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1.
Front Plant Sci ; 15: 1368692, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736445

RESUMEN

In recent years, the ethylene-mediated ripening and softening of non-climacteric fruits have been widely mentioned. In this paper, recent research into the ethylene-mediated ripening and softening of non-climacteric fruits is summarized, including the involvement of ethylene biosynthesis and signal transduction. In addition, detailed studies on how ethylene interacts with other hormones to regulate the ripening and softening of non-climacteric fruits are also reviewed. These findings reveal that many regulators of ethylene biosynthesis and signal transduction are linked with the ripening and softening of non-climacteric fruits. Meanwhile, the perspectives of future research on the regulation of ethylene in non-climacteric fruit are also proposed. The overview of the progress of ethylene on the ripening and softening of non-climacteric fruit will aid in the identification and characterization of key genes associated with ethylene perception and signal transduction during non-climacteric fruit ripening and softening.

2.
Int J Cancer ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38733360

RESUMEN

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

3.
Food Chem ; 452: 139572, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38733686

RESUMEN

The discarded longan shell-derived porous carbon material (LPC) served as a scaffold for synthesizing bismuth nanoparticle-loaded longan porous carbon nanocomposite (BiNPs@LPC) via a hydrothermal method. Then BiNPs@LPC was utilized to modify screen-printed carbon electrodes (SPCE) for simultaneous detection of Pb(II) and Cd(II) by square wave anodic stripping voltammetry (SWASV). The material was thoroughly characterized by scanning electron microscopy, X-ray diffraction, Raman spectra, Brunauer-Emmett-Teller analysis, electrochemical impedance spectroscopy and cyclic voltammetry. BiNPs@LPC exhibited abundant porous structures, high surface area, and numerous active sites, which could improve significantly response sensitivity. Under optimal conditions, the peak currents of Pb(II) and Cd(II) exhibited favorable linear relationships with the concentration within a range of 0.1-150 µg L-1, with detection limits (S/N = 3) of 0.02 µg L-1 and 0.03 µg L-1, respectively. BiNPs@LPC/SPCE demonstrated remarkable selectivity, stability and repeatability. The proposed method was successfully applied for the detection of Pb(II) and Cd(II) in seafoods achieving satisfying recovery of 97.8%-108.3% and 96.7%-106.4%. These excellent test properties were coupled with convenience for batch preparation of the modified electrodes, highlighting its potential for practical applications in heavy metal detection of real samples.

4.
Hum Vaccin Immunother ; 20(1): 2350101, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38738709

RESUMEN

Clinical guidelines have recently advised combination therapy involving immunotherapy (IO) and tyrosine kinase inhibitors (TKI) as the first-line therapy approach for advanced renal cell carcinoma (RCC). Nevertheless, there is currently no available biomarker that can effectively distinguish the progression-free survival (PFS). RNA-sequencing and immunohistochemistry were conducted on our cohort of metastatic RCC patients, namely ZS-MRCC, who received combination therapy consisting of IO and TKI. We further applied RNA-sequencing, immunohistochemistry, and flow cytometry to examine the immune cell infiltration and functionality inside the tumor microenvironment of high-risk localized RCC samples. SPP1 expression was significantly higher in non-responders to IO-TKI therapy. Elevated levels of SPP1 were associated with poor PFS in both the ZS-MRCC cohort (HR = 2.73, p = .018) and validated in the JAVELIN Renal 101 cohort (HR = 1.61, p = .004). By multivariate Cox analysis, SPP1 was identified as a significant independent prognosticator. Furthermore, there existed a negative correlation between elevated levels of SPP1 and the presence of GZMB+CD8+ T cells (Spearman's ρ= -0.48, p < .001). Conversely, SPP1 expression is associated with T cell exhaustion markers. A significant increase in the abundance of Tregs was observed in tumors with high levels of SPP1. Additionally, a machine-learning-based model was constructed to predict the benefit of IO-TKI treatment. High SPP1 is associated with therapeutic resistance and unfavorable PFS in IO-TKI therapy. SPP1 expression have also been observed to be indicative of malfunction and exhaustion in T cells. Increased SPP1 expression has the potential to serve as a potential biomarker for treatment selection of metastatic RCC.


Asunto(s)
Carcinoma de Células Renales , Inmunoterapia , Neoplasias Renales , Osteopontina , Inhibidores de Proteínas Quinasas , Humanos , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/terapia , Neoplasias Renales/patología , Masculino , Femenino , Inmunoterapia/métodos , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Osteopontina/metabolismo , Osteopontina/genética , Anciano , Microambiente Tumoral/inmunología , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Pronóstico , Resultado del Tratamiento , Adulto , Linfocitos T CD8-positivos/inmunología , Estudios de Cohortes , Terapia Combinada
5.
Sensors (Basel) ; 24(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38732862

RESUMEN

Online monitoring and real-time feedback on inclusions in molten metal are essential for metal quality control. However, existing methods for detecting aluminum melt inclusions face challenges, including interference, prolonged processing times, and latency. This paper presents the design and development of an online monitoring system for molten metal inclusions. Initially, the system facilitates real-time adjustment of signal acquisition parameters through a multiplexer. Subsequently, it employs a detection algorithm capable of swiftly extracting pulse peaks, with this task integrated into our proprietary host computer software to ensure timely detection and data visualization. Ultimately, we developed a monitoring device integrated with this online monitoring system, enabling the online monitoring of the aluminum alloy filtration process. Our findings indicate that the system can accurately measure the size and concentration of inclusions during the filtration process in real time, offering enhanced detection speed and stability compared to the industrial LiMCA CM (liquid metal cleanliness analyzer continuous monitoring) standard. Furthermore, our evaluation of the filtration process demonstrates that the effectiveness of filtration significantly improves with the increase in inclusion sizes, and the synergistic effect of combining CFF (ceramic foam filter) and MCF (metallics cartridge filter) filtration methods exceeds the performance of the CFF method alone. This system thus provides valuable technical support for optimizing filtration processes and controlling inclusion quality.

6.
Sensors (Basel) ; 24(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38732873

RESUMEN

Traditional methods for assessing the cleanliness of liquid metal are characterized by prolonged detection times, delays, and susceptibility to variations in sampling conditions. To address these limitations, an online cleanliness-analyzing system grounded in the method of the electrical sensing zone has been developed. This system facilitates real-time, in situ, and quantitative analysis of inclusion size and amount in liquid metal. Comprising pneumatic, embedded, and host computer modules, the system supports the continuous, online evaluation of metal cleanliness across various metallurgical processes in high-temperature environments. Tests conducted with gallium liquid at 90 °C and aluminum melt at 800 °C have validated the system's ability to precisely and quantitatively detect inclusions in molten metal in real time. The detection procedure is stable and reliable, offering immediate data feedback that effectively captures fluctuations in inclusion amount, thereby meeting the metallurgical industry's demand for real-time analyzing and control of inclusion cleanliness in liquid metal. Additionally, the system was used to analyze inclusion size distribution during the hot-dip galvanizing process. At a zinc melt temperature of 500 °C, it achieved a detection limit of 21 µm, simultaneously providing real-time data on the size and amount distribution of inclusions. This represents a novel strategy for the online monitoring and quality control of zinc slag throughout the hot-dip galvanizing process.

7.
Clin Transl Oncol ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38769216

RESUMEN

PURPOSE: Emerging evidence suggests that vaginal micro-environment disorder is closely related to the development of cervical lesions. Low-grade cervical intraepithelial neoplasia (CIN1), as an early stage of cervical lesions, exhibits a high risk of progressing to high-grade lesions or even cervical cancer. However, the effect of vaginal micro-environment on the malignant prognosis of CIN1 remains uncertain. METHODS: A total of 504 patients diagnosed with CIN1 by pathology, who were from the population-based cohorts established in Shanxi Province, China, were enrolled and followed up for 2 years. Micro-environmental factors such as vaginal pH, cleanliness, hydrogen peroxide (H2O2), ß-glucuronidase (GUSB), leucocyte esterase (LE), and sialidase (SNA) were detected to evaluate their effect on the malignant prognosis of CIN1. RESULTS: Abnormal vaginal pH (HR = 1.472, 95%CI 1.071-2.022), cleanliness (HR = 1.446, 95%CI 1.067-1.960), H2O2 (HR = 1.525, 95%CI 1.155-2.013), GUSB (HR = 1.739, 95%CI 1.235-2.448), LE (HR = 1.434, 95%CI 1.038-1.981), and SNA (HR = 1.411, 95%CI 1.065-1.870) could promote a higher incidence of CIN1 malignant prognosis, and the combined effects of these micro-environmental factors resulted in a nearly twofold increased risk (HR = 2.492, 95%CI 1.773-3.504) compared to any single factor alone, especially under the high-risk human papillomavirus (HR-HPV) infection. Notably, the cumulative incidence of malignant prognosis for CIN1 gradually increased during the early follow-up period, reaching its peak at approximately 8 months, and then stabilizing. CONCLUSION: Vaginal micro-environment disorder could promote CIN1 malignant prognosis, particularly in HR-HPV-infected women. Taking micro-environmental factors as the breakthrough, our study provides a feasible vision for preventing early stage cervical lesions.

8.
J Fluoresc ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771406

RESUMEN

The tip of a piece of plastic fiber was dyed with thymol blue to form a temperature probe. The fiber optic sensor was calibrated on a heatboard by comparison with a K-type thermal couple. Fluorescence characteristics including fluorescence intensity, emission bandwidth, peak & barycenter wavelengths, and self-referenced intensity ratio were used to carry the information of environment temperature. Accordingly, more than five temperature sensing functions were retrieved from the fluorescent sensor. Among such functions, the emission band barycenter showed premium precision. Temperature-driven shift of the emission band barycenter has a sensitivity of 0.095 nm/K, with a nonlinearity of 2.2%FS, resolution of 4 K and repeatability of 1.8%FS. The sensor can find its applications in wearable devices and radiofrequency ablation. Finally in a verification experiment, the sensor was used to monitor the temperature of a microwave oven chamber in real time.

9.
Pharmacol Res ; 204: 107209, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38740147

RESUMEN

Considerable progress has recently been made in cancer immunotherapy, including immune checkpoint blockade, cancer vaccine, and adoptive T cell methods. The lack of effective targets is a major cause of the low immunotherapy response rate in colorectal cancer (CRC). Here, we used a proteogenomic strategy comprising immunopeptidomics, whole exome sequencing, and 16 S ribosomal DNA sequencing analyses of 8 patients with CRC to identify neoantigens and bacterial peptides that can serve as antitumor targets. This study directly identified several personalized neoantigens and bacterial immunopeptides. Immunoassays showed that all neoantigens and 5 of 8 bacterial immunopeptides could be recognized by autologous T cells. Additionally, T cell receptor (TCR) αß sequencing revealed the TCR repertoire of epitope-reactive CD8+ T cells. Functional studies showed that T cell receptor-T (TCR-T) could be activated by epitope pulsed lymphoblastoid cells. Overall, this study comprehensively profiled the CRC immunopeptidome, revealing several neoantigens and bacterial peptides with potential to serve as immunotherapy targets in CRC.

10.
Med Biol Eng Comput ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38698189

RESUMEN

Retinal optical coherence tomography (OCT) images provide crucial insights into the health of the posterior ocular segment. Therefore, the advancement of automated image analysis methods is imperative to equip clinicians and researchers with quantitative data, thereby facilitating informed decision-making. The application of deep learning (DL)-based approaches has gained extensive traction for executing these analysis tasks, demonstrating remarkable performance compared to labor-intensive manual analyses. However, the acquisition of retinal OCT images often presents challenges stemming from privacy concerns and the resource-intensive labeling procedures, which contradicts the prevailing notion that DL models necessitate substantial data volumes for achieving superior performance. Moreover, limitations in available computational resources constrain the progress of high-performance medical artificial intelligence, particularly in less developed regions and countries. This paper introduces a novel ensemble learning mechanism designed for recognizing retinal diseases under limited resources (e.g., data, computation). The mechanism leverages insights from multiple pre-trained models, facilitating the transfer and adaptation of their knowledge to retinal OCT images. This approach establishes a robust model even when confronted with limited labeled data, eliminating the need for an extensive array of parameters, as required in learning from scratch. Comprehensive experimentation on real-world datasets demonstrates that the ensemble models constructed by the proposed ensemble method show superior performance over the baseline models under sparse labeled data, especially the triple ensemble model, which achieves the accuracy of 92.06%, which is 8.27%, 7.99%, and 11.14% better than the three baseline models, respectively. In addition, compared with the three baseline models learned from scratch, the triple ensemble model has fewer trainable parameters, only 3.677M, which is lower than the three baseline models of 8.013M, 4.302M, and 20.158M, respectively.

11.
Eur J Med Chem ; 272: 116458, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38703557

RESUMEN

Microtubules are recognized as one of the most vital and attractive targets in anticancer therapy. The development of novel tubulin-targeting agents with a new action mechanism is imperative. Based on the hydrophobic tagging strategy, the molecular scaffold of tirbanibulin was selected as tubulin target-binding moiety, subsequent to which a series of target compounds were rationally designed by selecting various combinations of linkers and hydrophobic tags. A set of novel molecules were synthesized and most of them exhibited potent antiproliferative activity against tumor cells in vitro. The most active compound 14b inhibited polymerization of purified recombinant tubulin and induced degradation of α- and ß-tubulin in MCF-7 cells. Notably, following treatment with compound 14b, an unexpected phenomenon of "microtubules fragmentation" was observed via immunofluorescence staining. Furthermore, compound 14b possessed antitumor activity in the 4T1 allograft models with TGI of 74.27 % without significant toxicity. In this work, we report the discovery of novel dual-mechanism tubulin-targeting agents.

12.
Genome Biol ; 25(1): 84, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38566207

RESUMEN

BACKGROUND: Epigenetic marks are reprogrammed during sexual reproduction. In flowering plants, DNA methylation is only partially remodeled in the gametes and the zygote. However, the timing and functional significance of the remodeling during plant gametogenesis remain obscure. RESULTS: Here we show that DNA methylation remodeling starts after male meiosis in rice, with non-CG methylation, particularly at CHG sites, being first enhanced in the microspore and subsequently decreased in sperm. Functional analysis of rice CHG methyltransferase genes CMT3a and CMT3b indicates that CMT3a functions as the major CHG methyltransferase in rice meiocyte, while CMT3b is responsible for the increase of CHG methylation in microspore. The function of the two histone demethylases JMJ706 and JMJ707 that remove H3K9me2 may contribute to the decreased CHG methylation in sperm. During male gametogenesis CMT3a mainly silences TE and TE-related genes while CMT3b is required for repression of genes encoding factors involved in transcriptional and translational activities. In addition, CMT3b functions to repress zygotic gene expression in egg and participates in establishing the zygotic epigenome upon fertilization. CONCLUSION: Collectively, the results indicate that DNA methylation is dynamically remodeled during male gametogenesis, distinguish the function of CMT3a and CMT3b in sex cells, and underpin the functional significance of DNA methylation remodeling during rice reproduction.


Asunto(s)
Metilación de ADN , Oryza , Oryza/genética , Oryza/metabolismo , Semillas/metabolismo , Metiltransferasas/metabolismo , Gametogénesis , Regulación de la Expresión Génica de las Plantas
13.
Molecules ; 29(7)2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38611953

RESUMEN

Bacterial virulence factors and biofilm development can be controlled by the quorum-sensing (QS) system, which is also intimately linked to antibiotic resistance in bacteria. In previous studies, many researchers found that quorum-sensing inhibitors (QSIs) can affect the development of bacterial biofilms and prevent the synthesis of many virulence factors. However, QSIs alone have a limited ability to suppress bacteria. Fortunately, when QSIs are combined with antibiotics, they have a better therapeutic effect, and it has even been demonstrated that the two together have a synergistic antibacterial effect, which not only ensures bactericidal efficiency but also avoids the resistance caused by excessive use of antibiotics. In addition, some progress has been made through in vivo studies on the combination of QSIs and antibiotics. This article mainly expounds on the specific effect of QSIs combined with antibiotics on bacteria and the combined antibacterial mechanism of some QSIs and antibiotics. These studies will provide new strategies and means for the clinical treatment of bacterial infections in the future.


Asunto(s)
Antibacterianos , Infecciones Bacterianas , Humanos , Antibacterianos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Percepción de Quorum , Biopelículas , Factores de Virulencia
14.
Urology ; 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38657872

RESUMEN

OBJECTIVE: To investigate the association between physical activity (PA) and the prevalence of kidney stones. METHODS: A cross-section study was conducted using data from National Health and Nutrition Examination Survey 2007-2018. PA was evaluated based on the Global Physical Activity Questionnaire. Multivariable logistic regression was performed to elucidate the association between PA (patterns, intensity, duration, and frequency of moderate and vigorous PA) and the prevalence of kidney stones after adjusting for potential confounders. Stratified and interaction analyses were conducted to detect potential effect modifiers. In addition, PA was assessed using metabolic equivalent and physical volume, and followed the regression above. Water intake was obtained from the day 2 dietary recall and was included in the sensitivity analysis. RESULTS: A total of 34,390 participants were included in the analysis. The multivariable logistic regression revealed that individuals who engaged in moderate PA for 30-60 minutes per day had a significant inverse association with the prevalence of kidney stones in the fully adjusted model (odds ratio=0.804, 95% confidence interval 0.700 to 0.923), while no more significant finding was observed for other PA parameters. Interaction and stratified analyses indicated no covariate modifying the association. The results above were robust in the sensitivity analysis. CONCLUSION: The duration of moderate PA (30-60 min/d) is inversely associated with the prevalence of kidney stones, while no more significant association was observed between other PA parameters (including patterns, intensity, duration, and frequency of vigorous PA, frequency of moderate PA) and kidney stones.

15.
Int J Mol Sci ; 25(7)2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38612723

RESUMEN

Bone morphogenetic protein 2 (BMP2) has been reported to regulate adipogenesis, but its role in porcine beige adipocyte formation remains unclear. Our data reveal that BMP2 is significantly induced at the early stages of porcine beige adipocyte differentiation. Additionally, supplementing rhBMP2 during the early stages, but not the late stages of differentiation, significantly enhances porcine SVF adipogenesis, thermogenesis, and proliferation. Furthermore, compared to the empty plasmid-transfected-SVFs, BMP2-overexpressed SVFs had the enhanced lipid accumulation and thermogenesis, while knockdown of BMP2 in SVFs exhibited the opposite effect. The RNA-seq of the above three types of cells revealed the enrichment of the annotation of thermogenesis, brown cell differentiation, etc. In addition, the analysis also highlights the significant enrichment of cell adhesion, the MAPK cascade, and PPARγ signaling. Mechanistically, BMP2 positively regulates the adipogenic and thermogenic capacities of porcine beige adipocytes by activating PPARγ expression through AKT/mTOR and MAPK signaling pathways.


Asunto(s)
Adipogénesis , Proteínas Proto-Oncogénicas c-akt , Porcinos , Animales , Adipogénesis/genética , Proteína Morfogenética Ósea 2/genética , PPAR gamma , Transducción de Señal , Serina-Treonina Quinasas TOR/genética
16.
Gastroenterology ; 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38583724

RESUMEN

BACKGROUND & AIMS: Benign ulcerative colorectal diseases (UCDs) such as ulcerative colitis, Crohn's disease, ischemic colitis, and intestinal tuberculosis share similar phenotypes with different etiologies and treatment strategies. To accurately diagnose closely related diseases like UCDs, we hypothesize that contextual learning is critical in enhancing the ability of the artificial intelligence models to differentiate the subtle differences in lesions amidst the vastly divergent spatial contexts. METHODS: White-light colonoscopy datasets of patients with confirmed UCDs and healthy controls were retrospectively collected. We developed a Multiclass Contextual Classification (MCC) model that can differentiate among the mentioned UCDs and healthy controls by incorporating the tissue object contexts surrounding the individual lesion region in a scene and spatial information from other endoscopic frames (video-level) into a unified framework. Internal and external datasets were used to validate the model's performance. RESULTS: Training datasets included 762 patients, and the internal and external testing cohorts included 257 patients and 293 patients, respectively. Our MCC model provided a rapid reference diagnosis on internal test sets with a high averaged area under the receiver operating characteristic curve (image-level: 0.950 and video-level: 0.973) and balanced accuracy (image-level: 76.1% and video-level: 80.8%), which was superior to junior endoscopists (accuracy: 71.8%, P < .0001) and similar to experts (accuracy: 79.7%, P = .732). The MCC model achieved an area under the receiver operating characteristic curve of 0.988 and balanced accuracy of 85.8% using external testing datasets. CONCLUSIONS: These results enable this model to fit in the routine endoscopic workflow, and the contextual framework to be adopted for diagnosing other closely related diseases.

17.
Cancer Immunol Immunother ; 73(5): 95, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38607586

RESUMEN

BACKGROUND: Homologous recombination deficiency (HRD), though largely uncharacterized in clear cell renal cell carcinoma (ccRCC), was found associated with RAD51 loss of expression. PBRM1 is the second most common mutated genes in ccRCC. Here, we introduce a HRD function-based PBRM1-RAD51 ccRCC classification endowed with diverse immune checkpoint blockade (ICB) responses. METHODS: Totally 1542 patients from four independent cohorts were enrolled, including our localized Zhongshan hospital (ZSHS) cohort and Zhongshan hospital metastatic RCC (ZSHS-mRCC) cohort, The Cancer Genome Atlas (TCGA) cohort and CheckMate cohort. The genomic profile and immune microenvironment were depicted by genomic, transcriptome data and immunohistochemistry. RESULTS: We observed that PBRM1-loss ccRCC harbored enriched HRD-associated mutational signature 3 and loss of RAD51. Dual-loss of PBRM1 and RAD51 identified patients hyper-sensitive to immunotherapy. This dual-loss subtype was featured by M1 macrophage infiltration. Dual-loss was, albeit homologous recombination defective, with high chromosomal stability. CONCLUSIONS: PBRM1 and RAD51 dual-loss ccRCC indicates superior responses to immunotherapy. Dual-loss ccRCC harbors an immune-desert microenvironment but enriched with M1 macrophages. Dual-loss ccRCC is susceptible to defective homologous recombination but possesses high chromosomal stability.


Asunto(s)
Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/terapia , Inmunoterapia , Neoplasias Renales/genética , Neoplasias Renales/terapia , Inestabilidad Cromosómica , Microambiente Tumoral , Recombinasa Rad51 , Proteínas de Unión al ADN/genética , Factores de Transcripción/genética
18.
J Nanobiotechnology ; 22(1): 152, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38575979

RESUMEN

Infected wound healing remains a challenging task in clinical practice due to several factors: (I) drug-resistant infections caused by various pathogens, (II) persistent inflammation that hinders tissue regeneration and (III) the ability of pathogens to persist intracellularly and evade antibiotic treatment. Microneedle patches (MNs), recognized for their effecacious and painless subcutaneous drug delivery, could greatly enhance wound healing if integrated with antibacterial functionality and tissue regenerative potential. A multifunctional agent with subcellular targeting capability and contained novel antibacterial components, upon loading onto MNs, could yield excellent therapeutic effects on wound infections. In this study, we sythesised a zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) loaded with low molecular weight fucoidan (Fu) and further coating by hyaluronic acid (HA), obtained a multifunctional HAZ@Fu NPs, which could hinders Methicillin-resistant Staphylococcus aureus (MRSA) growth and promotes M2 polarization in macrophages. We mixed HAZ@Fu NPs with photocrosslinked gelatin methacryloyl (GelMA) and loaded it into the tips of the MNs (HAZ@Fu MNs), administered to mice model with MRSA-infected full-thickness cutaneous wounds. MNs are able to penetrate the skin barrier, delivering HAZ@Fu NPs into the dermal layer. Since cells within infected tissues extensively express the HA receptor CD44, we also confirmed the HA endows the nanoparticles with the ability to target MRSA in subcellular level. In vitro and in vivo murine studies have demonstrated that MNs are capable of delivering HAZ@Fu NPs deep into the dermal layers. And facilitated by the HA coating, HAZ@Fu NPs could target MRSA surviving at the subcellular level. The effective components, such as zinc ions, Fu, and hyaluronic acid could sustainably released, which contributes to antibacterial activity, mitigates inflammation, promotes epithelial regeneration and fosters neovascularization. Through the RNA sequencing of macrophages post co-culture with HAZ@Fu, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis reveals that the biological functionalities associated with wound healing could potentially be facilitated through the PI3K-Akt pathway. The results indicate that the synergistic application of HAZ@Fu NPs with biodegradable MNs may serve as a significant adjunct in the treatment of infected wounds. The intricate mechanisms driving its biological effects merit further investigation.


Asunto(s)
Antiinfecciosos , Staphylococcus aureus Resistente a Meticilina , Polisacáridos , Infección de Heridas , Ratones , Animales , Ácido Hialurónico/farmacología , Fosfatidilinositol 3-Quinasas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Cicatrización de Heridas , Antiinfecciosos/farmacología , Infección de Heridas/tratamiento farmacológico , Inflamación
19.
Molecules ; 29(8)2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38675691

RESUMEN

The properties of supports (such as oxygen vacancies, oxygen species properties, etc.) significantly impact the anti-carbon ability due to their promotional effect on the activation of CO2 in dry reforming of methane (DRM). Herein, pyrochlore-type La2Ce2O7 compounds prepared using co-precipitation (CP), glycine nitrate combustion (GNC) and sol-gel (S-G) methods, which have highly thermal stability and unique oxygen mobility, are applied as supports to prepare Ni-based catalysts for DRM. The effect of the calcining temperature (500, 600 and 700 °C) on La2Ce2O7(CP) has also been investigated. Based on multi-technique characterizations, it is found that the synthesis method and calcination temperature can influence the particle size of the La2Ce2O7 support. Changes in particle size strongly modulate the pore volume, specific surface area and numbers of surface oxygen vacancies of the La2Ce2O7 support. As a result, the distribution of supported Ni components is affected due to the different metal-support interaction, thereby altering the activity of the catalysts for cracking CH4. Moreover, the supports' abilities to adsorb and activate CO2 are also adjusted accordingly, accelerating the removal of the carbon deposited on the catalysts. Finally, La2Ce2O7(CP 600) with an appropriate particle size exhibits the best catalytic activity and stability in DRM.

20.
Int J Biol Macromol ; 267(Pt 2): 131486, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38604420

RESUMEN

The molecular brush structures have been developed on cotton textiles for long-term and efficient broad-spectrum antimicrobial performances through the cooperation of alkyl-chain and quaternary ammonium sites. Results show that efficient antibacterial performances can be achieved by the regulation of the alkyl chain length and quaternary ammonium sites. The antibacterial efficiency of the optimized molecular brush structure of [3-(N,N-Dimethylamino)propyl]trimethoxysilane with cetyl modification on cotton textiles (CT-DM-16) can reach more than 99 % against both E. coli and S. aureus. Alkyl-chain grafting displayed significantly improvement in the antibacterial activity against S. aureus with (N,N-Diethyl-3-aminopropyl)trimethoxysilane modification on cotton textiles (CT-DE) based materials. The positive N sites and alkyl chains played important roles in the antibacterial process. Proteomic analysis reveals that the contributions of cytoskeleton and membrane-enclosed lumen in differentially expressed proteins have been increased for the S. aureus antibacterial process, confirming the promoted puncture capacity with alkyl-chain grafting. Theoretical calculations indicate that the positive charge of N sites can be enhanced through alkyl-chain grafting, and the possible distortion of the brush structure in application can further increase the positive charge of N sites. Uncovering the regulation mechanism is considered to be important guidance to develop novel and practical antibacterial materials.


Asunto(s)
Antibacterianos , Fibra de Algodón , Escherichia coli , Staphylococcus aureus , Textiles , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/farmacología , Silanos/química
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