RESUMEN
circRNADisease v2.0 is an enhanced and reliable database that offers experimentally verified relationships between circular RNAs (circRNAs) and various diseases. It is accessible at http://cgga.org.cn/circRNADisease/ or http://cgga.org.cn:9091/circRNADisease/. The database currently includes 6998 circRNA-disease entries across multiple species, representing a remarkable 19.77-fold increase compared to the previous version. This expansion consists of a substantial rise in the number of circRNAs (from 330 to 4246), types of diseases (from 48 to 330) and covered species (from human only to 12 species). Furthermore, a new section has been introduced in the database, which collects information on circRNA-associated factors (genes, proteins and microRNAs), molecular mechanisms (molecular pathways), biological functions (proliferation, migration, invasion, etc.), tumor and/or cell line and/or patient-derived xenograft (PDX) details, and prognostic evidence in diseases. In addition, we identified 7 159 865 relationships between mutations and circRNAs among 30 TCGA cancer types. Due to notable enhancements and extensive data expansions, the circRNADisease 2.0 database has become an invaluable asset for both clinical practice and fundamental research. It enables researchers to develop a more comprehensive understanding of how circRNAs impact complex diseases.
Asunto(s)
Bases de Datos Genéticas , Neoplasias , ARN Circular , Humanos , Línea Celular , Neoplasias/genéticaRESUMEN
BACKGROUND: Precision oncology pharmacotherapy relies on precise patient-specific alterations that impact drug responses. Due to rapid advances in clinical tumor sequencing, an urgent need exists for a clinical support tool that automatically interprets sequencing results based on a structured knowledge base of alteration events associated with clinical implications. RESULTS: Here, we introduced the Oncology Pharmacotherapy Decision Support System (OncoPDSS), a web server that systematically annotates the effects of alterations on drug responses. The platform integrates actionable evidence from several well-known resources, distills drug indications from anti-cancer drug labels, and extracts cancer clinical trial data from the ClinicalTrials.gov database. A therapy-centric classification strategy was used to identify potentially effective and non-effective pharmacotherapies from user-uploaded alterations of multi-omics based on integrative evidence. For each potentially effective therapy, clinical trials with faculty information were listed to help patients and their health care providers find the most suitable one. CONCLUSIONS: OncoPDSS can serve as both an integrative knowledge base on cancer precision medicine, as well as a clinical decision support system for cancer researchers and clinical oncologists. It receives multi-omics alterations as input and interprets them into pharmacotherapy-centered information, thus helping clinicians to make clinical pharmacotherapy decisions. The OncoPDSS web server is freely accessible at https://oncopdss.capitalbiobigdata.com .
Asunto(s)
Bases de Datos Factuales , Sistemas de Apoyo a Decisiones Clínicas , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Medicina de Precisión , Navegador Web , Antineoplásicos/uso terapéutico , Ensayos Clínicos como Asunto , Humanos , Anotación de Secuencia Molecular , Interfaz Usuario-ComputadorRESUMEN
Design of stable adsorbents for selective gold recovery with large capacity and fast adsorption kinetics is of great challenge, but significant for the economy and the environment. Herein, we show the design and preparation of an irreversible amide-linked covalent organic framework (COF) JNU-1 via a building block exchange strategy for efficient recovery of gold. JNU-1 was synthesized through the exchange of 4,4'-biphenyldicarboxaldehyde (BA) in mother COF TzBA consisting of 4,4',4''-(1,3,5-triazine-2,4,6-triyl)trianiline (Tz) and BA with terephthaloyl chloride. The irreversible amide linked JNU-1 gave good stability, unprecedented fast kinetics, excellent selectivity and outstanding adsorption capacity for gold recovery. X-ray photoelectron spectroscopy along with thermodynamic study and quantum mechanics calculation reveals that the excellent performance of JNU-1 for gold recovery results from the formation of hydrogen bonds C(N)-Hâ â â Cl and coordinate interaction of O and Au. The rational design of irreversible bonds as both inherent linkage and functional groups in COFs is a promising way to prepare stable COFs for diverse applications.
RESUMEN
Stroke is one of the predominant causes of death and disability. Currently, besides thrombolytic therapy, neuroprotection is also generally recognized as a promising way for stroke treatment, which would be very important for the functional recovery of stroke patients. However, it's reported that all the current available neuroprotective drugs have failed in clinical investigations of stroke treatments so far. Lyoniresinol (LNO) is a natural lignan with powerful antioxidant and cytoprotective activities. In this study, OGD/R leaded HT22 cell damage models and Middle Cerebral Artery Occlusion (MCAO) rats were used to investigate the effect of LNO on cerebral ischemic stroke injury and related mechanisms. The cell experiments revealed LNO can suppress the oxygen glucose deprivation-reoxygenation (OGD/R) induced apoptosis of HT22 cells. Subsequently, LNO can improve nerve function deficit and brain injury in MCAO rats with a higher neurological function scores and less infarct size. And the further molecular mechanisms studies suggested LNO activated the PI3K/AKT/GSK-3ß/NRF2 signaling and improved the oxidative stress in cells to inhibit the OGD/R induced apoptosis in HT22 cells. Collectively, our findings would be useflu for the further drug development of LNO as new drug for stroke and its related diseases.
Asunto(s)
Lesiones Encefálicas , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Fármacos Neuroprotectores , Daño por Reperfusión , Accidente Cerebrovascular , Humanos , Ratas , Animales , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/prevención & control , Glucógeno Sintasa Quinasa 3 beta , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Accidente Cerebrovascular/tratamiento farmacológico , Estrés Oxidativo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Lesiones Encefálicas/tratamiento farmacológico , Daño por Reperfusión/tratamiento farmacológicoRESUMEN
Annotating cells in the analysis of single-cell RNA-seq (scRNA-seq) data is one of the most challenging tasks that researchers are actively addressing. Manual cell annotation is generally considered the gold standard method, although it is labor intensive and independent of prior knowledge. At present, the relationship between high-quality, known marker genes and cell types is very limited, especially for a variety of species other than humans and mice. The singleCellBase is a manually curated resource of high-quality cell types and gene markers associations across multiple species. In details, it offers 9,158 entries spanning a total of 1,221 cell types and linking with 8,740 genes (cell markers), covering 464 diseases/status, and 165 types of tissues across 31 species. The singleCellBase provides a user-friendly interface to the scientific community to browse, search, download and submit records of marker genes and cell types. The resource providing ineluctable prior knowledge required by manual cell annotation, which is valuable to interpret scRNA-seq data and elucidate what cell type or cell state that a cell population represents.
RESUMEN
Preparation of porphyrin-based covalent organic frameworks (Por-COFs) with high photosensitizing activity for photodynamic inactivation of bacteria is of great challenge, but significant for economy and human health. Herein, we show a conjugation-regulating strategy to design and synthesize Por-COFs with high photosensitizing activity for the photodynamic inactivation of bacteria. Terephthalaldehyde (Da), 2,5-Dihydroxyterephthalaldehyde (Dha), and 2,5-Diethoxyterephthalaldehyde (Deta) with different conjugation degrees are selected to condense with 5,10,15,20-Tetrakis(4-aminophenyl)porphyrin (Tph) to synthesize COF-366, DhaTph, and JNU-2, respectively. The higher conjugation of Dha and Deta than Da leads to the higher conjugation of DhaTph and JNU-2, respectively. Moreover, the hydroxyl group in Dha and the ethoxy group in Deta further expand the conjugation of DhaTph and JNU-2 via the formation of intralayer extended π-cloud delocalization and p-π conjunction, respectively. The extension of conjugation for DhaTph and JNU-2 results in the increase of intersystem crossing process and significantly improves their photosensitizing activity. Furthermore, JNU-2 with the highest photosensitizing activity exhibits superior antibacterial effects toward Staphylococcus aureus (99.1%) and Escherichia coli (96.8%). This study offers a new conjugation-regulating strategy for designing high photosensitizing activity of Por-COFs for the inactivation of bacteria.
Asunto(s)
Estructuras Metalorgánicas , Porfirinas , Antibacterianos/farmacología , Humanos , Fármacos Fotosensibilizantes/farmacología , Porfirinas/farmacología , Staphylococcus aureusRESUMEN
Reliable efficacy is very important to continuing treatment for patients with erectile dysfunction. Vardenafil is a potent, highly selective phosphodiesterase 5 (PDE5) inhibitor. The efficacy and safety of vardenafil has been confirmed in many clinical studies. This paper analyzed the efficacy reliability of vardenafil in clinical trials and real-life practice, concluded that it provided reliable efficacy for key parameters of erection and improved treatment compliance.
Asunto(s)
Disfunción Eréctil/tratamiento farmacológico , Imidazoles/uso terapéutico , Inhibidores de Fosfodiesterasa/uso terapéutico , Piperazinas/uso terapéutico , Adulto , Anciano , Ensayos Clínicos Fase III como Asunto , Método Doble Ciego , Humanos , Imidazoles/efectos adversos , Masculino , Persona de Mediana Edad , Inhibidores de Fosfodiesterasa/efectos adversos , Piperazinas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Sulfonas/efectos adversos , Sulfonas/uso terapéutico , Triazinas/efectos adversos , Triazinas/uso terapéutico , Diclorhidrato de VardenafilRESUMEN
In the last few decades, anti-negative pressure facility (ANPF) has been emerged as a revolutionary approach for sloving the pollution in the Second Water Supply System (SWSS) in China. This study analyzed implications of the safety in SWSS with ANPF, utilizing the water distribution network hydraulic model. A method of hydraulic simulation and security assessment was presented which was able to reflect the number and location of nodes that can be installed in ANPF. Benchmark results through two instance networks showed that 67% and 89% of nodes in each network did not fit the ANPFs for installation. The simple and pratical algorithm was recommended in the water distribution network design and planing in order to increase the security of SWSS.
Asunto(s)
Hidrodinámica , Contaminación del Agua/prevención & control , Abastecimiento de Agua/análisis , Simulación por Computador , Modelos Teóricos , Presión , Medición de Riesgo/métodos , Seguridad , Contaminación del Agua/análisis , Abastecimiento de Agua/normasRESUMEN
The method of locating online sensor on a water distribution system for monitoring water quality was investigated. A flaw of demand coverage method was identified. To overcome this flaw, a demand coverage index based method was proposed in this paper. The demand coverage index method evaluates a node's representativeness by taking both the total amount of demand coverage and its temporal distribution into account. This increases the calculation accuracy and data representativeness. In order to increase the speed of optimization, a genetic algorithm was employed to solve the optimization problem in this work. Two example water distribution systems were employed to evaluate the performances of both methods. It was obtained that more than 85% of node demand can be covered by 7 monitoring stations for the example water distribution system with 95 nodes. Example applications show that results from this method have better representativeness than the one from demand coverage method. An online monitoring network based on optimal locations obtained from demand coverage method can better represent water quality of the distribution systems.