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1.
Front Cell Dev Biol ; 12: 1490040, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39493348

RESUMEN

In this protocol, we detail a seven-stage differentiation methodology for generating pancreatic delta cells (SC-delta cells) from human pluripotent stem cells (hPSCs). In the first step, definitive endoderm is generated by activin A and CHIR99021, followed by induction of primitive gut tube and posterior foregut by treatment with FGF7, SANT1, LDN193189, PdBU, and retinoic acid (RA). The subsequent endocrine generation and directed SC-delta cell induction is achieved by a combined treatment of the FGF7 with FGF2 during stage 4 and 5, together with RA, XXI, ALK5 inhibitor II, SANT1, Betacellulin and LDN193189. The planar cultivation is converted to a suspended system after stage 5, allowing cells to aggregate into delta cell-containing spheroids. The differentiation takes approximately 4-5 weeks for delta cell generation and an additional 1-2 weeks for cell expansion and evaluation. We believe that this amenable and simplified protocol can provide a stable source of SC-delta cells from efficient differentiation, facilitating further investigation of the physiological role of delta cells as well as refinement of islet cell therapeutic strategies.

2.
Commun Biol ; 7(1): 1341, 2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39420210

RESUMEN

There is cumulative evidence that lipid metabolism plays a key role in the pathogenesis of various neurodegenerative disorders including Alzheimer's disease (AD). Visualising lipid content in a non-destructive label-free manner can aid in elucidating the AD phenotypes towards a better understanding of the disease. In this study, we combined multiple optical molecular-specific methods, Fourier transform infrared (FTIR) spectroscopic imaging, synchrotron radiation-infrared (SR-IR) microscopy, Raman and stimulated Raman scattering (SRS) microscopy, and optical-photothermal infrared (O-PTIR) microscopy with multivariate data analysis, to investigate the biochemistry of brain hippocampus in situ using a mouse model of tauopathy (rTg4510). We observed a significant difference in the morphology and lipid content between transgenic (TG) and wild type (WT) samples. Immunohistochemical staining revealed some degree of microglia co-localisation with elevated lipids in the brain. These results provide new evidence of tauopathy-related dysfunction in a preclinical study at a subcellular level.


Asunto(s)
Enfermedad de Alzheimer , Encéfalo , Modelos Animales de Enfermedad , Metabolismo de los Lípidos , Ratones Transgénicos , Tauopatías , Animales , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Ratones , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Tauopatías/metabolismo , Tauopatías/patología , Lípidos/análisis , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Hipocampo/metabolismo , Hipocampo/patología , Hipocampo/diagnóstico por imagen
3.
Nano Lett ; 24(43): 13708-13717, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39417607

RESUMEN

Reactive oxygen species (ROS)-responsive drug delivery systems possess immense potential for targeted delivery and controlled release of therapeutics. However, the rapid responsiveness to ROS and sustained release of antibacterial drugs are often limited by the challenging microenvironment of periodontitis. Integrating ROS-responsive drug delivery systems with photocatalytic technologies presents a strategic approach to overcome these limitations. Herein, a pillararene-embedded covalent organic framework (PCOF) incorporating the antibacterial prodrug thioacetal (TA) has been developed to treat periodontitis. This drug-loaded nanoplatform, namely TA-loaded PCOF, utilizes the self-amplifying ROS property to enhance therapeutic efficacy. PCOFs demonstrate exceptional photosensitivity and ROS generation capabilities when employed as drug carriers. When exposed to ROS, TA within the nanoplatform was activated and cleaved into cinnamaldehyde (CA), a highly potent antibacterial compound. By leveraging visible light to activate the site-specific infection targeting, TA-loaded PCOF effectively alleviated periodontitis, thereby advancing the field of antibacterial drug delivery systems.


Asunto(s)
Antibacterianos , Periodontitis , Fotoquimioterapia , Especies Reactivas de Oxígeno , Periodontitis/tratamiento farmacológico , Periodontitis/microbiología , Fotoquimioterapia/métodos , Especies Reactivas de Oxígeno/metabolismo , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Animales , Sistemas de Liberación de Medicamentos , Portadores de Fármacos/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Humanos , Profármacos/química , Profármacos/farmacología , Profármacos/uso terapéutico , Ratones , Acroleína/análogos & derivados
4.
Adv Mater ; : e2411194, 2024 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-39444055

RESUMEN

Diabetic wounds are a major devastating complication of diabetes due to hyperglycemia, bacterial invasion, and persistent inflammation, and the current antibiotic treatments can lead to the emergence of multidrug-resistant bacteria. Herein, a bimetallic nanozyme-based biomimetic bio-cocklebur (GNR@CeO2@GNPs) is designed and synthesized for diabetic wound management by depositing spiky ceria (CeO2) shells and gold nanoparticles (GNPs) on a gold nanorod (GNR) nanoantenna. The plasmonic-enhanced nanozyme catalysis and self-cascade reaction properties simultaneously boost the two-step enzyme-mimicking catalytic activity of GNR@CeO2@GNPs, leading to a significant improvement in overall therapeutic efficacy rather than mere additive effects. Under the glucose activation and 808 nm laser irradiation, GNR@CeO2@GNPs material captures photons and promotes the transfer of hot electrons from GNR and GNPs into CeO2, realizing a "butterfly effect" of consuming local glucose, overcoming the limited antibacterial efficiency of an individual PTT modality, and providing substantial reactive oxygen species. In vitro and in vivo experiments demonstrate the material's exceptional antibacterial and antibiofilm properties against Gram-negative and Gram-positive bacteria, which can reduce inflammation, promote collagen deposition, and facilitate angiogenesis, thereby accelerating wound healing. This study provides a promising new strategy to develop plasmonic-enhanced nanozymes with a catalytic cascade mode for the antibiotic-free synergistic treatment of infected diabetic wounds.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39269797

RESUMEN

Benefiting from advances in large-scale pre-training, foundation models, have demonstrated remarkable capability in the fields of natural language processing, computer vision, among others. However, to achieve expert-level performance in specific applications, such models often need to be fine-tuned with domain-specific knowledge. In this paper, we focus on enabling vision-language models to unleash more potential for visual understanding tasks under few-shot tuning. Specifically, we propose a novel adapter, dubbed as lusterAdapter, which is based on trainable multiple prototypes clustering algorithm, for tuning the CLIP model. It can not only alleviate the concern of catastrophic forgetting of foundation models by introducing anchors to inherit common knowledge, but also improve the utilization efficiency of few annotated samples via bringing in clustering and domain priors, thereby improving the performance of few-shot tuning. We have conducted extensive experiments on 11 common classification benchmarks. The results show our method significantly surpasses the original CLIP and achieves state-of-the-art (SOTA) performance under all benchmarks and settings. For example, under the 16-shot setting, our method exhibits a remarkable improvement over the original CLIP by 19.6%, and also surpasses TIP-Adapter and GraphAdapter by 2.7% and 2.2%, respectively, in terms of average accuracy across the 11 benchmarks. Code is available at https://github.com/uyzhang/Cluster-Adapter.

6.
Small ; : e2405946, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39246162

RESUMEN

Under large current densities, the excessive hydroxide ion (OH) consumption hampers alkaline water splitting involving the oxygen evolution reaction (OER). High OH concentration (≈30 wt.%) is often used to enhance the catalytic activity of OER, but it also leads to higher corrosion in practical systems. To achieve higher catalytic activity in low OH concentration, catalysts on magnetic frame (CMF) are built to utilize the local magnetic convection induced from the host frame's magnetic field distributions. This way, a higher reaction rate can be achieved in relatively lower OH concentrations. A CMF model system with catalytically active CoFeOx nanograins grown on the magnetic Ni foam is demonstrated. The OER current of CoFeOx@NF receives ≈90% enhancement under 400 mT (900 mA cm-2 at 1.65 V) compared to that in zero field, and exhibits remarkable durability over 120 h. As a demonstration, the water-splitting performance sees a maximum 45% magnetic enhancement under 400 mT in 1 m KOH (700 mA cm-2 at 2.4 V), equivalent to the concentration enhancement of the same electrode in a more corrosive 2 m KOH electrolyte. Therefore, the catalyst-on-magnetic-frame strategy can make efficient use of the catalysts and achieve higher catalytic activity in low OH concentration by harvesting local magnetic convection.

7.
Polymers (Basel) ; 16(16)2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39204595

RESUMEN

The α-diimine late transition metal catalyst represents a new strategy for the synthesis of atactic polypropylene elastomer. Taking into account the properties of the material, enhancing the molecular weight of polypropylene at an elevated temperature through modifying the catalyst structure, and further increasing the activity of α-diimine catalyst for propylene polymerization, are urgent problems to be solved. In this work, two α-diimine nickel(II) catalysts with multiple hydroxymethyl phenyl substituents were synthesized and used for propylene homopolymerization. The maximum catalytic activity was 5.40 × 105 gPP/molNi·h, and the activity was still maintained above 105 gPP/molNi·h at 50 °C. The large steric hindrance of catalysts inhibited the chain-walking and chain-transfer reactions, resulting in polypropylene with high molecular weights (407~1101 kg/mol) and low 1,3-enchainment content (3.57~16.96%) in toluene. The low tensile strength (0.3~1.0 MPa), high elongation at break (218~403%) and strain recovery properties (S.R. ~50%, 10 tension cycles) of the resulting polypropylenes, as well as the visible light transmittance of approximately 90%, indicate the characteristics of the transparent elastomer.

8.
J Cell Mol Med ; 28(15): e18577, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39099000

RESUMEN

Lung cancer remains the leading cause of cancer-related deaths, with cigarette smoking being the most critical factor, linked to nearly 90% of lung cancer cases. NNK, a highly carcinogenic nitrosamine found in tobacco, is implicated in the lung cancer-causing effects of cigarette smoke. Although NNK is known to mutate or activate certain oncogenes, its potential interaction with p27 in modulating these carcinogenic effects is currently unexplored. Recent studies have identified specific downregulation of p27 in human squamous cell carcinoma, in contrast to adenocarcinoma. Additionally, exposure to NNK significantly suppresses p27 expression in human bronchial epithelial cells. Subsequent studies indicates that the downregulation of p27 is pivotal in NNK-induced cell transformation. Mechanistic investigations have shown that reduced p27 expression leads to increased level of ITCH, which facilitates the degradation of Jun B protein. This degradation in turn, augments miR-494 expression and its direct regulation of JAK1 mRNA stability and protein expression, ultimately activating STAT3 and driving cell transformation. In summary, our findings reveal that: (1) the downregulation of p27 increases Jun B expression by upregulating Jun B E3 ligase ITCH, which then boosts miR-494 transcription; (2) Elevated miR-494 directly binds to 3'-UTR of JAK1 mRNA, enhancing its stability and protein expression; and (3) The JAK1/STAT3 pathway is a downstream effector of p27, mediating the oncogenic effect of NNK in lung cancer. These findings provide significant insight into understanding the participation of mechanisms underlying p27 inhibition of NNK induced lung squamous cell carcinogenic effect.


Asunto(s)
Bronquios , Carcinoma de Células Escamosas , Transformación Celular Neoplásica , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Células Epiteliales , Neoplasias Pulmonares , Nitrosaminas , Humanos , Nitrosaminas/toxicidad , Bronquios/metabolismo , Bronquios/patología , Bronquios/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Carcinoma de Células Escamosas/inducido químicamente , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/genética , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/efectos de los fármacos , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Carcinógenos/toxicidad
9.
Small ; : e2405309, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39148192

RESUMEN

Zinc-air batteries employing non-Pt cathodes hold significant promise for advancing cathodic oxygen reduction reaction (ORR). However, poor intrinsic electrical conductivity and aggregation tendency hinder the application of metal-organic frameworks (MOFs) as active ORR cathodes. Conductive MOFs possess various atomically dispersed metal centers and well-aligned inherent topologies, eliminating the additional carbonization processes for achieving high conductivity. Here, a novel room-temperature electrochemical cathodic electrodeposition method is introduced for fabricating uniform and continuous layered 2D bimetallic conductive MOF films cathodes without polymeric binders, employing the organic ligand 2,3,6,7,10,11-hexaiminotriphenylene (HITP) and varying the Ni/Cu ratio. The influence of metal centers on modulating the ORR performance is investigated by density functional theory (DFT), demonstrating the performance of bimetallic conductive MOFs can be effectively tuned by the unpaired 3d electrons and the Jahn-Teller effect in the doped Cu. The resulting bimetallic Ni2.1Cu0.9(HITP)2 exhibits superior ORR performance, boasting a high onset potential of 0.93 V. Moreover, the assembled aqueous zinc-air battery demonstrates high specific capacity of 706.2 mA h g-1, and exceptional long-term charge/discharge stability exceeding 1250 cycles.

10.
Biomed Environ Sci ; 37(6): 639-646, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38988114

RESUMEN

Objective: To develop a highly sensitive and rapid nucleic acid detection method for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We designed, developed, and manufactured an integrated disposable device for SARS-CoV-2 nucleic acid extraction and detection. The precision of the liquid transfer and temperature control was tested. A comparison between our device and a commercial kit for SARS-Cov-2 nucleic acid extraction was performed using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). The entire process, from SARS-CoV-2 nucleic acid extraction to amplification, was evaluated. Results: The precision of the syringe transfer volume was 19.2 ± 1.9 µL (set value was 20), 32.2 ± 1.6 (set value was 30), and 57.2 ± 3.5 (set value was 60). Temperature control in the amplification tube was measured at 60.0 ± 0.0 °C (set value was 60) and 95.1 ± 0.2 °C (set value was 95) respectively. SARS-Cov-2 nucleic acid extraction yield through the device was 7.10 × 10 6 copies/mL, while a commercial kit yielded 2.98 × 10 6 copies/mL. The mean time to complete the entire assay, from SARS-CoV-2 nucleic acid extraction to amplification detection, was 36 min and 45 s. The detection limit for SARS-CoV-2 nucleic acid was 250 copies/mL. Conclusion: The integrated disposable devices may be used for SARS-CoV-2 Point-of-Care test (POCT).


Asunto(s)
COVID-19 , Equipos Desechables , ARN Viral , SARS-CoV-2 , SARS-CoV-2/aislamiento & purificación , COVID-19/diagnóstico , COVID-19/virología , Humanos , ARN Viral/aislamiento & purificación , ARN Viral/análisis , Prueba de Ácido Nucleico para COVID-19/instrumentación , Prueba de Ácido Nucleico para COVID-19/métodos , Técnicas de Amplificación de Ácido Nucleico/instrumentación , Técnicas de Amplificación de Ácido Nucleico/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/instrumentación
11.
Physiol Mol Biol Plants ; 30(6): 877-891, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38974354

RESUMEN

Natural leaf senescence is critical for plant fitness. Drought-induced premature leaf senescence affects grape yield and quality. However, reports on the regulatory mechanisms underlying premature leaf senescence under drought stress are limited. In this study, two-year-old potted 'Muscat Hamburg' grape plants were subjected to continuous natural drought treatment until mature leaves exhibited senescence symptoms. Physiological and biochemical indices related to drought stress and senescence were monitored. Transcriptome and transgenic Arabidopsis were used to perform expression analyses and functional identification of drought-induced senescence-associated genes. Twelve days of continuous drought stress was sufficient to cause various physiological disruptions and visible senescence symptoms in mature 'Muscat Hamburg' leaves. These disruptions included malondialdehyde and H2O2 accumulation, and decreased catalase activity and chlorophyll (Chl) levels. Transcriptome analysis revealed that most genes involved in photosynthesis and Chl synthesis were downregulated after 12 d of drought treatment. Three key Chl catabolic genes (SGR, NYC1, and PAO) were significantly upregulated. Overexpression of VvSGR in wild Arabidopsis further confirmed that SGR directly promoted early yellowing of cotyledons and leaves. In addition, drought treatment decreased expression of gibberellic acid signaling repressors (GAI and GAI1) and cytokinin signal components (AHK4, AHK2, RR22, RR9-1, RR9-2, RR6, and RR4) but significantly increased the expression of abscisic acid, jasmonic acid, and salicylic acid signaling components and responsive transcription factors (bZIP40/ABF2, WRKY54/75/70, ANAC019, and MYC2). Moreover, some NAC members (NAC0002, NAC019, and NAC048) may also be drought-induced senescence-associated genes. These results provide extensive information on candidate genes involved in drought-induced senescence in grape leaves. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01465-2.

12.
J Nanobiotechnology ; 22(1): 420, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014462

RESUMEN

Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.


Asunto(s)
Antineoplásicos , Antígeno B7-H1 , Curcumina , Ginsenósidos , Animales , Curcumina/farmacología , Curcumina/química , Ginsenósidos/química , Ginsenósidos/farmacología , Humanos , Concentración de Iones de Hidrógeno , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Femenino , Antígeno B7-H1/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Micelas , Ratones Endogámicos BALB C , Polímeros/química , Polímeros/farmacología , Células Dendríticas/efectos de los fármacos , Nanopartículas/química , Células Madre Neoplásicas/efectos de los fármacos , Portadores de Fármacos/química , Óxidos/química , Óxidos/farmacología
13.
Nat Commun ; 15(1): 6344, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39068220

RESUMEN

Dysfunction of pancreatic δ cells contributes to the etiology of diabetes. Despite their important role, human δ cells are scarce, limiting physiological studies and drug discovery targeting δ cells. To date, no directed δ-cell differentiation method has been established. Here, we demonstrate that fibroblast growth factor (FGF) 7 promotes pancreatic endoderm/progenitor differentiation, whereas FGF2 biases cells towards the pancreatic δ-cell lineage via FGF receptor 1. We develop a differentiation method to generate δ cells from human stem cells by combining FGF2 with FGF7, which synergistically directs pancreatic lineage differentiation and modulates the expression of transcription factors and SST activators during endoderm/endocrine precursor induction. These δ cells display mature RNA profiles and fine secretory granules, secrete somatostatin in response to various stimuli, and suppress insulin secretion from in vitro co-cultured ß cells and mouse ß cells upon transplantation. The generation of human pancreatic δ cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation studies in diabetes.


Asunto(s)
Diferenciación Celular , Células Madre Pluripotentes , Humanos , Animales , Ratones , Células Madre Pluripotentes/metabolismo , Células Madre Pluripotentes/citología , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Factor 2 de Crecimiento de Fibroblastos/farmacología , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/citología , Células Secretoras de Somatostatina/metabolismo , Células Secretoras de Somatostatina/citología , Endodermo/citología , Endodermo/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Páncreas/citología , Páncreas/metabolismo , Somatostatina/metabolismo , Linaje de la Célula , Insulina/metabolismo , Secreción de Insulina
14.
Molecules ; 29(14)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39064925

RESUMEN

The effect of H2 activation on the performance of CuFeOx catalyst for low-temperature CO oxidation was investigated. The characterizations of XRD, XPS, H2-TPR, O2-TPD, and in situ DRIFTS were employed to establish the relationship between physicochemical property and catalytic activity. The results showed that the CuFeOx catalyst activated with H2 at 100 °C displayed higher performance, which achieved 99.6% CO conversion at 175 °C. In addition, the H2 activation promoted the generation of Fe2+ species, and more oxygen vacancy could be formation with higher concentration of Oα species, which improved the migration rate of oxygen species in the reaction process. Furthermore, the reducibility of the catalyst was enhanced significantly, which increased the low-temperature activity. Moreover, the in situ DRIFTS experiments revealed that the reaction pathway of CO oxidation followed MvK mechanism at low temperature (<175 °C), and both MvK and L-H mechanism was involved at high temperature. The Cu+-CO and carbonate species were the main reactive intermediates, and the H2 activation increased the concentration of Cu+ species and accelerated the decomposition carbonate species, thus improving the catalytic performance effectively.

15.
Sci Rep ; 14(1): 15877, 2024 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-38982267

RESUMEN

Develop a radiomics nomogram that integrates deep learning, radiomics, and clinical variables to predict epidermal growth factor receptor (EGFR) mutation status in patients with stage I non-small cell lung cancer (NSCLC). We retrospectively included 438 patients who underwent curative surgery and completed driver-gene mutation tests for stage I NSCLC from four academic medical centers. Predictive models were established by extracting and analyzing radiomic features in intratumoral, peritumoral, and habitat regions of CT images to identify EGFR mutation status in stage I NSCLC. Additionally, three deep learning models based on the intratumoral region were constructed. A nomogram was developed by integrating representative radiomic signatures, deep learning, and clinical features. Model performance was assessed by calculating the area under the receiver operating characteristic (ROC) curve. The established habitat radiomics features demonstrated encouraging performance in discriminating between EGFR mutant and wild-type, with predictive ability superior to other single models (AUC 0.886, 0.812, and 0.790 for the training, validation, and external test sets, respectively). The radiomics-based nomogram exhibited excellent performance, achieving the highest AUC values of 0.917, 0.837, and 0.809 in the training, validation, and external test sets, respectively. Decision curve analysis (DCA) indicated that the nomogram provided a higher net benefit than other radiomics models, offering valuable information for treatment.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Aprendizaje Profundo , Receptores ErbB , Neoplasias Pulmonares , Mutación , Nomogramas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Estadificación de Neoplasias , Adulto , Curva ROC , Anciano de 80 o más Años , Radiómica
16.
Sci Rep ; 14(1): 15431, 2024 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965239

RESUMEN

To detect the contaminate of faucets in hospitals and the splash during hand washing, and to explore the reasonable layout of hand washing pools. Two faucets with roughly the same spatial layout in the ICU of a third-class first-class general hospital were selected, and the farthest splashing distance and specific splashing points were measured by color paper. Samples were detected by ATP detection technology and routine microbial detection method, and the contaminate of faucets was analyzed. After 72 h of daily hand-washing activities, the furthest distance to the splash point was about 100 cm around the faucet, and the place 40-110 cm around the faucet was contaminated seriously. The farthest distance that the splash point reached was about 80 cm around the faucet with the center of the circle, and the area 40-60 cm around the faucet was heavily contaminated. The distance from the water outlet of the long handle and the short handle faucet to the detection point had a high negative correlation (r = - 0.811, P < 0.001) and a moderate negative correlation (r = - 0.475, P = 0.001) with the number of splash points, respectively. The qualified rates of ATP detection and microbial culture were 25% and 15%, respectively. Pseudomonas aeruginosa, Staphylococcus epidermidis, and other pathogenic bacteria were detected in the water outlet of the faucet and the surrounding environment. Safe hand hygiene facilities are one of the important guarantees of hand hygiene effect. Clean objects and objects related to patients should not be placed within 1 m range near the water outlet of faucet. Anti-splash baffle should be installed as much as possible when conditions permit to reduce the contaminate caused by splash during hand washing.


Asunto(s)
Desinfección de las Manos , Unidades de Cuidados Intensivos , Humanos , Infección Hospitalaria/prevención & control
17.
Microb Biotechnol ; 17(7): e14531, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-39031514

RESUMEN

Pseudomonas putida has become an increasingly important chassis for producing valuable bioproducts. This development is not least due to the ever-improving genetic toolbox, including gene and genome editing techniques. Here, we present a novel, one-plasmid design of a critical genetic tool, the pEMG/pSW system, guaranteeing one engineering cycle to be finalized in 3 days. The pEMG/pSW system proved in the last decade to be valuable for targeted genome engineering in Pseudomonas, as it enables the deletion of large regions of the genome, the integration of heterologous gene clusters or the targeted generation of point mutations. Here, to expedite genetic engineering, two alternative plasmids were constructed: (1) The sacB gene from Bacillus subtilis was integrated into the I-SceI expressing plasmid pSW-2 as a counterselection marker to accelerated plasmid curing; (2) double-strand break introducing gene I-sceI and sacB counterselection marker were integrated into the backbone of the original pEMG vector, named pEMG-RIS. The single plasmid of pEMG-RIS allows rapid genome editing despite the low transcriptional activity of a single copy of the I-SceI encoding gene. Here, the usability of the pEMG-RIS is shown in P. putida KT2440 by integrating an expression cassette including an msfGFP gene in 3 days. In addition, a large fragment of 12.1 kb was also integrated. In summary, we present an updated pEMG/pSW genome editing system that allows efficient and rapid genome editing in P. putida. All plasmids designed in this study will be available via the Addgene platform.


Asunto(s)
Edición Génica , Plásmidos , Pseudomonas putida , Recombinación Genética , Pseudomonas putida/genética , Pseudomonas putida/metabolismo , Plásmidos/genética , Edición Génica/métodos , Vectores Genéticos/genética , Bacillus subtilis/genética
18.
Inorg Chem ; 63(26): 12190-12199, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38946342

RESUMEN

Quantum dots (QDs) of metal sulfides were proven to be excellent cocatalysts in visible-light-driven photocatalytic reactions. Metal organic frameworks (MOFs) possess a 3D porous channel that effectively confines small QDs and preserves their high catalytic activity by preventing their aggregation. In order to precisely construct the ternary metal sulfides of ZnS/ZnIn2S4/In2S3 with well-maintained Zn-AgInS2 (ZAIS) QDs, an in situ sulfurization combining a subsequent Zn(II)-exchange strategy was employed in this work. First, the ZAIS QDs were incorporated into MIL-68(In), which were then used as the precursors to precisely construct the ternary metal sulfides of ZnS/ZnIn2S4/In2S3 with well maintained ZAIS QDs through an in situ sulfurization combining subsequent Zn(II)-exchange strategy. When the optimized nanocomposites (QDs@M-t-Zn, where t is the sulfurization time) were applied in visible light-induced photocatalytic hydrogen generation, the resulting QDs@M-24h-Zn showed a significantly improved hydrogen evolution rate of 448.96 µmol g-1 h-1, which values are clearly higher than those of MIL-68(In), QDs@MIL-68(In), and M-24h-Zn without the presence of ZAIS QDs. To elucidate the increased photocatalytic mechanism, the optical patterns and the batch electrochemical investigations were combined. It has been discovered that the matching band potentials and the close contact heterojunction enhance interface charge transfer, which in turn encourages photocatalytic hydrogen production. This study demonstrates the well-thought-out design of the uniform confinement architecture inherited from MOF QD-assisted multinary metal sulfides photocatalysts.

19.
Exp Brain Res ; 242(9): 2083-2091, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38963560

RESUMEN

Transcranial electrical stimulation (tES) often targets the EEG-guided C3/C4 area that may not accurately represent M1 for hand muscles. This study aimed to determine if the neuroanatomy-based scalp acupuncture-guided site (AC) was a more effective spot than the C3 site for neuromodulation. Fifteen healthy subjects received one 20-minute session of high-definition transcranial alternating current stimulation (HD-tACS) intervention (20 Hz at 2 mA) at the AC or C3 sites randomly with a 1-week washout period. Subjects performed ball-squeezing exercises with the dominant hand during the HD-tACS intervention. The AC site was indiscernible from the finger flexor hotspot detected by TMS. At the baseline, the MEP amplitude from finger flexors was greater with less variability at the AC site than at the C3 site. HD-tACS intervention at the AC site significantly increased the MEP amplitude. However, no significant changes were observed after tACS was applied to the C3 site. Our results provide evidence that HD-tACS at the AC site produces better neuromodulation effects on the flexor digitorum superficialis (FDS) muscle compared to the C3 site. The AC localization approach can be used for future tES studies.


Asunto(s)
Potenciales Evocados Motores , Mano , Cuero Cabelludo , Estimulación Transcraneal de Corriente Directa , Humanos , Masculino , Femenino , Estimulación Transcraneal de Corriente Directa/métodos , Adulto , Mano/fisiología , Cuero Cabelludo/fisiología , Adulto Joven , Potenciales Evocados Motores/fisiología , Músculo Esquelético/fisiología , Electromiografía , Corteza Motora/fisiología , Electroencefalografía/métodos
20.
Environ Res ; 257: 119326, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38849002

RESUMEN

With the burgeoning growth of the livestock and aquaculture industries, antibiotic residues in treated wastewater have become a serious ecological threat. Traditional biological wastewater treatment technologies-while effective for removing conventional pollutants, such as organic carbon, ammonia and phosphate-struggle to eliminate emerging contaminants, notably antibiotics. Recently, the use of microalgae has emerged as a sustainable and promising approach for the removal of antibiotics due to their non-target status, rapid growth and carbon recovery capabilities. This review aims to analyse the current state of antibiotic removal from wastewater using algae-bacteria symbiosis systems and provide valuable recommendations for the development of livestock/aquaculture wastewater treatment technologies. It (1) summarises the biological removal mechanisms of typical antibiotics, including bioadsorption, bioaccumulation, biodegradation and co-metabolism; (2) discusses the roles of intracellular regulation, involving extracellular polymeric substances, pigments, antioxidant enzyme systems, signalling molecules and metabolic pathways; (3) analyses the role of treatment facilities in facilitating algae-bacteria symbiosis, such as sequencing batch reactors, stabilisation ponds, membrane bioreactors and bioelectrochemical systems; and (4) provides insights into bottlenecks and potential solutions. This review offers valuable information on the mechanisms and strategies involved in the removal of antibiotics from livestock/aquaculture wastewater through the symbiosis of microalgae and bacteria.


Asunto(s)
Antibacterianos , Acuicultura , Ganado , Microalgas , Simbiosis , Aguas Residuales , Contaminantes Químicos del Agua , Acuicultura/métodos , Aguas Residuales/química , Aguas Residuales/microbiología , Microalgas/metabolismo , Animales , Contaminantes Químicos del Agua/metabolismo , Bacterias/metabolismo , Eliminación de Residuos Líquidos/métodos , Biodegradación Ambiental
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