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1.
Brief Bioinform ; 25(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38366802

RESUMEN

Anti-coronavirus peptides (ACVPs) represent a relatively novel approach of inhibiting the adsorption and fusion of the virus with human cells. Several peptide-based inhibitors showed promise as potential therapeutic drug candidates. However, identifying such peptides in laboratory experiments is both costly and time consuming. Therefore, there is growing interest in using computational methods to predict ACVPs. Here, we describe a model for the prediction of ACVPs that is based on the combination of feature engineering (FE) optimization and deep representation learning. FEOpti-ACVP was pre-trained using two feature extraction frameworks. At the next step, several machine learning approaches were tested in to construct the final algorithm. The final version of FEOpti-ACVP outperformed existing methods used for ACVPs prediction and it has the potential to become a valuable tool in ACVP drug design. A user-friendly webserver of FEOpti-ACVP can be accessed at http://servers.aibiochem.net/soft/FEOpti-ACVP/.


Asunto(s)
Algoritmos , Péptidos , Humanos , Secuencia de Aminoácidos , Péptidos/farmacología , Aprendizaje Automático
2.
Annu Rev Microbiol ; 74: 455-475, 2020 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-32905752

RESUMEN

Mosquito-transmitted diseases, including malaria and dengue, are a major threat to human health around the globe, affecting millions each year. A diverse array of next-generation tools has been designed to eliminate mosquito populations or to replace them with mosquitoes that are less capable of transmitting key pathogens. Many of these new approaches have been built on recent advances in CRISPR/Cas9-based genome editing. These initiatives have driven the development of pathogen-resistant lines, new genetics-based sexing methods, and new methods of driving desirable genetic traits into mosquito populations. Many other emerging tools involve microorganisms, including two strategies involving Wolbachia that are achieving great success in the field. At the same time, other mosquito-associated bacteria, fungi, and even viruses represent untapped sources of new mosquitocidal or antipathogen compounds. Although there are still hurdles to be overcome, the prospect that such approaches will reduce the impact of these diseases is highly encouraging.


Asunto(s)
Agentes de Control Biológico , Control de Enfermedades Transmisibles , Enfermedades Transmisibles/parasitología , Enfermedades Transmisibles/virología , Culicidae/genética , Control de Mosquitos/métodos , Animales , Enfermedades Transmisibles/transmisión , Culicidae/parasitología , Culicidae/fisiología , Culicidae/virología , Humanos , Infertilidad , Malaria , Wolbachia/genética
3.
Am J Respir Crit Care Med ; 209(4): 444-453, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-37972230

RESUMEN

Rationale: Respiratory resistance (Rrs) and reactance (Xrs) as measured by oscillometry and their intrabreath changes have emerged as sensitive parameters for detecting early pathological impairments during tidal breathing. Objectives: This study evaluates the prevalence and association of abnormal oscillometry parameters with respiratory symptoms and respiratory diseases in a general adult population. Methods: A total of 7,560 subjects in the Austrian LEAD (Lung, hEart, sociAl, boDy) Study with oscillometry measurements (computed with the Resmon Pro FULL; Restech Srl) were included in this study. The presence of respiratory symptoms and doctor-diagnosed respiratory diseases was assessed using an interview-based questionnaire. Rrs and Xrs at 5 Hz, their inspiratory and expiratory components, the area above the Xrs curve, and the presence of tidal expiratory flow limitation were analyzed. Normality ranges for oscillometry parameters were defined. Measurements and Main Results: The overall prevalence of abnormal oscillometry parameters was 20%. The incidence of abnormal oscillometry increased in the presence of symptoms or diagnoses: 17% (16-18%) versus 27% (25-29%), P < 0.0001. All abnormal oscillometry parameters except Rrs at 5 Hz were significantly associated with respiratory symptoms/diseases. Significant associations were found, even in subjects with normal spirometry, with abnormal oscillometry incidence rates increasing by 6% (4-8%; P < 0.0001) in subjects with symptoms or diagnoses. Conclusions: Abnormal oscillometry parameters are present in one-fifth of this adult population and are significantly associated with respiratory symptoms and disease. Our findings underscore the potential of oscillometry as a tool for detecting and evaluating respiratory impairments, even in individuals with normal spirometry.


Asunto(s)
Pulmón , Enfermedades Respiratorias , Adulto , Humanos , Oscilometría , Respiración , Espiración , Espirometría , Volumen Espiratorio Forzado , Resistencia de las Vías Respiratorias
4.
Nano Lett ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38593418

RESUMEN

Localized emission in atomically thin semiconductors has sparked significant interest as single-photon sources. Despite comprehensive studies into the correlation between localized strain and exciton emission, the impacts of charge transfer on nanobubble emission remains elusive. Here, we report the observation of core/shell-like localized emission from monolayer WSe2 nanobubbles at room temperature through near-field studies. By altering the electronic junction between monolayer WSe2 and the Au substrate, one can effectively adjust the semiconductor to metal junction from a Schottky to an Ohmic junction. Through concurrent analysis of topography, potential, tip-enhanced photoluminescence, and a piezo response force microscope, we attribute the core/shell-like emissions to strong piezoelectric potential aided by induced polarity at the WSe2-Au Schottky interface which results in spatial confinement of the excitons. Our findings present a new approach for manipulating charge confinement and engineering localized emission within atomically thin semiconductor nanobubbles. These insights hold implications for advancing the nano and quantum photonics with low-dimensional semiconductors.

5.
Nano Lett ; 24(20): 6183-6191, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38728596

RESUMEN

Two-dimensional (2D) materials are promising candidates for spintronic applications. Maintaining their atomically smooth interfaces during integration of ferromagnetic (FM) electrodes is crucial since conventional metal deposition tends to induce defects at the interfaces. Meanwhile, the difficulties in picking up FM metals with strong adhesion and in achieving conductance match between FM electrodes and spin transport channels make it challenging to fabricate high-quality 2D spintronic devices using metal transfer techniques. Here, we report a solvent-free magnetic electrode transfer technique that employs a graphene layer to assist in the transfer of FM metals. It also serves as part of the FM electrode after transfer for optimizing spin injection, which enables the realization of spin valves with excellent performance based on various 2D materials. In addition to two-terminal devices, we demonstrate that the technique is applicable for four-terminal spin valves with nonlocal geometry. Our results provide a promising future of realizing 2D spintronic applications using the developed magnetic electrode transfer technique.

6.
Nano Lett ; 24(18): 5656-5661, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38657275

RESUMEN

A physical platform for nodes of the envisioned quantum Internet is long-sought. Here we propose such a platform, along with a conceptually simple and experimentally uncomplicated quantum information processing scheme, realized in a system of multiple crystal-phase quantum dots. We introduce novel location qubits, describe a method to construct a universal set of all-optical quantum gates, and simulate their performance in realistic structures, including decoherence sources. Our results show that location qubits are robust against the main decoherence mechanisms, and realistic single-qubit gate fidelities exceed 99.9%. Our scheme paves a clear way toward constructing multiqubit solid-state quantum registers with a built-in photonic interface─a key building block of the forthcoming quantum Internet.

7.
J Proteome Res ; 23(8): 3188-3199, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-38412258

RESUMEN

Colorectal cancer (CRC) contains considerable heterogeneity; therefore, models of the disease must also reflect the multifarious components. Compared to traditional 2D models, 3D cellular models, such as tumor spheroids, have the utility to determine the drug efficacy of potential therapeutics. Monoculture spheroids are well-known to recapitulate gene expression, cell signaling, and pathophysiological gradients of avascularized tumors. However, they fail to mimic the stromal cell influence present in CRC, which is known to perturb drug efficacy and is associated with metastatic, late-stage colorectal cancer. This study seeks to develop a cocultured spheroid model using carcinoma and noncancerous fibroblast cells. We characterized the proteomic profile of cocultured spheroids in comparison to monocultured spheroids using data-independent acquisition with gas-phase fractionation. Specifically, we determined that proteomic differences related to translation and mTOR signaling are significantly increased in cocultured spheroids compared to monocultured spheroids. Proteins related to fibroblast function, such as exocytosis of coated vesicles and secretion of growth factors, were significantly differentially expressed in the cocultured spheroids. Finally, we compared the proteomic profiles of both the monocultured and cocultured spheroids against a publicly available data set derived from solid CRC tumors. We found that the proteome of the cocultured spheroids more closely resembles that of the patient samples, indicating their potential as tumor mimics.


Asunto(s)
Técnicas de Cocultivo , Proteómica , Transducción de Señal , Esferoides Celulares , Humanos , Esferoides Celulares/metabolismo , Esferoides Celulares/patología , Proteómica/métodos , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Línea Celular Tumoral , Biosíntesis de Proteínas , Fibroblastos/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Proteoma/análisis , Proteoma/metabolismo
8.
J Biol Chem ; 299(6): 104751, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37100287

RESUMEN

As a typical biomarker, the expression of microRNA is closely related to the occurrence of cancer. However, in recent years, the detection methods have had some limitations in the research and application of microRNAs. In this paper, an autocatalytic platform was constructed through the combination of a nonlinear hybridization chain reaction and DNAzyme to achieve efficient detection of microRNA-21. Fluorescently labeled fuel probes can form branched nanostructures and new DNAzyme under the action of the target, and the newly formed DNAzyme can trigger a new round of reactions, resulting in enhanced fluorescence signals. This platform is a simple, efficient, fast, low-cost, and selective method for the detection of microRNA-21, which can detect microRNA-21 at concentrations as low as 0.004 nM and can distinguish sequence differences by single-base differences. In tissue samples from patients with liver cancer, the platform shows the same detection accuracy as real-time PCR but with better reproducibility. In addition, through the flexible design of the trigger chain, our method could be adapted to detect other nucleic acid biomarkers.


Asunto(s)
Técnicas Biosensibles , ADN Catalítico , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/análisis , ADN Catalítico/química , Reproducibilidad de los Resultados , Límite de Detección , Hibridación de Ácido Nucleico , Biomarcadores , Técnicas Biosensibles/métodos
9.
Crit Rev Clin Lab Sci ; 61(4): 298-316, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38146650

RESUMEN

Evidence derived from laboratory medicine plays a pivotal role in the diagnosis, treatment monitoring, and prognosis of various diseases. Reference intervals (RIs) are indispensable tools for assessing test results. The accuracy of clinical decision-making relies directly on the appropriateness of RIs. With the increase in real-world studies and advances in computational power, there has been increased interest in establishing RIs using big data. This approach has demonstrated cost-effectiveness and applicability across diverse scenarios, thereby enhancing the overall suitability of the RI to a certain extent. However, challenges persist when tests results are influenced by age and sex. Reliance on a single RI or a grouping of RIs based on age and sex can lead to erroneous interpretation of results with significant implications for clinical decision-making. To address this issue, the development of next generation of reference interval models has arisen at an historic moment. Such models establish a curve relationship to derive continuously changing reference intervals for test results across different age and sex categories. By automatically selecting appropriate RIs based on the age and sex of patients during result interpretation, this approach facilitates clinical decision-making and enhances disease diagnosis/treatment as well as health management practices. Development of next-generation reference interval models use direct or indirect sampling techniques to select reference individuals and then employed curve fitting methods such as splines, polynomial regression and others to establish continuous models. In light of these studies, several observations can be made: Firstly, to date, limited interest has been shown in developing next-generation reference interval models, with only a few models currently available. Secondly, there are a wide range of methods and algorithms for constructing such models, and their diversity may lead to confusion. Thirdly, the process of constructing next-generation reference interval models can be complex, particularly when employing indirect sampling techniques. At present, normative documents pertaining to the development of next-generation reference interval models are lacking. In summary, this review aims to provide an overview of the current state of development of next-generation reference interval models by defining them, highlighting inherent advantages, and addressing existing challenges. It also describes the process, advanced algorithms for model building, the tools required and the diagnosis and validation of models. Additionally, a discussion on the prospects of utilizing big data for developing next-generation reference interval models is presented. The ultimate objective is to equip clinical laboratories with the theoretical framework and practical tools necessary for developing and optimizing next-generation reference interval models to establish next-generation reference intervals while enhancing the use of medical data resources to facilitate precision medicine.


Asunto(s)
Algoritmos , Humanos , Valores de Referencia
10.
Am J Physiol Lung Cell Mol Physiol ; 327(2): L203-L217, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38771135

RESUMEN

This study investigated the relationship between three respiratory support approaches on lung volume recruitment during the first 2 h of postnatal life in preterm lambs. We estimated changes in lung aeration, measuring respiratory resistance and reactance by oscillometry at 5 Hz. We also measured intratracheal pressure in subsets of lambs. The first main finding is that sustained inflation (SI) applied noninvasively (Mask SI; n = 7) or invasively [endotracheal tube (ETT) SI; n = 6] led to similar rapid lung volume recruitment (∼6 min). In contrast, Mask continuous positive airway pressure (CPAP) without SI (n = 6) resuscitation took longer (∼30-45 min) to reach similar lung volume recruitment. The second main finding is that, in the first 15 min of postnatal life, the Mask CPAP without SI group closed their larynx during custom ventilator-driven expiration, leading to intratracheal positive end-expiratory pressure of ∼17 cmH2O (instead of 8 cmH2O provided by the ventilator). In contrast, the Mask SI group used the larynx to limit inspiratory pressure to ∼26 cmH2O (instead of 30 cmH2O provided by the ventilator). These different responses affected tidal volume, being larger in the Mask CPAP without SI group [8.4 mL/kg; 6.7-9.3 interquartile range (IQR)] compared to the Mask SI (5.0 mL/kg; 4.4-5.2 IQR) and ETT SI groups (3.3 mL/kg; 2.6-3.7 IQR). Distinct physiological responses suggest that spontaneous respiratory activity of the larynx of preterm lambs at birth can uncouple pressure applied by the ventilator to that applied to the lung, leading to unpredictable lung pressure and tidal volume delivery independently from the ventilator settings.NEW & NOTEWORTHY We compared invasive and noninvasive resuscitation on lambs at birth, including or not sustained inflation (SI). Lung volume recruitment was faster in those receiving SI. During noninvasive resuscitation, larynx modulation reduced tracheal pressure from that applied to the mask in lambs receiving SI, while it led to increased auto-positive end-expiratory pressure and very large tidal volumes in lambs not receiving SI. Our results highlight the need for individualizing pressures and monitoring tidal volumes during resuscitation at birth.


Asunto(s)
Animales Recién Nacidos , Pulmón , Volumen de Ventilación Pulmonar , Tráquea , Animales , Volumen de Ventilación Pulmonar/fisiología , Ovinos , Pulmón/fisiología , Tráquea/fisiología , Mecánica Respiratoria/fisiología , Presión de las Vías Aéreas Positiva Contínua/métodos , Resucitación/métodos , Intubación Intratraqueal/métodos , Presión , Respiración con Presión Positiva/métodos
11.
J Neurophysiol ; 131(3): 541-547, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38264793

RESUMEN

Transcranial magnetic stimulation (TMS) causes repetitive spinal motoneuron discharges (repMNDs), but the effects of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) on repMNDs remain unknown. Triple stimulation technique (TST) and the extended TST-protocols that include a fourth and fifth stimulation, the Quadruple (QuadS) and Quintuple (QuintS) stimulation, respectively, offer a precise estimate of cortical and spinal motor neuron discharges, including repMNDs. The objective of our study was to explore the effects of SICI and ICF on repMNDs. We explored conventional paired-pulse TMS protocols of SICI and ICF with the TMS, TST, the QuadS, and the QuintS protocols, in a randomized study design in 20 healthy volunteers. We found significantly less repMNDs in the SICI paradigm compared with a single-pulse TMS (SP-TMS). No significant difference was observed in the ICF paradigm. There was a significant inter- and intrasubject variability in both SICI and ICF. We demonstrate a significant reduction of repMNDs in SICI, which may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no increase in repMNDs in ICF suggesting another mechanism underlying facilitation. This study provides the proof that a reduction of repMNDs mediates the inhibition seen in SICI.NEW & NOTEWORTHY Significant reduction of repetitive motor neuron discharges (repMNDs) in short-interval intracortical inhibition (SICI) may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no change in the number of repMNDs in intracortical facilitation (ICF). There was a significant variability in SICI and ICF in healthy subjects.


Asunto(s)
Corteza Motora , Estimulación Magnética Transcraneal , Humanos , Electromiografía , Potenciales Evocados Motores/fisiología , Corteza Motora/fisiología , Neuronas Motoras , Inhibición Neural/fisiología , Estimulación Magnética Transcraneal/métodos
12.
Rep Prog Phys ; 87(7)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38957891

RESUMEN

Electron-phonon (e-p) coupling plays a crucial role in various physical phenomena, and regulation of e-p coupling is vital for the exploration and design of high-performance materials. However, the current research on this topic lacks accurate quantification, hindering further understanding of the underlying physical processes and its applications. In this work, we demonstrate quantitative regulation of e-p coupling, by pressure engineering andin-situspectroscopy. We successfully observe both a distinct vibrational mode and a strong Stokes shift in layered CrBr3, which are clear signatures of e-p coupling. This allows us to achieve precise quantification of the Huang-Rhys factorSat the actual sample temperature, thus accurately determining the e-p coupling strength. We further reveal that pressure efficiently regulates the e-p coupling in CrBr3, evidenced by a remarkable 40% increase inSvalue. Our results offer an approach for quantifying and modulating e-p coupling, which can be leveraged for exploring and designing functional materials with targeted e-p coupling strengths.

13.
Curr Issues Mol Biol ; 46(7): 7686-7701, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39057096

RESUMEN

The importance of decellularized extracellular matrix (dECM) as a natural biomaterial in tissue engineering and regenerative medicine is rapidly growing. The core objective of the decellularization process is to eliminate cellular components while maximizing the preservation of the ECM's primary structure and components. Establishing a rapid, effective, and minimally destructive decellularization technique is essential for obtaining high-quality dECM to construct regenerative organs. This study focused on human umbilical cord tissue, designing different reagent combinations for decellularization protocols while maintaining a consistent processing time. The impact of these protocols on the decellularization efficiency of human umbilical cord tissue was evaluated. The results suggested that the composite decellularization strategy utilizing trypsin/EDTA + Triton X-100 + sodium deoxycholate was the optimal approach in this study for preparing decellularized human umbilical cord dECM. After 5 h of decellularization treatment, most cellular components were eliminated, confirmed through dsDNA quantitative detection, hematoxylin and eosin (HE) staining, and DAPI staining. Meanwhile, Masson staining, periodic acid-silver methenamine (PASM) staining, periodic acid-Schiff (PAS) staining, and immunofluorescent tissue section staining results revealed that the decellularized scaffold retained extracellular matrix components, including collagen and glycosaminoglycans (GAGs). Compared to native umbilical cord tissue, electron microscopy results demonstrated that the microstructure of the extracellular matrix was well preserved after decellularization. Furthermore, Fourier-transform infrared spectroscopy (FTIR) findings indicated that the decellularization process successfully retained the main functional group structures of extracellular matrix (ECM) components. The quantitative analysis of collagen, elastin, and GAG content validated the advantages of this decellularization process in preserving and purifying ECM components. Additionally, it was confirmed that this decellularized matrix exhibited no cytotoxicity in vitro. This study achieved short-term decellularization preparation for umbilical cord tissue through a combined decellularization strategy.

14.
Cancer ; 130(15): 2703-2712, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38642369

RESUMEN

PURPOSE: To evaluate outcomes following percutaneous image-guided ablation of soft tissue sarcoma metastases to the liver. MATERIALS AND METHODS: A single-institution retrospective analysis of patients with a diagnosis of metastatic soft tissue sarcoma who underwent percutaneous image-guided ablation of hepatic metastases between January 2011 and December 2021 was performed. Patients with less than 60 days of follow-up after ablation were excluded. The primary outcome was local tumor progression-free survival (LPFS). Secondary outcomes included overall survival, liver-specific progression-free survival. and chemotherapy-free survival. RESULTS: Fifty-five patients who underwent percutaneous ablation for 84 metastatic liver lesions were included. The most common histopathological subtypes were leiomyosarcoma (23/55), followed by gastrointestinal stromal tumor (22/55). The median treated liver lesions was 2 (range, 1-8), whereas the median size of metastases were 1.8 cm (0.3-8.7 cm). Complete response at 2 months was achieved in 90.5% of the treated lesions. LPFS was 83% at 1 year and 80% at 2 years. Liver-specific progression-free survival was 66% at 1 year and 40% at 2 years. The overall survival at 1 and 2 years was 98% and 94%. The chemotherapy-free holiday from the start of ablation was 71.2% at 12 months. The complication rate was 3.6% (2/55); one of the complications was Common Terminology Criteria for Adverse Events grade 3 or higher. LPFS subgroup analysis for leiomyosarcoma versus gastrointestinal stromal tumor suggests histology-agnostic outcomes (2 years, 89% vs 82%, p = .35). CONCLUSION: Percutaneous image-guided liver ablation of soft tissue sarcoma metastases is safe and efficacious.


Asunto(s)
Neoplasias Hepáticas , Sarcoma , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Femenino , Masculino , Persona de Mediana Edad , Sarcoma/cirugía , Sarcoma/patología , Sarcoma/secundario , Sarcoma/mortalidad , Anciano , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años , Leiomiosarcoma/cirugía , Leiomiosarcoma/patología , Leiomiosarcoma/secundario , Leiomiosarcoma/mortalidad , Resultado del Tratamiento , Supervivencia sin Progresión , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/mortalidad , Ablación por Catéter/métodos , Ablación por Catéter/efectos adversos
15.
Am J Transplant ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39002782

RESUMEN

A transplant of a portion of the bladder with an en bloc kidney from a 2-year-old donor was previously reported in a 12-month-old girl due to her extremely small bladder. Bilateral kidneys were transplanted en bloc with their ureters connected to a patch of the donor bladder (bladder patch technique). The long-term outcomes and complications of this technique have not been documented. Here, we report a long-term, 17-year follow-up of this patient with an evaluation of whole bladder functions at 18 years of age. The patient has had no episodes of urinary tract infections. Cystoscopy showed a viable transplanted bladder with a well-perfused mucosa. We observed that the native bladder has stretched over time, forming more than half of the bladder wall. Urodynamic studies showed preserved bladder compliance at 43 mL/cmH2O, and native bladder contractility was preserved. Prolonged voiding time and postvoid residual urine were also observed. These findings were suggestive of detrusor underactivity. No reflux across the donor ureterovesical junctions was observed. The recipient was instructed to continue timed voiding and double voiding to empty the bladder. In conclusion, en bloc kidney transplantation with a bladder patch is a feasible and safe option for kidney transplant recipients with a small bladder capacity.

16.
BMC Biotechnol ; 24(1): 7, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38302991

RESUMEN

BACKGROUND: The Mediterranean fruit fly, Ceratitis capitata, is a significant agricultural pest managed through area-wide integrated pest management (AW-IPM) including a sterile insect technique (SIT) component. Male-only releases increase the efficiency and cost-effectiveness of SIT programs, which can be achieved through the development of genetic sexing strains (GSS). The most successful GSS developed to date is the C. capitata VIENNA 8 GSS, constructed using classical genetic approaches and an irradiation-induced translocation with two selectable markers: the white pupae (wp) and temperature-sensitive lethal (tsl) genes. However, currently used methods for selecting suitable markers and inducing translocations are stochastic and non-specific, resulting in a laborious and time-consuming process. Recent efforts have focused on identifying the gene(s) and the causal mutation(s) for suitable phenotypes, such as wp and tsl, which could be used as selectable markers for developing a generic approach for constructing GSS. The wp gene was recently identified, and efforts have been initiated to identify the tsl gene. This study investigates Ceratitis capitata deep orange (Ccdor) as a tsl candidate gene and its potential to induce tsl phenotypes. RESULTS: An integrated approach based on cytogenetics, genomics, bioinformatics, and gene editing was used to characterize the Ccdor. Its location was confirmed on the right arm of chromosome 5 in the putative tsl genomic region. Knock-out of Ccdor using CRISPR/Cas9-NHEJ and targeting the fourth exon resulted in lethality at mid- and late-pupal stage, while the successful application of CRISPR HDR introducing a point mutation on the sixth exon resulted in the establishment of the desired strain and two additional strains (dor 12del and dor 51dup), all of them expressing tsl phenotypes and presenting no (or minimal) fitness cost when reared at 25 °C. One of the strains exhibited complete lethality when embryos were exposed at 36 °C. CONCLUSIONS: Gene editing of the deep orange gene in Ceratitis capitata resulted in the establishment of temperature-sensitive lethal mutant strains. The induced mutations did not significantly affect the rearing efficiency of the strains. As deep orange is a highly conserved gene, these data suggest that it can be considered a target for the development of tsl mutations which could potentially be used to develop novel genetic sexing strains in insect pests and disease vectors.


Asunto(s)
Ceratitis capitata , Animales , Masculino , Ceratitis capitata/genética , Edición Génica , Temperatura , Mutación , Fenotipo , Control Biológico de Vectores/métodos
17.
Small ; 20(37): e2311207, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38751193

RESUMEN

Janus structure plays a crucial role in achieving chemically driven nanomotors with exceptional motion performance. However, Janus-structured chemically driven nanomotors with magnetic responsiveness are commonly fabricated by sputtering metal films. In the study, a self-assembly technique is employed to asymmetrically modify the surfaces of magnetic silica (SiO2@Fe3O4) nanoparticles with platinum nanoparticles, resulting in the formation of this kind nanomotors. Compared to platinum film, platinum nanoparticles exhibit a larger surface area and a higher catalytic activity. Hence, the nanomotors demonstrate improved diffusion capabilities at a significantly lower concentration (0.05%) of hydrogen peroxide (H2O2). Meanwhile, exosomes have gained attention as a potential tool for the efficient delivery of biological therapeutic drugs due to their biocompatibility. However, the clinical applications of exosomes are limited by their restricted tropism. The previously obtained nanomotors are utilized to deliver exosomes, greatly enhancing its targetability. The drug doxorubicin (DOX) is subsequently encapsulated within exosomes, acting as a representative drug model. Under the conditions of H2O2 concentration at the tumor site, the exosomes exhibited a significantly enhanced rate of entry into the breast cancer cells. The utilization of the nanomotors for exosomes presents a novel approach in the development of hybrid chemically and magnetically responsive nanomotors.


Asunto(s)
Doxorrubicina , Sistemas de Liberación de Medicamentos , Exosomas , Peróxido de Hidrógeno , Platino (Metal) , Dióxido de Silicio , Exosomas/química , Exosomas/metabolismo , Humanos , Doxorrubicina/farmacología , Doxorrubicina/química , Peróxido de Hidrógeno/química , Dióxido de Silicio/química , Platino (Metal)/química , Sistemas de Liberación de Medicamentos/métodos , Magnetismo , Línea Celular Tumoral
18.
Small ; 20(13): e2304150, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37964398

RESUMEN

Rheumatoid arthritis (RA), a systemic autoimmune disease, poses a significant human health threat. Iguratimod (IGUR), a novel disease-modifying antirheumatic drug (DMARD), has attracted great attention for RA treatment. Due to IGUR's hydrophobic nature, there's a pressing need for effective pharmaceutical formulations to enhance bioavailability and therapeutic efficacy. The high-gravity nanoprecipitation technique (HGNPT) emerges as a promising approach for formulating poorly water-soluble drugs. In this study, IGUR nanodrugs (NanoIGUR) are synthesized using HGNPT, with a focus on optimizing various operational parameters. The outcomes revealed that HGNPT enabled the continuous production of NanoIGUR with smaller sizes (ranging from 300 to 1000 nm), more uniform shapes, and reduced crystallinity. In vitro drug release tests demonstrated improved dissolution rates with decreasing particle size and crystallinity. Notably, in vitro and in vivo investigations showcased NanoIGUR's efficacy in inhibiting synovial fibroblast proliferation, migration, and invasion, as well as reducing inflammation in collagen-induced arthritis. This study introduces a promising strategy to enhance and broaden the application of poorly water-soluble drugs.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Cromonas , Nanopartículas , Sulfonamidas , Humanos , Alcohol Polivinílico , Artritis Reumatoide/tratamiento farmacológico , Antirreumáticos/química , Antirreumáticos/farmacología , Antirreumáticos/uso terapéutico , Agua
19.
Small ; 20(8): e2305607, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37817357

RESUMEN

The molecule-electrode coupling plays an essential role in photoresponsive devices with photochromic molecules, and the strong coupling between the molecule and the conventional electrodes leads to/ the quenching effect and limits the reversibility of molecular photoswitches. In this work, we developed a strategy of using transition metal dichalcogenides (TMDCs) electrodes to fabricate the thiol azobenzene (TAB) self-assembled monolayers (SAMs) junctions with the eutectic gallium-indium (EGaIn) technique. The current-voltage characteristics of the EGaIn/GaOx //TAB/TMDCs photoswitches showed an almost 100% reversible photoswitching behavior, which increased by ∼28% compared to EGaIn/GaOx //TAB/AuTS photoswitches. Density functional theory (DFT) calculations showed the coupling strength of the TAB-TMDCs electrode decreased by 42% compared to that of the TAB-AuTS electrode, giving rise to improved reversibility. our work demonstrated the feasibility of 2D TMDCs for fabricating SAMs-based photoswitches with unprecedentedly high reversibility.

20.
Small ; 20(7): e2305605, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37803918

RESUMEN

Neuromorphic computing is a potential approach for imitating massive parallel processing capabilities of a bio-synapse. To date, memristors have emerged as the most appropriate device for designing artificial synapses for this purpose due to their excellent analog switching capacities with high endurance and retention. However, to build an operational neuromorphic platform capable of processing high-density information, memristive synapses with nanoscale footprint are important, albeit with device size scaled down, retaining analog plasticity and low power requirement often become a challenge. This paper demonstrates site-selective self-assembly of Au nanoparticles on a patterned TiOx layer formed as a result of ion-induced self-organization, resulting in site-specific resistive switching and emulation of bio-synaptic behavior (e.g., potentiation, depression, spike rate-dependent and spike timing-dependent plasticity, paired pulse facilitation, and post tetanic potentiation) at nanoscale. The use of local probe-based methods enables nanoscale probing on the anisotropic films. With the help of various microscopic and spectroscopic analytical tools, the observed results are attributed to defect migration and self-assembly of implanted Au atoms on self-organized TiOx surfaces. By leveraging the site-selective evolution of gold-nanostructures, the functionalized TiOx surface holds significant potential in a multitude of fields for developing cutting-edge neuromorphic computing platforms and Au-based biosensors with high-density integration.

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