Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 528
Filtrar
1.
Nurs Educ Perspect ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39007677

RESUMO

ABSTRACT: Utilizing Healthcare Simulation Standards of Best Practice™, a virtual reality (VR) platform was created to meet American Association of Colleges of Nursing Essential and Quad Council Public Health competencies. The scenario, involving major depressive disorder with suicidal ideation and alcohol dependency, engages learners in assessing suicide risk, recognizing symptoms, and recommending treatment. Eighty-four prelicensure nursing students have taken part in this mental health VR simulation since spring 2023. Although no significant difference was observed between pre-post knowledge, learners appreciated the VR experience. Student ratings were lowest for how physically demanding the task was and highest for their focus and interest in successfully doing the simulation.

2.
Infect Drug Resist ; 17: 2823-2832, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39005857

RESUMO

Introduction: Recent studies suggested the potential benefits of extended infusion times to optimize the treatment efficacy of ceftazidime/avibactam, which indicated that the current pharmacokinetic/pharmacodynamic (PK/PD) target may not be sufficient, especially for severe infections. The purpose of this study is to assess the adequacy of dosing strategies and infusion durations of ceftazidime/avibactam when applying higher PK/PD targets. Methods: This study utilized published PK parameters to conduct Monte Carlo simulations. Different dosages including the recommended regimen based on renal function were simulated and evaluated by the probability of target attainment (PTA) and cumulative fraction of response (CFR). Different PK/PD targets were set for ceftazidime and avibactam. MIC distributions from various sources were used to calculate the CFR. Results: Multiple PK/PD targets have been set in this study, All recommended dosage could easily achieve the target of 50%fT ≥ MIC (ceftazidime) and 50%fT ≥ CT=1.0 mg/L (avibactam). However, for severe infection patients with normal renal function and augmented renal clearance at the recommended dosage (2000 mg/500 mg, every 8 hours), the infusion duration needs to be extended to 3 hours and 4 hours to achieve the targets of 100%fT ≥ MIC and 100%fT ≥ CT=1.0 mg/L. Only continuous infusion at higher dosages achieved 100%fT ≥ 4×MIC and 100%fT ≥ CT=4.0 mg/L targets to all currently recommended regimens. According to the varying MIC distributions, higher concentrations are needed for Pseudomonas aeruginosa, with the attainment rates vary across different regions. Conclusion: The current recommended dosing regimen of ceftazidime/avibactam is insufficient for severe infection patients, and continuous infusion is suggested.

3.
ACS Nano ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990779

RESUMO

Use of a template triggers an epitaxial interaction with the depositing material during synthesis. Recent studies have demonstrated that two-dimensional tellurium (tellurene) can be directionally oriented when grown on transition metal dichalcogenide (TMD) templates. Specifically, employing a T-phase TMD, such as WTe2, restricts the growth direction even further due to its anisotropic nature, which allows for the synthesis of well-oriented tellurene films. Despite this, producing large-area epitaxial films still remains a significant challenge. Here, we report the continuous synthesis of a 1T'-MoTe2 template via chemical vapor deposition and tellurene via vapor transport. The interaction between helical Te and the 1T'-MoTe2 template facilitates the Te chains to collapse into ribbon shapes, enhancing lateral growth at a rate approximately 6 times higher than in the vertical direction, as confirmed by scanning electron microscopy and atomic force microscopy. Interestingly, despite the predominance of the lateral growth, cross-sectional transmission electron microscopy analysis of the tellurene ribbons revealed a consistent 60-degree incline at the edges. This suggests that the edges of the tellurene ribbons, where they contact the template surface, are favorable sites for additional Te absorption, which then stacks along the incline angle to expand. Furthermore, controlling the synthesis temperature, duration, and preheating time has facilitated the successful synthesis of tellurene films. The resultant tellurene exhibited hole mobility as high as ∼400 cm2/V s. After removing the underlying metallic template with plasma treatment, the film showed a current on/off ratio of ∼103. This ratio was confirmed by two-terminal field-effect transistor measurements and supported by near-field terahertz (THz) spectroscopy mapping.

4.
Plant Sci ; 346: 112170, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38906181

RESUMO

Plant tau glutathione S-transferase (GSTU) is a kind of multiple functions enzyme, but its specific roles in poplar disease resistance remain uncertain. In this study, 27 PdbGSTU-encoding genes from Populus davidiana × P. bollena were cloned and their protein architectures and phylogenetic relationships were subsequently analyzed. Expression analysis revealed that PdbGSTUs were differentially expressed under Alternaria alternate infection. Then, the PdbGSTU10 was further induced by phytohormones and H2O2, especially salicylic acid (SA), indicating its potential role in the pathogen defense of poplar. Subsequently, gain- and loss-of-function assays showed that overexpressed PdbGSTU10 activated antioxidant enzymes and significantly decreased reactive oxygen species (ROS) content, ultimately improving the resistance to A. alternate in poplar. Conversely, silencing PdbGSTU10 had the opposite effect. Moreover, overexpressed PdbGSTU10 also increased the content of SA and induced the expression of SA signal-related genes. These results showed that PdbGSTU10 may enhance disease resistance in poplar by scavenging ROS and affecting the SA signaling pathway. Our findings contribute to the understanding of the functions of GSTU in woody plants, particularly in disease resistance.


Assuntos
Alternaria , Resistência à Doença , Doenças das Plantas , Proteínas de Plantas , Populus , Populus/genética , Populus/microbiologia , Populus/enzimologia , Populus/metabolismo , Populus/imunologia , Alternaria/fisiologia , Resistência à Doença/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Filogenia , Espécies Reativas de Oxigênio/metabolismo , Ácido Salicílico/metabolismo
5.
Hum Genomics ; 18(1): 69, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902839

RESUMO

BACKGROUND: Single cell RNA sequencing technology (scRNA-seq) has been proven useful in understanding cell-specific disease mechanisms. However, identifying genes of interest remains a key challenge. Pseudo-bulk methods that pool scRNA-seq counts in the same biological replicates have been commonly used to identify differentially expressed genes. However, such methods may lack power due to the limited sample size of scRNA-seq datasets, which can be prohibitively expensive. RESULTS: Motivated by this, we proposed to use the Bayesian-frequentist hybrid (BFH) framework to increase the power and we showed in simulated scenario, the proposed BFH would be an optimal method when compared with other popular single cell differential expression methods if both FDR and power were considered. As an example, the method was applied to an idiopathic pulmonary fibrosis (IPF) case study. CONCLUSION: In our IPF example, we demonstrated that with a proper informative prior, the BFH approach identified more genes of interest. Furthermore, these genes were reasonable based on the current knowledge of IPF. Thus, the BFH offers a unique and flexible framework for future scRNA-seq analyses.


Assuntos
Teorema de Bayes , RNA-Seq , Análise de Sequência de RNA , Análise de Célula Única , Análise de Célula Única/métodos , Humanos , RNA-Seq/métodos , Análise de Sequência de RNA/métodos , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/patologia , Perfilação da Expressão Gênica/métodos , Algoritmos
6.
Artigo em Inglês | MEDLINE | ID: mdl-38884772

RESUMO

OCCUPATIONAL APPLICATIONSIn this study, we found that workers who use stand-biased desks stood more and sat less during their workday compared to workers who use traditional desks. Stand-biased users also experienced significantly less lower back discomfort compared to both traditional and sit-stand workstation users. Based on these findings, we recommend that the use of stand-biased workstations be considered when designing or renovating work office workspaces. The health risks of sedentary behavior are inherent in most office work, but these risks can be alleviated with intentional equipment choices. Using stand-biased desks can encourage workers to move more throughout the workday without their productivity or comfort being disturbed.


Background: Sedentary activity, especially occupational sitting, is a leading cause of musculoskeletal discomfort among office workers. The amount of time employees spend seated is associated with the type of workstation that they utilize.Purpose: We investigated differences in computer utilization, physical activity, and discomfort among office workers who used three workstation types (stand-biased, sit-stand, or traditional).Methods: Among a sample of office workers (n = 61), we used data-logging software to measure computer utilization over 10 days, activity sensors to measure daily general activity levels (i.e., sitting, standing, running, etc.) during the 8am­5pm workday and the 24-h day, and the Nordic Musculoskeletal Questionnaire (NMQ) to evaluate discomfort.Results: There was no significant difference in the number of keyclicks between the three groups; however, the stand-biased group had a significantly higher word count and more errors than the traditional group. The 24-h activity data revealed that the stand-biased group had significantly more standing time, less sitting time, and fewer transitions per hour compared to their traditional counterparts.Conclusions: Stand-biased workstations can be a viable workstation alternative to reduce sitting time without decreasing activity or creating additional discomfort.

7.
J Extracell Vesicles ; 13(6): e12462, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840457

RESUMO

Ulcerative colitis (UC) manifests clinically with chronic intestinal inflammation and microflora dysbiosis. Although biologics can effectively control inflammation, efficient delivery to the colon and colon epithelial cells remains challenging. Milk-derived extracellular vesicles (EV) show promise as an oral delivery tool, however, the ability to load biologics into EV presents challenges to therapeutic applications. Here, we demonstrate that fusing cell-penetrating peptide (TAT) to green fluorescent protein (GFP) enabled biologics loading into EV and protected against degradation in the gastrointestinal environment in vitro and in vivo after oral delivery. Oral administration of EV loaded with anti-tumour necrosis factor-α (TNF-α) nanobody (VHHm3F) (EVVHH) via TAT significantly reduced tissue TNF-α levels and alleviated pathologies in mice with acute UC, compared to VHH alone. In mice with chronic UC, simultaneously introducing VHH and an antimicrobial peptide LL37 into EV (EVLV), then administering orally improved intestinal barrier, inflammation and microbiota balance, resulted in relief of UC-induced depression and anxiety. Collectively, we demonstrated that oral delivery of EVLV effectively alleviated UC in mice and TAT efficiently loaded biologics into EV to confer protection from degradation in the gastrointestinal tract. This therapeutic strategy is promising for UC and is a simple and generalizable approach towards drug-loaded orally-administrable EV treatment for other diseases.


Assuntos
Colite Ulcerativa , Vesículas Extracelulares , Leite , Anticorpos de Domínio Único , Fator de Necrose Tumoral alfa , Animais , Colite Ulcerativa/tratamento farmacológico , Vesículas Extracelulares/metabolismo , Camundongos , Fator de Necrose Tumoral alfa/metabolismo , Anticorpos de Domínio Único/farmacologia , Anticorpos de Domínio Único/uso terapêutico , Peptídeos Antimicrobianos/farmacologia , Catelicidinas , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Peptídeos Penetradores de Células/farmacologia , Humanos , Administração Oral , Masculino , Feminino
9.
ACS Omega ; 9(19): 21587-21594, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38764616

RESUMO

Transition metal dichalcogenides (TMDs) are promising candidates for ultrathin functional semiconductor devices. In particular, incorporating plasmonic nanoparticles into TMD-based devices enhances the light-matter interaction for increased absorption efficiency and enables control of device performance such as electronic, electrical, and optical properties. In this heterohybrid structure, manipulating the number of TMD layers and the aggregate size of plasmonic nanoparticles is a straightforward approach to tailoring device performance. In this study, we use photoluminescence (PL) spectroscopy, which is a commonly employed technique for monitoring device performance, to analyze the changes in electronic and optical properties depending on the number of MoS2 layers and the size of the gold nanoparticle (AuNP) aggregate under nonresonant and resonant excitation conditions. The PL intensity in monolayer MoS2/AuNPs increases as the size of aggregates increases irrespective of the excitation conditions. The strain induced by AuNPs causes a red shift, but as the aggregates grow larger, the effect of p-doping increases and the blue shift becomes prominent. In multilayer MoS2/AuNPs, quenched PL intensity is observed under nonresonant excitation, while enhancement is noted under resonant excitation, which is mainly contributed by p-doping and LSPR, respectively. Remarkably, the alteration in the spectral shape due to resonant excitation is evident solely in small aggregates of AuNPs across all layers.

10.
ACS Nano ; 18(21): 13528-13537, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38747549

RESUMO

Dental caries is a widespread oral disease that poses a significant medical challenge. Traditional caries prevention methods, primarily the application of fluoride, often fall short in effectively destroying biofilms and preventing enamel demineralization, thereby providing limited efficacy in halting the progression of caries over time. To address this issue, we have developed a green and cost-effective synergistic strategy for the prevention of dental caries. By combining natural sodium phytate and chitosan, we have created chitosan-sodium phytate nanoparticles that offer both the antimicrobial properties of chitosan and the enamel demineralization-inhibiting capabilities of sodium phytate. In an ex vivo biofilm model of human teeth, we found that these nanoparticles effectively prevent biofilm buildup and acid damage to the mineralized tissue. Additionally, topical treatment of dental caries in rodent models has shown that these nanoparticles effectively suppress disease progression without negatively impacting oral microbiota diversity or causing harm to the gingival-mucosal tissues, unlike traditional prevention methods.


Assuntos
Biofilmes , Quitosana , Cárie Dentária , Nanopartículas , Ácido Fítico , Cárie Dentária/prevenção & controle , Quitosana/química , Quitosana/farmacologia , Humanos , Nanopartículas/química , Ácido Fítico/química , Ácido Fítico/farmacologia , Ácido Fítico/administração & dosagem , Animais , Biofilmes/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Camundongos
11.
J Appl Gerontol ; : 7334648241251735, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741336

RESUMO

We examined factors associated with incident (one) and recurrent (2+) falls among 7207 non-Hispanic White (NHW) (89.7%), non-Hispanic Black (NHB) (5.0%), and Hispanic (5.3%) men ages ≥60 years with ≥1 chronic conditions, enrolled in an evidence-based fall program. Multinomial and binary regression analyses were used to assess factors associated with incident and recurrent falls. Relative to zero falls, NHB and Hispanic men were less likely to report incident (OR = 0.55, p < .001 and OR = 0.70, p = .015, respectively) and recurrent (OR = 0.41, p < .001 and OR = 0.58, p < .001, respectively) falls. Men who reported fear of falling and restricting activities were more likely to report incident (OR = 1.16, p < .001 and OR = 1.32, p < .001, respectively) recurrent and (OR = 1.46, p < .001 and OR = 1.71, p < .001, respectively) falls. Men with more comorbidities were more likely to report recurrent falls (OR = 1.10, p < .001). Compared to those who experienced one fall, men who reported fear of falling (OR = 1.28, p < .001) and restricting activities (OR = 1.31, p < .001) were more likely to report recurrent falls. Findings highlight the importance of multi-component interventions to prevent falls.

12.
J Prim Care Community Health ; 15: 21501319241253791, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38773826

RESUMO

INTRODUCTION: Type 2 diabetes impacts millions and poor maintenance of diabetes can lead to preventable complications, which is why achieving and maintaining target A1C levels is critical. Thus, we aimed to examine inequities in A1C over time, place, and individual characteristics, given known inequities across these indicators and the need to provide continued surveillance. METHODS: Secondary de-identified data from medical claims from a single payer in Texas was merged with population health data. Generalized Estimating Equations were utilized to assess multiple years of data examining the likelihood of having non-target (>7% and ≥7%, two slightly different cut points based on different sources) and separately uncontrolled (>9%) A1C. Adults in Texas, with a Type 2 Diabetes (T2D) flag and with A1C reported in first quarter of the year using data from 2016 and 2019 were included in analyses. RESULTS: Approximately 50% had A1Cs within target ranges (<7% and ≤7%), with 50% considered having non-target (>7% and ≥7%) A1Cs; with 83% within the controlled ranges (≤9%) as compared to approximately 17% having uncontrolled (>9%) A1Cs. The likelihood of non-target A1C was higher among those individuals residing in rural (vs urban) areas (P < .0001); similar for the likelihood of reporting uncontrolled A1C, where those in rural areas were more likely to report uncontrolled A1C (P < .0001). In adjusted analysis, ACA enrollees in 2016 were approx. 5% more likely (OR = 1.049, 95% CI = 1.002-1.099) to have non-target A1C (≥7%) compared to 2019; in contrast non-ACA enrollees were approx. 4% more likely to have non-target A1C (≥7%) in 2019 compared to 2016 (OR = 1.039, 95% CI = 1.001-1.079). In adjusted analysis, ACA enrollees in 2016 were 9% more likely (OR = 1.093, 95% CI = 1.025-1.164) to have uncontrolled A1C compared to 2019; whereas there was no significant change among non-ACA enrollees. CONCLUSIONS: This study can inform health care interactions in diabetes care settings and help health policy makers explore strategies to reduce health inequities among patients with diabetes. Key partners should consider interventions to aid those enrolled in ACA plans, those in rural and border areas, and who may have coexisting health inequities.


Assuntos
Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Masculino , Pessoa de Meia-Idade , Feminino , Texas/epidemiologia , Adulto , Hemoglobinas Glicadas/análise , Idoso , Desigualdades de Saúde , Disparidades em Assistência à Saúde
13.
Foods ; 13(8)2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38672867

RESUMO

To understand the flavor and metabolite differences between the three commercial dried jujube cultivars Huizao (HZ), Hamazao 1 (HMZ), and Qiyuexian (QYX), their soluble sugars, organic acids, volatiles, and metabolites were systematically investigated. The results show that sucrose and malic acid were the main soluble sugar and organic acids contained in these dried jujubes, respectively. Sucrose (573.89 mg/g DW) had the highest presence in HZ, and the total sugar content (898.33 mg/g DW) was the highest in QYX. Both of these had a low total acid content, resulting in relatively high sugar-acid ratios (105.49 and 127.86, respectively) compared to that of HMZ (51.50). Additionally, 66 volatile components were detected in the 3 jujubes. These mainly included acids, aldehydes, esters, and ketones (90.5-96.49%). Among them, (E)-2-nonenal, (E)-2-decenal, heptanal, decanal, nonanal, and octanal were identified as the key aromatic substances of the dried jujubes, and their contents were the highest in HMZ. Moreover, 454 metabolites were identified, including alkaloids, amino acids, flavonoids, lipids, nucleotides, and terpenoids. The highest contents of flavonoids (5.6%) and lipids (24.9%) were detected in HMZ, the highest contents of nucleotides (10.2%) and alkaloids (27%) were found in QYX, and the contents of saccharides (5.7%) and amino acids (23.6%) were high in HZ. Overall, HZ, HMZ, and QYX significantly differ in their flavor and nutrition. HZ tastes better, HMZ is more fragrant, and QYX and HMZ possess higher nutritional values.

14.
Nat Commun ; 15(1): 3247, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622169

RESUMO

Photo-crosslinking polymerization stands as a fundamental pillar in the domains of chemistry, biology, and medicine. Yet, prevailing strategies heavily rely on ultraviolet/visible (UV/Vis) light to elicit in situ crosslinking. The inherent perils associated with UV radiation, namely the potential for DNA damage, coupled with the limited depth of tissue penetration exhibited by UV/Vis light, severely restrict the scope of photo-crosslinking within living organisms. Although near-infrared light has been explored as an external excitation source, enabling partial mitigation of these constraints, its penetration depth remains insufficient, particularly within bone tissues. In this study, we introduce an approach employing X-ray activation for deep-tissue hydrogel formation, surpassing all previous boundaries. Our approach harnesses a low-dose X-ray-activated persistent luminescent phosphor, triggering on demand in situ photo-crosslinking reactions and enabling the formation of hydrogels in male rats. A breakthrough of our method lies in its capability to penetrate deep even within thick bovine bone, demonstrating unmatched potential for bone penetration. By extending the reach of hydrogel formation within such formidable depths, our study represents an advancement in the field. This application of X-ray-activated polymerization enables precise and safe deep-tissue photo-crosslinking hydrogel formation, with profound implications for a multitude of disciplines.


Assuntos
Hidrogéis , Raios Ultravioleta , Masculino , Animais , Bovinos , Ratos , Hidrogéis/química , Raios X , Polimerização , Raios Infravermelhos
15.
ACS Nano ; 18(18): 11910-11920, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38680054

RESUMO

Personalized antitumor immunotherapy utilizing neoantigen vaccines holds great promise. However, the limited immunogenicity of existing recognized neoantigens and the inadequate stimulation of antitumor immune responses by conventional adjuvants pose significant challenges. To address these limitations, we developed a nanovaccine that combines a BCG bacterial cell wall skeleton (BCG-CWS) based nanoscale adjuvant (BCNA) with peptide neoantigens (M27 and M30). This integrated approach provides an efficient translational strategy for cancer immunotherapy. The BCNA nanovaccine, formulated with PLGA as an emulsifier, exhibits excellent biocompatibility and superior antigen presentation compared with conventional BCG-CWS adjuvants. Subcutaneous immunization with the BCNA-based nanovaccine effectively targets lymph nodes, eliciting robust innate and tumor-specific immune responses. Importantly, our findings demonstrate that BCNAs significantly enhance neoantigen immunogenicity while minimizing acute systemic toxicity. Furthermore, when combined with a mouse PD-L1 antibody, our strategy achieves complete tumor elimination in 60% of cases and prevents 25% of tumor growth in a melanoma mouse model. In conclusion, our BCNA-based nanovaccine represents a promising avenue for advancing personalized therapeutic neoantigen vaccines and holds significant implications for enhancing personalized immunotherapy and improving patient outcomes in the field of cancer treatment.


Assuntos
Adjuvantes Imunológicos , Vacinas Anticâncer , Imunoterapia , Animais , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Antígenos de Neoplasias/imunologia , Feminino , Humanos , Parede Celular/imunologia , Parede Celular/química , Mycobacterium bovis/imunologia , Nanopartículas/química , Vacina BCG/imunologia , Linhagem Celular Tumoral
16.
Cancer Med ; 13(7): e7092, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581123

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) accounts for the majority of gastric cancer (GC) cases globally. The present study found that H. pylori promoted GC stem cell (CSC)-like properties, therefore, the regulatory mechanism of how H. pylori promotes GC stemness was explored. METHODS: Spheroid-formation experiments were performed to explore the self-renewal capacity of GC cells. The expression of R-spondin 3 (RSPO3), Nanog homeobox, organic cation/carnitine transporter-4 (OCT-4), SRY-box transcription factor 2 (SOX-2), CD44, Akt, glycogen synthase kinase-3ß (GSK-3ß), p-Akt, p-GSK-3ß, ß-catenin, and G protein subunit gamma 7 (GNG7) were detected by RT-qPCR, western blotting, immunohistochemistry (IHC), and immunofluorescence. Co-immunoprecipitation (CoIP) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) were performed to identify proteins interacting with RSPO3. Lentivirus-based RNA interference constructed short hairpin (sh)-RSPO3 GC cells. Small interfering RNA transfection was performed to inhibit GNG7. The in vivo mechanism was verified using a tumor peritoneal seeding model in nude mice. RESULTS: H. pylori extracts promoted a CSC-like phenotype in GC cells and elevated the expression of RSPO3. RSPO3 knockdown significantly reduced the CSC-like properties induced by H. pylori. Previous studies have demonstrated that RSPO3 potentiates the Wnt/ß-catenin signaling pathway, but the inhibitor of Wnt cannot diminish the RSPO3-induced activation of ß-catenin. CoIP and LC-MS/MS revealed that GNG7 is one of the transmembrane proteins interacting with RSPO3, and it was confirmed that RSPO3 directly interacted with GNG7. Recombinant RSPO3 protein increased the phosphorylation level of Akt and GSK-3ß, and the expression of ß-catenin in GC cells, but this regulatory effect of RSPO3 could be blocked by GNG7 knockdown. Of note, GNG7 suppression could diminish the promoting effect of RSPO3 to CSC-like properties. In addition, RSPO3 suppression inhibited MKN45 tumor peritoneal seeding in vivo. IHC staining also showed that RSPO3, CD44, OCT-4, and SOX-2 were elevated in H. pylori GC tissues. CONCLUSION: RSPO3 enhanced the stemness of H. pylori extracts-infected GC cells through the GNG7/ß-catenin signaling pathway.


Assuntos
Helicobacter pylori , Neoplasias Gástricas , Animais , Camundongos , Helicobacter pylori/fisiologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Camundongos Nus , Cromatografia Líquida , Linhagem Celular Tumoral , Espectrometria de Massas em Tandem , Via de Sinalização Wnt , Neoplasias Gástricas/patologia , Células-Tronco Neoplásicas/metabolismo , Proliferação de Células
17.
Comput Biol Med ; 174: 108489, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38640633

RESUMO

Deep neural networks (DNNs) involve advanced image processing but depend on large quantities of high-quality labeled data. The presence of noisy data significantly degrades the DNN model performance. In the medical field, where model accuracy is crucial and labels for pathological images are scarce and expensive to obtain, the need to handle noisy data is even more urgent. Deep networks exhibit a memorization effect, they tend to prioritize remembering clean labels initially. Therefore, early stopping is highly effective in managing learning with noisy labels. Previous research has often concentrated on developing robust loss functions or implementing training constraints to mitigate the impact of noisy labels; however, such approaches have frequently resulted in underfitting. We propose using knowledge distillation to slow the learning process of the target network rather than preventing late-stage training from being affected by noisy labels. In this paper, we introduce a data sample self-selection strategy based on early stopping to filter out most of the noisy data. Additionally, we employ the distillation training method with dual teacher networks to ensure the steady learning of the student network. The experimental results show that our method outperforms current state-of-the-art methods for handling noisy labels on both synthetic and real-world noisy datasets. In particular, on the real-world pathological image dataset Chaoyang, the highest classification accuracy increased by 2.39 %. Our method leverages the model's predictions based on training history to select cleaner datasets and retrains them using these cleaner datasets, significantly mitigating the impact of noisy labels on model performance.


Assuntos
Redes Neurais de Computação , Humanos , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Algoritmos
18.
Nat Rev Chem ; 8(4): 238-255, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38514833

RESUMO

Photon upconversion is a method for harnessing high-energy excited states from low-energy photons. Such photons, particularly in the red and near-infrared wavelength ranges, can penetrate tissue deeply and undergo less competitive absorption in coloured reaction media, enhancing the efficiency of large-scale reactions and in vivo phototherapy. Among various upconversion methodologies, the organic-based triplet-triplet annihilation upconversion (TTA-UC) stands out - demonstrating high upconversion efficiencies, requiring low excitation power densities and featuring tunable absorption and emission wavelengths. These factors contribute to improved photochemical reactions for fields such as photoredox catalysis, photoactivation, 3D printing and immunotherapy. In this Review, we explore concepts and design principles of organic TTA-UC-mediated photochemical reactions, highlighting notable advancements in the field, as well as identify challenges and propose potential solutions. This Review sheds light on the potential of organic TTA-UC to advance beyond the traditional photochemical reactions and paves the way for research in various fields and clinical applications.

19.
EMBO Mol Med ; 16(4): 1027-1045, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38448545

RESUMO

Clinical deployment of oligonucleotides requires delivery technologies that improve stability, target tissue accumulation and cellular internalization. Exosomes show potential as ideal delivery vehicles. However, an affordable generalizable system for efficient loading of oligonucleotides on exosomes remain lacking. Here, we identified an Exosomal Anchor DNA Aptamer (EAA) via SELEX against exosomes immobilized with our proprietary CP05 peptides. EAA shows high binding affinity to different exosomes and enables efficient loading of nucleic acid drugs on exosomes. Serum stability of thrombin inhibitor NU172 was prolonged by exosome-loading, resulting in increased blood flow after injury in vivo. Importantly, Duchenne Muscular Dystrophy PMO can be readily loaded on exosomes via EAA (EXOEAA-PMO). EXOEAA-PMO elicited significantly greater muscle cell uptake, tissue accumulation and dystrophin expression than PMO in vitro and in vivo. Systemic administration of EXOEAA-PMO elicited therapeutic levels of dystrophin restoration and functional improvements in mdx mice. Altogether, our study demonstrates that EAA enables efficient loading of different nucleic acid drugs on exosomes, thus providing an easy and generalizable strategy for loading nucleic acid therapeutics on exosomes.


Assuntos
Exossomos , Distrofia Muscular de Duchenne , Animais , Camundongos , Distrofina/genética , Camundongos Endogâmicos mdx , Exossomos/metabolismo , Morfolinos/metabolismo , Morfolinos/farmacologia , Morfolinos/uso terapêutico , Distrofia Muscular de Duchenne/tratamento farmacológico , Distrofia Muscular de Duchenne/genética , Oligonucleotídeos/metabolismo , Oligonucleotídeos/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...