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1.
J Environ Sci (China) ; 148: 298-305, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39095166

RESUMEN

Ultrasonic humidifiers are commonly used in households to maintain indoor humidity and generate a large number of droplets or spray aerosols. However, there have been various health concerns associated with humidifier use, largely due to aerosols generated during operation. Here, we investigated the size distribution, chemical composition, and charged fraction of aerosol particles emitted from commercial ultrasonic humidifiers. Heavy metals in water used for humidifiers were found to be highly enriched in the ultrasonic humidifier aerosols (UHA), with the enrichment factors ranging from 102 to 107. This enrichment may pose health concerns for the building occupants, as UHA concentrations of up to 106 particles/cm3 or 3 mg/m3 were observed. Furthermore, approximately 90% of UHA were observed to be electrically charged, for the first time according to our knowledge. Based on this discovery, we proposed and tested a new method to remove UHA by using a simple electrical field. The designed electrical field in this work can efficiently remove 81.4% of UHA. Therefore, applying this electrical field could be an effective method to significantly reduce the health risks by UHA.


Asunto(s)
Aerosoles , Humidificadores , Metales Pesados , Aerosoles/análisis , Metales Pesados/análisis , Contaminación del Aire Interior/prevención & control , Contaminación del Aire Interior/análisis , Contaminantes Atmosféricos/análisis , Ultrasonido , Monitoreo del Ambiente/métodos
2.
Molecules ; 29(17)2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39274876

RESUMEN

Gaussia luciferase (Gluc) is currently known as the smallest naturally secreted luciferase. Due to its small molecular size, high sensitivity, short half-life, and high secretion efficiency, it has become an ideal reporter gene and is widely used in monitoring promoter activity, studying protein-protein interactions, protein localization, high-throughput drug screening, and real-time monitoring of tumor occurrence and development. Although studies have shown that different Gluc mutations exhibit different bioluminescent properties, their mechanisms have not been further investigated. The purpose of this study is to reveal the relationship between the conformational changes of Gluc mutants and their bioluminescent properties through molecular dynamics simulation combined with neural relationship inference (NRI) and Markov models. Our results indicate that, after binding to the luciferin coelenterazine (CTZ), the α-helices of the 109-119 residues of the Gluc Mutant2 (GlucM2, the flash-type mutant) are partially unraveled, while the α-helices of the same part of the Gluc Mutant1 (GlucM1, the glow-type mutant) are clearly formed. The results of Markov flux analysis indicate that the conformational differences between glow-type and flash-type mutants when combined with luciferin substrate CTZ mainly involve the helicity change of α7. The most representative conformation and active pocket distance analysis indicate that compared to the flash-type mutant GlucM2, the glow-type mutant GlucM1 has a higher degree of active site closure and tighter binding. In summary, we provide a theoretical basis for exploring the relationship between the conformational changes of Gluc mutants and their bioluminescent properties, which can serve as a reference for the modification and evolution of luciferases.


Asunto(s)
Luciferasas , Cadenas de Markov , Simulación de Dinámica Molecular , Luciferasas/metabolismo , Luciferasas/genética , Luciferasas/química , Conformación Proteica , Mutación , Animales , Copépodos/enzimología , Copépodos/genética , Imidazoles/química , Imidazoles/metabolismo , Unión Proteica , Mediciones Luminiscentes , Pirazinas
3.
Cell Mol Life Sci ; 81(1): 406, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287798

RESUMEN

Doxorubicin (DOX) is an effective chemotherapeutic drug, but its use can lead to cardiomyopathy, which is the leading cause of mortality among cancer patients. Macrophages play a role in DOX-induced cardiomyopathy (DCM), but the mechanisms undlerlying this relationship remain unclear. This study aimed to investigate how IKKα regulates macrophage activation and contributes to DCM in a mouse model. Specifically, the role of macrophage IKKα was evaluated in macrophage-specific IKKα knockout mice that received DOX injections. The findings revealed increased expression of IKKα in heart tissues after DOX administration. In mice lacking macrophage IKKα, myocardial injury, ventricular remodeling, inflammation, and proinflammatory macrophage activation worsened in response to DOX administration. Bone marrow transplant studies confirmed that IKKα deficiency exacerbated cardiac dysfunction. Macrophage IKKα knockout also led to mitochondrial damage and metabolic dysfunction in macrophages, thereby resulting in increased cardiomyocyte injury and oxidative stress. Single-cell sequencing analysis revealed that IKKα directly binds to STAT3, leading to the activation of STAT3 phosphorylation at S727. Interestingly, the inhibition of STAT3-S727 phosphorylation suppressed both DCM and cardiomyocyte injury. In conclusion, the IKKα-STAT3-S727 signaling pathway was found to play a crucial role in DOX-induced cardiomyopathy. Targeting this pathway could be a promising therapeutic strategy for treating DOX-related heart failure.


Asunto(s)
Cardiomiopatías , Doxorrubicina , Quinasa I-kappa B , Macrófagos , Ratones Noqueados , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Doxorrubicina/efectos adversos , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Cardiomiopatías/inducido químicamente , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Cardiomiopatías/genética , Ratones , Quinasa I-kappa B/metabolismo , Quinasa I-kappa B/genética , Transducción de Señal/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Miocitos Cardíacos/efectos de los fármacos , Ratones Endogámicos C57BL , Fosforilación/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Modelos Animales de Enfermedad , Activación de Macrófagos/efectos de los fármacos , Miocardio/metabolismo , Miocardio/patología
4.
Pestic Biochem Physiol ; 204: 106079, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39277392

RESUMEN

Root-knot nematodes (Meloidogyne spp.) are highly destructive pests that cause significant yield losses annually. Biological control of nematodes has emerged as a potential alternative in sustainable agriculture. In this study, we originally isolated Bacillus cereus G5 from the rhizosphere soil of rice (Oryza sativa). Treatment with the fermentation supernatant of G5 in vitro demonstrated high toxicity to second-stage juveniles (J2) of Meloidogyne graminicola and remarkably inhibited egg hatching. Moreover, G5 steadily colonized rhizosphere soil and rice seedlings, and exhibited excellent biocontrol efficacy against M. graminicola under greenhouse conditions. Notably, the volatile organic compounds (VOCs) produced by G5 displayed high fumigant activity against M. graminicola. The G5 VOCs efficiently reduced the gall index and nematode population in rice roots, while also promoting rice growth in double-layered pot tests. Additionally, the expression of defense genes involved in the salicylic acid (OsNPR1, OsWRKY45, OsPAL1), jasmonic acid (OsJaMYB, OsAOS2) and ethylene (OsACS1) signalling pathways was significantly upregulated in rice seedlings treated with G5 VOCs. This suggests that G5 VOCs contribute to eliciting plant defense responses. Furthermore, we identified 14 major VOCs produced by G5 using solid-phase micro-extraction gas chromatography and mass spectrometry (SPEM-GC-MS). Notably, allomatrine, morantel, 1-octen-3-ol and 3-methyl-2-butanol displayed strong contact nematicidal activity. Among these, only 1-octen-3-ol demonstrated fumigant activity against J2s of M. graminicola, with an LC50 value of 758.95 mg/L at 24 h. Overall, these results indicated that the B. cereus G5 and its synthetic VOCs possess high potential as biocontrol agents for managing root-knot nematodes.


Asunto(s)
Bacillus cereus , Oryza , Tylenchoidea , Compuestos Orgánicos Volátiles , Animales , Tylenchoidea/efectos de los fármacos , Tylenchoidea/fisiología , Bacillus cereus/efectos de los fármacos , Compuestos Orgánicos Volátiles/farmacología , Compuestos Orgánicos Volátiles/metabolismo , Oryza/parasitología , Oryza/microbiología , Control Biológico de Vectores/métodos , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/parasitología , Enfermedades de las Plantas/microbiología , Raíces de Plantas/parasitología , Rizosfera , Agentes de Control Biológico/farmacología
5.
Chem Commun (Camb) ; 60(74): 10212-10215, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39206734

RESUMEN

Herein, chiral metal-organic frameworks (MOFs), DCF-20 and LCF-20, were utilized as matrices for both chirality transfer and energy transfer. HBT1@MOFs and HBT2@MOFs emit excitation-dependent circularly polarized luminescence (CPL) due to excited-state intramolecular proton transfer (ESIPT). HBT1/C152/NIR@MOFs exhibit full-color and white CPL. The luminescence dissymmetry factors (glum) were significantly increased, benefiting from the efficient chirality space transfer and high luminescence efficiency.

6.
Inorg Chem ; 63(35): 16284-16292, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39152397

RESUMEN

Multicolor-tunable room-temperature phosphorescence (RTP) is attracting wide attention in optoelectronic applications. Here, we propose a coordination-oriented assembly approach to achieve wide-range RTP with a benzimidazole derivative (2,7-diazabenzimidazole, DZBIM) as a luminogen. These two compounds exhibit unexpected excitation-responsive RTP emission, and the phosphorescence emission nearly covers the entire visible region with the change of the excitation wavelength from 360 to 620 nm. To the best of our knowledge, this is the first report of coordination polymers with such a full-color-tunable RTP. Compound 1 also shows white-light emission upon excitation at 280 nm. Experimental and theoretical results demonstrate that multiple intermolecular interactions and emission centers from different aggregates are responsible for the generation of multicolor emission. The white-light emission and multiple anticounterfeiting are explored. Besides, compound 1 exhibits high antibacterial activity benefiting from efficient 1O2 generation. This work provides an efficient way to prepare a color-tunable RTP.

7.
Anal Sci ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39207655

RESUMEN

One key aspect pushing the frontiers of biomedical RS is dedicated machine- or deep- learning (ML or DL) algorithms. Yet, systematic comparative study between ML and DL algorithms has not been conducted for biomedical RS, largely due to the limited availability of open-source and large Raman spectra dataset. Therefore we compared typical ML partial least square-discriminant analysis (PLS-DA) and DL one dimensional convolution neural network (1D-CNN) based pathogenic microbe identification on 12,000 Raman spectra from six species of microbe (i.e., K. aerogenes (Klebsiella aerogenes), C. albicans (Candida albicans), C. glabrata (Candida glabrata), Group A Strep. (Group A Streptococcus), E. coli1 (Escherichia coli1), E. coli2 (Escherichia coli2)) when 100%, 75%, 50% and 25% of the 12,000 Raman spectra were retained. The total Raman dataset was analyzed with 80% split for training and 20% for testing. The 100% retained testing dataset accuracy, area under curve (AUC) of the receiver operating characteristic (ROC) curve were 95.25% and 0.997 for 1D-CNN, which are higher than those (89.42% and 0.979) of PLS-DA. Yet, PLS-DA outperforms 1D-CNN for 75%, 50% and 25% retained testing dataset. The resultant accuracies and AUCs demonstrated the performance reliance of PLS-DA and 1D-CNN on Raman spectra number. Besides, both loadings on the latent variables of PLS-DA and the saliency maps of 1D-CNN largely captured Raman peaks arising from DNA and proteins with comparable interpretability. The results of the current work indicated that both ML and DL algorithms should be explored for application-wise Raman spectra identification to select whichever with higher accuracies and AUCs.

8.
Exp Ther Med ; 28(3): 349, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39071907

RESUMEN

Ischemic heart disease (IHD) remains a leading cause of mortalities worldwide, necessitating timely reperfusion to reduce acute mortality. Paradoxically, reperfusion can induce myocardial ischemia/reperfusion (I/R) injury, which is primarily characterized by mitochondrial dysfunction. Translocator protein (TSPO) participates in multiple cellular events; however, its role in IHD, especially in the process of myocardial I/R injury, has not been well determined. The aim of the present study was to investigate the functional role of TSPO in myocardial I/R injury and dissect the concomitant cellular events involved. This study utilized small interfering RNA (siRNA) technology to knock down TSPO expression. The I/R process was simulated using an anoxia/reoxygenation (A/R) model. The role of TSPO in H9c2 cardiomyocytes was assessed using various techniques, such as Western blotting, Flow cytometry, Reverse transcription-quantitative PCR (RT-qPCR), Immunofluorescence, Co-immunoprecipitation (co-IP) and similar methods. It was found that A/R markedly upregulated the expression of TSPO in cardiomyocytes. Inhibition of TSPO improved myocardial cell apoptosis and damage following A/R stimulation. Additionally, targeting TSPO alleviated mitochondrial damage, reduced mitochondrial ROS release and enhanced ATP synthesis following A/R stimulation. It was further confirmed that A/R stimulation induced a significant increase in the expression of pivotal markers [phosporylated-PKR-like ER kinase (PERK)/PERK, activating transcription factor 6 (ATF6) and inositol-requiring enzyme 1] involved in the adaptive unfolded protein response, which is accompanied by downstream signaling during endoplasmic reticulum (ER) stress. Notably, TSPO knockdown increased the expression of the aforementioned markers and, subsequently, TSPO was confirmed to interact with ATF6, suggesting that TSPO might play a role in ER stress during myocardial I/R injury. Finally, inhibition of TSPO upregulated mitophagy, as indicated by further decreases in P62 and increases in Parkin and PINK1 levels following A/R stimulation. Together, the results suggest that TSPO plays a multifaceted role in myocardial I/R injury. Understanding TSPO-induced cellular responses could inform targeted therapeutic strategies for patients with IHD.

9.
J Clin Invest ; 134(15)2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842946

RESUMEN

Aberrant activation of RAS/MAPK signaling is common in cancer, and efforts to inhibit pathway components have yielded drugs with promising clinical activities. Unfortunately, treatment-provoked adaptive resistance mechanisms inevitably develop, limiting their therapeutic potential. As a central node essential for receptor tyrosine kinase-mediated RAS activation, SHP2 has emerged as an attractive cancer target. Consequently, many SHP2 allosteric inhibitors are now in clinical testing. Here we discovered a previously unrecognized off-target effect associated with SHP2 allosteric inhibitors. We found that these inhibitors accumulate in the lysosome and block autophagic flux in an SHP2-independent manner. We showed that off-target autophagy inhibition by SHP2 allosteric inhibitors contributes to their antitumor activity. We also demonstrated that SHP2 allosteric inhibitors harboring this off-target activity not only suppress oncogenic RAS signaling but also overcome drug resistance such as MAPK rebound and protective autophagy in response to RAS/MAPK pathway blockage. Finally, we exemplified a therapeutic framework that harnesses both the on- and off-target activities of SHP2 allosteric inhibitors for improved treatment of mutant RAS-driven and drug-resistant malignancies such as pancreatic and colorectal cancers.


Asunto(s)
Autofagia , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Proteínas ras , Animales , Humanos , Ratones , Regulación Alostérica/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/enzimología , Proteína Tirosina Fosfatasa no Receptora Tipo 11/antagonistas & inhibidores , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Proteínas ras/metabolismo , Proteínas ras/genética , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Materials (Basel) ; 17(11)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38893751

RESUMEN

Lightweight and high-strength insulation materials have important application prospects in the aerospace, metallurgical, and nuclear industries. In this study, a highly porous silica fiber reinforced phenolic resin matrix composite was prepared by vacuum impregnation and atmospheric drying using quartz fiber needled felt as reinforcement and anhydrous ethanol as a pore-making agent. The effects of curing agent content on the structure, composition, density, and thermal conductivity of the composite were studied. The mechanical properties of the composite in the xy direction and z direction were analyzed. The results showed that this process can also produce porous phenolic resin (PR) with a density as low as 0.291 g/cm3, where spherical phenolic resin particles are interconnected to form a porous network structure with a particle size of about 5.43 µm. The fiber-reinforced porous PR had low density (0.372~0.397 g/cm3) and low thermal conductivity (0.085~0.095 W/m·K). The spherical phenolic resin particles inside the composite were well combined with the fiber at the interface and uniformly distributed in the fiber lap network. The composite possessed enhanced mechanical properties with compressive strength of 3.5-5.1 MPa in the xy direction and appeared as gradual compaction rather than destruction as the strain reached 30% in the z direction. This research provides a lightweight and high-strength insulation material with a simple preparation process and excellent performance.

11.
iScience ; 27(6): 110041, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38868178

RESUMEN

Compared to traditional methods, using machine learning to assess or predict the odor of molecules can save costs in various aspects. Our research aims to collect molecules with coffee odor and summarize the regularity of these molecules, ultimately creating a binary classifier that can determine whether a molecule has a coffee odor. In this study, a total of 371 coffee-odor molecules and 9,700 non-coffee-odor molecules were collected. The Knowledge-guided Pre-training of Graph Transformer (KPGT), support vector machine (SVM), random forest (RF), multi-layer perceptron (MLP), and message-passing neural networks (MPNN) were used to train the data. The model with the best performance was selected as the basis of the predictor. The prediction accuracy value of the KPGT model exceeded 0.84 and the predictor has been deployed as a webserver PredCoffee.

12.
BMC Neurol ; 24(1): 198, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38867178

RESUMEN

BACKGROUND: At present, the most effective treatment for symptomatic moyamoya disease (MMD) is surgery. However, the high incidence of postoperative complications is a serious problem plaguing the surgical treatment of MMD, especially the acute cerebral infarction. Decreased cerebrovascular reserve is an independent risk factor for ischemic infarction, and the pulsatility index (PI) of transcranial Doppler (TCD) is a common intuitive index for evaluating intracranial vascular compliance. However, the relationship between PI and the occurrence of ischemic stroke after operation is unclear. OBJECTIVE: To explore whether the PI in the middle cerebral artery (MCA) could serve as a potential predictor for the occurrence of ischemic infarction after bypass surgery in MMD. METHODS: We performed a retrospective analysis of data from 71 patients who underwent combined revascularization surgery, including superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-synangiosis (EDMS). The patients were divided into two groups according to the median of ipsilateral MCA-PI before operation, low PI group (MCA-PI < 0.614) and high PI group (MCA-PI ≥ 0.614). Univariate and multivariate regression analysis were used to explore risk factors affecting the occurrence of postoperative cerebral infarction. RESULTS: Among the 71 patients with moyamoya disease, 11 patients had cerebral infarction within one week after revascularization. Among them, 10 patients' ipsilateral MCA-PI were less than 0.614, and another one's MCA- PI is higher than 0.614. Univariate analysis showed that the lower ipsilateral MCA-PI (0.448 ± 0.109 vs. 0.637 ± 0.124; P = 0.001) and higher Suzuki stage (P = 0.025) were linked to postoperative cerebral infarction. Multivariate analysis revealed that lower ipsilateral MCA-PI was an independent risk factor for predicting postoperative cerebral infarction (adjusted OR = 14.063; 95% CI = 6.265 ~ 37.308; P = 0.009). CONCLUSIONS: A lower PI in the ipsilateral MCA may predict the cerebral infarction after combined revascularization surgery with high specificity. And combined revascularization appears to be safer for the moyamoya patients in early stages.


Asunto(s)
Infarto Cerebral , Revascularización Cerebral , Enfermedad de Moyamoya , Complicaciones Posoperatorias , Ultrasonografía Doppler Transcraneal , Humanos , Enfermedad de Moyamoya/cirugía , Enfermedad de Moyamoya/diagnóstico por imagen , Masculino , Femenino , Adulto , Infarto Cerebral/etiología , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/epidemiología , Estudios Retrospectivos , Revascularización Cerebral/efectos adversos , Revascularización Cerebral/métodos , Ultrasonografía Doppler Transcraneal/métodos , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/cirugía , Flujo Pulsátil/fisiología , Adulto Joven , Factores de Riesgo
13.
Food Sci Nutr ; 12(6): 4435-4442, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38873477

RESUMEN

4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) is a flavor compound widely found in natural products and is used in food as a flavor-enhancing agent. Quinone oxidoreductase (QOR) was verified as a key enzyme to synthesize HDMF in strawberry, while its impact on HDMF production by Zygosaccharomyces rouxii was still unknown. The QOR gene was cloned and overexpressed in Z. rouxii, and its impact on HDMF production by Z. rouxii was then further analyzed. At the same time, it is expected to obtain engineered strains of Z. rouxii with high HDMF production. The results showed that the engineered strains of Z. rouxii exhibit different levels of QOR gene expression and HDMF production; among them, the QOR6 strain exhibiting the highest gene expression level and HDMF production was named as ZrQOR. The HDMF production of the ZrQOR strain was significantly higher than that of wild-type Z. rouxii at 3 and 5 days of culture, with 1.41-fold and 1.08-fold increases, respectively. At 3 days of fermentation, the highest HDMF yield of ZrQOR strain was obtained (2.75 mg/L), 2 days ahead of the reported highest HDMF production by Z. rouxii. At 3, 5, and 7 days, QOR gene expression was 4.8-fold, 3.3-fold, and 5.6-fold higher in the ZrQOR strain than in the wild-type Z. rouxii, respectively. Therefore, overexpression of the QOR gene facilitates HDMF synthesis. The genetic stability of the 0-20 generation ZrQOR strain was stable, and there was no significant difference in colony shape, QOR expression, or HDMF production compared to the wild type. In this study, the genetic engineering Z. rouxii strain was used to improve HDMF production. This research has laid the groundwork for further industrial production of HDMF via microbial synthesis.

14.
Biomed Mater ; 19(4)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38740051

RESUMEN

Infectious diseases severely threaten human health, and traditional treatment techniques face multiple limitations. As an important component of immune cells, macrophages display unique biological properties, such as biocompatibility, immunocompatibility, targeting specificity, and immunoregulatory activity, and play a critical role in protecting the body against infections. The macrophage membrane-coated nanoparticles not only maintain the functions of the inner nanoparticles but also inherit the characteristics of macrophages, making them excellent tools for improving drug delivery and therapeutic implications in infectious diseases (IDs). In this review, we describe the characteristics and functions of macrophage membrane-coated nanoparticles and their advantages and challenges in ID therapy. We first summarize the pathological features of IDs, providing insight into how to fight them. Next, we focus on the classification, characteristics, and preparation of macrophage membrane-coated nanoparticles. Finally, we comprehensively describe the progress of macrophage membrane-coated nanoparticles in combating IDs, including drug delivery, inhibition and killing of pathogens, and immune modulation. At the end of this review, a look forward to the challenges of this aspect is presented.


Asunto(s)
Membrana Celular , Enfermedades Transmisibles , Sistemas de Liberación de Medicamentos , Macrófagos , Nanopartículas , Humanos , Nanopartículas/química , Macrófagos/metabolismo , Animales , Enfermedades Transmisibles/tratamiento farmacológico , Membrana Celular/metabolismo , Materiales Biocompatibles Revestidos/química
16.
Int J Infect Dis ; 145: 107080, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38701913

RESUMEN

OBJECTIVES: To explore whether COVID-19 vaccination protects against hospital admission by preventing infections and severe disease. METHODS: We leveraged the UK Biobank and studied associations of COVID-19 vaccination (BioNTech-BNT162b2 or Oxford-AstraZeneca-ChAdOx1) with hospitalizations from cardiovascular and other selected diseases (N = 393,544; median follow-up = 54 days among vaccinated individuals). Multivariable Cox, Poisson regression, propensity score matching, and inverse probability treatment weighting analyses were performed. We also performed adjustment using prescription-time distribution matching, and prior event rate ratio. RESULTS: We observed that COVID-19 vaccination (at least one dose), compared with no vaccination, was associated with reduced short-term risks of hospitalizations from stroke (hazard ratio [HR] = 0.178, 95% confidence interval [CI]: 0.127-0.250, P = 1.50e-23), venous thromboembolism (HR = 0.426, CI: 0.270-0.673, P = 2.51e-4), dementia (HR = 0.114, CI: 0.060-0.216; P = 2.24e-11), non-COVID-19 pneumonia (HR = 0.108, CI: 0.080-0.145; P = 2.20e-49), coronary artery disease (HR = 0.563, CI: 0.416-0.762; P = 2.05e-4), chronic obstructive pulmonary disease (HR = 0.212, CI: 0.126-0.357; P = 4.92e-9), type 2 diabetes (HR = 0.216, CI: 0.096-0.486, P = 2.12e-4), heart failure (HR = 0.174, CI: 0.118-0.256, P = 1.34e-18), and renal failure (HR = 0.415, CI: 0.255-0.677, P = 4.19e-4), based on standard Cox regression models. Among the previously mentioned results, reduced hospitalizations for stroke, heart failure, non-COVID-19 pneumonia, and dementia were consistently observed across regression, propensity score matching/inverse probability treatment weighting, prescription-time distribution matching, and prior event rate ratio. The results for two-dose vaccination were similar. CONCLUSIONS: Taken together, this study provides further support to the safety and benefits of COVID-19 vaccination, and such benefits may extend beyond reduction of infection risk or severity per se. However, causal relationship cannot be concluded and further studies are required.


Asunto(s)
Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Enfermedades Cardiovasculares , Hospitalización , Humanos , Hospitalización/estadística & datos numéricos , Masculino , Reino Unido/epidemiología , Femenino , COVID-19/prevención & control , COVID-19/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Persona de Mediana Edad , Anciano , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , Vacuna BNT162/administración & dosificación , SARS-CoV-2 , Bancos de Muestras Biológicas , ChAdOx1 nCoV-19 , Vacunación , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Biobanco del Reino Unido
17.
J Chromatogr A ; 1728: 465019, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-38810573

RESUMEN

A stable isotope dilution-liquid chromatography-tandem mass spectrometry method based on a derivatisation strategy involving an N,N'-carbonylimidazole solution (CDI) with 4-(dimethylamino)-benzenemethanamine was developed for the determination of 11 free fatty acids (FFAs) in human blood samples. Serum samples were subjected to liquid‒liquid extraction and centrifuged, and the supernatant was collected for a two-step derivatisation reaction with a CDI and 4-(dimethylamino)-aniline acetonitrile solution. The derivatised solution was separated on a ACQUITY UPLC HSS T3 column (2.1 × 50 mm, 1.8 µm) column with a mobile phase consisting of water-acetonitrile in gradient elution and then detected by tandem mass spectrometry using electrospray ionisation (ESI) and multiple reaction monitoring (MRM) in positive ion mode and quantified using the isotope internal standard method. The effects of the derivatisation reaction time, temperature and concentration of derivatisation reagents on the response values of the analytes were investigated. The optimal conditions were as follows: 1.0 mg mL-1 CDI acetonitrile solution at 25 °C for 25 min, followed by a reaction with a 1.0 mg mL-1 4-(dimethylamino)-benzenemethanamine acetonitrile solution at 70 °C for 30 min. Under the optimal conditions, the limits of detection (LODs) of the 11 FFAs were in the range of 3.0-14.0 ng mL-1; the limits of quantification (LOQs) were in the range of 8.0-45.0 ng mL-1; and the mean recoveries ranged from 83.4 to 112.8%, with intraday and interday precisions ranging from 0.7 to 9.1% and 3.7-9.5%, respectively. The experimental method is simple in terms of the pretreatment operation, accurate and reliable, and can be applied to the sensitive determination of FFAs in human blood samples.


Asunto(s)
Ácidos Grasos no Esterificados , Espectrometría de Masas en Tándem , Humanos , Espectrometría de Masas en Tándem/métodos , Ácidos Grasos no Esterificados/sangre , Límite de Detección , Cromatografía Liquida/métodos , Reproducibilidad de los Resultados , Imidazoles/sangre , Imidazoles/química , Extracción Líquido-Líquido/métodos , Espectrometría de Masa por Ionización de Electrospray/métodos , Cromatografía Líquida de Alta Presión/métodos , Masculino
18.
NPJ Sci Learn ; 9(1): 26, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38538593

RESUMEN

Dyslexia and developmental language disorders are important learning difficulties. However, their genetic basis remains poorly understood, and most genetic studies were performed on Europeans. There is a lack of genome-wide association studies (GWAS) on literacy phenotypes of Chinese as a native language and English as a second language (ESL) in a Chinese population. In this study, we conducted GWAS on 34 reading/language-related phenotypes in Hong Kong Chinese bilingual children (including both twins and singletons; total N = 1046). We performed association tests at the single-variant, gene, and pathway levels. In addition, we tested genetic overlap of these phenotypes with other neuropsychiatric disorders, as well as cognitive performance (CP) and educational attainment (EA) using polygenic risk score (PRS) analysis. Totally 5 independent loci (LD-clumped at r2 = 0.01; MAF > 0.05) reached genome-wide significance (p < 5e-08; filtered by imputation quality metric Rsq>0.3 and having at least 2 correlated SNPs (r2 > 0.5) with p < 1e-3). The loci were associated with a range of language/literacy traits such as Chinese vocabulary, character and word reading, and rapid digit naming, as well as English lexical decision. Several SNPs from these loci mapped to genes that were reported to be associated with EA and other neuropsychiatric phenotypes, such as MANEA and PLXNC1. In PRS analysis, EA and CP showed the most consistent and significant polygenic overlap with a variety of language traits, especially English literacy skills. To summarize, this study revealed the genetic basis of Chinese and English abilities in a group of Chinese bilingual children. Further studies are warranted to replicate the findings.

19.
New Phytol ; 242(5): 2115-2131, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38358006

RESUMEN

Drought is one of the major environmental constraints for wheat production world-wide. As the progenitor and genetic reservoir of common wheat, emmer wheat is considered as an invaluable gene pool for breeding drought-tolerant wheat. Combining GWAS and eGWAS analysis of 107 accessions, we identified 86 QTLs, 105 462 eQTLs as well as 68 eQTL hotspots associating with drought tolerance (DT) in emmer wheat. A complex regulatory network composed of 185 upstream regulator and 2432 downstream drought-responsive candidates was developed, of which TtOTS1 was found to play a negative effect in determining DT through affecting root development. This study sheds light on revealing the genetic basis underlying DT, which will provide the indispensable genes and germplasm resources for elite drought tolerance wheat improvement and breeding.


Asunto(s)
Resistencia a la Sequía , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Triticum , Adaptación Fisiológica/genética , Resistencia a la Sequía/genética , Regulación de la Expresión Génica de las Plantas , Redes Reguladoras de Genes , Genes de Plantas , Fenotipo , Raíces de Plantas/genética , Raíces de Plantas/fisiología , Polimorfismo de Nucleótido Simple , Triticum/genética , Triticum/fisiología
20.
Int J Biol Macromol ; 263(Pt 2): 130407, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38417747

RESUMEN

This study focuses on enhancing interventional medical devices, specifically catheters, using a novel composite material. Challenges like corrosion and contamination in vivo, often caused by body fluids' pH, bacteria, and proteins, lead to mechanical damage, bacterial colonization, and biofilm formation on devices like catheters. The objective of this study was to prepare a versatile composite (HFs) by designing polyurethanes (HPU) with an ionic chain extender (HIID) and blending them with amphiphilic nanofibrillated cellulose (Am-CNF). The composite leverages dynamic interactions such as hydrogen bonding and electrostatic forces, as evidenced by Molecular Mechanics (MM) calculations. The H4F0.75 composite exhibited exceptional properties: 99 % length recovery post 600 stretching cycles at 100 % strain, rapid self-healing in artificial urine, high bactericidal activity, and excellent cell viability. Moreover, mechanical aging tests and UV-vis spectral analysis confirmed the material's durability and safety. These findings suggest that the HFs composite holds significant promise for improving catheters' performance in medical applications.


Asunto(s)
Incrustaciones Biológicas , Celulosa , Celulosa/farmacología , Celulosa/química , Poliuretanos/farmacología , Poliuretanos/química , Incrustaciones Biológicas/prevención & control , Catéteres , Antibacterianos/farmacología , Antibacterianos/química
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