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1.
Angew Chem Int Ed Engl ; : e202405868, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977413

RESUMO

Consequences of intramolecular ionic interactions in determining the reactivity of functional groups are of interest because they provide insights into how nature deploys seemingly reactive functionalities to be rather ubiquitous. Of specific interest are the quaternary ammonium ions in lipids. In this work, we investigate the effect of intramolecular electrostatic interactions in zwitterionic functionalities by judiciously incorporating them as leaving groups at the α-position of an α,ß-unsaturated ester-based lipid headgroup. We find that electrostatic stabilization indeed plays a critical role in both the reaction kinetics with nucleophiles and the thermodynamics of lipid formation. We further leverage these findings to fabricate both triggerable assembly and disassembly of liposomal supramolecular assemblies in the presence of nucleophiles.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38833045

RESUMO

To investigate noninvasive pressure-strain loop (PSL) combined with two-dimensional speck tracking imaging and left ventricular pressure measurement in the evaluation of cardiac function changes in anemia of prematurity (AOP) with different modes of respiratory support, and to explore its value in detecting subclinical myocardial injury in preterm infants. This retrospective study included 79 preterm infants with anemia, according to different modes of respiratory support, who were divided into invasive respiratory support group (39 cases) and noninvasive respiratory support group (40 cases). A control group of 40 nonanemic preterm infants with matched age, sex, and gestational age were also included. Complete echocardiography was performed for each included infant. There are PSL parameters that used to evaluate cardiac function, including global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) among the three groups were compared. Compared with the control group, the value of GWI, GCW, and GWE were significantly lower and GWW was higher in the AOP groups (P < 0.05), and GWI, GCW and GWE were much significantly lower in the invasive respiratory support group than in the noninvasive respiratory support group (P < 0.05). There was no significant difference in GLS among the three groups (P > 0.05). Noninvasive PSL analysis can quantitatively assess myocardial work in AOP with different respiratory support, which is more sensitive than other conventional echocardiographic indices. This technique may provide a new method for monitoring subclinical myocardial injury with AOP.

3.
Food Res Int ; 190: 114627, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38945580

RESUMO

The effect of varying proportions (w/w) of natural aromatic extract of black tea (NAEBT) with pre-emulsification on the water-holding capacity (WHC) of pork meat batter was investigated. The addition of NAEBT significantly reduced the cooking loss (CL) of pork meat batter from 23.95 % to 18.30 % (P < 0.05). Furthermore, NAEBT with pre-emulsification significantly improved the color stability and increased the springiness (P < 0.05). The results of TBARS and carbonyls indicated that NAEBT with pre-emulsification significantly alleviated oxidative damage to proteins (P < 0.05), resulting in an increased level of ß-sheet (P < 0.05), as confirmed by FT-IR analysis. As a result, the water mobility of pork meat batter was restricted (P < 0.05), resulting in an increase in the energy storage modulus (P < 0.05) and a decrease in the pore size. In summary, the WHC of pork meat batter was improved by the antioxidant effect of the NAEBT.


Assuntos
Antioxidantes , Produtos da Carne , Extratos Vegetais , Carne de Porco , Chá , Água , Água/química , Extratos Vegetais/química , Carne de Porco/análise , Animais , Chá/química , Produtos da Carne/análise , Antioxidantes/análise , Suínos , Culinária , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Espectroscopia de Infravermelho com Transformada de Fourier
4.
Inorg Chem ; 63(19): 8919-8924, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38698558

RESUMO

The introduction of transition metal (TM) ions into polyoxometalates (POMs) cannot only bring about interesting structural diversities but also enable changes in properties. However, TM-containing Silverton-type polyoxomolybdates are still lacking in terms of structural diversity and application development. Herein, two Zn(II)-containing Silverton-type {UMo12O42}-based polyoxomolybdates, H1.89Na4.11(H2O)9Zn[UMo12O42]·4.5H2O (Zn-1) and H1.8Na4.2(H2O)12Zn[UMo12O42] (Zn-2) were hydrothermally synthesized, demonstrating a practical strategy to assembly of TM-containing Silverton-type POMs. Zn-1 is proven to be an excellent and recyclable heterogeneous catalyst in cross-dehydrogenation coupling of 1,4-naphthoquinones with amines reactions, and a series of 2-amino-1,4-naphthoquinones with potential medicinal value have been constructed.

5.
Nat Commun ; 15(1): 3884, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719909

RESUMO

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.


Assuntos
Antígeno B7-1 , Antígeno B7-H1 , Vesículas Extracelulares , Receptor de Morte Celular Programada 1 , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Humanos , Antígeno B7-1/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Animais , Camundongos , Linhagem Celular Tumoral , Feminino , Neoplasias/imunologia , Neoplasias/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Tolerância Imunológica , Camundongos Endogâmicos C57BL , Masculino , Microambiente Tumoral/imunologia
6.
J Int Med Res ; 52(4): 3000605241234574, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38597095

RESUMO

Blood-disseminated Aspergillus spondylitis in immunocompetent individuals is rare. The clinical, imaging, and pathological manifestations of this condition are not specific. Therefore, this disease is prone to misdiagnosis and a missed diagnosis. Systemic antifungal therapy is the main treatment for Aspergillus spondylitis. We report a case of blood-disseminated Aspergillus versicolor spondylitis in a patient with normal immune function. The first antifungal treatment lasted for 4 months, but Aspergillus spondylitis recurred a few months later. A second antifungal treatment course was initiated for at least 1 year, and follow-up has been ongoing. Currently, there has been no recurrence.


Assuntos
Aspergilose , Espondilartrite , Espondilite , Humanos , Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergillus , Espondilite/diagnóstico por imagem , Espondilite/tratamento farmacológico
7.
Oral Dis ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424736

RESUMO

OBJECTIVES: Ameloblastoma (AM), a locally aggressive tumor with extensive growth capacity, causes significant damage to the jaw and affects facial appearance. Although the high prevalence of BRAF V600E mutation in AM is known, its specific impacts on patients with AM remain unclear. Thus, the present study investigated the role of BRAF V600E mutation, thereby focusing on its impact on AM invasion and growth. MATERIALS AND METHODS: Immunohistochemical analysis was used to compare BRAF V600E, MMP2, MMP9, and Ki-67 expressions in AM (n = 49), normal oral mucosa (NOM) (n = 10), and odontogenic keratocyst (OKC) (n = 15) tissues. AM was further classified according to the presence or absence of BRAF V600E. The relationship between BRAF V600E and invasion as well as growth was evaluated. In addition, correlation analysis was performed using immunohistochemistry and confirmed via double-labeling immunofluorescence. Finally, comparative analyses using mass spectrometry, immunohistochemistry, and immunofluorescence were performed to explore and identify underlying mechanisms. RESULTS: AM exhibited a higher incidence of BRAF V600E mutation than NOM and OKC. BRAF V600E expression was positively correlated with the invasion-associated proteins MMP2 and MMP9 and the growth-related protein Ki-67. Proteomic data revealed that BRAF V600E primarily activates the MAPK signaling pathway in AM, particularly driving the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). CONCLUSIONS: In summary, the findings suggested that the BRAF V600E mutation enhances the invasion and growth abilities of AM via the MAPK/ERK signaling pathway. Thus, targeting BRAF V600E or the MAPK/ERK pathway may be a potential AM therapy.

8.
J Phys Chem A ; 128(12): 2457-2471, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38382058

RESUMO

Luminescent organic semiconducting doublet-spin radicals are unique and emergent optical materials because their fluorescent quantum yields (Φfl) are not compromised by the spin-flipping intersystem crossing (ISC) into a dark high-spin state. The multiconfigurational nature of these radicals challenges their electronic structure calculations in the framework of single-reference density functional theory (DFT) and introduces room for method improvement. In the present study, we extended our earlier development of ML-ωPBE [J. Phys. Chem. Lett., 2021, 12, 9516-9524], a range-separated hybrid (RSH) exchange-correlation (XC) functional constructed using the stacked ensemble machine learning (SEML) algorithm, from closed-shell organic semiconducting molecules to doublet-spin organic semiconducting radicals. We assessed its performance for a new test set of 64 doublet-spin radicals from five categories while placing all previously compiled 3926 closed-shell molecules in the new training set. Interestingly, ML-ωPBE agrees with the nonempirical OT-ωPBE functional regarding the prediction of the molecule-dependent range-separation parameter (ω), with a small mean absolute error (MAE) of 0.0197 a0-1, but saves the computational cost by 2.46 orders of magnitude. This result demonstrates an outstanding domain adaptation capacity of ML-ωPBE for diverse organic semiconducting species. To further assess the predictive power of ML-ωPBE in experimental observables, we also applied it to evaluate absorption and fluorescence energies (Eabs and Efl) using linear-response time-dependent DFT (TDDFT), and we compared its behavior with nine popular XC functionals. For most radicals, ML-ωPBE reproduces experimental measurements of Eabs and Efl with small MAEs of 0.299 and 0.254 eV, only marginally different from those of OT-ωPBE. Our work illustrates a successful extension of the SEML framework from closed-shell molecules to doublet-spin radicals and will open the venue for calculating optical properties for organic semiconductors using single-reference TDDFT.

9.
Anal Chem ; 96(6): 2658-2665, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38311857

RESUMO

Liquid biopsy is of great significance in tumor early diagnosis and treatment stratification. PD-L1-positive small extracellular vesicles (PD-L1+ sEVs) are closely related to tumor growth and immunotherapy response, which are considered valuable liquid biopsy biomarkers. In contrast to conventional in vitro detection, in vivo detection has the ability to improve the detection efficiency and enable continuous or real-time dynamic monitoring. However, in vivo detection of PD-L1+ sEVs has multiple difficulties, such as high cell background, complex blood environments, and lack of a specific and stable detection method. Herein, the in vivo detection of PD-L1+ sEVs method was constructed, which efficiently separated sEVs based on the microfluidic device and quantitatively analyzed PD-L1+ sEVs by aptamer recognition and hybridization chain reaction. The concentration of PD-L1+ sEVs was continuously monitored, and significant differences at different stages of tumor as well as a correlation with tumor volume were found. Diseased and healthy individuals could also be effectively distinguished based on the concentration of PD-L1+ sEVs. The method with good stability, biocompatibility, and detection performance provided a powerful means for in vivo detection of PD-L1+ sEVs, contributing to the clinical diagnosis and treatment of tumor.


Assuntos
Vesículas Extracelulares , Neoplasias , Humanos , Antígeno B7-H1 , Neoplasias/diagnóstico , Biópsia Líquida , Dispositivos Lab-On-A-Chip
10.
Klin Padiatr ; 236(1): 5-10, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37678408

RESUMO

OBJECTIVES: Congenital pyriform sinus fistula (CPSF) is a rare disease that can be easily misdiagnosed. This study investigates the value of ultrasonography in the early diagnosis and treatment of CPSF in children. METHODS: Clinical features and ultrasonography images of 31 CPSF pediatric patients confirmed by operation were retrospectively analyzed, different sonographic features during the infection period and the quiescence period were summarized and the consistency test of ultrasonic recognition and diagnosis between observers was conducted. RESULTS: In this study, 25 CPSF children had thick-walled cystic masses during the infection period, and cystic masses of 8 cases showed gas echo inside; after the modified valsalva maneuver, gas echo was found in another 5 cases. The detection rate of gas can be enhanced through the modified valsalva maneuver and infants' cry so as to provide an important basis for the diagnosis of pyriform sinus fistula. During the quiescent period of inflammation of 6 cases, fistula can be completely shown, and the wall structure has not been completely destroyed, so that the running position of fistula can be clearly seen. Ultrasonography boasted a good inter-observer consistency in identification and determination (Kappa:0.799-0.857; P<0.001). CONCLUSION: Ultrasonography could clearly reveal the position and direction of CPSF fistula. Different ultrasonic characteristics in different periods could provide relevant information for the selection of clinical operation timing and evaluate the post-operative effects.


Assuntos
Fístula , Seio Piriforme , Lactente , Criança , Humanos , Seio Piriforme/diagnóstico por imagem , Seio Piriforme/cirurgia , Fístula/diagnóstico por imagem , Fístula/cirurgia , Estudos Retrospectivos , Ultrassonografia
11.
Journal of Clinical Hepatology ; (12): 700-705, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1016512

RESUMO

ObjectiveTo investigate the association of the polymorphisms of the acetyl-CoA acetyltransferase 1 (ACAT1) gene and the melatonin receptor 1B (MTNR1B) gene with the susceptibility to nonalcoholic fatty liver disease (NAFLD). MethodsA total of 164 healthy controls and 228 NAFLD patients were enrolled in this study. PCR and sequencing methods were used to determine the genotypes of the polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus, and fasting venous blood samples were collected for biochemical analysis. The t-test was used for comparison of normally distributed continuous data between groups, and the non-parametric Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. ResultsThere were no significant differences between the NAFLD group and the healthy control group in the genotype distribution of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus (all P>0.05). The carriers of AA genotype at the rs1044925 locus of the ACAT1 gene had a significantly higher level of low-density lipoprotein than the carriers of C allele (Z=-2.08, P=0.04), and the carriers of G allele at the rs10830963 locus of the MTNR1B gene had a significantly higher level of fasting blood glucose than the carriers of CC genotype (Z=-3.01, P<0.01). ConclusionThe polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus were not associated with the susceptibility to NAFLD. The rs1044925 locus of the ACAT1 gene and the rs10830963 locus of the MTNR1B gene are associated with the levels of low-density lipoprotein and fasting blood glucose, respectively.

12.
Med Ultrason ; 26(1): 91-93, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38150698

RESUMO

In many patients with pancreatic cancer the definite pathological diagnosis is limited due to the lack of safe needle entry routes, the high risk of conventional ultrasound-guided puncture and the low positive rate of single needle. To solve the situations in which there are no safe path for pancreatic biopsy, we used water isolation technology combined with contrast-enhanced ultrasound to perform puncture biopsy in 3 patients with pancreatic mass occupying under the guidance of coaxial needle in this study and remarkable results were achieved. The water isolation technique was used to avoid the damage to theimportant organs in front of the occupying area.


Assuntos
Neoplasias Pancreáticas , Humanos , Biópsia por Agulha/métodos , Neoplasias Pancreáticas/patologia , Ultrassonografia , Ultrassonografia de Intervenção
13.
Int J Mol Sci ; 24(17)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37685910

RESUMO

Oral squamous cell carcinoma (OSCC) is the most prevalent subtype of head and neck tumors, highly prone to lymph node metastasis. This study aims to examine the expression pattern of Ras-related protein Rab-27A (RAB27A) and explore its potential implications in OSCC. The expression of RAB27A was assessed through immunohistochemical analysis utilizing tissue microarrays. In vitro experiments were conducted using RAB27A-knockdown cells to investigate its impact on OSCC tumor cells. Additionally, transcriptome sequencing was performed to elucidate potential underlying mechanisms. RAB27A was significantly overexpressed in OSCC, and particularly in metastatic lymph nodes. It was positively correlated with the clinical progression and poor survival prognosis. Silencing RAB27A notably decreased the proliferation, migration, and invasion abilities of OSCC cells in vitro. A Gene Ontology (GO) enrichment analysis indicated a strong association between RAB27A and the epidermal growth factor receptor (EGFR) signaling pathway. Further investigations revealed that RAB27A regulated the palmitoylation of EGFR via zinc finger DHHC-type containing 13 (ZDHHC13). These findings provide insights into OSCC progression and highlight RAB27A as a potential therapeutic target for combating this aggressive cancer.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Receptores ErbB/genética , Proteínas rab27 de Ligação ao GTP
14.
Br J Cancer ; 129(6): 925-934, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37532831

RESUMO

BACKGROUND: The PD-L1 on tumor cell-derived small extracellular vesicles (sEVs) can suppress the proliferation and cytokine production of T cells. However, PD-L1 can also be expressed by non-tumor cells. The present study is designed to test whether immunocytes release immunosuppressive PD-L1-positive sEVs. METHODS: sEVs were isolated from different clinical samples of head and neck squamous cell carcinoma (HNSCC) patients, the level and cellular origins of PD-L1-positive sEVs were assessed. Co-expression of CD80 on PD-L1-positive sEVs was examined to evaluate the immunosuppressive and tumor-promotive effects. RESULTS: PD-L1-positive sEVs in HNSCC patients had various cellular origins, including tumor cell, T cell, B cell, dendritic cell and monocyte/macrophage. However, PD-L1-positive sEVs derived from immune cells did not exert immunosuppressive functions due to the co-expression of CD80. It was verified that co-expression of CD80 disrupted the binding of sEV PD-L1 to its receptor PD-1 on T cells and attenuated the immunosuppression mediated by sEV PD-L1 both in vitro and in vivo. CONCLUSION: The study suggests that PD-L1-positive sEVs have the cellular origin and functional heterogeneity. Co-expression of CD80 could restrict the immunosuppressive effect of sEV PD-L1. A greater understanding of PD-L1-positive sEV subsets is required to further improve their clinical application.


Assuntos
Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Antígeno B7-H1/metabolismo , Linfócitos T , Vesículas Extracelulares/metabolismo
15.
Anal Chem ; 95(19): 7753-7760, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37130010

RESUMO

Extracellular vesicles (EVs), acting as important mediators of intercellular communication, play an essential role in physiological processes, which have unique potential in the medical field. However, the heterogeneity of EVs limits their development for disease diagnosis and therapy, making the EV subpopulation analysis extremely valuable. In this article, a simple microfluidic approach was presented for the on-chip specific isolation and detection of two phenotypes of EVs (Annexin V+ EGFR+ EVs and Annexin V- EGFR+ EVs) based on different biomolecule-modified magnetic nanospheres and a fluorescence labeling technique. Combined with the control of the magnetic field in the microzone and fluid flow, it was easy to form two separate functional regions in the chip to capture different EV subpopulations. This method was successfully applied to the tests of clinical saliva samples in 75 oral squamous cell carcinoma (OSCC) patients and 10 healthy people. The results showed that the total level of EGFR+ EVs was much higher in OSCC patients that in healthy people. Meantime, the ratio of Annexin V+ EGFR+ EVs to Annexin V- EGFR+ EVs was found to be negatively correlated with tumor T stage of OSCC patients with a statistical difference, which suggested the ratio as a clinical index for monitoring the progression of OSCC in real time based on a noninvasive method. The approach provided a novel idea for evaluating the tumor T stage of OSCC and a powerful tool for clinical application.


Assuntos
Carcinoma de Células Escamosas , Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Saliva/metabolismo , Anexina A5 , Vesículas Extracelulares/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Receptores ErbB/metabolismo
16.
Environ Sci Pollut Res Int ; 30(19): 57050-57057, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36930313

RESUMO

In this article, an innovative sorbent (Fe-FA) is prepared from fly ash; ferrous sulfate-containing waste slag (FSS), which are industrial wastes; and NaOH by a hydrothermal method at 100 °C. As a result, in comparison to several conventional sorbents, such as ZnO, Fe2O3, 13X zeolite, and activated carbon, Fe-FA had the best adsorption performance for H2S adsorption. Fe-FA had not only a higher adsorption capacity (near 150 mg/g) but also a longer breakthrough time (near 400 min) when gas hourly space velocity was 8000 h-1. Then, characterizations of XRD, BET, NH3-TPD, FTIR, and XPS analyzed basic properties of Fe-FA and revealed reasons for the excellent adsorption performance. In general, the excellent adsorption performance of Fe-FA for H2S is mainly due to the high content of iron species (almost 50%) and suitable mesoporous structure in the Fe-FA.


Assuntos
Sulfeto de Hidrogênio , Ferro , Cinza de Carvão/química , Sulfeto de Hidrogênio/química , Adsorção , Resíduos Industriais
17.
J Child Health Care ; : 13674935231151748, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647285

RESUMO

Increased patient advocacy has resulted in a shift toward more active patient engagement in the research. A scoping review was conducted to explore the literature on healthcare research priority settings wherein children, youths, or their families were involved in the priority-setting process. Six databases including MEDLINE, CINAHL, PsycINFO, Embase, Web of Science, and Global Health and the James Lind Alliance website were searched up until September 2019. All primary studies involving children (<18 years of age) or families in developing research priorities in health care were included. All retrieved references were uploaded into Covidence, and two independent reviewers screened the search results. Descriptive thematic analysis was used to identify common themes. A total of 30 studies with 4247 participants were included. Less than half of the participants (n = 1237, (33%) were pediatric patients and their families. A total of 455 research priorities were identified. Three common themes emerged: (i) quality of care delivery, (ii) self-efficacy in health behaviors, and (iii) community engagement in care. This scoping review revealed priority research health topics from the perspectives of children, youths, or their families. The findings may be used as a foundation for future research to improve the health outcomes of children, youths, or their families according to their identified priorities.

18.
J Cancer Res Clin Oncol ; 149(9): 5975-5987, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36609710

RESUMO

PURPOSE: We constructed a zebrafish xenograft tumor model to compare and quantify the antiangiogenic efficacy and safety of nine vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), axitinib, lenvatinib, pazopanib, apatinib, cabozantinib, sunitinib, semaxanib, sorafenib, and regorafenib, in parallel. METHODS: CT26 and GL261 tumor cells were implanted into the perivitelline space of Tg (flk1: eGFP) zebrafish to construct a xenograft tumor model. VEGFR-TKIs' antiangiogenic efficacy was quantified using AngioTool software, and the median effective dose (ED50) was calculated. The toxicity was evaluated by calculating the median lethal dose (LD50) and gross morphological changes. Cardiac toxicity was further assessed by heart rate, heart rhythm, the distance between the sinus venosus (SV) and bulbus arteriosus (BA), and pericardial edema. RESULTS: Using the zebrafish xenograft tumor model, we found that all nine VEGFR-TKIs exhibited antiangiogenic abilities, but the effectiveness of semaxanib was worse than that of other VEGFR-TKIs. Meanwhile, the zebrafish toxicity assay showed that all tested VEGFR-TKIs were associated with cardiac-related toxicity, especially apatinib and axitinib, which caused serious pericardial edema in zebrafish at relatively low concentrations. A narrow therapeutic window was found for most VEGFR-TKIs, and the simultaneous occurrence of toxic effects of semaxanib was recognized. CONCLUSION: Our findings showed the potential of using a zebrafish xenograft tumor model to accelerate VEGFR-TKI screening and further the development of more efficient and less toxic VEGFR-TKIs.


Assuntos
Neoplasias , Peixe-Zebra , Animais , Humanos , Proteínas Tirosina Quinases/uso terapêutico , Axitinibe/uso terapêutico , Xenoenxertos , Fator A de Crescimento do Endotélio Vascular , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Modelos Animais de Doenças , Edema/complicações , Edema/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico
19.
Cancer Immunol Res ; 11(2): 228-240, 2023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36484721

RESUMO

PD-L1 localized to immunosuppressive small extracellular vesicles (sEV PD-L1) contributes to tumor progression and is associated with resistance to immune-checkpoint blockade (ICB) therapy. Here, by establishing a screening strategy with a combination of tissue microarray (TMA), IHC staining, and measurement of circulating sEV PD-L1, we found that the endosomal sorting complex required for transport (ESCRT) member protein hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) was the key regulator of circulating sEV PD-L1 in head and neck squamous cell carcinoma (HNSCC) patients. Increased HRS expression was found in tumor tissues and positively correlated with elevated circulating sEV PD-L1 in patients with HNSCC. The expression of HRS was also negatively correlated to the infiltration of CD8+ T cells. Knockdown of HRS markedly reduced PD-L1 expression in HNSCC cell-derived sEVs, and these sEVs from HRS knockdown cells showed decreased immunosuppressive effects on CD8+ T cells. Knockout of HRS inhibited tumor growth in immunocompetent mice together with PD-1 blockade. Moreover, a higher HRS expression was associated with a lower response rate to anti-PD-1 therapy in patients with HNSCC. In summary, our study reveals HRS, the core component of ESCRT-0, regulates sEV PD-L1 secretion, and is associated with the response to ICB therapy in patients with HNSCC, suggesting HRS is a promising target to improve cancer immunotherapy.


Assuntos
Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , Animais , Camundongos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Antígeno B7-H1 , Camundongos Knockout , Resultado do Tratamento , Vesículas Extracelulares/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte
20.
Small ; 19(10): e2206052, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36549675

RESUMO

Precisely controlling the selectivity of nanocatalysts has always been a hot topic in heterogeneous catalysis but remains difficult owing to their complex and inhomogeneous catalytic sites. Herein, an effective strategy to regulate the chemoselectivity of Pd nanocatalysts for selective hydrogenation reactions by inserting single-atom Zn into Pd nanoparticles is reported. Taking advantage of the tannic acid coating-confinement strategy, small-sized Pd nanoparticles with inserted single-atom Zn are obtained on the O-doped carbon-coated alumina. Compared with the pure Pd nanocatalyst, the Pd nanocatalyst with single-atom Zn insertion exhibits prominent selectivity for the hydrogenation of p-iodonitrobenzene to afford the hydrodeiodination product instead of nitro hydrogenation ones. Further computational studies reveal that the single-atom Zn on Pd nanoparticles strengthens the adsorption of the nitro group to avoid its reduction and increases the d-band center of Pd atoms to facilitate the reduction of the iodo group, which leads to enhanced selectivity. This work provides new guidelines to tune the selectivity of nanocatalysts with guest single-atom sites.

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