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1.
J Clin Neurosci ; 125: 43-50, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38749330

RESUMEN

BACKGROUND: The D-dimer-to-fibrinogen ratio (DFR) is a good indicator of thrombus activity in thrombotic diseases, but its clinical role in acute ischaemic stroke (AIS) patients with different etiologies has not been studied. We evaluated the diagnostic value of the DFR for different subtypes of AIS. METHODS: We conducted a single-center retrospective study of 269 patients with AIS who were referred to our stroke center within 4.5 h from Jan 2017 to Oct 2019. Coagulation data including DFRs were compared among the different stroke subtypes, and a separate retrospective validation sample was utilized to evaluate the prediction efficiency of the DFR for subtype diagnosis. RESULTS: A higher DFR was observed in patients with cardioembolism than in those with large artery atherosclerosis (LAA) (odds ratio (OR) per 0.1 increase of the DFR: 1.49 [1.01-2.18]) after we adjusted for vascular risk factors. The diagnostic value of the DFR for detecting cardioembolism (AUC = 0.722, 95 % CI = 0.623-0.820) exceeded that of isolated D-dimer or fibrinogen. The validation sample (n = 117) further supported the notion that a diagnosis of cardioembolism was more common in patients with a DFR > 0.11 (multivariable risk ratio = 3.11[1.33-7.31], P = 0.009). CONCLUSION: High DFRs were associated with cardioembolism in patients with AIS. The utilization of DFR can be beneficial for distinguishing a cardiac embolic source from atherosclerotic stroke.

2.
Mol Plant ; 17(5): 772-787, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38581129

RESUMEN

The phytohormone auxin plays a pivotal role in governing plant growth and development. Although the TRANSPORT INHIBITOR RESPONSE1/AUXIN SIGNALING F-BOX (TIR1/AFB) receptors function in both the nucleus and cytoplasm, the mechanism governing the distribution of TIR1/AFBs between these cellular compartments remains unknown. In this study, we demonstrate that auxin-mediated oxidation of TIR1/AFB2 is essential for their targeting to the nucleus. We showed that small active molecules, reactive oxygen species (ROS) and nitric oxide (NO), are indispensable for the nucleo-cytoplasmic distribution of TIR1/AFB2 in trichoblasts and root hairs. Further studies revealed that this process is regulated by the FERONIA receptor kinase-NADPH oxidase signaling pathway. Interestingly, ROS and NO initiate oxidative modifications in TIR1C140/516 and AFB2C135/511, facilitating their subsequent nuclear import. The oxidized forms of TIR1C140/516 and AFB2C135/511 play a crucial role in enhancing the function of TIR1 and AFB2 in transcriptional auxin responses. Collectively, our study reveals a novel mechanism by which auxin stimulates the transport of TIR1/AFB2 from the cytoplasm to the nucleus, orchestrated by the FERONIA-ROS signaling pathway.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas F-Box , Ácidos Indolacéticos , Oxidación-Reducción , Receptores de Superficie Celular , Transducción de Señal , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas F-Box/metabolismo , Receptores de Superficie Celular/metabolismo , Proteínas de Arabidopsis/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Núcleo Celular/metabolismo , Óxido Nítrico/metabolismo , Fosfotransferasas/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas Serina-Treonina Quinasas
3.
Neurologist ; 29(3): 146-151, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38323983

RESUMEN

OBJECTIVES: Elevation of the systemic immune inflammation (SII) index and system inflammation response index (SIRI) is known to be associated with higher risk of stroke and all-cause death. However, no study has reported their correlation with early neurological deterioration (END) following recombinant tissue-type plasminogen activator (IV-rtPA) in acute ischemic stroke patients. The aim of this study was to explore the correlation of SII and SIRI with the risk of END after IV-rtPA. METHODS: Included in this study were 466 consecutive patients treated with IV-rtPA. SII and SIRI were calculated according to blood cell counts before IV-rtPA. Patients were divided into 3 groups based on trisectional quantiles according to SII and SIRI values. The risk of END was assessed by multivariate regression. The overall discriminative ability of SII and SIRI in predicting END was assessed by receiver operating characteristic curve analysis. RESULTS: Of the 466 included patients, 62 (13.3%) were identified as having END. Compared with the first tertile of SII, multivariable regression analysis demonstrated that patients were more likely to have END (odds ratio 2.54; 95% CI: 1.23-5.23) and poor outcome at 90 days (odds ratio 2.02; 95% CI: 1.06-3.86) in third tertile after adjustment for potential confounders. In addition, a cutoff value of 591.63 for SII was detected in predicting post-thrombolysis END with a sensitivity of 58.1% and a specificity of 64.6% (area under the curve 0.61; 95% CI: 0.54-0.69). CONCLUSIONS: Higher SII but not SIRI may prove to be a predictor for high risk of END and a poor functional outcome at 90 days after IV-rtPA.


Asunto(s)
Inflamación , Accidente Cerebrovascular Isquémico , Terapia Trombolítica , Activador de Tejido Plasminógeno , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Anciano , Persona de Mediana Edad , Terapia Trombolítica/efectos adversos , Activador de Tejido Plasminógeno/administración & dosificación , Inflamación/tratamiento farmacológico , Fibrinolíticos/administración & dosificación , Anciano de 80 o más Años
4.
Talanta ; 272: 125735, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38364556

RESUMEN

Accurate and precise detection of disease-associated proteins, such as C-reactive protein (CRP), remains a challenge in biosensor development. Herein, we present a novel approach-an integrated disposable aptasensor array-designed for precise, ultra-sensitive, and parallel detection of CRP in plasma samples. This integrated biosensing array platform enables multiplex parallel testing, ensuring the accuracy and reliability in sample analysis. The ultra-sensitivity of this biosensor is achieved through multiplex signal amplification. Leveraging the superior conductivity and extensive surface area of MOF-derived nanoporous carbon material (CMOF), the biosensor enhances recognition elements (aptamers) by catalyzing the horseradish peroxidase (HRP) label enzyme reaction to multiply the number of probe molecules. Optimized conditions yielded exceptional performance, exhibiting high accuracy (relative standard deviation, RSD≤10.0 %), a low detection limit (0.3 pg/mL, S/N = 3), ultra-sensitivity (0.16 µA/ng mL-1 mm-2), and a rapid response (seven parallel tests within 60 min). Importantly, this multi-unit integrated disposable aptasensor array accurately quantified CRP in human serum, demonstrating comparable results to commercial enzyme-linked immunosorbent assay (ELISA). This technology showcases promise for detecting various biomarkers using a unified approach, presenting an appealing strategy for early disease diagnosis and biological analysis.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Nanopartículas del Metal , Humanos , Proteína C-Reactiva , Aptámeros de Nucleótidos/química , Carbono , Reproducibilidad de los Resultados , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Límite de Detección , Oro/química , Nanopartículas del Metal/química
6.
Int J Biol Macromol ; 261(Pt 2): 129718, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38296129

RESUMEN

Recently, conductive hydrogels have shown great promise in flexible electronics and are ideal materials for the preparation of wearable strain sensors. However, developing a simple method to produce conductive hydrogels with excellent mechanical properties, self-adhesion, transparency, anti-freezing, and UV resistance remains a significant challenge. A novel sodium lignosulfonate/xanthan gum/sodium alginate/polyacrylamide/Zn2+/DMSO (SLS/XG/SA/PAM/Zn2+/DMSO) ionic conductive hydrogel was developed using a one-pot method. The resulting ionic conductive hydrogels have excellent mechanical properties (stress: 0.13 MPa, strain: 1629 %), high anti-fatigue properties, self-adhesion properties (iron: 7.37 kPa, pigskin: 4.74 kPa), anti-freezing (freezing point: -33.49 °C) and UV resistance by constructing a chemical and physical hybrid cross-linking network. In particular, the conductivity of G hydrogel reached 6.02 S/m at room temperature and 5.52 S/m at -20 °C. Thus, the hydrogel was assembled into a flexible sensor that could distinguish a variety of large and small scales human movements, such as joint bending, swallowing and speaking in real time with high stability and sensitivity. Moreover, the hydrogel could be used as electronic skin just like human skin and touch screen pen to write.


Asunto(s)
Resinas Acrílicas , Alginatos , Dimetilsulfóxido , Lignina/análogos & derivados , Polisacáridos Bacterianos , Humanos , Conductividad Eléctrica , Hidrogeles , Iones , Sodio
7.
J Control Release ; 367: 184-196, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38242212

RESUMEN

The microneedle (MN) delivery system presents an attractive administration route for patients with Alzheimer's disease (AD). However, the passive drug delivery mode and low drug loading of MNs often result in unsatisfactory therapeutic efficiency. To address these dilemmas, we developed dual engine-drive bionic MNs for robust AD treatment. Specifically, free rivastigmine (RVT) and RVT particles were co-loaded within the MNs to construct the valve and chambers of the guava, respectively, which can serve as an active engine to promote drug permeation by generating capillary force. K2CO3 and citric acid were introduced as a pneumatic engine into the MNs to promote the permeation of free RVT into deeper skin layers for early intervention in AD. Further, the RVT particles served as a drug depot to provide continuous drug release for prolonged AD treatment. Compared with free RVT-loaded MNs, the dual engine-driven bionic MNs showed an increase in drug loading, cumulative transdermal permeability, and normalized bioavailability of approximately 40%, 22%, and 49%, respectively. Pharmacodynamic studies further confirmed that the dual engine-driven bionic MNs were most effective in restoring memory and recognition functions in mice with short-term memory dysfunction. Therefore, the dual engine-driven bionic MNs hold great promise for highly efficient AD treatment.


Asunto(s)
Enfermedad de Alzheimer , Biónica , Humanos , Ratones , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Piel , Administración Cutánea , Preparaciones Farmacéuticas , Sistemas de Liberación de Medicamentos , Agujas
8.
BMC Cancer ; 24(1): 6, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166698

RESUMEN

BACKGROUND: Anlotinib is a multi-target tyrosine kinase inhibitor (TKI) targeting the vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), and c-Kit. This phase II study aimed to assess the efficacy and safety of anlotinib, either alone or in combination with bevacizumab (Bev) for recurrent high-grade glioma (rHGG) (NCT04822805, 30/03/2021). METHODS: Eligible patients had a histological diagnosis of rHGG with first or subsequent recurrences. All patients received oral anlotinib 12 mg or 10 mg on days 1-14 (repeated every 21 days). In cases where brain magnetic resonance imaging examination revealed an increase in peritumoral edema without worsening of symptoms, patients received a temporary treatment of intravenous bevacizumab 10 mg/kg to alleviate edema. The primary endpoint was the median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and safety. RESULTS: Twenty-five patients with rHGG were included in the efficacy and safety assessments. Eighteen patients received anlotinib alone, and seven patients received anlotinib in combination with Bev. For all patients, the mPFS and mOS were 5.0 months and 13.6 months, respectively. The ORR was 32%, and the DCR was 96%. It is noteworthy that the survival and response data of recurrent glioblastoma (rGBM) exhibit similarities to those of rHGG. For rGBM patients, there were no significant differences in mPFS, mOS, ORR, or DCR between the anlotinib alone and anlotinib + Bev groups. However, the incidence of treatment-related adverse events of any grade was higher in the anlotinib + Bev group compared to the anlotinib alone group (100% vs. 78%, p = 0.041). CONCLUSIONS: Both anlotinib alone and its combination with Bev demonstrated good efficacy and safety in the treatment of rHGG.


Asunto(s)
Glioblastoma , Glioma , Humanos , Bevacizumab/efectos adversos , Estudios Prospectivos , Factor A de Crecimiento Endotelial Vascular , Glioma/tratamiento farmacológico , Glioma/patología , Edema
9.
Biomacromolecules ; 25(2): 614-625, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38241010

RESUMEN

Conductive hydrogels integrate the conductive performance and soft nature, which is like that of human skin. Thus, they are more suitable for the preparation of wearable human-motion sensors. Nevertheless, the integration of outstanding multiple functionalities, such as stretchability, toughness, biocompatibility, self-healing, adhesion, strain sensitivity, and durability, by a simple way is still a huge challenge. Herein, we have developed a multifunctional chitosan/oxidized hyaluronic acid/hydroxypropyl methylcellulose/poly(acrylic acid)/tannic acid/Al3+ hydrogel (CS/OHA/HPMC/PAA/TA/Al3+) by using a two-step method with hydroxypropyl methylcellulose (HPMC), acrylic acid (AA), tannic acid (TA), chitosan (CS), oxidized hyaluronic acid (OHA), and aluminum chloride hexahydrate (AlCl3·6H2O). Due to the synergistic effect of dynamic imine bonds between CS and OHA, dynamic metal coordination bonds between Al3+ and -COOH and/or TA as well as reversible hydrogen, the hydrogel showed excellent tensile property (elongation at break of 3168%) and desirable toughness (0.79 MJ/m3). The mechanical self-healing efficiency can reach 95.5% at 30 min, and the conductivity can recover in 5.2 s at room temperature without stimulation. The favorable attribute of high transparency (98.5% transmittance) facilitates the transmission of the optical signal and enables visualization of the sensor. It also shows good adhesiveness to various materials and is easy to peel off without residue. The resistance of the hydrogel-based sensors shows good electrical conductivity (2.33 S m-1), good durability, high sensing sensitivity (GF value of 4.12 under 1600% strain), low detection limit (less than 1%), and short response/recovery time (0.54/0.31 s). It adhered to human skin and monitored human movements such as the bending movements of joints, swallowing, and speaking successfully. Therefore, the obtained multifunctional conductive hydrogel has great potential applications in wearable strain sensors.


Asunto(s)
Quitosano , Polifenoles , Dispositivos Electrónicos Vestibles , Humanos , Adhesivos , Ácido Hialurónico , Derivados de la Hipromelosa , Cementos de Resina , Conductividad Eléctrica , Hidrogeles , Iones
10.
Int J Biol Macromol ; 258(Pt 2): 128896, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38143067

RESUMEN

The pandemic of the porcine reproductive and respiratory syndrome virus (PRRSV) has caused huge economic losses and continues to threaten the swine industry worldwide. Nucleocapsid protein (N protein) is the primary antigen of PRRSV for development of sensitive diagnostic assays. Two high affinity nanobodies against N protein, Nb12 and Nb35, were selected and employed to develop a sandwich ELISA. Further we improved the ELISA method to obtain greater sensitivity, a trivalent nanobody (3 × Nb35) and a bivalent nanobody-HRP fusion protein (2 × Nb12-HRP) were expressed and used. This modified ELISA was found to have high sensitivity for detecting PRRSV, with a detection limit of 10 TCID50/ml (median tissue culture infectious dose), which was approximately 200-fold greater than the single-copy nanobody-based sandwich ELISA. The developed assay shows high specificity and can detect almost all circulating lineages of PRRSV-2 in China. This study provides suggestions for reforming nanobodies and for the further development of multivalent nanobody-based ELISAs for other various viruses.


Asunto(s)
Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Anticuerpos de Dominio Único , Animales , Porcinos , Anticuerpos de Dominio Único/metabolismo , Ensayo de Inmunoadsorción Enzimática/métodos , Antígenos Virales , Proteínas de la Nucleocápside , Anticuerpos Antivirales , Sensibilidad y Especificidad
11.
JAMA Intern Med ; 184(2): 209-210, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38147321

RESUMEN

This case report presents the electrocardiogram findings of a pregnant patient in their 30s with a family history of hypertrophic obstructive cardiomyopathy.


Asunto(s)
Cardiomiopatía Hipertrófica , Infarto del Miocardio , Embarazo , Femenino , Humanos , Infarto del Miocardio/diagnóstico , Electrocardiografía
12.
Plants (Basel) ; 12(23)2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38068589

RESUMEN

This study investigated the efficacy of carvone, abscisic acid (ABA), gibberellin (GA3), and variable temperature in managing dormancy and sprouting in aeroponically grown mini-tuber potato (Solanum tuberosum L.) seeds. The results showed that carvone treatment effectively reduced the weight loss rate by 12.25% and decay rate by 3.33% at day 25 compared to control. ABA treatment significantly enhanced the germination rate, increasing it to 97.33%. GA3 treatment resulted in the longest sprouts of 14.24 mm and reduced the MDA content by 23.08% at day 30, indicating its potential in shortening dormancy and maintaining membrane integrity. The variable-temperature treatment demonstrated a balanced performance in reducing weight loss and maintaining a lower relative conductivity, indicating less cellular damage. The enzymatic activities of α-amylase, CAT, and SOD were modulated by the treatments, ensuring a balanced enzymatic environment for seed vitality. These results establish a solid basis for improving postharvest management strategies to optimize germination uniformity and preserve the quality of aeroponic potato seeds during extended dormancy, promising enhanced yield and productivity in potato cultivation.

13.
Horm Metab Res ; 55(12): 869-875, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38040022

RESUMEN

Differentiation between benign and malignant thyroid nodules has been a challenge in clinical practice. Exploring a novel biomarker to determine the malignancy of thyroid nodules has important implications. We semi-quantitatively determined the DNA methylation levels of four CpG sites located at the gene body of HYAL1 in formalin-fixed paraffin-embedded (FFPE) tissue samples from 190 early-stage papillary thyroid cancer (PTC) cases and 190 age- and gender-matched subjects with benign thyroid nodule (BTN). HYAL1 expression was evaluated by immunohistochemical (IHC) staining in another cohort of 55 PTC and 55 matched BTN cases. Covariates-adjusted odds ratios (ORs) for 10% increased methylation were calculated by binary logistic regression. A 165 bp amplicon covering four CpG sites at the second exon of HYAL1 gene was designed. After adjusted for all covariates, higher methylation level of HYAL1_CpG_3,4 in the FFPE tissue was associated with PTC (OR per 10% increased methylation=1.53, p=0.025), even with stage І PTC (OR per 10% increased methylation=1.58, p=0.021). Hypermethylation of HYAL1_CpG_3,4 had a significant association with early-stage PTC in the females (OR per 10% increased methylation=1.60, p=0.028) rather than in the males. Besides, we found the higher expression of HYAL1 protein in PTC than that in BTN patients (IHC score: 2.3 vs. 0.5, p=1.00E-06). Our study suggested altered methylation and expression of HYAL1 could be a novel and potential biomarker in distinguishing malignant and benign thyroid nodules.


Asunto(s)
Biomarcadores , Neoplasias de la Tiroides , Nódulo Tiroideo , Femenino , Humanos , Masculino , Biomarcadores/metabolismo , Metilación de ADN/genética , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/genética , Nódulo Tiroideo/patología
14.
Epigenomics ; 15(23): 1257-1272, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38126720

RESUMEN

Aim: It remains a challenge to accurately identify malignancy of thyroid nodules when biopsy is indeterminate. The authors aimed to investigate the abnormal DNA methylation signatures in papillary thyroid cancer (PTC) compared with benign thyroid nodules (BTNs). Methods: The authors performed genome profiling by 850K array and RNA sequencing in early-stage PTC and BTN tissue samples. The identified gene was validated in two independent case-control studies using mass spectrometry. Results: Hypomethylation of RUNX1 in PTC was identified and verified (all odds ratios: ≥1.50). RUNX1 methylation achieved good accuracy in differentiating early-stage PTC from BTNs, especially for younger women. Conclusion: The authors disclosed a significant association between RUNX1 hypomethylation and PTC, suggesting RUNX1 methylation as a potential biomarker for companion diagnosis of malignant thyroid nodules.


Asunto(s)
Biomarcadores de Tumor , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Neoplasias de la Tiroides , Nódulo Tiroideo , Femenino , Humanos , Biomarcadores de Tumor/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Metilación de ADN , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/genética , Nódulo Tiroideo/patología
15.
Artículo en Inglés | MEDLINE | ID: mdl-37944967

RESUMEN

Background: Percutaneous coronary intervention (PCI) has emerged as a pivotal intervention in reducing mortality among ST-segment elevation myocardial infarction (STEMI) patients. Objective: This study aimed to evaluate the clinical effectiveness of PCI in the management of acute myocardial infarction (AMI). Design: A retrospective study design was adopted. Setting: The study was conducted at the Affiliated Taizhou People's Hospital of Nanjing Medical University. Participants: A total of 126 AMI patients were selected and categorized into two groups based on their treatment regimen: the study group (n=76) underwent PCI, while the control group (n=50) received standard drug therapy. Interventions: The control group was managed with conventional drug treatment, while the study group underwent PCI. Primary Outcome Measures: The primary outcome measures included (1) N-terminal pro-B-type natriuretic peptide levels, (2) cardiac function, (3) total clinical effectiveness, (4) incidence of adverse cardiovascular events, and (5) quality of life. Results: After treatment, both groups exhibited a reduction in N-terminal pro-B-type natriuretic peptide levels, with a more significant decrease observed in the study group compared to the control group (P < .05). Post-treatment left ventricular end-diastolic and end-systolic volumes decreased, while left ventricular ejection fraction increased in both groups. The study group exhibited more substantial improvements in these parameters compared to the control group (P < .05). The study group also demonstrated a higher total clinical effectiveness rate (χ2 = 9.95, P < 0.05) and a lower incidence of adverse cardiovascular events during follow-up (P < .05). Additionally, both groups reported an increase in quality-of-life scores, with the study group experiencing a more significant improvement (P < .05). Conclusions: This study suggests that PCI, when applied in the clinical management of AMI patients, can significantly reduce N-terminal pro-B-type natriuretic peptide levels, enhance cardiac function, lower the occurrence of cardiovascular adverse events, and improve patients' overall quality of life.

16.
Infect Dis (Lond) ; 55(12): 839-846, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37624684

RESUMEN

BACKGROUND: Data on the coincidence of Tuberculosis (TB) and Coronavirus disease 2019 (COVID-19) are limited. We sought to investigate the clinical characteristics and outcomes of coinfected patients in Henan and identify whether TB disease is associated with an increased risk of intensive care unit (ICU) admission and mortality. METHOD: We conducted a retrospective matched cohort study of COVID-19 inpatients involving 41 TB-positive patients with 82 patients without TB. Leveraging data was collected from electronic medical records. RESULTS: There were no significant differences in clinical manifestations, the need for mechanical ventilation and vasopressors, ICU admission, or in-hospital mortality between 2 groups. TB-positive patients had a lower lymphocyte counts (1.24 ± 0.54 vs. 1.59 ± 0.58, p = 0.01), B cells (99/µl vs. 201/µl, p < 0.01), CD4+ T cells (382/µl vs. 667/µl, p < 0.01), CD8+ T cells (243/µl vs. 423/µl, p < 0.01), NK cells (145/µl vs. 216/µl, p = 0.01), IL-2 (14.18 ± 11.23 vs. 31.86 ± 34.55, p < 0.01) and TNF-α (3.42 ± 2.93 vs. 5.62 ± 3.69, p < 0.01). Notably, the TB-positive group had a longer duration of SARS-CoV-2 shedding (67 days vs. 22 days, p < 0.01). CONCLUSIONS: Concomitant TB does not significantly impact clinical outcomes of hospitalised patients with acute COVID-19. However, TB-positive patients had longer duration of SARS-COV-2-RNA positivity.


Asunto(s)
COVID-19 , Coinfección , Tuberculosis , Humanos , COVID-19/complicaciones , COVID-19/terapia , SARS-CoV-2 , Estudios Retrospectivos , Estudios de Cohortes , Coinfección/epidemiología , Tuberculosis/complicaciones
17.
J Med Chem ; 66(16): 11118-11132, 2023 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-37552553

RESUMEN

The DNA-encoded library (DEL) is a powerful hit-generation tool in drug discovery. This study describes a new DEL with a privileged scaffold quinazolin-4(3H)-one developed by a robust DNA-compatible multicomponent reaction and a series of novel glutathione S-transferase (GST) inhibitors that were identified through affinity-mediated DEL selection. A novel inhibitor 16 was subsequently verified with an inhibitory potency value of 1.55 ± 0.02 µM against SjGST and 2.02 ± 0.20 µM against hGSTM2. Further optimization was carried out via various structure-activity relationship studies. And especially, the co-crystal structure of the compound 16 with the SjGST was unveiled, which clearly demonstrated its binding mode was quite different from the known GSH-like compounds. This new type of probe is likely to play a different role compared with the GSH, which may provide new opportunities to discover more potent GST inhibitors.


Asunto(s)
Inhibidores Enzimáticos , Glutatión Transferasa , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Relación Estructura-Actividad
18.
J Colloid Interface Sci ; 652(Pt A): 557-566, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37607418

RESUMEN

Controllable construction and manipulation of artificial multi-compartmental structures are crucial in understanding and imitating smart molecular elements such as biological cells and on-demand delivery systems. Here, we report a liquid crystal droplet (LCD) based three-dimensional system for controllable and reversible ingestion and release of guest aqueous droplets (GADs). Induced by interfacial thermodynamic fluctuation and internal topological defect, microscale LCDs with perpendicular anchoring condition at the interface would spontaneously ingest external components from the surroundings and transform them as radially assembled tiny GADs inside LCDs. Landau-de Gennes free-energy model is applied to describe and explain the assembly dynamics and morphologies of these tiny GADs, which presents a good agreement with experimental observations. Furthermore, the release of these ingested GADs can be actively triggered by changing the anchoring conditions at the interface of LCDs. Since those ingestion and release processes are controllable and happen very gently at room temperature and neutral pH environment without extra energy input, these microscale LCDs are very prospective to provide a unique and viable route for constructing hierarchical 3D structures with tunable components and compartments.

19.
Cereb Cortex ; 33(18): 10087-10097, 2023 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-37522299

RESUMEN

Pediatric overweight/obesity can lead to sleep-disordered breathing (SDB), abnormal neurological and cognitive development, and psychiatric problems, but the associations and interactions between these factors have not been fully explored. Therefore, we investigated the associations between body mass index (BMI), SDB, psychiatric and cognitive measures, and brain morphometry in 8484 children 9-11 years old using the Adolescent Brain Cognitive Development dataset. BMI was positively associated with SDB, and both were negatively correlated with cortical thickness in lingual gyrus and lateral orbitofrontal cortex, and cortical volumes in postcentral gyrus, precentral gyrus, precuneus, superior parietal lobule, and insula. Mediation analysis showed that SDB partially mediated the effect of overweight/obesity on these brain regions. Dimensional psychopathology (including aggressive behavior and externalizing problem) and cognitive function were correlated with BMI and SDB. SDB and cortical volumes in precentral gyrus and insula mediated the correlations between BMI and externalizing problem and matrix reasoning ability. Comparisons by sex showed that obesity and SDB had a greater impact on brain measures, cognitive function, and mental health in girls than in boys. These findings suggest that preventing childhood obesity will help decrease SDB symptom burden, abnormal neurological and cognitive development, and psychiatric problems.


Asunto(s)
Obesidad Infantil , Síndromes de la Apnea del Sueño , Masculino , Femenino , Adolescente , Humanos , Niño , Índice de Masa Corporal , Sobrepeso , Polisomnografía/métodos , Síndromes de la Apnea del Sueño/diagnóstico por imagen , Síndromes de la Apnea del Sueño/complicaciones , Encéfalo/diagnóstico por imagen
20.
Soft Matter ; 19(30): 5723-5736, 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37458401

RESUMEN

Conductive hydrogels have been widely studied for their potential application as wearable sensors due to their flexibility and biocompatibility. However, the simultaneous incorporation of excellent stretchability, toughness, conductivity, self-healing, and adhesion via a simple method remains a great challenge. Herein, a multifunctional hydrogel with self-adhesion, self-healing, conductivity, and mechanical properties was fabricated by ionic cross-linking of chitosan (CS), the acrylic acid (AA) polymer, and tea polyphenols (TPs) in the presence of graphitized carbon nanotubes (CNTs) in this work. The resultant hydrogel has unique self-healing properties (94.11% for strain self-healing and 90.60% for stress self-healing) and mechanical properties. The fracture stress was 0.075 MPa when the strain was 1184%, and the toughness reached 0.48 MJ m-3. The synergistic effect of free ions and CNTs endows the hydrogel with an excellent electrical conductivity (6.67 S m-1). Moreover, the hydrogel can adhere to various organic and inorganic materials. It exhibits repeatable self-adhesion to human skin and can be peeled off completely without any residual, irritation or allergic reactions. Additionally, the hydrogel also has good strain sensitivity and exhibits stable output signals in motion monitoring of the human body as a biosensor. Therefore, this work provides a new prospect for the design of multifunctional hydrogels for their potential applications in wearable biosensors.

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