lipid droplets (LDs) in the brain. However, the precise mechanisms and roles of DDHD2 in regulating lipid homeostasis are not yet fully understood. Through Affinity Purification-Mass Spectroscopy (AP-MS) analysis, we identify that DDHD2 interacts with multiple members of the ATG8 family proteins (LC3, GABARAPs), which play crucial roles in lipophagy. Mutational analysis reveals the presence of two authentic LIR motifs in DDHD2 protein that are essential for its binding to LC3/GABARAPs. We show that DDHD2 deficiency leads to LD accumulation, while enhanced DDHD2 expression reduces LD formation. The LC3/GABARAP-binding capacity of DDHD2 and the canonical autophagy pathway both contribute to its LD-eliminating activity. Moreover, DDHD2 enhances the colocalization between LC3B and LDs to promote lipophagy. LD·ATTEC, a small molecule that tethers LC3 to LDs to enhance their autophagic clearance, effectively counteracts DDHD2 deficiency-induced LD accumulation. These findings provide valuable insights into the regulatory roles of DDHD2 in LD catabolism and offer a potential therapeutic approach for treating SPG54 patients.


Asunto(s)
Fosfolipasas , Paraplejía Espástica Hereditaria , Humanos , Autofagia/genética , Familia de las Proteínas 8 Relacionadas con la Autofagia , Mutación/genética , Fosfolipasas/genética , Paraplejía Espástica Hereditaria/genética , Paraplejía Espástica Hereditaria/patología
3.
Nucleic Acids Res ; 52(D1): D835-D849, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-37889051

RESUMEN

The high cost of large-scale, high-coverage whole-genome sequencing has limited its application in genomics and genetics research. The common approach has been to impute whole-genome sequence variants obtained from a few individuals for a larger population of interest individually genotyped using SNP chip. An alternative involves low-coverage whole-genome sequencing (lcWGS) of all individuals in the larger population, followed by imputation to sequence resolution. To overcome limitations of processing lcWGS data and meeting specific genotype imputation requirements, we developed AGIDB (https://agidb.pro), a website comprising tools and database with an unprecedented sample size and comprehensive variant decoding for animals. AGIDB integrates whole-genome sequencing and chip data from 17 360 and 174 945 individuals, respectively, across 89 species to identify over one billion variants, totaling a massive 688.57 TB of processed data. AGIDB focuses on integrating multiple genotype imputation scenarios. It also provides user-friendly searching and data analysis modules that enable comprehensive annotation of genetic variants for specific populations. To meet a wide range of research requirements, AGIDB offers downloadable reference panels for each species in addition to its extensive dataset, variant decoding and utility tools. We hope that AGIDB will become a key foundational resource in genetics and breeding, providing robust support to researchers.


Asunto(s)
Bases de Datos Genéticas , Genómica , Polimorfismo de Nucleótido Simple , Animales , Humanos , Genoma , Estudio de Asociación del Genoma Completo , Genotipo , Análisis de Secuencia , Uso de Internet
4.
Sci Bull (Beijing) ; 68(23): 3013-3026, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37940449

RESUMEN

Increased mitochondrial damage plays a critical role in many neurodegeneration-related diseases such as Parkinson's disease (PD) and Down syndrome (DS). Thus, enhancement of mitochondrial degradation by small molecule compounds may provide promising new strategies to tackle these diseases. Here, we explored the strategy to induce clearance of mitochondria by targeting them to the autophagy machinery by autophagy-tethering compounds (ATTECs). We provided the proof-of-concept evidence demonstrating that the bifunctional compound (mT1) binding to both the outer mitochondrial membrane protein TSPO and the autophagosome protein LC3B simultaneously may enhance the engulfment of damaged mitochondria by autophagosomes and subsequent autophagic degradation of them. In addition, preliminary experiments suggest that mT1 attenuated disease-relevant phenotypes in both a PD cellular model and a DS organoid model. Taken together, we demonstrate the possibility of degrading mitochondria by bifunctional ATTECs, which confirms the capability of degrading organelles by ATTECs and provides potential new strategies in the intervention of mitochondria-related disorders.


Asunto(s)
Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Autofagia/genética , Mitocondrias/metabolismo , Autofagosomas/metabolismo , Mitofagia , Membranas Mitocondriales/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedades Neurodegenerativas/metabolismo , Receptores de GABA/metabolismo
5.
Pharm Res ; 40(11): 2541-2554, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37498500

RESUMEN

BACKGROUND: Cerebral vascular protection is critical for stroke treatment. Adenosine modulates vascular flow and exhibits neuroprotective effects, in which brain extracellular concentration of adenosine is dramatically increased during ischemic events and ischemia-reperfusion. Since the equilibrative nucleoside transporter-2 (Ent2) is important in regulating brain adenosine homeostasis, the present study aimed to investigate the role of Ent2 in mice with cerebral ischemia-reperfusion. METHODS: Cerebral ischemia-reperfusion injury was examined in mice with transient middle cerebral artery occlusion (tMCAO) for 90 minutes, followed by 24-hour reperfusion. Infarct volume, brain edema, neuroinflammation, microvascular structure, regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (CMRO2), and the production of reactive oxygen species (ROS) were examined following the reperfusion. RESULTS: Ent2 deletion reduced the infarct volume, brain edema, and neuroinflammation in mice with cerebral ischemia-reperfusion. tMCAO-induced disruption of brain microvessels was ameliorated in Ent2-/- mice, with a reduced expression of matrix metalloproteinases-9 and aquaporin-4 proteins. Following the reperfusion, the rCBF of the wild-type (WT) mice was quickly restored to the baseline, whereas, in Ent2-/- mice, rCBF was slowly recovered initially, but was then higher than that in the WT mice at the later phase of reperfusion. The improved CMRO2 and reduced ROS level support the beneficial effects caused by the changes in the rCBF of Ent2-/- mice. Further studies showed that the protective effects of Ent2 deletion in mice with tMCAO involve adenosine receptor A2AR. CONCLUSIONS: Ent2 plays a critical role in modulating cerebral collateral circulation and ameliorating pathological events of brain ischemia and reperfusion injury.


Asunto(s)
Edema Encefálico , Isquemia Encefálica , Daño por Reperfusión , Animales , Ratones , Adenosina , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/patología , Isquemia Encefálica/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Enfermedades Neuroinflamatorias , Proteínas de Transporte de Nucleósidos , Especies Reactivas de Oxígeno/metabolismo , Reperfusión , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo
6.
BMC Plant Biol ; 23(1): 327, 2023 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-37340442

RESUMEN

BACKGROUND: Valine-glutamine (VQ) proteins are non-specific plant proteins that have a highly conserved motif: FxxhVQxhTG. These proteins are involved in the development of various plant organs such as seeds, hypocotyls, flowers, leaves and also play a role in response to salt, drought and cold stresses. Despite their importance, there is limited information available on the evolutionary and structural characteristics of VQ family genes in Coix lacryma-jobi. RESULTS: In this study, a total of 31 VQ genes were identified from the coix genome and classified into seven subgroups (I-VII) based on phylogenetic analysis. These genes were found to be unevenly distributed on 10 chromosomes. Gene structure analysis revealed that these genes had a similar type of structure within each subfamily. Moreover, 27 of ClVQ genes were found to have no introns. Conserved domain and multiple sequence alignment analysis revealed the presence of a highly conserved sequences in the ClVQ protein. This research utilized quantitative real-time PCR (qRT-PCR) and promoter analysis to investigate the expression of ClVQ genes under different stress conditions. Results showed that most ClVQ genes responded to polyethylene glycol, heat treatment, salt, abscisic acid and methyl jasmonate treatment with varying degrees of expression. Furthermore, some ClVQ genes exhibited significant correlation in expression changes under abiotic stress, indicating that these genes may act synergistically in response to adversarial stress. Additionally, yeast dihybrid verification revealed an interaction between ClVQ4, ClVQ12, and ClVQ26. CONCLUSIONS: This study conducted a genome-wide analysis of the VQ gene family in coix, including an examination of phylogenetic relationships, conserved domains, cis-elements and expression patterns. The goal of the study was to identify potential drought resistance candidate genes, providing a theoretical foundation for molecular resistance breeding.


Asunto(s)
Coix , Coix/genética , Filogenia , Genoma , Proteínas de Plantas/química , Estrés Fisiológico/genética
8.
Autophagy ; 19(10): 2668-2681, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37266932

RESUMEN

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly, and there is currently no clinical treatment targeting the primary impairment of AMD. The earliest clinical hallmark of AMD is drusen, which are yellowish spots mainly composed of lipid droplets (LDs) accumulated under the retinal pigment epithelium (RPE). However, the potential pathogenic role of this excessive LD accumulation in AMD is yet to be determined, partially due to a lack of chemical tools to manipulate LDs specifically. Here, we employed our recently developed Lipid Droplets·AuTophagy Tethering Compounds (LD∙ATTECs) to degrade LDs and to evaluate its consequence on the AMD-like phenotypes in apoe-/- (apolipoprotein E; B6/JGpt-Apoeem1Cd82/Gpt) mouse model. apoe-/- mice fed with high-fat diet (apoe-/--HFD) exhibited excessive LD accumulation in the retina, particularly with AMD-like phenotypes including RPE degeneration, Bruch's membrane (BrM) thickening, drusen-like deposits, and photoreceptor dysfunction. LD·ATTEC treatment significantly cleared LDs in RPE/choroidal tissues without perturbing lipid synthesis-related proteins and rescued RPE degeneration and photoreceptor dysfunction in apoe-/--HFD mice. This observation implied a causal relationship between LD accumulation and AMD-relevant phenotypes. Mechanically, the apoe-/--HFD mice exhibited elevated oxidative stress and inflammatory signals, both of which were mitigated by the LD·ATTEC treatment. Collectively, this study demonstrated that LD accumulation was a trigger for the process of AMD and provided entry points for the treatment of the initial insult of AMD by degrading LDs.Abbreviations: AMD: age-related macular degeneration; APOE: apolipoprotein E; ATTECs: autophagy-tethering compounds; BODIPY: boron-dipyrromethene; BrM: Bruch's membrane; ERG: electroretinogram; HFD: high-fat diet; LD·ATTECs: Lipid Droplets·AuTophagy Tethering Compounds; LDs: lipid droplets; OA: oleic acid; OPL: outer plexiform layer; ROS: reactive oxygen species; RPE: retinal pigment epithelium.


Asunto(s)
Gotas Lipídicas , Degeneración Macular , Ratones , Animales , Gotas Lipídicas/metabolismo , Autofagia , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/metabolismo , Degeneración Macular/patología , Epitelio Pigmentado de la Retina/metabolismo , Apolipoproteínas E , Fenotipo , Apolipoproteínas/metabolismo
9.
Phenomics ; 3(2): 119-129, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37197643

RESUMEN

Lipid droplets (LDs) are intracellular organelles that store neutral lipids, and their aberrant accumulation is associated with many diseases including metabolic disorders such as obesity and diabetes. Meanwhile, the potential pathological contributions of LDs in these diseases are unclear, likely due to a lack of chemical biology tools to clear LDs. We recently developed LD-clearance small molecule compounds, Lipid Droplets·AuTophagy TEthering Compounds (LD·ATTECs), that are able to induce autophagic clearance of LDs in cells and in the liver of db/db (C57BL/6J Leprdb/Leprdb) mouse model, which is a widely used genetic model for obesity-diabetes. Meanwhile, the potential effects on the metabolic phenotype remain to be elucidated. Here, using the metabolic cage assay and the blood glucose assay, we performed phenotypic characterization of the effects of the autophagic degradation of LDs by LD·ATTECs in the db/db mouse model. The study reveals that LD·ATTECs increased the oxygen uptake of mice and the release of carbon dioxide, enhanced the heat production of animals, partially enhanced the exercise during the dark phase, decreased the blood glucose level and improved insulin sensitivity. Collectively, the study characterized the metabolic phenotypes induced by LD·ATTECs in an obesity-diabetes mouse model, revealing novel functional impacts of autophagic clearance of LDs and providing insights into LD biology and obesity-diabetes pathogenesis from the phenotypic perspective.

10.
Front Cell Dev Biol ; 11: 1125723, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36923253

RESUMEN

Pulmonary hypertension (PH) is a group of syndromes characterized by irreversible vascular remodeling and persistent elevation of pulmonary vascular resistance and pressure, leading to ultimately right heart failure and even death. Current therapeutic strategies mainly focus on symptoms alleviation by stimulating pulmonary vessel dilation. Unfortunately, the mechanism and interventional management of vascular remodeling are still yet unrevealed. Hypoxia plays a central role in the pathogenesis of PH and numerous studies have shown the relationship between PH and hypoxia-inducible factors family. EPAS1, known as hypoxia-inducible factor-2 alpha (HIF-2α), functions as a transcription factor participating in various cellular pathways. However, the detailed mechanism of EPAS1 has not been fully and systematically described. This article exhibited a comprehensive summary of EPAS1 including the molecular structure, biological function and regulatory network in PH and other relevant cardiovascular diseases, and furthermore, provided theoretical reference for the potential novel target for future PH intervention.

11.
Nucleic Acids Res ; 51(8): 3501-3512, 2023 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-36809800

RESUMEN

Human diseases and agricultural traits can be predicted by modeling a genetic random polygenic effect in linear mixed models. To estimate variance components and predict random effects of the model efficiently with limited computational resources has always been of primary concern, especially when it involves increasing the genotype data scale in the current genomic era. Here, we thoroughly reviewed the development history of statistical algorithms used in genetic evaluation and theoretically compared their computational complexity and applicability for different data scenarios. Most importantly, we presented a computationally efficient, functionally enriched, multi-platform and user-friendly software package named 'HIBLUP' to address the challenges that are faced currently using big genomic data. Powered by advanced algorithms, elaborate design and efficient programming, HIBLUP computed fastest while using the lowest memory in analyses, and the greater the number of individuals that are genotyped, the greater the computational benefits from HIBLUP. We also demonstrated that HIBLUP is the only tool which can accomplish the analyses for a UK Biobank-scale dataset within 1 h using the proposed efficient 'HE + PCG' strategy. It is foreseeable that HIBLUP will facilitate genetic research for human, plants and animals. The HIBLUP software and user manual can be accessed freely at https://www.hiblup.com.


Both human diseases and agricultural traits can be predicted by incorporating phenotypic observations and a relationship matrix among individuals in a linear mixed model. Due to the great demand for processing massive data of genotyped individuals, the existing algorithms that require several repetitions of inverse computing on increasingly big dense matrices (e.g. the relationship matrix and the coefficient matrix of mixed model equations) have encountered a bottleneck. Here, we presented a software tool named 'HIBLUP' to address the challenges. Powered by our advanced algorithms (e.g. HE + PCG), elaborate design and efficient programming, HIBLUP can successfully avoid the inverse computing for any big matrix and compute fastest under the lowest memory, which makes it very promising for genetic evaluation using big genomic data.


Asunto(s)
Genómica , Modelos Genéticos , Animales , Humanos , Algoritmos , Genoma , Genotipo , Modelos Lineales
12.
Brief Bioinform ; 24(1)2023 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-36575830

RESUMEN

Creating synthetic lines is the standard mating mode for commercial pig production. Traditional mating performance was evaluated through a strictly designed cross-combination test at the 'breed level' to maximize the benefits of production. The Duroc-Landrace-Yorkshire (DLY) three-way crossbred production system became the most widely used breeding scheme for pigs. Here, we proposed an 'individual level' genomic mating procedure that can be applied to commercial pig production with efficient algorithms for estimating marker effects and for allocating the appropriate boar-sow pairs, which can be freely accessed to public in our developed HIBLUP software at https://www.hiblup.com/tutorials#genomic-mating. A total of 875 Duroc boars, 350 Landrace-Yorkshire sows and 3573 DLY pigs were used to carry out the genomic mating to assess the production benefits theoretically. The results showed that genomic mating significantly improved the performances of progeny across different traits compared with random mating, such as the feed conversion rate, days from 30 to 120 kg and eye muscle area could be improved by -0.12, -4.64 d and 2.65 cm2, respectively, which were consistent with the real experimental validations. Overall, our findings indicated that genomic mating is an effective strategy to improve the performances of progeny by maximizing their total genetic merit with consideration of both additive and dominant effects. Also, a herd of boars from a richer genetic source will increase the effectiveness of genomic mating further.


Asunto(s)
Comunicación Celular , Genómica , Porcinos/genética , Animales , Femenino , Masculino , Cruzamientos Genéticos , Fenotipo
13.
Nucleic Acids Res ; 51(D1): D1312-D1324, 2023 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-36300629

RESUMEN

With the exponential growth of multi-omics data, its integration and utilization have brought unprecedented opportunities for the interpretation of gene regulation mechanisms and the comprehensive analyses of biological systems. IAnimal (https://ianimal.pro/), a cross-species, multi-omics knowledgebase, was developed to improve the utilization of massive public data and simplify the integration of multi-omics information to mine the genetic mechanisms of objective traits. Currently, IAnimal provides 61 191 individual omics data of genome (WGS), transcriptome (RNA-Seq), epigenome (ChIP-Seq, ATAC-Seq) and genome annotation information for 21 species, such as mice, pigs, cattle, chickens, and macaques. The scale of its total clean data has reached 846.46 TB. To better understand the biological significance of omics information, a deep learning model for IAnimal was built based on BioBERT and AutoNER to mine 'gene' and 'trait' entities from 2 794 237 abstracts, which has practical significance for comprehending how each omics layer regulates genes to affect traits. By means of user-friendly web interfaces, flexible data application programming interfaces, and abundant functional modules, IAnimal enables users to easily query, mine, and visualize characteristics in various omics, and to infer how genes play biological roles under the influence of various omics layers.


Asunto(s)
Bases de Datos Genéticas , Animales , Regulación de la Expresión Génica , Genoma , Bases del Conocimiento , Programas Informáticos , Multiómica
14.
Front Plant Sci ; 13: 955904, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35968134

RESUMEN

Canna edulis Ker-Gawl and Canna indica L. are species belonging to the Cannaceae family and both have a very high economic value. Here, we aimed to assemble genomes of C. edulis and C. indica at the chromosome level to generate a reference genome for the Cannaceae family. We also comparatively analyzed the genomes of C. edulis and C. indica and examined the molecular mechanisms responsible for the remarkable differences in plant characteristics in C. edulis varieties. Our results indicated that genome-wide duplication events had recently occurred in C. edulis and C. indica. The comparative analysis of the genomes of C. edulis and C. indica revealed that C. edulis exhibited a remarkable level of replication of genes in the starch and sucrose metabolic pathways, especially during sucrose hydrolysis. This finding is consistent with the fact that the starch content of the C. edulis tuber is higher than that of C. indica. Simplified genome re-sequencing revealed the population structure of 241 C. edulis genes, and a genome-wide association study of leaf traits revealed the location of key genes related to leaf color and morphology. These findings extend our understanding of Cannaceade at the molecular level, and provide an effective theoretical basis for further study and utilization of Cannaceae plants.

16.
BMC Biol ; 20(1): 136, 2022 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-35681201

RESUMEN

BACKGROUND: Gene expression programs are intimately linked to the interplay of active cis regulatory elements mediated by chromatin contacts and associated RNAs. Genome-wide association studies (GWAS) have identified many variants in these regulatory elements that can contribute to phenotypic diversity. However, the functional interpretation of these variants remains nontrivial due to the lack of chromatin contact information or limited contact resolution. Furthermore, the distribution and role of chromatin-associated RNAs in gene expression and chromatin conformation remain poorly understood. To address this, we first present a comprehensive interaction map of nuclear dynamics of 3D chromatin-chromatin interactions (H3K27ac BL-HiChIP) and RNA-chromatin interactions (GRID-seq) to reveal genomic variants that contribute to complex skeletal muscle traits. RESULTS: In a genome-wide scan, we provide systematic fine mapping and gene prioritization from GWAS leading signals that underlie phenotypic variability of growth rate, meat quality, and carcass performance. A set of candidate functional variants and 54 target genes previously not detected were identified, with 71% of these candidate functional variants choosing to skip over their nearest gene to regulate the target gene in a long-range manner. The effects of three functional variants regulating KLF6 (related to days to 100 kg), MXRA8 (related to lean meat percentage), and TAF11 (related to loin muscle depth) were observed in two pig populations. Moreover, we find that this multi-omics interaction map consists of functional communities that are enriched in specific biological functions, and GWAS target genes can serve as core genes for exploring peripheral trait-relevant genes. CONCLUSIONS: Our results provide a valuable resource of candidate functional variants for complex skeletal muscle-related traits and establish an integrated approach to complement existing 3D genomics by exploiting RNA-chromatin and chromatin-chromatin interactions for future association studies.


Asunto(s)
Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Animales , Cromatina/genética , Músculo Esquelético , Polimorfismo de Nucleótido Simple , ARN , Porcinos
18.
ACS Synth Biol ; 11(1): 383-396, 2022 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-34937346

RESUMEN

Rapid diagnosis based on naked-eye colorimetric detection remains challenging, but it could build new capacities for molecular point-of-care testing (POCT). In this study, we evaluated the performance of 16 types of single-stranded DNA-fluorophore-quencher (ssDNA-FQ) reporters for use with clusters of regularly spaced short palindrome repeats (CRISPR)/Cas12a-based visual colorimetric assays. Among them, nine ssDNA-FQ reporters were found to be suitable for direct visual colorimetric detection, with especially very strong performance using ROX-labeled reporters. We optimized the reaction concentrations of these ssDNA-FQ reporters for a naked-eye read-out of assay results (no transducing component required for visualization). In particular, we developed a convolutional neural network algorithm to standardize and automate the analytical colorimetric assessment of images and integrated this into the MagicEye mobile phone software. A field-deployable assay platform named RApid VIsual CRISPR (RAVI-CRISPR) based on a ROX-labeled reporter with isothermal amplification and CRISPR/Cas12a targeting was established. We deployed RAVI-CRISPR in a single tube toward an instrument-less colorimetric POCT format that required only a portable rechargeable hand warmer for incubation. The RAVI-CRISPR was successfully used for the high-sensitivity detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and African swine fever virus (ASFV). Our study demonstrates this RAVI-CRISPR/MagicEye system to be suitable for distinguishing different pathogenic nucleic acid targets with high specificity and sensitivity as the simplest-to-date platform for rapid pen- or bed-side testing.


Asunto(s)
Virus de la Fiebre Porcina Africana/genética , Fiebre Porcina Africana , Prueba de Ácido Nucleico para COVID-19 , COVID-19 , Sistemas CRISPR-Cas , SARS-CoV-2/genética , Fiebre Porcina Africana/diagnóstico , Fiebre Porcina Africana/genética , Animales , COVID-19/diagnóstico , COVID-19/genética , Colorimetría , Humanos , Porcinos
19.
Medicine (Baltimore) ; 101(51): e32340, 2022 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-36595789

RESUMEN

BACKGROUND: The mammalian target of rapamycin (mTOR) has a crucial role in carcinogenesis, angiogenesis, cellular proliferation, and metastasis; however, its significance in non-small cell lung cancer (NSCLC) remains contentious. Consequently, this study aims to assess the clinicopathological and prognostic importance of mTOR/p-mTOR expression in NSCLC. METHODS: Literature retrieval was undertaken by searching English databases PubMed, EMBASE, Web of Science, and Cochrane Library as well as Chinese databases CNKI, Wan Fang, and VIP for full-text publications that satisfied our eligibility criteria up to November 2021. STATA 12.0 was used to conduct statistical analysis (STATA Corporation, College Station, TX). RESULTS: This meta-analysis includes a total of 4683 patients from 28 primary publications. mTOR/p-mTOR expression was associated with sex (OR = 0.608, 95% CI: 0.442-0.836), lymph node metastasis (OR = 2.084, 95% CI: 1.437-3.182), and CEA (OR = 1.584, 95% CI: 1.135-2.209), but not with age, histological type, depth of tumor invasion, distant metastasis, TNM stage, differentiation degree, tumor size, or smoking. In addition, the expression of mTOR/p-mTOR is related to shorter overall survival in NSCLC patients (HR = 1.415, 95% CI: 1.051-1.905). CONCLUSION: Positive mTOR/p-mTOR expression was substantially correlated with unfavorable conditions on the sex, lymph node metastases, and CEA levels. mTOR/p-mTOR may indicate a bad prognosis for NSCLC. The current findings must be confirmed and changed by other high-quality research employing a multivariate analysis on bigger sample size.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Pronóstico , Neoplasias Pulmonares/patología , Metástasis Linfática , Serina-Treonina Quinasas TOR/metabolismo , Biomarcadores de Tumor/metabolismo
20.
Ann Palliat Med ; 10(8): 9259-9266, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34488411

RESUMEN

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is a disease associated with elevated blood pressure during pregnancy, accounting for 5-10% of all pregnancies, which includes: gestational hypertension, preeclampsia (PE), eclampsia, chronic hypertension with superimposed PE and chronic hypertension. PE is the most prevalent type of HDP that seriously threatens the life and health of mothers and infants. In-depth exploration of the pathogenesis can play an early role in predicting the disease. METHODS: A literature search was conducted in PubMed, Embase, Google Scholar, and other databases in the article. It was investigated by searching for literature published between 1993 and March 2021; the subject terms included-"vascular endothelial growth factor", "preeclampsia", and "pathogenesis". In the article, the inclusion criteria of literature should meet the definition of PE. It was excluded as reviews, case reports, narrative reviews, and publications that lack key information. RESULTS: Vascular endothelial growth factor (VEGF) family factor research provides pivotal value for early clinical prediction of PE. Soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) became a marker for early prediction of PE. Through the included 51 articles, the analysis of VEGF in PE and its pathway factors was summarized to clarify the pathogenesis further and provide innovative ideas for future research directions and clinical diagnosis. DISCUSSION: A systematic review of the VEGF family in the pathogenesis of PE was concluded in the study to find angiogenesis markers of PE from the pathogenesis of the available literature. Therefore, early intervention of clinical diseases could reduce maternal complications and ensure the maximum health of mothers and babies. There are differences in the research results of factors in the VEGF family, and further research is needed to provide accurate clinical evidence.


Asunto(s)
Preeclampsia , Factor A de Crecimiento Endotelial Vascular , Biomarcadores , Femenino , Humanos , Factor de Crecimiento Placentario , Embarazo , Receptor 1 de Factores de Crecimiento Endotelial Vascular
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA