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1.
Langmuir ; 40(23): 12207-12215, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38822806

RESUMEN

Photocatalytic ammonia synthesis (PAS) represents an emerging environmentally friendly approach to ammonia production. In this work, we employed Fe doping to modify the cocatalyst 1T MoS2, enhancing the active N2 sites on Fe-1T MoS2 by inducing defects on the surface of 1T MoS2. Afterward, Fe-1T MoS2 was loaded onto a hollow coral-like graphitic carbon nitride (CCN)/FeOCl composite. Under simulated sunlight, the efficiency of 5% Fe-1T MoS2@CCN/FeOCl (Fe-MCN/FeOCl) reached 367.62 µmol g-1 h-1, surpassing 1T MoS2@CCN(MCN) by 3.2 times, CCN by 16.9 times, and g-C3N4 by 32.5 times, where 5% means the doping amount of Fe in 1T MoS2. The good performance of Fe MCN/FeOCl should be attributed to the Fe doping in Fe-MCN/FeOCl which not only increases the separation efficiency of active sites and charge carriers, but also reduces the sample impedance significantly through the heterojunction formed between CCN and FeOCl. This work also presents a method for creating more efficient and stable photocatalysts for ammonia synthesis.

2.
J Environ Manage ; 365: 121504, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38908155

RESUMEN

In the face of escalating urban pluvial floods exacerbated by climate change, conventional roof systems fall short of effectively managing precipitation extremes. This paper introduces a smart predictive solution: the Smart Internal Drainage Roof (SIDR) system, which leverages forecasted data to enhance the mitigation of pluvial floods in Central Business District (CBD) areas. Unlike traditional approaches, SIDRs utilize a synergistic combination of Rule-based Control (RBC) and Model Predictive Control (MPC) algorithms, tailored to optimize the operational efficiency of both grey and green roofs. Within the examined 1.3 km2 area in Beijing, China, SIDRs, covering 11% of the site, decreased total flooded areas by 30%-50% and eliminated 60%-100% of high-risk zones during three actual events. Moreover, SIDRs streamlined outflow processes without extending discharge time and reduced flood duration at a high-risk underpass by more than half. The SIDR's distinct features, including a high control resolution of 5 min, integration with existing waterproofs, and advanced 2D dynamic runoff visualization, position it as a scalable and cost-efficient upgrade in urban flood resilience strategies.

3.
Adv Sci (Weinh) ; : e2402565, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38894600

RESUMEN

Light-harvesting is of vital importance for many events, such as photosynthesis. To efficiently gather and transfer solar energy, delicate antenna is needed, which has been achieved by algae and plants. However, construction of efficient light-harvesting systems using multiple, artificial building blocks is still challenging. Here, blue-emitting organosilicone capsules containing carbon dots (denoted as CDs-Si) in ethanol are prepared, which can effectively transfer energy to green-emitting (silicone-functionalized bodipy, Si-BODIPY) or red-emitting (rhodamine b, RhB) dyes. In ternary system, sequential Förster resonance energy transfer from CDs-Si to Si-BODIPY and further to RhB is realized, which is accompanied with a less pronounced, parallel FRET directly from CDs-Si to RhB. The overall efficiency of energy transfer reaches ≈86%. By introducing a photoswitch (1,2-bis(2,4-dimethyl-5-phenyl-3-thienyl)-3,3,4,4,5,5-hexafluoro-1-cyclopentene, DAE) to the system, the emission becomes switchable under alternative illumination with UV and visible light, leading to the formation of smart artificial light-harvesting systems.

4.
J Immunother ; 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38800996

RESUMEN

RAD51, a key recombinase that catalyzes homologous recombination (HR), is commonly overexpressed in multiple cancers. It is curial for DNA damage repair (DDR) to maintain genomic integrity which could further determine the therapeutic response. Herein, we attempt to explore the clinical value of RAD51 in therapeutic guidance in muscle-invasive bladder cancer (MIBC). In this retrospective study, a total of 823 patients with MIBC were included. Zhongshan hospital (ZSHS) cohort (n=134) and The Cancer Genome Atlas-Bladder Cancer (TCGA-BLCA) cohort (n=391) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n=298) was utilized to interrogate the predictive efficacy of RAD51 status to programmed cell death ligand-1 (PD-L1) blockade. In addition, the association of RAD51 with genomic instability and tumor immune contexture was investigated. Patients with RAD51 overexpression were more likely to benefit from both platinum-based chemotherapy and immunotherapy rather than RAD51-low patients. The TMB high PD-L1 high RAD51 high subgroup possessed the best clinical benefits from PD-L1 blockade. RAD51-high tumors featured by genomic instability were correlated to highly inflamed and immunogenic contexture with activated immunotherapeutic pathway in MIBC. RAD51 could serve as a prognosticator for treatment response to platinum-based chemotherapy and PD-L1 inhibitor in MIBC patients. Besides, it could also improve the predictive efficacy of TMB and PD-L1.

5.
World J Gastroenterol ; 30(19): 2564-2574, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38817663

RESUMEN

BACKGROUND: Cell division cyclin 25C (CDC25C) is a protein that plays a critical role in the cell cycle, specifically in the transition from the G2 phase to the M phase. Recent research has shown that CDC25C could be a potential therapeutic target for cancers, particularly for hepatocellular carcinoma (HCC). However, the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely understood. AIM: To explore the impact of CDC25C on cell proliferation and apoptosis, as well as its regulatory mechanisms in HCC development. METHODS: Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences (LV-CDC25C shRNA) to knock down CDC25C. Subsequently, a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in vivo. Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays, respectively. The expression of endoplasmic reticulum (ER) stress-related molecules (glucose-regulated protein 78, X-box binding protein-1, and C/EBP homologous protein) was measured in both cells and subcutaneous xenografts using quantitative real-time PCR (qRT-PCR) and western blotting. Additionally, apoptosis was investigated using flow cytometry, qRT-PCR, and western blotting. RESULTS: CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction. A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in mice. CDC25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response, ultimately promoting ER stress-induced apoptosis in HCC cells. CONCLUSION: The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.


Asunto(s)
Apoptosis , Carcinoma Hepatocelular , Movimiento Celular , Proliferación Celular , Estrés del Retículo Endoplásmico , Técnicas de Silenciamiento del Gen , Neoplasias Hepáticas , Ratones Endogámicos C57BL , Fosfatasas cdc25 , Animales , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Fosfatasas cdc25/metabolismo , Fosfatasas cdc25/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Línea Celular Tumoral , Ratones , Humanos , ARN Interferente Pequeño/metabolismo , Masculino , Regulación Neoplásica de la Expresión Génica , Ensayos Antitumor por Modelo de Xenoinjerto , Carcinogénesis/genética
6.
Nat Commun ; 15(1): 4458, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38796508

RESUMEN

The impact of interbasin linkage on the weather/climate and ecosystems is significantly broader and profounder than that of only appearing in an individual basin. Here, we reveal that a decadal linkage of sea surface temperature (SST) has emerged between western Australian coast and western-central tropical Pacific since 1985, associated with continuous intensification of decadal variabilities (8-16 years). The rapid SST changes in both tropical Indian Ocean and Indo-Pacific warm pool in association to greenhouse gases and volcanoes are emerging factors resulting in enhanced decadal co-variabilities between these two regions since 1985. These SST changes induce enhanced convection variability over the Maritime Continent, leading to stronger easterlies in the western-central tropical Pacific during the warm phase off western Australian coast. The above changes bring about cooling in the western-central tropical Pacific and strengthened Leeuwin Current and anomalous cyclonic wind off western Australian coast, and ultimately resulting in enhanced coupling between these two regions. Our results suggest that enhanced decadal interbasin connections can offer further understanding of decadal changes under future warmer conditions.

7.
Chem Asian J ; 19(11): e202400292, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38639574

RESUMEN

Cu catalysts with different compositions and different Cu and promoter contents were prepared by precipitation-gel method and studied for the selective hydrogenation of syngas or biomass-based diethyl malonate (DEM) to valuable 1,3-propanediol (1,3-PDO). The Ga-promoted 70Cu6Ga/SiO2 catalyst was found to exhibit the highest catalytic performance, achieving 100 % DEM conversion and 76.6 % 1,3-PDO selectivity under reaction conditions of 160 °C and 8 MPa H2. The 70Cu6Ga/SiO2 bimetallic catalyst also presented obviously better stability than that of the monometallic 70Cu/SiO2 catalyst in a continuous flow reactor over 180 h time-on stream. Characterization results showed that the incorporation of Ga increased the interaction between Cu and Ga species, hindered the full reduction of Cu2+ species, and thus increased the proportion of Cu+ and the number of Lewis acidic sites on the catalyst surface. The synergistic effect between Cu0 and Cu+ enhanced the adsorption and activation of ester carbonyl groups and their subsequent hydrogenation, eventually contributed to the outstanding performances of the CuGa/SiO2 bimetallic catalysts.

8.
Artículo en Inglés | MEDLINE | ID: mdl-38603891

RESUMEN

The specific enrichment of multi-phosphopeptides in the presence of non-phosphopeptides and mono-phosphopeptides was still a challenge for phosphoproteomics research. Most of these enrichment materials relied on Zn, Ti, Sn, and other rare precious metals as the bonding center to enrich multi-phosphopeptides while ignoring the use of common metal elements. The addition of rare metals increased the cost of the experiment, which was not conducive to their large-scale application in biomedical proteomics laboratories. In addition, multiple high-speed centrifugation steps also resulted in the loss of low-abundance multi-phosphopeptides in the treatment procedure of biological samples. This study proposed the use of calcium, a common element, as the central bonding agent for synthesizing magnetic calcium phosphate materials (designated as CaP-Fe3O4). These materials aim to capture multi-phosphopeptides and identifying phosphorylation sites. The current results demonstrate that CaP-Fe3O4 exhibited excellent selection specificity, high sensitivity, and stability in the enrichment of multi-phosphopeptides and the identification of phosphorylation sites. Additionally, the introduction of magnetic separation not only reduced the time required for multi-phosphopeptides enrichment but also prevented the loss of these peptides during high-speed centrifugation. These findings contribute to the widespread application and advancement of phosphoproteomics research.


Asunto(s)
Fosfatos de Calcio , Fosfopéptidos , Fosfopéptidos/análisis , Fosfopéptidos/aislamiento & purificación , Fosfopéptidos/química , Fosfatos de Calcio/química , Humanos , Proteómica/métodos , Fosforilación , Espectrometría de Masas en Tándem/métodos
9.
Cell Mol Biol (Noisy-le-grand) ; 70(4): 202-211, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38678604

RESUMEN

DNA replication and sister chromatid cohesion 1 (DSCC1) exerts various functions including sister chromatid cohesion. DSCC1 overexpression plays an important role in cancer development, such as in colorectal, breast, and hepatocellular cancers. The specific role of DSCC1 in tumor progression remains largely unknown, necessitating a pan-cancer investigation to understand the potential function of DSCC1 in various cancers. In this study, we obtained data on physiological conditions, transcriptional expression, survival prognosis, genomic alteration, genomic instability, enriched pathways, immune infiltration, and immunotherapy from The Cancer Genome Atlas, The Genotype-Tissue Expression, cBioPortal, and other publicly available databases to systematically characterize the oncogenic and immunological roles of DSCC1 in 33 different cancers. We found that DSCC1 expression was upregulated at both mRNA and protein levels in various cancers. Additionally, DSCC1 expression was associated with higher tumor stage and grade in specific cancers. DSCC1 was a potential pan-cancer prognostic biomarker for its close association with patient prognosis and a diagnostic biomarker for its high predictive value in distinguishing tumor tissues from normal tissues. DSCC1 was universally amplified across different cancers and tightly associated with genomic instability. Moreover, DSCC1 had a close relationship with tumor immune cell infiltration; thus, it could be used as a potential biomarker for predicting the response and survival of patients with cancer who receive immune checkpoint blockade treatment. To sum up, our study revealed that DSCC1 is a promising target for tumor therapy.


Asunto(s)
Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Inestabilidad Genómica , Neoplasias , Proteínas Nucleares , Humanos , Biomarcadores de Tumor/genética , Inmunoterapia , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/diagnóstico , Pronóstico , Proteínas Nucleares/genética , Proteínas Nucleares/inmunología
10.
J Transl Med ; 22(1): 220, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38429732

RESUMEN

BACKGROUND: Targeting CD47/SIRPα axis has emerged as a promising strategy in cancer immunotherapy. Despite the encouraging clinical efficacy observed in hematologic malignancies through CD47-SIRPα blockade, there are safety concerns related to the binding of anti-CD47 antibodies to CD47 on the membrane of peripheral blood cells. METHODS: In order to enhance the selectivity and therapeutic efficacy of the antibody, we developed a humanized anti-CD47 monoclonal antibody called Gentulizumab (GenSci059). The binding capacity of GenSci059 to CD47 was evaluated using flow cytometry and surface plasmon resonance (SPR) methods, the inhibitory effect of GenSci059 on the CD47-SIRPα interaction was evaluated through competitive ELISA assays. The anti-tumor activity of GenSci059 was assessed using in vitro macrophage models and in vivo patient-derived xenograft (PDX) models. To evaluate the safety profile of GenSci059, binding assays were conducted using blood cells. Additionally, we investigated the underlying mechanisms contributing to the weaker binding of GenSci059 to erythrocytes. Finally, toxicity studies were performed in non-human primates to assess the potential risks associated with GenSci059. RESULTS: GenSci059 displayed strong binding to CD47 in both human and monkey, and effectively inhibited the CD47-SIRPα interaction. With doses ranging from 5 to 20 mg/kg, GenSci059 demonstrated potent inhibition of the growth of subcutaneous tumor with the inhibition rates ranged from 30.3% to complete regression. Combination of GenSci059 with 2.5 mg/kg Rituximab at a dose of 2.5 mg/kg showed enhanced tumor inhibition compared to monotherapy, exhibiting synergistic effects. GenSci059 exhibited minimal binding to hRBCs compared to Hu5F9-G4. The binding of GenSci059 to CD47 depended on the cyclization of N-terminal pyroglutamic acid and the spatial conformation of CD47, but was not affected by its glycosylation modifications. A maximum tolerated dose (MTD) of 450 mg/kg was observed for GenSci059, and no significant adverse effects were observed in repeated dosages up to 10 + 300 mg/kg, indicating a favorable safety profile. CONCLUSION: GenSci059 selectively binds to CD47, effectively blocks the CD47/SIRPα axis signaling pathway and enhances the phagocytosis effects of macrophages toward tumor cells. This monoclonal antibody demonstrates potent antitumor activity and exhibits a favorable safety profile, positioning it as a promising and effective therapeutic option for cancer.


Asunto(s)
Antígeno CD47 , Neoplasias , Animales , Humanos , Neoplasias/patología , Fagocitosis , Macrófagos/metabolismo , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Inmunoterapia/métodos , Modelos Animales de Enfermedad , Antígenos de Diferenciación/metabolismo , Antígenos de Diferenciación/farmacología , Antígenos de Diferenciación/uso terapéutico
11.
J Org Chem ; 89(7): 4979-4989, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38536713

RESUMEN

Two efficient and convenient methods for the synthesis of 3-alkylideneoxindoles are described in this paper. The InCl3/TfOH-mediated tandem Knoevenagel condensation-deacylation sequence of various 2-oxindoles with 1,3-diones or acetoacetate furnished 3-alkylideneoxindoles in satisfactory to excellent yields (up to >99% yield). Employing the reaction system, the condensation of 2-oxindoles with ketones or aldehydes also proceeded smoothly to produce 3-alkylideneoxindoles. This protocol can be amenable to scale up. The effect of acids on this condensation reaction and intermolecular competition experiments were investigated to understand the aspect of the reaction.

12.
Cancer Immunol Immunother ; 73(4): 66, 2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38430246

RESUMEN

BACKGROUND: Luminal and Basal are the primary intrinsic subtypes of muscle-invasive bladder cancer (MIBC). The presence of CD8+ T cells infiltration holds significant immunological relevance, potentially influencing the efficacy of antitumor responses. This study aims to synergize the influence of molecular subtypes and CD8+ T cells infiltration in MIBC. METHODS: This study included 889 patients with MIBC from Zhongshan Hospital, The Cancer Genome Atlas, IMvigor210 and NCT03179943 cohorts. We classified the patients into four distinct groups, based on the interplay of molecular subtypes and CD8+ T cells and probed into the clinical implications of these subgroups in MIBC. RESULTS: Among patients with Luminal-CD8+Thigh tumors, the confluence of elevated tumor mutational burden and PD-L1 expression correlated with a heightened potential for positive responses to immunotherapy. In contrast, patients featured by Luminal-CD8+Tlow displayed a proclivity for deriving clinical advantages from innovative targeted interventions. The Basal-CD8+Tlow subgroup exhibited the least favorable three-year overall survival outcome, whereas their Basal-CD8+Thigh counterparts exhibited a heightened responsiveness to chemotherapy. CONCLUSIONS: We emphasized the significant role of immune-molecular subtypes in shaping therapeutic approaches for MIBC. This insight establishes a foundation to refine the process of selecting subtype-specific treatments, thereby advancing personalized interventions for patients.


Asunto(s)
Linfocitos T CD8-positivos , Neoplasias de la Vejiga Urinaria , Humanos , Pronóstico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Biomarcadores de Tumor/genética , Músculos/patología
13.
Cancer Med ; 13(4): e6962, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38457207

RESUMEN

BACKGROUND: Though programmed cell death-ligand 1 (PD-L1) has been used in predicting the efficacy of immune checkpoint blockade (ICB), it is insufficient as a single biomarker. As a key effector of an intrinsically mutagenic microhomology-mediated end joining (MMEJ) pathway, DNA polymerase theta (POLQ) was overexpressed in various malignancies, whose expression might have an influence on genomic stability, therefore altering the sensitivity to chemotherapy and immunotherapy. METHODS: A total of 1304 patients with muscle-invasive bladder cancer (MIBC) from six independent cohorts were included in this study. The Zhongshan Hospital (ZSHS) cohort (n = 134), The Cancer Genome Atlas (TCGA) cohort (n = 391), and the Neo-cohort (n = 148) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n = 234) and the UNC-108 cohort (n = 89) were used for the assessment of immunotherapeutic response. In addition, the relationship between POLQ and the immune microenvironment was assessed, and GSE32894 (n = 308) was used only for the evaluation of the immune microenvironment. RESULTS: We identified POLQhigh PD-L1high patients could benefit more from immunotherapy and platinum-based chemotherapy. Further analysis revealed that high POLQ expression was linked to chromosome instability and higher tumor mutational burden (TMB), which might elicit the production of neoantigens. Further, high POLQ expression was associated with an active tumor immune microenvironment with abundant infiltration of immune effector cells and molecules. CONCLUSIONS: The study demonstrated that high POLQ expression was correlated with chromosome instability and antitumor immune microenvironment in MIBC, and the combination of POLQ and PD-L1 could be used as a superior companion biomarker for predicting the efficacy of immunotherapy.


Asunto(s)
Antígeno B7-H1 , Neoplasias de la Vejiga Urinaria , Humanos , Antígeno B7-H1/metabolismo , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapia , Neoplasias de la Vejiga Urinaria/metabolismo , Biomarcadores , Inmunoterapia , Inestabilidad Cromosómica , Músculos/metabolismo , Músculos/patología , Microambiente Tumoral
14.
Sci Total Environ ; 924: 171700, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38490408

RESUMEN

The speciation, bioaccumulation, and toxicity of the newly deposited atmospheric heavy metals in the soil-earthworm (Eisenia fetida) system were investigated by a fully factorial atmospheric exposure experiment using soils exposed to 0.8-year and 1.8-year atmospheric depositions. The results shown that the newly deposited metals (Cu, Cd, and Pb) primarily accumulated in the topsoil (0-6 cm) and were present as the highly bioavailable speciation. They can migrate further to increase the concentrations of Cu, Cd, and Pb in soil solution of the deeper layer (at 10 cm) by 12 %-436 %. Earthworms tended to preferentially accumulate the newly deposited metals, which contributed 10 %-61 % of Cu, Cd, and Pb in earthworms. Further, for the unpolluted and moderately polluted soils, the newly deposited metals induced the significant oxidative stress in earthworms, resulting in significant increases in antioxidant enzyme activities (SOD, CAT, and GSH-Px). No significant differences were observed in the levels of heavy metals in soil solutions, bioaccumulation, and enzyme activities in earthworms exposed to 0.8-year and 1.8-year depositions, indicating the bioavailability of atmospheric metals deposited into soils was rapidly decreased with time. This study highlights the high bioaccumulation and toxicity of heavy metals to earthworm from the new atmospheric deposition during the earthworm growing period.


Asunto(s)
Metales Pesados , Oligoquetos , Contaminantes del Suelo , Animales , Cobre/toxicidad , Cobre/análisis , Cadmio , Suelo , Bioacumulación , Plomo , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Metales Pesados/toxicidad , Metales Pesados/análisis
15.
RSC Adv ; 14(14): 10034-10038, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38533100

RESUMEN

We introduce a mild method for the ligand-promoted copper-catalyzed coupling of 2-halophenol to construct DBDO using cost-effective copper salts, ligands, and alkaline reagents. This method cleverly makes 2-bromophenol complete the Ullman reaction twice, achieves efficient C-O(S) bond coupling and intermolecular cyclization, and yields high amounts of oxygen(sulfur)-containing six-membered ring products. Less reactive 2-chlorophenol was also applied in this catalytic system. The application range of the copper-amide catalytic system was further expanded. Moreover, the success of a gram-scale reaction demonstrated that this operationally simple process is scalable.

16.
Animal Model Exp Med ; 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38477441

RESUMEN

BACKGROUND: Medulloblastoma (MB) is one of the most common malignant brain tumors that mainly affect children. Various approaches have been used to model MB to facilitate investigating tumorigenesis. This study aims to compare the recapitulation of MB between subcutaneous patient-derived xenograft (sPDX), intracranial patient-derived xenograft (iPDX), and genetically engineered mouse models (GEMM) at the single-cell level. METHODS: We obtained primary human sonic hedgehog (SHH) and group 3 (G3) MB samples from six patients. For each patient specimen, we developed two sPDX and iPDX models, respectively. Three Patch+/- GEMM models were also included for sequencing. Single-cell RNA sequencing was performed to compare gene expression profiles, cellular composition, and functional pathway enrichment. Bulk RNA-seq deconvolution was performed to compare cellular composition across models and human samples. RESULTS: Our results showed that the sPDX tumor model demonstrated the highest correlation to the overall transcriptomic profiles of primary human tumors at the single-cell level within the SHH and G3 subgroups, followed by the GEMM model and iPDX. The GEMM tumor model was able to recapitulate all subpopulations of tumor microenvironment (TME) cells that can be clustered in human SHH tumors, including a higher proportion of tumor-associated astrocytes and immune cells, and an additional cluster of vascular endothelia when compared to human SHH tumors. CONCLUSIONS: This study was the first to compare experimental models for MB at the single-cell level, providing value insights into model selection for different research purposes. sPDX and iPDX are suitable for drug testing and personalized therapy screenings, whereas GEMM models are valuable for investigating the interaction between tumor and TME cells.

17.
BMC Cancer ; 24(1): 321, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38454345

RESUMEN

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioradioterapia , Quimioterapia de Consolidación , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/patología , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase III como Asunto , Estudios de Equivalencia como Asunto
18.
J Pathol ; 263(2): 139-149, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38380548

RESUMEN

TP53 mutation is one of the most common genetic alterations in urothelial carcinoma (UrCa), and heterogeneity of TP53 mutants leads to heterogeneous clinical outcomes. This study aimed to investigate the clinical relevance of specific TP53 mutations in UrCa. In this study, a total of eight cohorts were enrolled, along with matched clinical annotation. TP53 mutations were classified as disruptive and nondisruptive according to the degree of disturbance of p53 protein function and structure. We evaluated the clinical significance of TP53 mutations in our local datasets and publicly available datasets. The co-occurring events of TP53 mutations in UrCa, along with their therapeutic indications, functional effects, and the tumor immune microenvironment, were also investigated. TP53 mutations were identified in 49.7% of the UrCa patients. Within this group, 25.1% of patients carried TP53Disruptive mutations, a genetic alteration correlated with a significantly poorer overall survival (OS) when compared to individuals with TP53Nondisruptive mutations and those with wild-type TP53. Significantly, patients with TP53Disruptive mutations exhibit an increased probability of responding favorably to PD-1/PD-L1 blockade and chemoimmunotherapy. Meanwhile, there was no noteworthy distinction in OS among patients with varying TP53 mutation status who underwent chemotherapy. Samples with TP53Disruptive mutations showed an enriched APOBEC- and POLE-related mutational signature, as well as an elevated tumor mutation burden. The sensitivity to immunotherapy in tumors carrying TP53Disruptive mutation may be attributed to the inflamed tumor microenvironment characterized by increased CD8+T cell infiltration and interferon-gamma signaling activation. In conclusion, UrCa patients with TP53Disruptive mutations have shown reduced survival rates, yet they may respond well to PD-1/PD-L1 blockade therapy and chemoimmunotherapy. By distinguishing specific TP53 mutations, we can improve risk stratification and offer personalized genomics-guided therapy to UrCa patients. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Asunto(s)
Antígeno B7-H1 , Inhibidores de Puntos de Control Inmunológico , Mutación , Receptor de Muerte Celular Programada 1 , Microambiente Tumoral , Proteína p53 Supresora de Tumor , Neoplasias de la Vejiga Urinaria , Humanos , Proteína p53 Supresora de Tumor/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/inmunología , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/inmunología , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/mortalidad , Biomarcadores de Tumor/genética , Masculino , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Persona de Mediana Edad
19.
Sensors (Basel) ; 24(3)2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38339655

RESUMEN

During a heavy traffic flow featuring a substantial number of vehicles, the data reflecting the strain response of asphalt pavement under the vehicle load exhibit notable fluctuations with abnormal values, which can be attributed to the complex operating environment. Thus, there is a need to create a real-time anomalous-data diagnosis system which could effectively extract dynamic strain features, such as peak values and peak separation from the large amount of data. This paper presents a dynamic response signal data analysis method that utilizes the DBSCAN clustering algorithm and the findpeaks function. This method is designed to analyze data collected by sensors installed within the pavement. The first step involves denoising the data using low-pass filters and other techniques. Subsequently, the DBSCAN algorithm, which has been improved using the K-Dist method, is used to diagnose abnormal data after denoising. The refined findpeaks function is further implemented to carry out the adaptive feature extraction of the denoised data which is free from anomalies. The enhanced DBSCAN algorithm is tested via simulation and illustrates its effectiveness while detecting abnormal data in the road dynamic response signal. The findpeaks function enables the relatively accurate identification of peak values, thus leading to the identification of strain signal peaks of complex multi-axle lorries. This study is valuable for efficient data processing and effective information utilization in pavement monitoring.

20.
Int J Biol Macromol ; 263(Pt 2): 130449, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38423422

RESUMEN

The electrochemical performance of polyaniline-based all-gel-state supercapacitor (AGSSC) is significantly depended on the dispersity and mass loaded of polyaniline (PANI). In this manuscript, inspired by the properties of surfactant, sodium dodecylbenzene sulfonate (SDBS) was introduced to prepare various PANI-polyacrylamide/sodium alginate/SDBS (PANIy-PSSx) AGSSCs. With presence of SDBS, the electrochemical performance of PANIy-PSSx AGSSCs was greatly improved, displaying a trend of initial rise and then decrease with increasing concentration of SDBS from 0 to 0.75 wt%. As the content of SDBS was 0.5 wt%, the resulting PANI1.0-PSS0.5 AGSSC displayed the optimum electrochemical properties with area capacitance and energy density of 913.79 mF/cm2 and 81.23 µWh/cm2, respectively. The capacitance rate of PANI1.0-PSS0.5 AGSSC was still more than 93 % after 2000 cycles of sequential CV scans at the scan rate of 200 mV/s. These data were greatly higher than many reported PANI-based AGSSCs. Moreover, the resultant PANI1.0-PSS0.5 AGSSC could maintain high electrochemical performance even after various operations, such as compression, puncture, fluctuating temperature, bending situations and various voltage windows and series-parallel connections. The resultant PANI1.0-PSS0.5 AGSSC had the wide potentials to satisfy the real application requirements. This study offered a facile strategy for design and preparation of flexible supercapacitor with excellent electrochemical performance.


Asunto(s)
Resinas Acrílicas , Compuestos de Anilina , Lipoproteínas , Tensoactivos , Alginatos , Hidrogeles
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