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1.
Brief Bioinform ; 24(5)2023 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-37649383

RESUMEN

Single-cell high-throughput chromatin conformation capture technologies (scHi-C) has been used to map chromatin spatial organization in complex tissues. However, computational tools to detect differential chromatin contacts (DCCs) from scHi-C datasets in development and through disease pathogenesis are still lacking. Here, we present SnapHiC-D, a computational pipeline to identify DCCs between two scHi-C datasets. Compared to methods designed for bulk Hi-C data, SnapHiC-D detects DCCs with high sensitivity and accuracy. We used SnapHiC-D to identify cell-type-specific chromatin contacts at 10 Kb resolution in mouse hippocampal and human prefrontal cortical tissues, demonstrating that DCCs detected in the hippocampal and cortical cell types are generally associated with cell-type-specific gene expression patterns and epigenomic features. SnapHiC-D is freely available at https://github.com/HuMingLab/SnapHiC-D.


Asunto(s)
Cromatina , Epigenómica , Humanos , Animales , Ratones , Cromatina/genética , Hipocampo
2.
Nucleic Acids Res ; 51(5): 2137-2150, 2023 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-36718943

RESUMEN

Transcriptional Mediator controls diverse gene programs for various developmental and pathological processes. The human Mediator MED23/R617Q mutation was reported in a familial intellectual disability (ID) disorder, although the underlying mechanisms remain poorly understood. Constructed by gene editing, the Med23/R617Q knock-in mutant mice exhibited embryonic lethality due to the largely reduced Med23/R617Q protein level, but the R617Q mutation in HEK293T cells didn't change its expression and incorporation into Mediator Complex. RNA-seq revealed that MED23/R617Q mutation disturbed gene expression, related to neural development, learning and memory. Specifically, R617Q mutation reduced the MED23-dependent activities of ELK1 and E1A, but in contrast, upregulated the MAPK/ELK1-driven early immediate genes (IEGs) JUN and FOS. ChIP-seq and Hi-C revealed that the MED23 R617Q mutation reprogramed a subset of enhancers and local chromatin interactions, which correlated well with the corresponding gene expression. Importantly, the enhancers and chromatin interactions surrounding IEGs were unchanged by the R617Q mutation, but DACH1, an upstream repressor of IEGs, showed reduced enhancer-promoter interactions and decreased expression in mutant cells, thus relieving its inhibition to the intellectual-related IEGs. Overall, unraveling the MED23-DACH1-IEG axis provides a mechanistic explanation for the effects of the MED23/R617Q mutation on gene dysregulation and inherited ID.


Asunto(s)
Discapacidad Intelectual , Complejo Mediador , Animales , Humanos , Ratones , Cromatina/genética , Expresión Génica , Células HEK293 , Discapacidad Intelectual/genética , Complejo Mediador/genética , Complejo Mediador/metabolismo , Mutación
3.
EMBO J ; 39(24): e105896, 2020 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-33140861

RESUMEN

COVID-19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID-19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID-19-infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN-I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID-19-infected patients experiencing milder disease symptoms showed robust T-cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19.


Asunto(s)
COVID-19/sangre , COVID-19/patología , Biomarcadores/sangre , COVID-19/inmunología , COVID-19/virología , Femenino , Genómica/métodos , Humanos , Lipoproteínas/metabolismo , Masculino , Metabolómica/métodos , SARS-CoV-2/fisiología , Índice de Severidad de la Enfermedad , Carga Viral
4.
Nat Methods ; 18(9): 1056-1059, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34446921

RESUMEN

Single-cell Hi-C (scHi-C) analysis has been increasingly used to map chromatin architecture in diverse tissue contexts, but computational tools to define chromatin loops at high resolution from scHi-C data are still lacking. Here, we describe Single-Nucleus Analysis Pipeline for Hi-C (SnapHiC), a method that can identify chromatin loops at high resolution and accuracy from scHi-C data. Using scHi-C data from 742 mouse embryonic stem cells, we benchmark SnapHiC against a number of computational tools developed for mapping chromatin loops and interactions from bulk Hi-C. We further demonstrate its use by analyzing single-nucleus methyl-3C-seq data from 2,869 human prefrontal cortical cells, which uncovers cell type-specific chromatin loops and predicts putative target genes for noncoding sequence variants associated with neuropsychiatric disorders. Our results indicate that SnapHiC could facilitate the analysis of cell type-specific chromatin architecture and gene regulatory programs in complex tissues.


Asunto(s)
Cromatina/química , Biología Computacional/métodos , Análisis de la Célula Individual/métodos , Algoritmos , Animales , Cromatina/genética , Secuenciación de Inmunoprecipitación de Cromatina , Visualización de Datos , Bases de Datos Factuales , Expresión Génica , Humanos , Trastornos Mentales/genética , Ratones , Células Madre Embrionarias de Ratones/citología , Células Madre Embrionarias de Ratones/fisiología , Polimorfismo de Nucleótido Simple , Corteza Prefrontal/citología , Reproducibilidad de los Resultados , Análisis de Secuencia de ADN/métodos
5.
Macromol Rapid Commun ; 45(4): e2300568, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37956305

RESUMEN

Fibrous strain sensing materials with both high sensitivity and high linearity are of significant importance for wearable sensors, yet they still face great challenges. Herein, a photo-spun reaction encapsulation strategy is proposed for the continuous fabrication of fibrous strain sensor materials (AMGF) with a core-sheath structure. Metallogels (MOGs) formed by bacterial cellulose (BC) nanofibers and Ag nanoparticles (AgNPs), and thermoplastic elastomers (TPE) are employed as the core and sheath, respectively. The in situ ultraviolet light reduction of Ag+ ensured AgNPs to maintain the interconnections between the BC nanofibers and form electron conductive networks (0.31 S m-1 ). Under applied strain, the BC nanofibers experience separation, bringing AMGF a high sensitivity (gauge factor 4.36). The concentration of free ions in the MOGs uniformly varies with applied deformation, endowing AMGF with high linearity and a goodness-of-fit of 0.98. The sheath TPE provided AMGF sensor with stable working life (>10 000 s). Furthermore, the AMGF sensors are demonstrated to monitor complex deformations of the dummy joints in real-time as a wearable sensor. Therefore, the fibrous hybrid conductive network fibers fabricated via the photo-spun reaction encapsulation strategy provide a new route for addressing the challenge of achieving both high sensitivity and high linearity.


Asunto(s)
Nanopartículas del Metal , Dispositivos Electrónicos Vestibles , Nanopartículas del Metal/química , Electrones , Plata/química , Elastómeros/química
6.
Neurosurg Rev ; 46(1): 320, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38038775

RESUMEN

Xanthine oxidase (XO) may be involved in the induction of oxidative stress and inflammation. We measured serum XO levels at multiple days to determine whether it is associated with the severity and prognosis of severe traumatic brain injury (sTBI). In this prospective cohort study, we quantified serum XO levels in 112 sTBI patients and 112 controls. Serum XO levels of patients were measured at admission and at days 1, 3, 5, 7, and 10 after sTBI. Extended Glasgow outcome scale scores of 1-4 at post-trauma 180 days were defined as a poor prognosis. Multivariate analysis was employed to determine the relationship between poor prognosis and serum XO levels at multiple days. Serum XO levels were significantly increased at admission among patients, afterwards elevated gradually, peaked at day 3, and then diminished gradually until day 10, and were substantially higher during 10 days in patients than in controls. Serum XO levels at 6 different days were all correlated with admission Rotterdam computed tomography (CT) scores and Glasgow coma scale (GCS) scores. Serum XO levels at 6 different days were all substantially higher in patients with poor prognosis than in those with good prognosis. Serum XO levels at days 7 and 10, but not at days 1, 3, and 5, had significantly lower area under receiver operating characteristic (AUC) than those at admission. Serum XO levels at admission and at days 1 and 3, but not at day 5, were independently associated with 180-day poor prognosis. Prognostic prediction model containing GCS scores, Rotterdam CT scores, and serum XO levels at admission (or at days 1 and 3) showed substantially higher AUC than GCS scores and Rotterdam CT scores alone. The models were visually described using nomograms, which were comparatively stable under calibration curve and were relatively of clinical benefit under decision curve. Elevated serum XO levels during early period of sTBI are more closely associated with trauma severity and clinical adverse outcomes, assuming that serum XO may serve as a potential prognostic biomarker in sTBI.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Humanos , Xantina Oxidasa , Estudios Prospectivos , Pronóstico , Escala de Coma de Glasgow
7.
New Phytol ; 234(4): 1332-1346, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35094400

RESUMEN

Arabidopsis cryptochrome 1 (CRY1) is a blue light receptor distributed in the nucleus and cytoplasm. The nuclear CRY1, but not cytoplasmic CRY1, mediates blue light inhibition of hypocotyl elongation. However, the photobiochemical mechanisms distinguishing the CRY1 protein in the two subcellular compartments remains unclear. Here we show that the nuclear CRY1, but not the cytoplasmic CRY1, is regulated by phosphorylation, polyubiquitination and 26S proteasome-dependent proteolysis in response to blue light. The blue light-dependent CRY1 degradation is observed only under high fluences of blue light. The nuclear specificity and high fluence dependency of CRY1 explain why this photochemical regulatory mechanism of CRY1 was not observed previously and it further supports the hypothesis that CRY1 is a high light receptor regulating photomorphogenesis. We further show that the nuclear CRY1, but not cytoplasmic CRY1, undergoes blue light-dependent phosphorylation by photoregulatory protein kinase 1 (PPK1) followed by polyubiquitination by the E3 ubiquitin ligase Cul4COP1/SPAs , resulting in the blue light-dependent proteolysis. Both phosphorylation and ubiquitination of nuclear CRY1 are inhibited by blue-light inhibitor of cryptochromes 1 (BIC1), demonstrating the involvement of photo-oligomerization of the nuclear CRY1. These finding reveals a photochemical mechanism that differentially regulates the physiological activity of the CRY1 photoreceptor in distinct subcellular compartments.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Núcleo Celular/metabolismo , Criptocromos/metabolismo , Regulación de la Expresión Génica de las Plantas , Hipocótilo/metabolismo , Luz , Factores de Transcripción/metabolismo
8.
Eur J Nucl Med Mol Imaging ; 49(9): 3033-3045, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35190862

RESUMEN

BACKGROUND: Bladder cancer is the fifth most common malignancy in humans. Cystoscopy under white light imaging is the gold standard for bladder cancer diagnosis, but some tumors are difficult to visualize and can be overlooked, resulting in high recurrence rates. We previously developed a phage display-derived peptide-based near-infrared imaging probe, PLSWT7-DMI, which binds specifically to bladder cancer cells and is nontoxic to animals. Here, we report a clinical research of this probe for near-infrared fluorescence endoscopic detection of bladder cancer. RESULTS: The purity, efficacy, safety, and nontoxicity of PLSWT7-DMI were confirmed prior to its clinical application. Twenty-two patients diagnosed with suspected non-muscle invasive bladder cancer were enrolled in the present study. Following intravesical administration of the probe, the entire mucosa was imaged under white and near-infrared imaging using an in-house developed endoscope that could switch between these two modes. The illuminated lesions under near-infrared light were biopsied and sent for histopathological examination. We observed a 5.1-fold increase in the fluorescence intensity in the tumor samples compared to normal tissue, and the probe demonstrated a sensitivity and specificity of 91.2% and 90%, respectively. Common diagnostic challenges, such as small satellite tumors, carcinoma in situ, and benign suspicious mucosa, were visualized and could be distinguished from cancer. Furthermore, no adverse effects were observed in humans. These first-in-human results indicate that PLSWT7-DMI-based near-infrared fluorescence endoscopy is a safe and effective approach for the improved detection of bladder cancer, and may enable thorough resection to prevent recurrence.


Asunto(s)
Antineoplásicos , Carcinoma in Situ , Neoplasias de la Vejiga Urinaria , Animales , Cistoscopía/métodos , Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/patología
9.
J Nanobiotechnology ; 20(1): 484, 2022 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-36384524

RESUMEN

With the economy's globalization and the population's aging, cancer has become the leading cause of death in most countries. While imposing a considerable burden on society, the high morbidity and mortality rates have continuously prompted researchers to develop new oncology treatment options. Anti-tumor regimens have evolved from early single surgical treatment to combined (or not) chemoradiotherapy and then to the current stage of tumor immunotherapy. Tumor immunotherapy has undoubtedly pulled some patients back from the death. However, this strategy of activating or boosting the body's immune system hardly benefits most patients. It is limited by low bioavailability, low response rate and severe side effects. Thankfully, the rapid development of nanotechnology has broken through the bottleneck problem of anti-tumor immunotherapy. Multifunctional nanomaterials can not only kill tumors by combining anti-tumor drugs but also can be designed to enhance the body's immunity and thus achieve a multi-treatment effect. It is worth noting that the variety of nanomaterials, their modifiability, and the diversity of combinations allow them to shine in antitumor immunotherapy. In this paper, several nanobiotics commonly used in tumor immunotherapy at this stage are discussed, and they activate or enhance the body's immunity with their unique advantages. In conclusion, we reviewed recent advances in tumor immunotherapy based on nanomaterials, such as biological cell membrane modification, self-assembly, mesoporous, metal and hydrogels, to explore new directions and strategies for tumor immunotherapy.


Asunto(s)
Antineoplásicos , Nanoestructuras , Neoplasias , Humanos , Inmunoterapia , Neoplasias/tratamiento farmacológico , Nanotecnología , Nanoestructuras/uso terapéutico , Antineoplásicos/uso terapéutico
10.
J Xray Sci Technol ; 29(4): 635-643, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33935131

RESUMEN

PURPOSE: This study aims to evaluate the planned dose of stereotactic body radiation therapy (SBRT) for treating early peripheral non-small cell lung cancer (NSCLC) using the non-coplanar radiation from Cyberknife and Varian linac. Moreover, this study investigates whether Cyberknife and Varian linac are qualified for non-coplanar radiation SBRT for treating early peripheral NSCLC, and which one is better for protecting organs at risk (OARs). METHODS: Retrospective analysis was performed based on the Cyberknife radiation treatment plans (RTPs) and Varian Eclipse RTPs of 10 patients diagnosed with early peripheral NSCLC. The dose distributions in the target and OARs were compared between the RTPs of Cyberknife and Varian Eclipse using Mim medical imaging software. RESULTS: For PTV, no significant difference in D98 and D95 between the Cyberknife and Eclipse was observed (t = -0.35, -1.67, P > 0.05). The homogeneity indexes (HIs) of Cyberknife plans are higher (t = 71.86, P < 0.05) than those of Eclipse plans. The V10, V15, V20, V25, V30 and Dmean of the lung with NSCLC and the V20 of the whole lung for Cyberknife were less than those for Eclipse (t = -4.73, -5.62, -7.75, -6.38, -6.89, -3.14, -7.09, respectively, P < 0.05). Cyberknife plans have smaller spinal cord Dmax, trachea Dmax, heart Dmax, chest wall Dmax (t = -2.49, -2.57, -3.71, -3.56, respectively, P < 0.05) and esophagus Dmax (t = -1.95, P > 0.05) than Varian Eclipse plans. CONCLUSION: To fulfill SBRT by non-coplanar radiation, Cyberknife is recommended for the institutions equipped with Cyberknife, while Varian linac can be applied for the institutions that have not adopted Cyberknife in clinical radiotherapy yet.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Radiocirugia , Radioterapia de Intensidad Modulada , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Radiocirugia/métodos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos
11.
Opt Express ; 27(17): 23693-23706, 2019 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-31510270

RESUMEN

Inorganic scintillating material used in optical fibre sensors (OFS) when used as dosimeters for measuring percentage depth dose (PDD) characteristics have exhibited significant differences when compared to those measured using an ionization chamber (IC), which is the clinical gold standard for quality assurance (QA) assessments. The percentage difference between the two measurements is as high as 16.5% for a 10 × 10 cm2 field at 10 cm depth below the surface. Two reasons have been suggested for this: the presence of an energy effect and Cerenkov radiation. These two factors are analysed in detail and evaluated quantitatively. It is established that the influence of the energy effect is only a maximum of 2.5% difference for a beam size 10 × 10 cm2 compared with the measured ionization chamber values. And the influence of the Cerenkov radiation is less than 0.14% in an inorganic scintillating material in the case of OFS when using Gd2O2S:Tb as the luminescent material. Therefore, there must be other mechanisms leading to over-response. The luminescence mechanism of inorganic scintillating material is theoretically analysed and a new model is proposed and validated that helps explain the over-response phenomenon.

12.
Arch Virol ; 163(3): 731-735, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29214362

RESUMEN

Jasmine virus H (JaVH) is a novel virus associated with symptoms of yellow mosaic on jasmine. The JaVH genome is 3,867 nt in length with five open reading frames (ORFs) encoding a 27-kDa protein (ORF 1), an 87-kDa replicase protein (ORF 2), two centrally located movement proteins (ORF 3 and 4), and a 37-kDa capsid protein (ORF 5). Based on genomic and phylogenetic analysis, JaVH is predicted to be a member of the genus Pelarspovirus in the family Tombusviridae.


Asunto(s)
Genoma Viral , Jasminum/virología , Filogenia , ARN Viral/genética , Tombusviridae/genética , Secuencia de Bases , Proteínas de la Cápside/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Sistemas de Lectura Abierta , ARN Polimerasa Dependiente del ARN/genética , Tombusviridae/clasificación , Tombusviridae/aislamiento & purificación
13.
Chem Commun (Camb) ; 60(45): 5877, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38775135

RESUMEN

Correction for 'Facile preparation of a Ni-imidazole compound with high activity for ethylene dimerization' by Zhaohui Liu et al., Chem. Commun., 2024, 60, 188-191, https://doi.org/10.1039/D3CC04794F.

14.
J Hazard Mater ; 465: 133082, 2024 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-38016315

RESUMEN

Antibiotic resistance genes (ARGs) are prevalent in the livestock environment, but little is known about impacts of animal farming on the gut antibiotic resistome of local people. Here we conducted metagenomic sequencing to investigate gut microbiome and resistome of residents in a swine farming village as well as environmental relevance by comparing with a nearby non-farming village. Results showed a shift of gut microbiome towards unhealthy status in the residents of swine farming village, with an increased abundance and diversity in pathogens and ARGs. The resistome composition in human guts was more similar with that in swine feces and air than that in soil and water. Mobile gene elements were closely associated with the prevalence of gut resistome. Some plasmid-borne ARGs were colocalized in similar genetic contexts in gut and environmental samples. Metagenomic binning obtained 47 ARGs-carrying families in human guts, and therein Enterobacteriaceae posed the highest threats in antibiotic resistance and virulence. Several ARGs-carrying families were shared by gut and environmental samples (mainly in swine feces and air), and the ARGs were evolutionarily conservative within genera. The findings highlight that swine farming can shape gut resistome of local people with close linkage to farm environmental exposures.


Asunto(s)
Antibacterianos , Genes Bacterianos , Porcinos , Humanos , Animales , Granjas , Agricultura , Ganado
15.
Sci Rep ; 14(1): 10430, 2024 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714826

RESUMEN

Absent in melanoma 2 (AIM2) is implicated in neuroinflammation. Here, we explored the prognostic significance of serum AIM2 in human aneurysmal subarachnoid hemorrhage (aSAH). We conducted a consecutive enrollment of 127 patients, 56 of whom agreed with blood-drawings not only at admission but also at days 1, 2, 3, 5, 7 and 10 days after aSAH. Serum AIM2 levels of patients and 56 healthy controls were measured. Disease severity was assessed using the modified Fisher scale (mFisher) and World Federation of Neurological Surgeons Scale (WFNS). Neurological outcome at poststroke 90 days was evaluated via the modified Rankin Scale (mRS). Univariate analysis and multivariate analysis were sequentially done to ascertain relationship between serum AIM2 levels, severity, delayed cerebral ischemia (DCI) and 90-day poor prognosis (mRS scores of 3-6). Patients, in comparison to controls, had a significant elevation of serum AIM2 levels at admission and at days 1, 2, 3, 5, 7 and 10 days after aSAH, with the highest levels at days 1, 2, 3 and 5. AIM2 levels were independently correlated with WFNS scores and mFisher scores. Significantly higher serum AIM2 levels were detected in patients with a poor prognosis than in those with a good prognosis, as well as in patients with DCI than in those without DCI. Moreover, serum AIM2 levels independently predicted a poor prognosis and DCI, and were linearly correlated with their risks. Using subgroup analysis, there were no significant interactions between serum AIM2 levels and age, gender, hypertension and so on. There were substantially high predictive abilities of serum AIM2 for poor prognosis and DCI under the receiver operating characteristic curve. The combination models of DCI and poor prognosis, in which serum AIM2, WFNS scores and mFisher scores were incorporated, showed higher discriminatory efficiencies than anyone of the preceding three variables. Moreover, the models are delineated using the nomogram, and performed well under the calibration curve and decision curve. Serum AIM2 levels, with a substantial enhancement during early phase after aSAH, are closely related to bleeding severity, poor 90-day prognosis and DCI of patients, substantializing serum AIM2 as a potential prognostic biomarker of aSAH.


Asunto(s)
Proteínas de Unión al ADN , Hemorragia Subaracnoidea , Humanos , Masculino , Femenino , Persona de Mediana Edad , Hemorragia Subaracnoidea/sangre , Hemorragia Subaracnoidea/diagnóstico , Hemorragia Subaracnoidea/mortalidad , Pronóstico , Estudios Prospectivos , Proteínas de Unión al ADN/sangre , Anciano , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios Longitudinales , Índice de Severidad de la Enfermedad , Isquemia Encefálica/sangre
16.
Environ Int ; 186: 108639, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38603815

RESUMEN

Antimicrobial resistance is considered to be one of the biggest public health problems, and airborne transmission is an important but under-appreciated pathway for the spread of antibiotic resistance genes (ARGs) in the environment. Previous research has shown pharmaceutical factories to be a major source of ARGs and antibiotic resistant bacteria (ARB) in the surrounding receiving water and soil environments. Pharmaceutical factories are hotspots of antibiotic resistance, but the atmospheric transmission and its environmental risk remain more concerns. Here, we conducted a metagenomic investigation into the airborne microbiome and resistome in three pharmaceutical factories in China. Soil (average: 38.45%) and wastewater (average: 28.53%) were major contributors of airborne resistome. ARGs (vanR/vanS, blaOXA, and CfxA) conferring resistance to critically important clinically used antibiotics were identified in the air samples. The wastewater treatment area had significantly higher relative abundances of ARGs (average: 0.64 copies/16S rRNA). Approximately 28.2% of the detected airborne ARGs were found to be associated with plasmids, and this increased to about 50% in the wastewater treatment area. We have compiled a list of high-risk airborne ARGs found in pharmaceutical factories. Moreover, A total of 1,043 viral operational taxonomic units were identified and linked to 47 family-group taxa. Different CRISPR-Cas immune systems have been identified in bacterial hosts in response to phage infection. Similarly, higher phage abundance (average: 2451.70 PPM) was found in the air of the wastewater treatment area. Our data provide insights into the antibiotic resistance gene profiles and microbiome (bacterial and non-bacterial) in pharmaceutical factories and reveal the potential role of horizontal transfer in the spread of airborne ARGs, with implications for human and animal health.


Asunto(s)
Microbiología del Aire , Antibacterianos , Microbiota , Aguas Residuales , Microbiota/genética , Microbiota/efectos de los fármacos , China , Antibacterianos/farmacología , Aguas Residuales/microbiología , Bacterias/genética , Bacterias/efectos de los fármacos , Farmacorresistencia Microbiana/genética , Farmacorresistencia Bacteriana/genética
17.
JACC Basic Transl Sci ; 9(2): 244-256, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38510719

RESUMEN

This study assesses the feasibility, safety, and effectiveness of noninvasive stereotactic body radiotherapy (SBRT) as an approach for pulmonary artery denervation in canine models. SBRT with CyberKnife resulted in reduced mean pulmonary artery pressure, pulmonary capillary wedge pressure, and pulmonary vascular resistance, and insignificantly increased cardiac output. In comparison to the control group, serum norepinephrine levels at 1 month and 6 months were significantly lower in the CyberKnife group. Computed tomography, pulmonary angiography, and histology analysis revealed that SBRT was associated with minimal collateral damage.

18.
Clin Chim Acta ; 551: 117585, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37813327

RESUMEN

OBJECTIVE: Sphingosine-1-phosphate (S1P) may regulate neuroinflammatory immunity and blood-brain barrier integrity. This study was designed to assess the prognostic role of plasma S1P in intracerebral hemorrhage (ICH). METHODS: In this prospective cohort study, plasma S1P levels were measured in 51 controls, at admission in 114 ICH patients and at days 1, 3, 5 and 7 in 51 of all patients. Univariate analysis and multivariate analysis were sequentially used to investigate severity correlation and prognosis association. RESULTS: Plasma S1P levels were significantly elevated at admission, peaked at day 5, and declined at day 7, which were significantly higher during 7 days than those of controls (all P < 0.001). Areas under receiver operating characteristic curve (AUCs) of plasma S1P levels insignificant differed among all time points (all P > 0.05). Admission plasma S1P levels, in close correlation with National Institutes of Health Stroke Scale (NIHSS) scores [ß, 7.661; 95 % confidence interval (CI), 4.893-10.399; P < 0.001] and hematoma volume (ß, 1.285; 95 % CI, 0.348-2.230; P < 0.001), independently predicted 3-month poor prognosis (modified Rankin Scale scores of 3-6) (odds ratio, 3.184; 95 % CI, 1.057-9.597; P = 0.040). Admission plasma S1P levels had AUC of 0.799 (95 % CI, 0.713-0.868) for prognosis prediction. The levels > 240.4 ng/ml distinguished risk of poor prognosis with the maximum Youden index of 0.518. Prediction model integrating NIHSS scores, hematoma volume and admission plasma S1P levels had substantially higher prognostic predictive ability than NIHSS scores (P = 0.023), but not than hematoma volume (P = 0.061). CONCLUSION: There is a significant elevation of plasma S1P levels during early period after ICH, which were independently related to severity and poor prognosis. Thus, plasma S1P may be a potential prognostic biomarker of ICH.


Asunto(s)
Hemorragia Cerebral , Hematoma , Humanos , Pronóstico , Estudios Prospectivos , Hemorragia Cerebral/diagnóstico
19.
Adv Healthc Mater ; 12(26): e2300882, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37539730

RESUMEN

The application of nanomaterials in healthcare has emerged as a promising strategy due to their unique structural diversity, surface properties, and compositional diversity. In particular, nanomaterials have found a significant role in improving drug delivery and inhibiting the growth and metastasis of tumor cells. Moreover, recent studies have highlighted their potential in modulating the tumor microenvironment (TME) and enhancing the activity of immune cells to improve tumor therapy efficacy. Various types of nanomaterials are currently utilized as drug carriers, immunosuppressants, immune activators, immunoassay reagents, and more for tumor immunotherapy. Necessarily, nanomaterials used for tumor immunotherapy can be grouped into two categories: organic and inorganic nanomaterials. Though both have shown the ability to achieve the purpose of tumor immunotherapy, their composition and structural properties result in differences in their mechanisms and modes of action. Organic nanomaterials can be further divided into organic polymers, cell membranes, nanoemulsion-modified, and hydrogel forms. At the same time, inorganic nanomaterials can be broadly classified as nonmetallic and metallic nanomaterials. The current work aims to explore the mechanisms of action of these different types of nanomaterials and their prospects for promoting tumor immunotherapy.


Asunto(s)
Nanoestructuras , Neoplasias , Humanos , Sistemas de Liberación de Medicamentos , Portadores de Fármacos/química , Nanoestructuras/uso terapéutico , Nanoestructuras/química , Inmunoterapia , Microambiente Tumoral , Neoplasias/tratamiento farmacológico
20.
Chem Commun (Camb) ; 60(2): 188-191, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38044830

RESUMEN

A compound consisting of Ni and imidazole (Ni-imidazole) was synthesized in large quantities by a one-step co-precipitation method. The structure and stability of this Ni-imidazole were well studied by a series of characterization methods. The Ni-imidazole compound exhibited excellent catalytic properties for the dimerization of ethylene to 1-butene.

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