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1.
Mitochondrial DNA B Resour ; 9(10): 1365-1369, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39381362

RESUMEN

Camellia huulungensis Rosmann & Ninh 1997, belonging to the sect. Chrysantha, holds important ornamental value and medicinal value. In this study, the complete chloroplast genome sequence of C. huulungensis was assembled using high-throughput sequencing technology. The entire length of chloroplast genome is 156,546 bp and contains a small single-copy region (18,257 bp), a large single-copy region (86,219 bp), and a pair of inverted repeat regions (26,035 bp). A total of 133 genes were annotated, including 88 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content is 37.33%. The phylogenetic analysis showed that C. huulungensis is sister to C. aurea. The results can provide genetic data for further phylogenetic studies of Camellia.

2.
Sci Rep ; 14(1): 22283, 2024 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333210

RESUMEN

To evaluate the efficacy and safety of four techniques of partial breast irradiation (PBI) including interstitial brachytherapy (ISBT), balloon-based brachytherapy (BBT), Intraoperative radiotherapy (IORT) and three-dimensional conformal radiotherapy (3DCRT) in the treatment for early-stage breast cancer patients after breast-conserving surgery. A systematic search was performed according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines using the PubMed, Embase, Cochrane Library and Web of Science databases. The inclusion criteria were clinical trials and observational studies that reported on outcome measures of principal PBI techniques. The methodological quality of the included research data was assessed using bias risk assessment tool with the Methodological Index for Non-Randomized Studies (MINORS), and the research information were analyzed using data analysis software. Clinical studies were collected from the earliest available date until September 2023. Fifty-one studies were included, with a total sample size of 7708. The results of network meta-analysis (NMA) showed that ISBT can lower the local recurrence (SUCRA: 73.8%). In terms of reducing distant metastasis, 3DCRT may be the best choice (SUCRA: 52.5%). And IORT has the highest 5-year overall survival (SUCRA: 90%). Furthermore, ISBT also has the advantages of lowest risk with fat necrosis (SUCRA: 72.5%), infection (SUCRA: 78.3%) and breast pain (SUCRA: 86.2%). BBT may be the optimal solution for fibrosis (SUCRA: 76.9%) and hyperpigmentation (SUCRA: 66.7%). 3DCRT has lower incidence of telangiectasia (SUCRA: 56.7%) and better cosmetic result (SUCRA: 85%). Postoperative PBI treatment using ISBT after breast-conserving surgery in patients with early-stage breast cancer may be a more valuable choice based on the treatment efficacy and is associated with fewer late side-effects. Large-scale, prospective, long-term studies are warranted to clarify the role of different PBI techniques in selected patients.


Asunto(s)
Braquiterapia , Neoplasias de la Mama , Mastectomía Segmentaria , Humanos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Femenino , Mastectomía Segmentaria/métodos , Braquiterapia/efectos adversos , Braquiterapia/métodos , Recurrencia Local de Neoplasia , Resultado del Tratamiento , Radioterapia Conformacional/efectos adversos , Radioterapia Conformacional/métodos , Estadificación de Neoplasias , Radioterapia Adyuvante/efectos adversos , Radioterapia Adyuvante/métodos
3.
Nat Commun ; 15(1): 8408, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333121

RESUMEN

Glucagon-like peptide-1 (GLP-1) analogs are important therapeutics for type 2 diabetes and obesity. Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog. We conducted a Phase 2, randomized, double-blind, placebo-controlled study enrolling 145 adults with T2DM. Participants were randomized to 0.4, 0.8, or 1.2 mg ecnoglutide or placebo as once-weekly injections for 20 weeks. The primary objective was to evaluate the efficacy of ecnoglutide, as measured by HbA1c change from baseline at Week 20. Secondary endpoints included body weight, glucose and lipid parameters, as well as safety. We show that, at end of treatment, the 0.4, 0.8, and 1.2 mg groups had statistically significant HbA1c reductions from baseline of -1.81%, -1.90%, and -2.39%, respectively, compared to -0.55% for placebo (P < 0.0001). At end of treatment, 71.9% of the 1.2 mg group had HbA1c ≤ 6.5% versus 9.1% on placebo, and 33.3% had body weight reductions ≥5% versus 3.0% for placebo. Ecnoglutide was generally safe and well tolerated. China Drug Trials Registry CTR20211014.


Asunto(s)
Diabetes Mellitus Tipo 2 , Péptido 1 Similar al Glucagón , Hemoglobina Glucada , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Persona de Mediana Edad , Masculino , Femenino , Método Doble Ciego , Péptido 1 Similar al Glucagón/análogos & derivados , Péptido 1 Similar al Glucagón/uso terapéutico , Hemoglobina Glucada/metabolismo , Adulto , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/administración & dosificación , Anciano , Resultado del Tratamiento , Peso Corporal/efectos de los fármacos
4.
Biostatistics ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39255368

RESUMEN

Dynamic prediction models capable of retaining accuracy by evolving over time could play a significant role for monitoring disease progression in clinical practice. In biomedical studies with long-term follow up, participants are often monitored through periodic clinical visits with repeat measurements until an occurrence of the event of interest (e.g. disease onset) or the study end. Acknowledging the dynamic nature of disease risk and clinical information contained in the longitudinal markers, we propose an innovative concordance-assisted learning algorithm to derive a real-time risk stratification score. The proposed approach bypasses the need to fit regression models, such as joint models of the longitudinal markers and time-to-event outcome, and hence enjoys the desirable property of model robustness. Simulation studies confirmed that the proposed method has satisfactory performance in dynamically monitoring the risk of developing disease and differentiating high-risk and low-risk population over time. We apply the proposed method to the Alzheimer's Disease Neuroimaging Initiative data and develop a dynamic risk score of Alzheimer's Disease for patients with mild cognitive impairment using multiple longitudinal markers and baseline prognostic factors.

5.
Invest Ophthalmol Vis Sci ; 65(11): 4, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39230995

RESUMEN

Purpose: We assessed whether NICD1 expression, c-MYC expression, and P63 expression by immunohistochemistry (IHC) correlate with prognosis and high-risk clinicopathological features in lacrimal gland adenoid cystic carcinoma (ACC). Methods: Records of patients with lacrimal gland ACC who underwent surgery between 1998 to 2018 were reviewed. Clinicopathologic and treatment data were collected. Tumor tissues were subjected to light microscopy and IHC. Results: Of 43 patients treated during the study period, 21 had archived tumor tissue available and were included. The median age at diagnosis was 47 years, and 13 patients (62%) were male. Thirteen patients (62%) had T2 disease, and none had nodal or distant metastasis at diagnosis. Tumors were positive for NICD1 expression in eight cases (38%), c-MYC expression in eight (38%), and P63 expression in 11 (52%). Positive NICD1 expression was associated with predominantly solid (vs. cribriform/tubular) pattern (P < 0.001), treatment with orbital exenteration (vs. eye-sparing surgery) (P = 0.008), local recurrence (P = 0.047), and death (P = 0.012). Negative P63 expression was associated with predominantly solid pattern (P = 0.001), local recurrence (P = 0.012), distant metastasis (P = 0.001), and death (P = 0.035). A higher percentage of tumor cells staining for c-MYC was associated with presence of perineural invasion (P = 0.036). Positive NICD1 expression was associated with worse disease-free survival (hazard ratio, 6.27; 95% CI, 1.29-30.46), whereas positive P63 expression was associated with better disease-free survival (hazard ratio, 0.03; 95% CI, 0.0002-0.26). Conclusions: IHC for NICD1 and P63 should be considered in lacrimal gland ACC because of their prognostic value and potential as treatment targets.


Asunto(s)
Biomarcadores de Tumor , Carcinoma Adenoide Quístico , Neoplasias del Ojo , Enfermedades del Aparato Lagrimal , Proteínas Proto-Oncogénicas c-myc , Receptor Notch1 , Humanos , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/diagnóstico , Masculino , Persona de Mediana Edad , Femenino , Adulto , Pronóstico , Enfermedades del Aparato Lagrimal/metabolismo , Enfermedades del Aparato Lagrimal/patología , Enfermedades del Aparato Lagrimal/diagnóstico , Anciano , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Neoplasias del Ojo/metabolismo , Neoplasias del Ojo/patología , Neoplasias del Ojo/diagnóstico , Estudios Retrospectivos , Biomarcadores de Tumor/metabolismo , Receptor Notch1/metabolismo , Inmunohistoquímica , Adulto Joven , Proteínas de la Membrana , Factores de Transcripción , Proteínas Supresoras de Tumor
6.
Theranostics ; 14(12): 4570-4581, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39239512

RESUMEN

Purpose: This study aims to assess whole-mount Gleason grading (GG) in prostate cancer (PCa) accurately using a multiomics machine learning (ML) model and to compare its performance with biopsy-proven GG (bxGG) assessment. Materials and Methods: A total of 146 patients with PCa recruited in a pilot study of a prospective clinical trial (NCT02659527) were retrospectively included in the side study, all of whom underwent 68Ga-PSMA-11 integrated positron emission tomography (PET) / magnetic resonance (MR) before radical prostatectomy (RP) between May 2014 and April 2020. To establish a multiomics ML model, we quantified PET radiomics features, pathway-level genomics features from whole exome sequencing, and pathomics features derived from immunohistochemical staining of 11 biomarkers. Based on the multiomics dataset, five ML models were established and validated using 100-fold Monte Carlo cross-validation. Results: Among five ML models, the random forest (RF) model performed best in terms of the area under the curve (AUC). Compared to bxGG assessment alone, the RF model was superior in terms of AUC (0.87 vs 0.75), specificity (0.72 vs 0.61), positive predictive value (0.79 vs 0.75), and accuracy (0.78 vs 0.77) and showed slightly decreased sensitivity (0.83 vs 0.89) and negative predictive value (0.80 vs 0.81). Among the feature categories, bxGG was identified as the most important feature, followed by pathomics, clinical, radiomics and genomics features. The three important individual features were bxGG, PSA staining and one intensity-related radiomics feature. Conclusion: The findings demonstrate a superior assessment of the developed multiomics-based ML model in whole-mount GG compared to the current clinical baseline of bxGG. This enables personalized patient management by identifying high-risk PCa patients for RP.


Asunto(s)
Aprendizaje Automático , Clasificación del Tumor , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/diagnóstico por imagen , Prostatectomía/métodos , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Estudios Prospectivos , Proyectos Piloto , Tomografía de Emisión de Positrones/métodos , Imagen por Resonancia Magnética/métodos , Genómica/métodos , Multiómica
7.
J Gastrointest Oncol ; 15(4): 1431-1445, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39279978

RESUMEN

Background: CKLF-like MARVEL transmembrane domain-containing 4 (CMTM4) is involved in immune regulation and tumor progression; however, its role in gastric cancer (GC) remains unclear. This study explored the role and mechanism of CMTM4 in GC. Methods: Immunohistochemistry was used to analyze CMTM4 expression in human gastric biopsied cells from patients with GC (N=23) or chronic superficial gastritis (N=23). To investigate the function of CMTM4 in GC cells, the gene CMTM4 was knocked down and overexpressed in human gastric adenocarcinoma cell line AGS. The gene CMTM4 was overexpressed in AGS cells and human gastric cell line SGC7901. Cell Counting Kit 8 (CCK-8) and cell clonogenic assays were used to analyze the proliferation of the GC cells. Flow cytometry was used to analyze the effects of CMTM4 on apoptosis and the cell cycle. Wound healing and transwell assays were used to analyze the migration and invasion of the gastric cells, respectively. The mechanism of CMTM4 in GC cells was explored using the tandem mass tags (TMTs) proteome and verified by western blot analysis. Results: CMTM4 expression was more downregulated in the human GC tissues than the gastritis tissues. CMTM4 overexpression significantly inhibited the proliferation, migration, and invasion of the GC cells, whereas CMTM4 knockdown enhanced gastric cell proliferation (P>0.05), migration (P>0.05), and invasion (P>0.05). Flow cytometry showed that CMTM4 promoted apoptosis and resulted in G1/S arrest in the GC cells. In addition, the proteome and western blot results showed that STAT1 was significantly upregulated, and the STAT1 signaling pathways were enriched in the GC cells overexpressing CMTM4. Conclusions: Our results suggest that CMTM4 plays a tumor-suppressive role in GC and may affect the growth, migration, and invasion of GC cells through the STAT1 signaling pathway. CMTM4 might have potential value as a prognosis marker and potential therapeutic target for GC therapy.

8.
Methods ; 231: 61-69, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293728

RESUMEN

Arabidopsis thaliana synthesizes various medicinal compounds, and serves as a model plant for medicinal plant research. Single-cell transcriptomics technologies are essential for understanding the developmental trajectory of plant roots, facilitating the analysis of synthesis and accumulation patterns of medicinal compounds in different cell subpopulations. Although methods for interpreting single-cell transcriptomics data are rapidly advancing in Arabidopsis, challenges remain in precisely annotating cell identity due to the lack of marker genes for certain cell types. In this work, we trained a machine learning system, AtML, using sequencing datasets from six cell subpopulations, comprising a total of 6000 cells, to predict Arabidopsis root cell stages and identify biomarkers through complete model interpretability. Performance testing using an external dataset revealed that AtML achieved 96.50% accuracy and 96.51% recall. Through the interpretability provided by AtML, our model identified 160 important marker genes, contributing to the understanding of cell type annotations. In conclusion, we trained AtML to efficiently identify Arabidopsis root cell stages, providing a new tool for elucidating the mechanisms of medicinal compound accumulation in Arabidopsis roots.

9.
Virus Res ; 349: 199448, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39127240

RESUMEN

Adenoviral infections, particularly in children, remain a significant public health issue with no approved targeted treatments. Artemisinin and its derivatives, well-known for their use in malaria treatment, have shown antiviral activities in recent studies. However, their efficacy against human adenovirus (HAdV) remains unexplored. This study aimed to assess the activity of artemisinin and its derivatives against HAdV infection in vitro using cell lines and primary cells. Our data revealed that artemisinin exhibited dose-dependent anti-HAdV activity with no apparent cytotoxicity over a wide concentration range. Mechanistically, artemisinin did not affect viral attachment or entry into target cells, nor the viral genome entry into cell nucleus. Instead, it inhibited HAdV through suppression of viral DNA replication. Comparative analysis with its derivatives, artesunate and artemisone, showed distinct cytotoxicity and anti-adenoviral profiles, with artemisone showing superior efficacy and lower toxicity. Further validation using a primary airway epithelial cell model confirmed the anti-adenoviral activity of both artemisinin and artemisone against different virus strains. Together, our findings suggest that artemisinin and its derivatives may be promising candidates for anti-HAdV treatment.


Asunto(s)
Adenovirus Humanos , Antivirales , Artemisininas , Replicación Viral , Artemisininas/farmacología , Humanos , Antivirales/farmacología , Replicación Viral/efectos de los fármacos , Adenovirus Humanos/efectos de los fármacos , Adenovirus Humanos/fisiología , Línea Celular , Artesunato/farmacología , Células Epiteliales/virología , Células Epiteliales/efectos de los fármacos , Infecciones por Adenovirus Humanos/virología , Infecciones por Adenovirus Humanos/tratamiento farmacológico
10.
Elife ; 132024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196635

RESUMEN

Escape behaviors help animals avoid harm from predators and other threats in the environment. Successful escape relies on integrating information from multiple stimulus modalities (of external or internal origin) to compute trajectories toward safe locations, choose between actions that satisfy competing motivations, and execute other strategies that ensure survival. To this end, escape behaviors must be adaptive. When a Drosophila melanogaster larva encounters a noxious stimulus, such as the focal pressure a parasitic wasp applies to the larval cuticle via its ovipositor, it initiates a characteristic escape response. The escape sequence consists of an initial abrupt bending, lateral rolling, and finally rapid crawling. Previous work has shown that the detection of noxious stimuli primarily relies on class IV multi-dendritic arborization neurons (Class IV neurons) located beneath the body wall, and more recent studies have identified several important components in the nociceptive neural circuitry involved in rolling. However, the neural mechanisms that underlie the rolling-escape sequence remain unclear. Here, we present both functional and anatomical evidence suggesting that bilateral descending neurons within the subesophageal zone of D. melanogaster larva play a crucial role in regulating the termination of rolling and subsequent transition to escape crawling. We demonstrate that these descending neurons (designated SeIN128) are inhibitory and receive inputs from a second-order interneuron upstream (Basin-2) and an ascending neuron downstream of Basin-2 (A00c). Together with optogenetic experiments showing that co-activation of SeIN128 neurons and Basin-2 influence the temporal dynamics of rolling, our findings collectively suggest that the ensemble of SeIN128, Basin-2, and A00c neurons forms a GABAergic feedback loop onto Basin-2, which inhibits rolling and thereby facilitates the shift to escape crawling.


Asunto(s)
Drosophila melanogaster , Reacción de Fuga , Neuronas GABAérgicas , Larva , Animales , Larva/fisiología , Neuronas GABAérgicas/fisiología , Reacción de Fuga/fisiología , Drosophila melanogaster/fisiología , Retroalimentación Fisiológica
11.
Stat Methods Med Res ; 33(8): 1424-1436, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39053568

RESUMEN

This study investigates the heterogeneity of a biomarker's discriminative performance for predicting subsequent time-to-event outcomes across different patient subgroups. While the area under the curve (AUC) for the time-dependent receiver operating characteristic curve is commonly used to assess biomarker performance, the partial time-dependent AUC (PAUC) provides insights that are often more pertinent for population screening and diagnostic testing. To achieve this objective, we propose a regression model tailored for PAUC and develop two distinct estimation procedures for discrete and continuous covariates, employing a pseudo-partial likelihood method. Simulation studies are conducted to assess the performance of these procedures across various scenarios. We apply our model and inference procedure to the Alzheimer's Disease Neuroimaging Initiative data set to evaluate potential heterogeneities in the discriminative performance of biomarkers for early Alzheimer's disease diagnosis based on patients' characteristics.


Asunto(s)
Enfermedad de Alzheimer , Área Bajo la Curva , Biomarcadores , Curva ROC , Humanos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/diagnóstico por imagen , Modelos Estadísticos , Funciones de Verosimilitud , Simulación por Computador , Neuroimagen/estadística & datos numéricos
12.
Semin Cancer Biol ; 104-105: 1-15, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39032717

RESUMEN

Ovarian cancer is a common gynecological malignancy, and its treatment remains challenging. Although ovarian cancer may respond to immunotherapy because of endogenous immunity at the molecular or T cell level, immunotherapy has so far not had the desired effect. The functional status of preexisting T cells is an indispensable determinant of powerful antitumor immunity and immunotherapy. T cell exhaustion and senescence are two crucial states of T cell dysfunction, which share some overlapping phenotypic and functional features, but each status possesses unique molecular and developmental signatures. It has been widely accepted that exhaustion and senescence of T cells are important strategies for cancer cells to evade immunosurveillance and maintain the immunosuppressive microenvironment. Herein, this review summarizes the phenotypic and functional features of exhaust and senescent T cells, and describes the key drivers of the two T cell dysfunctional states in the tumor microenvironment and their functional roles in ovarian cancer. Furthermore, we present a summary of the molecular machinery and signaling pathways governing T cell exhaustion and senescence. Possible strategies that can prevent and/or reverse T cell dysfunction are also explored. An in-depth understanding of exhausted and senescent T cells will provide novel strategies to enhance immunotherapy of ovarian cancer through redirecting tumor-specific T cells away from a dysfunctional developmental trajectory.


Asunto(s)
Senescencia Celular , Inmunoterapia , Neoplasias Ováricas , Linfocitos T , Microambiente Tumoral , Humanos , Femenino , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/terapia , Neoplasias Ováricas/patología , Inmunoterapia/métodos , Senescencia Celular/inmunología , Microambiente Tumoral/inmunología , Linfocitos T/inmunología , Animales , Agotamiento de Células T
13.
Angew Chem Int Ed Engl ; 63(41): e202409217, 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-38989537

RESUMEN

Cytochrome P450 2D6 (CYP2D6) is a key enzyme that mediates the metabolism of various drugs and endogenous substances in humans. However, its biological role in drug-drug interactions especially mechanism-based inactivation (MBI), and various diseases remains poorly understood, owing to the lack of molecular tools suitable for selectively monitoring CYP2D6 in complex biological systems. Herein, using a tailored molecular strategy, we developed a fluorescent probe BDPM for CYP2D6. BDPM exhibits excellent specificity and imaging capability for CYP2D6, making it suitable for the real-time monitoring of endogenous CYP2D6 activity in living bio-samples. Therefore, our tailored strategy proved useful for constructing the highly selective and enzyme-activated fluorescent probes. BDPM as a molecular tool to explore the critical roles of CYP2D6 in the pathogenesis of diseases, high-throughput screening of inhibitors and intensive investigation of CYP2D6-induced MBI in natural systems.


Asunto(s)
Citocromo P-450 CYP2D6 , Colorantes Fluorescentes , Humanos , Colorantes Fluorescentes/química , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP2D6/química , Estructura Molecular
14.
Dermatopathology (Basel) ; 11(3): 200-208, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39051323

RESUMEN

Although extensively studied in cutaneous epithelial neoplasms, the TRPS1 immunoreactivity in cutaneous mesenchymal neoplasms and tumors of uncertain differentiation (CMNTUDs), such as atypical fibroxanthoma (AFX), remains largely unexplored. We assessed TRPS1 immunoreactivity in 135 CMNTUDs, comprising 46 fibrohistiocytic/fibroblastic tumors, 28 vascular tumors, 24 peripheral nerve sheath tumors (PNSTs), 21 tumors of uncertain differentiation, and 16 smooth muscle tumors. Additionally, we included selected cases of melanoma with spindled cell morphology or desmoplastic features (n = 9) and sarcomatoid squamous cell carcinoma (SSCC) (n = 5) to compare TRPS1 expression patterns with those of AFX. TRPS1 expression was prevalent in dermatofibromas (24/24), leiomyomas (8/8), AFXs/pleomorphic dermal sarcoma (PDS) (20/21), dermatofibrosarcomas protuberans (14/22), and leiomyosarcomas (6/8). It was uncommon in angiosarcomas (3/20), Kaposi sarcomas (2/8), and neurofibromas (5/17) and absent in perineuriomas (0/2). AFXs/PDS exhibited the highest median H-score of 240, contrasting with minimal TRPS1 immunoreactivity in vascular neoplasms and PNSTs, with median H-scores consistently below 10. Significant differences in H-score were observed between AFXs/PDS and angiosarcomas (p < 0.001), melanomas (p < 0.001), and leiomyosarcomas (p = 0.029). However, no significant difference was found compared to SSCCs, suggesting limited discriminatory power of TRPS1 in this context. This study sheds light on TRPS1 expression patterns in a subset of CMNTUDs, extending beyond prior studies primarily focused on epithelial tumors, while underscoring potential pitfalls associated with TRPS1 immunohistochemistry.

15.
Nanotechnology ; 35(42)2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39025078

RESUMEN

Flexible electronic device requires a novel micro-supercapacitors (MSCs) energy conversion-storage system based on two-dimensional (2D) materials to solve the problems of stiffness and complexity. Herein, we report a novel catalytic introduction method of graphene with adjustable porosity by high-energy photon beam. The graphene/Ti3C2Txheterostructure was constructed by electrostatic self-assembly, has a high cycle life (98% after 8000 cycles), energy density (11.02 mWh cm-3), and demonstrate excellent flexible alternating current line-filtering performance. The phase angle of -79.8° at 120 Hz and a resistance-capacitance constant of 0.068 ms. Furthermore, the porous graphene/Ti3C2Txstructures produced by multiple catalytic inductions allowed ions to deeply penetrate the electrode, thereby increasing the stacking density. The special 'pore-layer nesting' graphene structure with adjustable pores effectively increased the specific surface area, and its superior matching with electrolyte solutions greatly improved surface-active site utilization. This work offers an alternative strategy for fabricating a 2D heterostructure for an MSC.

16.
Gut Microbes ; 16(1): 2382766, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39068523

RESUMEN

CagA, a virulence factor of Helicobacter pylori (H. pylori), is known to drive inflammation in gastric epithelial cells and is typically degraded through autophagy. However, the molecular mechanism by which CagA evades autophagy-mediated degradation remains elusive. This study found that H. pylori inhibits autophagic flux by upregulating the expression of AU-rich element RNA-binding factor 1 (AUF1). We confirmed that AUF1 does not affect autophagy initiation but instead hampers lysosomal clearance, as evidenced by treatments with 3-MA, CQ and BafA1. Upregulated AUF1 stabilizes CagA protein levels by inhibiting the autolysosomal degradation of intracellular CagA in H. pylori-infected gastric epithelial cells. Knocking down AUF1 promotes CagA degradation, an effect that can be reversed by the lysosome inhibitor BafA1 and CQ. Transcriptome analysis of AUF1-knockdown gastric epithelial cells infected with H. pylori indicated that AUF1 regulates the expression of lysosomal-associated hydrolase genes, specifically CTSD, to inhibit autolysosomal degradation. Moreover, we observed that knockdown of AUF1 enhanced the stability of CTSD mRNA and identified AUF1 binding to the 3'UTR region of CTSD mRNA. AUF1-mediated downregulation of CTSD expression contributes to CagA stability, and AUF1 overexpression leads to an increase in CagA levels in exosomes, thus promoting extracellular inflammation. In clinical gastric mucosa, the expression of AUF1 and its cytoplasmic translocation are associated with H. pylori-associated gastritis, with CagA being necessary for the translocation of AUF1 into the cytoplasm. Our findings suggest that AUF1 is a novel host-positive regulator of CagA, and dysregulation of AUF1 expression increases the risk of H. pylori-associated gastritis.


Asunto(s)
Antígenos Bacterianos , Autofagia , Proteínas Bacterianas , Células Epiteliales , Mucosa Gástrica , Infecciones por Helicobacter , Helicobacter pylori , Ribonucleoproteína Nuclear Heterogénea D0 , Ribonucleoproteína Heterogénea-Nuclear Grupo D , Lisosomas , Antígenos Bacterianos/metabolismo , Antígenos Bacterianos/genética , Ribonucleoproteína Nuclear Heterogénea D0/metabolismo , Helicobacter pylori/metabolismo , Helicobacter pylori/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Humanos , Lisosomas/metabolismo , Lisosomas/microbiología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/patología , Ribonucleoproteína Heterogénea-Nuclear Grupo D/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo D/genética , Células Epiteliales/microbiología , Células Epiteliales/metabolismo , Mucosa Gástrica/microbiología , Mucosa Gástrica/metabolismo , Inflamación/metabolismo , Inflamación/microbiología , Factores de Virulencia/metabolismo , Factores de Virulencia/genética , Línea Celular
17.
Exp Dermatol ; 33(7): e15128, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38973249

RESUMEN

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal-regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine-induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p-ERK in the spinal cord in a dry skin mouse model induced by acetone-ether-water (AEW). q-PCR, Western blot, pharmacology and immunofluorescence  were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c-Fos and p-ERK expression in the spinal cord neurons were increased and co-labelled with GRPR-positive neurons in AEW mice. Furthermore, H4R agonist 4-methyhistamine dihydrochloride (4-MH)induced itch. Both 4-MH-induced itch and the spontaneous itch in AEW mice were blocked by p-ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p-ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW-induced dry skin mice.


Asunto(s)
Acetona , Quinasas MAP Reguladas por Señal Extracelular , Prurito , Receptores Histamínicos H4 , Médula Espinal , Animales , Prurito/inducido químicamente , Prurito/metabolismo , Receptores Histamínicos H4/metabolismo , Ratones , Médula Espinal/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Masculino , Acetona/farmacología , Agua , Éter , Modelos Animales de Enfermedad , Fosforilación , Indoles/farmacología , Butadienos/farmacología , Piperazinas/farmacología , Nitrilos/farmacología , Piel/metabolismo , Enfermedad Crónica , Metilhistaminas , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratones Endogámicos C57BL
18.
Front Mol Biosci ; 11: 1301099, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38993839

RESUMEN

Introduction: Hepatocellular carcinoma (HCC), which is closely associated with chronicinflammation, is the most common liver cancer and primarily involves dysregulated immune responses in the precancerous microenvironment. Currently, most studies have been limited to HCC incidence. However, the immunopathogenic mechanisms underlying precancerous lesions remain unknown. Methods: We obtained single-cell sequencing data (GSE136103) from two nonalcoholic fatty liver disease (NAFLD) cirrhosis samples and five healthy samples. Using pseudo-time analysis, we systematically identified five different T-cell differentiation states. Ten machine-learning algorithms were used in 81 combinations to integrate the frameworks and establish the best T-cell differentiation-related prognostic signature in a multi-cohort bulk transcriptome analysis. Results: LDHA was considered a core gene, and the results were validated using multiple external datasets. In addition, we validated LDHA expression using immunohistochemistry and flow cytometry. Conclusion: LDHA is a crucial marker gene in T cells for the progression of NAFLD cirrhosis to HCC.

19.
Sensors (Basel) ; 24(13)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-39001112

RESUMEN

A robust wood material crack detection algorithm, sensitive to small targets, is indispensable for production and building protection. However, the precise identification and localization of cracks in wooden materials present challenges owing to significant scale variations among cracks and the irregular quality of existing data. In response, we propose a crack detection algorithm tailored to wooden materials, leveraging advancements in the YOLOv8 model, named ICDW-YOLO (improved crack detection for wooden material-YOLO). The ICDW-YOLO model introduces novel designs for the neck network and layer structure, along with an anchor algorithm, which features a dual-layer attention mechanism and dynamic gradient gain characteristics to optimize and enhance the original model. Initially, a new layer structure was crafted using GSConv and GS bottleneck, improving the model's recognition accuracy by maximizing the preservation of hidden channel connections. Subsequently, enhancements to the network are achieved through the gather-distribute mechanism, aimed at augmenting the fusion capability of multi-scale features and introducing a higher-resolution input layer to enhance small target recognition. Empirical results obtained from a customized wooden material crack detection dataset demonstrate the efficacy of the proposed ICDW-YOLO algorithm in effectively detecting targets. Without significant augmentation in model complexity, the mAP50-95 metric attains 79.018%, marking a 1.869% improvement over YOLOv8. Further validation of our algorithm's effectiveness is conducted through experiments on fire and smoke detection datasets, aerial remote sensing image datasets, and the coco128 dataset. The results showcase that ICDW-YOLO achieves a mAP50 of 69.226% and a mAP50-95 of 44.210%, indicating robust generalization and competitiveness vis-à-vis state-of-the-art detectors.

20.
Arch Esp Urol ; 77(5): 517-524, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38982780

RESUMEN

OBJECTIVE: Upper urinary tract stones (UUTSs) are among the most common types of urinary stones, and their incidence rate has been increasing annually in recent years, seriously affecting the daily lives of patients. This study aimed to compare the treatment efficacy of one-stage and staged flexible ureteroscopic lithotripsy (FURL) for UUTSs. METHODS: A total of 142 patients with UUTSs admitted to our hospital between December 2019 and March 2023 were selected for retrospective analysis, including 76 patients who received staged FURL (control group) and 66 patients who received one-stage FURL (observation group). The duration of surgery, length of stay, stone clearance rate, incidence of postoperative complications (from postsurgery to discharge), and total hospitalization cost were analyzed in both groups. The visual analog scale (VAS) score and activities of daily living (ADL) score were assessed before surgery (T0), 3 days after surgery (T1), and 7 days after surgery (T2). Patients were followed up for 1 month after surgery, and their quality of life was assessed using the MOS Item Short Form Health Survey (SF-36). RESULTS: There was no difference in the stone clearance rate or incidence of postoperative complications between the two groups (p > 0.05). The operation time, hospitalization time and hospitalization cost in the observation group were 75.58 ± 15.91 min, 4.20 ± 1.24 days and 14312.62 ± 1078.89 yuan, respectively, which were lower than those in the control group (p < 0.05). In addition, the VAS score at T3 was decreased to 1.49 ± 0.70, while the ADL and SF-36 scores were higher in the observation group (p < 0.05). CONCLUSIONS: One-stage FURL shortens the duration of surgery and length of stay, reduces hospitalization costs, and improves the quality of life of patients with UUTSs.


Asunto(s)
Cálculos Renales , Cálculos Ureterales , Ureteroscopía , Humanos , Masculino , Femenino , Ureteroscopía/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Resultado del Tratamiento , Cálculos Renales/cirugía , Cálculos Ureterales/cirugía , Adulto , Litotricia/métodos , Ureteroscopios , Anciano
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