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1.
Gene ; 927: 148678, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906392

RESUMO

Estrogen and estrogen receptors (ERα and ERß) regulate a multitude of complicated physiological and pathological processes. Jan-Ake Gustafsson's group discovered ERß in 1996, this crucial finding gives us new insights into the understanding of estrogen signaling. ERß is highly expressed in the ovary and particularly exists in granulosa cells (GCs). ERß is a key transcription factor in the maintenance of ovarian granulosa cell growth, differentiation, and homeostasis, and the ovulation function of ovarian follicles and oocytes. Additionally, ERß can modulate the steroidogenic transcriptional program through phosphorylation and regulate both gonadotropin response and FOXL2 expression within the ovary. In this review, we focus on the role of ERß in regulating ovarian granulosa cell development and homeostasis, particularly its significance in ovarian cancer (OC), premature ovarian failure (POF), and polycystic ovary syndrome (PCOS). It also highlights the prospects of small molecule compounds targeting ERß, providing a new strategy for the treatment of ovarian-related diseases.

2.
J Invest Dermatol ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38844128

RESUMO

Granuloma annulare (GA) is an idiopathic condition characterized by granulomatous inflammation in the skin. Prior studies have suggested that GA develops from various triggers, leading to a complex interplay involving innate and adaptive immunity, tissue remodeling, and fibrosis. Macrophages are the major immune cells comprising GA granulomas, however, the molecular drivers and inflammatory signaling cascade behind macrophage activation is poorly understood. Histologically, GA exhibits both palisaded and interstitial patterns on histology, however the molecular composition of GA at the spatial level remains unexplored. GA is a condition without FDA-approved therapies despite the significant impact of GA on quality of life. Spatial transcriptomics is a valuable tool for profiling localized, genome-wide gene expression changes across tissue with emerging applications in clinical medicine. To improve our understanding of the spatially localized gene expression patterns underlying GA, we profiled the spatial gene expression landscape from six patients with GA. Our findings revealed mixed Th1 and Th2 signals comprising the GA microenvironment and spatially distinct M1 and M2 macrophage polarization characteristics. IFN-γ and TNF signals emerged as important regulators of GA granulomatous inflammation and interleukin-32 emerged as a key driver of granulomatous inflammation. Overall, our spatial transcriptomics data indicate that GA exhibits mixed immune and macrophage polarization.

3.
J Rheumatol ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38879192

RESUMO

OBJECTIVE: Psoriatic disease remains underdiagnosed and undertreated. We developed and validated a suite of novel, sensor-based smartphone assessments (Psorcast app) that can be self-administered to measure cutaneous and musculoskeletal signs and symptoms of psoriatic disease. METHODS: Participants with psoriasis (PsO) or psoriatic arthritis (PsA) and healthy controls were recruited between June 5, 2019, and November 10, 2021, at 2 academic medical centers. Concordance and accuracy of digital measures and image-based machine learning models were compared to their analogous clinical measures from trained rheumatologists and dermatologists. RESULTS: Of 104 study participants, 51 (49%) were female and 53 (51%) were male, with a mean age of 42.3 years (SD 12.6). Seventy-nine (76%) participants had PsA, 16 (15.4%) had PsO, and 9 (8.7%) were healthy controls. Digital patient assessment of percent body surface area (BSA) affected with PsO demonstrated very strong concordance (Lin concordance correlation coefficient [CCC] 0.94 [95% CI 0.91-0.96]) with physician-assessed BSA. The in-clinic and remote target plaque physician global assessments showed fair-to-moderate concordance (CCCerythema 0.72 [0.59-0.85]; CCCinduration 0.72 [0.62-0.82]; CCCscaling 0.60 [0.48-0.72]). Machine learning models of hand photos taken by patients accurately identified clinically diagnosed nail PsO with an accuracy of 0.76. The Digital Jar Open assessment categorized physician-assessed upper extremity involvement, considering joint tenderness or enthesitis (AUROC 0.68 [0.47-0.85]). CONCLUSION: The Psorcast digital assessments achieved significant clinical validity, although they require further validation in larger cohorts before use in evidence-based medicine or clinical trial settings. The smartphone software and analysis pipelines from the Psorcast suite are open source and freely available.

4.
Int J Biol Macromol ; 269(Pt 2): 132025, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38704076

RESUMO

The intestine defends against pathogenic microbial invasion via the secretion of host defense peptides (HDPs). Nutritional immunomodulation can stimulate the expression of endogenous HDPs and enhance the body's immune defense, representing a novel non-antibiotic strategy for disease prevention. The project aims to explore the regulatory mechanism of protegrin-1 (PG-1) expression using sodium phenylbutyrate (PBA) by omics sequencing technology and further investigate the role of key regulatory genes on intestinal health. The results showed that PBA promoted PG-1 expression in intestinal epithelial cells based on cell density through epidermal growth factor receptor (EGFR) and G protein-coupled receptor (GPR43). Transcriptome sequencing and microRNA sequencing revealed that C-X-C motif chemokine receptor 2 (CXCR2) exhibited interactions with PG-1. Pre-treatment cells with a CXCR2 inhibitor (SB225002) effectively suppressed the induction of PG-1 by PBA. Furthermore, SB225002 significantly suppressed the gene expression of HDPs in the jejunum of mice without influencing on the morphology, number of goblet cells, and proliferation of the intestine. CXCR2 inhibition significantly reduced the expression of HDPs during E. coli infection, and resulted in the edema of jejunal epithelial cells. The 16S rDNA analysis of cecal contents showed that the E. coli and SB225002 treatments changed gut microbiota diversity and composition at different taxonomic levels. Correlation analysis suggested a potential regulatory relationship between gut microbiota and HDPs. To that end, a gene involved in the HDP expression, CXCR2, has been identified in the study, which contributes to improving intestinal immune function. PBA may be used as a functional additive to regulate intestinal mucosal function, thereby enhancing the health of the intestinal and host.


Assuntos
Homeostase , Mucosa Intestinal , Receptores de Interleucina-8B , Animais , Humanos , Masculino , Camundongos , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Receptores ErbB/metabolismo , Receptores ErbB/genética , Infecções por Escherichia coli/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Receptores Acoplados a Proteínas G , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/metabolismo
5.
Sci Transl Med ; 16(743): eadk5395, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630847

RESUMO

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.


Assuntos
Aprendizado Profundo , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Lesões Pré-Cancerosas , Humanos , Pessoa de Meia-Idade , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Estudos Prospectivos , Lesões Pré-Cancerosas/patologia
6.
Heliyon ; 10(8): e29158, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38644876

RESUMO

Objective: To establish a predictive modeling for the risk of bloodstream infection associated with peripherally inserted central catheter (PICC). Methods: Patients receiving PICC treatment in Shenzhen People's Hospital from June 2020 to December 2020 were retrospectively enrolled and divided into the infection group and the non-infection group according to the presence and absence of PICC-related infections. Then, relevant clinical information of patients was collected and the predictors of PICC-related infection were screened by the least absolute shrinkage and selection operator regression (LASSO) model. Besides, multivariate logistic regression was used to analyze the influencing factors of PICC-related infection, A nomogram was constructed based on the results of the multivariate analysis. Ultimately, a receiver operating characteristic (ROC) curve was plotted to analyze the application value of influencing factors to predict PICC-related infections. Results: A total of 505 patients were included, including 75 patients with PICC-related infections (14.85%). The main pathogen was gram-positive cocci. The predictors screened by LASSO included age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Multivariate logistic regression analysis showed that independent risk factors of infections related to PICC included age >60 years [odds ratio (OR) = 1.722; 95% confidence interval (CI) = 1.312-3.579; P = 0.006], catheter movement (OR = 1.313; 95% CI = 1.119-3.240; P = 0.014), catheter maintenance cycle >7 days (OR = 2.199; 95% CI = 1.677-4.653; P = 0.000), direct insertion (OR = 1.036; 95% CI = 1.019-2.743; P = 0.000), poor immune function (OR = 2.322; 95% CI = 2.012-4.579; P = 0.000), complications (OR = 1.611; 95% CI = 1.133-3.454; P = 0.019), and body temperature ≥37.2 °C before PICC placement (OR = 1.713; 95% CI = 1.172-3.654; P = 0.012). Besides, the area under the ROC curve was 0.889. Conclusion: PICC-related infections are associated with factors such as age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Additionally, the LASSO model is moderately predictive for predicting the occurrence of PICC-related infections.

7.
Front Microbiol ; 15: 1290227, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38686109

RESUMO

Background: Tuberculosis (TB), mainly caused by Mycobacterium tuberculosis (Mtb), remains a serious public health problem. Increasing evidence supports that selective evolution is an important force affecting genomic determinants of Mtb phenotypes. It is necessary to further understand the Mtb selective evolution and identify the positively selected genes that probably drive the phenotype of Mtb. Methods: This study mainly focused on the positive selection of 807 Mtb strains from Southern Xinjiang of China using whole genome sequencing (WGS). PAML software was used for identifying the genes and sites under positive selection in 807 Mtb strains. Results: Lineage 2 (62.70%) strains were the dominant strains in this area, followed by lineage 3 (19.45%) and lineage 4 (17.84%) strains. There were 239 codons in 47 genes under positive selection, and the genes were majorly associated with the functions of transcription, defense mechanisms, and cell wall/membrane/envelope biogenesis. There were 28 codons (43 mutations) in eight genes (gyrA, rpoB, rpoC, katG, pncA, embB, gid, and cut1) under positive selection in multi-drug resistance (MDR) strains but not in drug-susceptible (DS) strains, in which 27 mutations were drug-resistant loci, 9 mutations were non-drug-resistant loci but were in drug-resistant genes, 2 mutations were compensatory mutations, and 5 mutations were in unknown drug-resistant gene of cut1. There was a codon in Rv0336 under positive selection in L3 strains but not in L2 and L4 strains. The epitopes of T and B cells were both hyper-conserved, particularly in the T-cell epitopes. Conclusion: This study revealed the ongoing selective evolution of Mtb. We found some special genes and sites under positive selection which may contribute to the advantage of MDR and L3 strains. It is necessary to further study these mutations to understand their impact on phenotypes for providing more useful information to develop new TB interventions.

8.
Clin Hemorheol Microcirc ; 87(2): 171-185, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38607754

RESUMO

OBJECTIVE: To investigate predictors of anticoagulation efficacy in deep venous thrombosis (DVT) by ultrasound elastography (UE). METHODS: The basic clinical, laboratory and ultrasound treatment data of fifty-eight patients with DVT were collected and analyzed. Then the results of ultrasound after 3-month anticoagulation treatment were compared among different groups. Multiple logistic regression analysis was used to identify independent risk factors that affected anticoagulation efficacy. The predictive efficacy of each independent risk factor was accessed by drawing operating characteristic (ROC) curves. RESULTS: According to the regression analysis, the elastic modulus (OR = 0.631, P = 0.001) and strain rate ratio (OR = 0.332, P = 0.006) were identified as independent risk factors for the effectiveness of anticoagulation therapy in patients with DVT. According to the ROC curves, elastic modulus and strain rate ratio could predict effective anticoagulation therapy for DVT, and the optimal threshold values were 22.10 kPa and 1.80 respectively. The corresponding AUC values were 0.879 and 0.854, with a sensitivity of 71.4% and 59.5%, a specificity of 93.7%, and a Youden index of 65.1% and 62.7%, respectively. CONCLUSIONS: The elastic modulus (≤22.10 kPa) or strain rate ratio (≤1.80) of the thrombus were independent predictors for the effectiveness of anticoagulation therapy.


Assuntos
Anticoagulantes , Técnicas de Imagem por Elasticidade , Extremidade Inferior , Trombose Venosa , Humanos , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológico , Técnicas de Imagem por Elasticidade/métodos , Masculino , Anticoagulantes/uso terapêutico , Feminino , Pessoa de Meia-Idade , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/diagnóstico por imagem , Adulto , Idoso , Fatores de Risco
9.
Int J Nanomedicine ; 19: 2957-2972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549840

RESUMO

Introduction: Nano-mesoporous bioactive glass and RGD peptide-coated collagen membranes have great potential in wound healing. However, the application of their compound has not been further studied. Our purpose is to prepare a novel bioactive collagen scaffold containing both NMBG stent and adhesion peptides (BM), which then proves its promising prospect the assessment of physical properties, biocompatibility, GSK-3ß/ß-catenin signaling axis and toxicological effects. Methods: The structural and morphological changes of BM were analyzed using scanning electron microscopy (SEM) and Energy Dispersive Spectroscopy (EDS). In vivo, wound healing of BM was assessed in SD rats through dynamic monitoring and calculation of wound healing rate. Immunohistofluorescence (IHF), H&E, and Masson staining were utilized; in vitro, primary cell culture, and a variety of assays including CCK-8, Transwell, Scratch, Immunocytofluorescence (ICF), and Western blot (WB) were performed, both for morphology and molecular analysis. Results and Discussion: Preparation of BM involved attaching NMBG to RGD-exposed collagen while avoiding the use of toxic chemical reagents. BM exhibited a distinctive superficial morphology with increased Si content, indicating successful NMBG attachment. In vivo studies on SD rats demonstrated the superior wound healing capability of BM, as evidenced by accelerated wound closure, thicker epithelial layers, and enhanced collagen deposition compared to the NC group. Additionally, BM promoted skin fibroblast migration and proliferation, possibly through activation of the GSK-3ß/ß-catenin signaling axis, which was crucial for tissue regeneration. This study underscored the potential of BM as an effective wound-healing dressing. Conclusion: A new method for synthesizing ECM-like membranes has been developed using nano-mesoporous bioactive glass and collagen-derived peptides. This approach enhances the bioactivity of biomaterials through surface functionalization and growth factor-free therapy.


Assuntos
Biomimética , beta Catenina , Ratos , Animais , Glicogênio Sintase Quinase 3 beta/metabolismo , beta Catenina/metabolismo , Ratos Sprague-Dawley , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos , Proliferação de Células , Peptídeos/farmacologia
10.
Nurse Educ Pract ; 76: 103945, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38554616

RESUMO

AIM: This study aims to evaluate the effect of team-based learning on the core competence of nursing students compared with traditional teaching methods. BACKGROUND: In recent years, team-based learning has been widely used as a learning and teaching method in the world. Not only the necessary knowledge, skills and attitudes, but also the core competence is necessary to cope with various clinical situations for nursing students. However, the effect of this new teaching method on core competence of nursing students is not consistent. DESIGN: The study was designed according to the preferred reporting entries guidelines statement for systematic reviews and meta-analyses and population, intervention, comparison, outcome and study. METHODS: Data were collected from PubMed, Embase, Web of Science, ScienceDirect and Scopus. The quality of studies was assessed using "The Newcastle Ottawa scale". A random-effect model of meta-analyses was conducted to generate pooled standardized mean differences (SMD) for core competence using Rev Man 5.4.1 software and STATASE 15. Moreover, subgroup, heterogeneity, sensitivity and publication bias analyses were conducted. RESULTS: A total of 14 articles with 1942 participants were included in the meta-analysis. Compared with the traditional pedagogy among nursing students, team-based learning pedagogy significantly increased theoretical performance, professional effects (self-directed learning ability and communication ability) but did not affect practice skills. In addition, one study found that learning attitudes were not improved in students with high or low academic performance. This might mean that the teaching model should be implemented for a long time, which essentially changed students' learning attitudes to improve students' self-directed learning ability and core competence, especially for students with low scores. CONCLUSIONS: In summary, findings indicated that team-based learning pedagogical approaches might be beneficial to improve teaching quality in nursing education. However, practice skills might not be sensitive to team-based learning because of the seriation of the original course. Nursing educators need to explore teaching strategies to cultivate high-quality nursing talents to cultivate nursing students with core competence and ensure that they are successfully qualified for new employment.


Assuntos
Educação em Enfermagem , Estudantes de Enfermagem , Humanos , Aprendizagem , Educação em Enfermagem/métodos , Competência Clínica , Docentes de Enfermagem
11.
Med Phys ; 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38340368

RESUMO

BACKGROUND: Spot-scanning Proton Arc (SPArc) has been of significant interest in recent years because of its superior plan quality. Currently, the primary focus of research and development is on deliverability and treatment efficiency. PURPOSE: To address the challenges in generating a deliverable and efficient SPArc plan for a proton therapy system with a massive gantry, we developed a novel SPArc optimization algorithm (SPArcDMPO ) by directly incorporating the machine-specific parameters such as gantry mechanical constraints and proton delivery sequence. METHODS: SPArc delivery sequence model (DSMarc ) was built based on the machine-specific parameters of the prototype arc delivery system, IBA ProteusONE®, including mechanical constraint (maximum gantry speed, acceleration, and deceleration) and proton delivery sequence (energy and spot delivery sequence, and irradiation time). SPArcDMPO resamples and adjusts each control point's delivery speed based on the DSMarc calculation through the iterative approach. In SPArcDMPO, users could set a reasonable arc delivery time during the plan optimization, which aims to minimize the gantry momentum changes and improve the delivery efficiency. Ten cases were selected to test SPArcDMPO . Two kinds of SPArc plans were generated using the same planning objective functions: (1) original SPArc plan (SPArcoriginal ); (2) SPArcDMPO plan with a user-pre-defined delivery time. Additionally, arc delivery sequence was simulated based on the DSMarc and was compared. Treatment delivery time was compared between SPArcoriginal and SPArcDMPO . Dynamic arc delivery time, the static irradiation time, and its corresponding time differential (time differential = dynamic arc delivery time-static irradiation time) were analyzed, respectively. The total gantry velocity change was accumulated throughout the treatment delivery. RESULTS: With a similar plan quality, objective value, number of energy layers, and spots, both SPArcoriginal and SPArcDMPO plans could be delivered continuously within the ± 1 degree tolerance window. However, compared to the SPArcoriginal , the strategy of SPArcDMPO is able to reduce the time differential from 30.55 ± 11.42%(90 ± 32 s) to 14.67 ± 6.97%(42 ± 20 s), p < 0.01. Furthermore, the corresponding total variations of gantry velocity during dynamic arc delivery are mitigated (SPArcoriginal vs. SPArcDMPO ) from 14.73 ± 9.14 degree/s to 4.28 ± 2.42 degree/s, p < 0.01. Consequently, the SPArcDMPO plans could minimize the gantry momentum change based on the clinical user's input compared to the SPArcoriginal plans, which could help relieve the mechanical challenge of accelerating or decelerating the massive proton gantry. CONCLUSIONS: For the first time, clinical users not only could generate a SPArc plan meeting the mechanical constraint of their proton system but also directly control the arc treatment speed and momentum changes of the gantry during the plan optimization process. This work paved the way for the routine clinical implementation of proton arc therapy in the treatment planning system.

12.
J Cancer ; 15(3): 841-857, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38213716

RESUMO

Background: Anoikis, a mechanism of programmed apoptosis, plays an important role in growth and metastasis of tumors. However, there are still few available comprehensive reports on the impact of anoikis on colorectal cancer. Method: A clustering analysis was done on 133 anoikis-related genes in GSE39582, and we compared clinical features between clusters, the tumor microenvironment was analyzed with algorithms such as "Cibersort" and "ssGSEA". We investigated risk scores of clinical feature groups and anoikis-associated gene mutations after creating a predictive model. We incorporated clinical traits to build a nomogram. Additionally, the quantitative real-time PCR was employed to investigate the mRNA expression of selected anoikis-associated genes. Result: We identified two anoikis-related clusters with distinct prognoses, clinical characteristics, and biological functions. One of the clusters was associated with anoikis resistance, which activated multiple pathways encouraging tumor metastasis. In our prognostic model, oxaliplatin may be a sensitive drug for low-risk patients. The nomogram showed good ability to predict survival time. And SIRT3, PIK3CA, ITGA3, DAPK1, and CASP3 increased in CRC group through the PCR assay. Conclusion: Our study identified two distinct modes of anoikis in colorectal cancer, with active metastasis-promoting pathways inducing an anti-anoikis subtype, which has a stronger propensity for metastasis and a worse prognosis than an anoikis-activated subtype. Massive immune cell infiltration may be an indicator of anoikis resistance. Anoikis' role in the colorectal cancer remains to be investigated.

13.
Eur J Med Res ; 29(1): 15, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38173021

RESUMO

Early diagnosis and pharmacological treatment of central nervous system (CNS) diseases has been a long-standing challenge for clinical research due to the presence of the blood-brain barrier. Specific proteins and RNAs in brain-derived extracellular vesicles (EVs) usually reflect the corresponding state of brain disease, and therefore, EVs can be used as diagnostic biomarkers for CNS diseases. In addition, EVs can be engineered and fused to target cells for delivery of cargo, demonstrating the great potential of EVs as a nanocarrier platform. We review the progress of EVs as markers and drug carriers in the diagnosis and treatment of neurological diseases. The main areas include visual imaging, biomarker diagnosis and drug loading therapy for different types of CNS diseases. It is hoped that increased knowledge of EVs will facilitate their clinical translation in CNS diseases.


Assuntos
Doenças do Sistema Nervoso Central , Vesículas Extracelulares , Humanos , Encéfalo , Vesículas Extracelulares/metabolismo , Barreira Hematoencefálica , Biomarcadores/metabolismo , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/terapia , Doenças do Sistema Nervoso Central/metabolismo
14.
Heliyon ; 10(1): e23426, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38173512

RESUMO

Ischemia-reperfusion (I/R) injury constitutes a significant risk factor for a range of diseases, including ischemic stroke, myocardial infarction, and trauma. Following the restoration of blood flow post-tissue ischemia, oxidative stress can lead to various forms of cell death, including necrosis, apoptosis, autophagy, and necroptosis. Recent evidence has highlighted the crucial role of mitochondrial dysfunction in I/R injury. Nevertheless, there remains much to be explored regarding the molecular signaling network governing cell death under conditions of oxidative stress. Voltage-dependent anion channel 1 (VDAC1), a major component in the outer mitochondrial membrane, is closely involved in the regulation of cell death. In a cellular model of oxygen-glucose deprivation and reoxygenation (OGD/R), which effectively simulates I/R injury in vitro, our study reveals that OGD/R induces VDAC1 oligomerization, consequently exacerbating cell death. Furthermore, we have revealed the translocation of mixed lineage kinase domain-like protein (MLKL) to the mitochondria, where it interacts with VDAC1 following OGD/R injury, leading to an increased mitochondrial membrane permeability. Notably, the inhibition of MLKL by necrosulfonamide hinders the binding of MLKL to VDAC1, primarily by affecting the membrane translocation of MLKL, and reduces OGD/R-induced VDAC1 oligomerization. Collectively, our findings provide preliminary evidence of the functional association between MLKL and VDAC1 in the regulation of necroptosis.

15.
STAR Protoc ; 5(1): 102766, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38085639

RESUMO

Here, we present a protocol for labeling and tracking individual molecules, particularly cell division proteins in live bacterial cells. The protocol encompasses strain construction, single-molecule imaging, trajectory segmentation, and motion property analysis. The protocol enables the identification of distinctive motion states associated with different cell division proteins. Subsequent assessments of the dynamic behaviors of these proteins provide insights into their activities and interactions at the septum during cell division. For complete details on the use and execution of this protocol, please refer to Yang et al. (2021),1 Lyu et al. (2022),2 and Mahone et al. (2024).3.


Assuntos
Proteínas de Bactérias , Imagem Individual de Molécula , Divisão Celular
16.
Med Phys ; 51(4): 3067-3075, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38064634

RESUMO

BACKGROUND: Spot-scanning proton arc (SPArc) has been drawing significant interests in recent years because of its capability of continuous proton irradiation during the gantry rotation. Previous studies demonstrated SPArc plans were delivered on a prototype of the DynamicARC solution, IBA ProteusONE. PURPOSE: We built a novel delivery sequence model through an independent experimental approach: the first SPArc delivery sequence model (DSMSPArc). Based on the model, we investigated SPArc treatment efficiency improvement in the routine proton clinical operation. METHODS: SPArc test plans were generated and delivered on a prototype of the DynamicARC solution, IBA ProteusONE. An independent gantry inclinometer and the machine logfiles were used to derive the DSMSPArc. Seventeen SPArc plans were used to validate the model's accuracy independently. Two random clinical operation dates (6th January and 22nd March, 2021) from a single-room proton therapy center (PTC) were selected to quantitatively assess the improvement of treatment efficiency compared to the IMPT. RESULTS: The difference between the logfile and DSMSPArc is about 3.2 ± 4.8%. SPArc reduced 58.1% of the average treatment delivery time per patient compared to IMPT (p < 0.01). Daily treatment throughput could be increased by 30% using SPArc using a single-room proton therapy system. CONCLUSIONS: The first model of dynamic arc therapy is established in this study through an independent experimental approach using logfiles and measurements which allows clinical users and investigators to simulate the dynamic treatment delivery and assess the daily treatment throughput improvement.


Assuntos
Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Prótons , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
17.
Small ; 20(6): e2307242, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37771206

RESUMO

Photovoltaic thin film solar cells based on kesterite Cu2 ZnSn(S, Se)4 (CZTSSe) have reached 13.8% sunlight-to-electricity conversion efficiency. However, this efficiency is still far from the Shockley-Queisser radiative limit and is hindered by the significant deficit in open circuit voltage (VOC ). The presence of high-density interface states between the absorber layer and buffer or window layer leads to the recombination of photogenerated carriers, thereby reducing effective carrier collection. To tackle this issue, a new window structure ZnO/AgNW/ZnO/AgNW (ZAZA) comprising layers of ZnO and silver nanowires (AgNWs) is proposed. This structure offers a simple and low-damage processing method, resulting in improved optoelectronic properties and junction quality. The ZAZA-based devices exhibit enhanced VOC due to the higher built-in voltage (Vbi ) and reduced interface recombination compared to the usual indium tin oxide (ITO) based structures. Additionally, improved carrier collection is demonstrated as a result of the shortened collection paths and the more uniform carrier lifetime distribution. These advances enable the fabrication of the first ITO-free CZTSSe solar cells with over 10% efficiency without an anti-reflective coating.

18.
Plants (Basel) ; 12(23)2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38068620

RESUMO

The role of melatonin in plant growth and response to environmental stress has been widely demonstrated. However, the physiological and molecular regulation of salt tolerance in wheat seedlings by melatonin remains unclear. In this study, we investigated changes in phenotype, physiology, photosynthetic parameters, and transcript levels in wheat seedlings to reveal the role of melatonin in the regulation of salt tolerance in wheat. The results indicate that the application of exogenous melatonin significantly alleviates growth inhibition, reactive oxygen species accumulation, and membrane oxidative damage induced by salt stress in wheat. Additionally, exogenous melatonin increased antioxidant enzyme activity and regulated photosynthetic gas exchange. Transcriptomic data showed a significant up-regulation of genes encoding light-harvesting chlorophyll protein complex proteins in photosynthesis and genes related to chlorophyll and carotenoid biosynthesis under the influence of melatonin. These results suggest that exogenous melatonin improves salt tolerance in wheat seedlings by enhancing the antioxidant, photoprotective, and photosynthesis activities.

19.
Home Health Care Manag Pract ; 35(3): 206-212, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38031569

RESUMO

The shortage of home health aides has been exacerbated in recent years partially because of low wages. Minimum wage (MW) policy changes may alleviate this workforce shortage. This study examined the effects of MW policies on wages and employment of home health aides. We performed a county-level longitudinal analysis using 2012 to 2018 national data. The study cohort included 2,496 counties and focused on all workers in the home health industry. Outcome variables included wages and the employment of home health aides. Key variables of interest included the consumer price index adjusted state MW and a set of variables that captured the effect of the Fair Labor Standards Act (FLSA) extension. This study found that home health aides' hourly wages were $1.00 higher (p = .011) in states that increased their MWs from below $8 to above $10. The FLSA extension was associated with $1.15 higher wages in states with higher MWs (i.e., state MW above $10 in 2014). The FLSA extension was associated with higher employment of home health aides in less-competitive markets, rather than high- or average-competitive markets. This study suggests that state MW increases combined with the FLSA extension may help maintain the current home health workforce and improve their wages.

20.
Eur J Oncol Nurs ; 66: 102402, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37738841

RESUMO

OBJECTIVE: Breast reconstruction (BR) is a positive contribution to aesthetic effect among breast cancer patients. Identification of influenced factors for participating satisfaction may provide insights on the decision-making theory to promote patient's autonomy in surgical choice. The purpose of this study was to examine the level of participating satisfaction with surgical treatment decision-making and its predictors among breast cancer patients with immediate BR. METHODS: A cross-sectional study was conducted including 163 breast cancer patients with immediate BR in Mainland China. Data was collected using patients' participation satisfaction in medical decision-making scale (PSMDS), Big five Short-Form (BFI) Scale, Patient Participation Competence Scale(PPCS) and Patients' Preference (MPP) scale. Descriptive, bivariate, and multivariate regression analyses were used. RESULTS: Scores of PSMD were 86.38 ± 15.74. Multiple regression analyses indicated autonomous decision-making, marital statue, information acquisition competence, agreeableness, and decision-making preferences as indicators, explaining 29.6% of the response variation (P < 0.05). CONCLUSIONS: The level of PSMD in breast cancer patients with immediate BR need to be improved. Patients with greater autonomous decision-making, married, higher information acquisition competence, agreeableness, and collaborative role are more likely to have an preferable PSMD. A comprehensive assessment and effective decision-making support are needed initially for BC patients to promote positive participation when making surgical decision.

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