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1.
Chemosphere ; 310: 136840, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36257392

RESUMO

The current work aims to advance the hydrophilicity, morphology, and antifouling characteristics of polyvinyl chloride (PVC) membranes for oily wastewater separation by incorporating modified bentonite. The surface of bentonite nanoparticles is altered by adopting the "grafting from" method using the surface-initiated atom transfer radical polymerization (SI-ATRP) approach. The PVC-based membrane is first prepared by blending acrylamide grafted bentonite (AAm-g-bentonite). AAm is grafted on bentonite in the presence of 2,2'-Bipyridyl and copper (I) bromide as a catalyst. The modified bentonite nanoparticles are studied using multiple techniques, such as fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), sedimentation tests, field emission scanning electron microscope (FE-SEM), etc. Flat-sheet PVC-based membrane is prepared by blending AAm-g-bentonite using the nonsolvent induced phase separation (NIPS) technique. Different methods, including FE-SEM, FTIR, sedimentation test, contact angle, porosity, antifouling property, and filtration studies of pure and oily water, are used to characterize and determine the performance of mixed-matrix membranes. Membrane performance is improved in the presence of modified bentonite (i.e., AAm-g-bentonite), with the best result achieved at PVC/AAm-g-ben-8 (i.e., 8 wt % of AAm-g-bentonite). Enhanced pure water flux (293.14 Lm-2h-1), permeate flux (123.96 Lm-2h-1), and oil rejection >93.2% are obtained by the reduced contact angle (49.1°) and improved porosity (71.22%).


Assuntos
Cloreto de Polivinila , Purificação da Água , Bentonita , Membranas Artificiais , Acrilamida , Purificação da Água/métodos , Óleos
2.
J Hazard Mater ; 443(Pt B): 130317, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36356518

RESUMO

Condensable particulate matter (CPM) is a major component of primary particulate matter emitted into the atmosphere from stationary sources. However, the factors affecting CPM generation remain unclear. In this study, we systematically investigated the role of sulphur and chlorine in CPM formation during coal combustion. To explore the influence of S, various concentrations of SO2 (0-2000 ppm) were added to the combustion process of high-S coal. The role of Cl in the generation of CPM was revealed by burning coal with a significant difference in the Cl content (0.51-9.70 mg/g). The results show that addition of SO2, especially in SO42-, to the combustion process increases the CPM inorganic fraction content from 5.83 to 48.3 mg/m3. In addition, we speculated that the presence of SO2 may have led post-break oxidation of long-chain alkanes to form esters, especially phthalates. At the same time, in experiments concerning Cl, the opposite trend was observed between S and Cl in the CPM inorganic fraction. As the Cl content in the fuel increased, the S content in the inorganic fraction of CPM gradually decreased. This is because Cl inhibits the conversion of SO2 to SO3, therefore, less S forms CPM as SO3 or as sulphides.

3.
Front Bioeng Biotechnol ; 10: 1031986, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338113

RESUMO

Metal-organic frameworks (MOFs) are a class of hybrid porous crystalline materials that are assembled with metal ions/clusters and organic linkers. The fungibility of organic ligands and metal centers endow MOFs that are easy to design and synthesize. Based on their unique structure, multifarious MOFs with diverse functionalities have recently been widely applied in various research areas. Particularly striking is the application of photo-responsive MOFs in biological sensing and imaging. Notably, the photoelectronic properties make photo-responsive MOFs an ideal platform for cancer phototherapy. Moreover, ultrahigh porosities and tunable pore sizes allow MOFs to load anticancer drugs, further enhancing the antitumor efficiency. In this review, the categories and developing strategies of MOFs are briefly introduced. The application fields of MOFs in bioimaging, such as up-conversion fluorescence imaging, single/two-photon fluorescence bioimaging, magnetic resonance imaging, etc., are summarized. The working mechanism of MOFs in photo-responsive, photothermal therapy (PTT), and photodynamic therapy (PDT) are expounded. Examples of using MOFs for cancer treatment, including PTT, PDT, chemotherapy, and radiotherapy, are also demonstrated. Lastly, current limitations, challenges, and future perspectives for bioimaging and cancer treatment of MOFs are discussed. We believe that the versatile MOF will bring the dawn to the next generation of cancer treatment.

6.
Heliyon ; 8(11): e11530, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36406714

RESUMO

Background: The secondary preventive medical remedies used in the U.S. general population, particularly those with numerous co-morbidities, are poorly understood. We aimed to assess health outcomes and the extent of their adherence to guideline-based secondary prevention medications among U.S. coronary heart disease (CHD) patients. Methods: We analysed information from the U.S. National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 on people in the United States aged 18 to 85 who had a personal history of coronary heart disease (CHD). Logistic regression analyses were used to identify characteristics related to healthcare access that were linked with not taking any indicated drugs among CHD and other co-morbidity patients in the U.S. Results: We gathered 4256 CHD patients aged 18 and above. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), statins, and antiplatelet medications were taken by 50.94%, 48.26%, 53.41 %, and 19.78% of the population, respectively. Surprising, not received recommended drugs was reached up to 21.12%, and taking all four drugs was only 7.64%. In conclusion, the logistic regression analysis revealed that the chance of not taking prescribed drugs increased with age (18-39), race (Hispanic and Non-Hispanic Black), low income, lack of insurance, and the absence of co-morbidities (hypertension, heart failure, and diabetes mellitus). Conclusions: The gap between the proposed secondary preventative measures and their actual execution remains sizable. In order to achieve 'Healthy Aging', a systematic approach for prevention of CHD is urgently needed.

7.
Sci Total Environ ; 858(Pt 2): 159932, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36343825

RESUMO

>80 % of applied pesticides in agriculture will enter the soil and be exposed to soil animals. Little is known about the stereoselective metabolic effects of epoxiconazole (EPO) on soil animals. In this study, EPO-mediated stereoselective enrichment, biotransformation, oxidative stress, detoxification, and global metabolic profiles in earthworms were investigated by exposure to EPO and its enantiomers at 1 mg/kg and 10 mg/kg doses. Preferential enrichment of (-)-EPO was observed, and the five transformation products (TPs) exhibited the chemically specific stereoselective accumulation with inconsistent configurations. Biochemical markers related to reactive oxygen species (ROS) and detoxification (·OH- content, SOD, CAT, GST, and CYP450 enzymes) showed a significant stereoselective activation overall at the low-level exposure (p-value <0.05). Based on untargeted metabolomic analysis, the steroid biosynthesis and ROS-related biotransformation, glutathione metabolism, TCA cycle, amino acid metabolism, purine and pyrimidine metabolism of earthworms were significantly interfered with by EPO and its enantiomer exposure. More pronounced stereoselectivity was observed at the level of the global metabolic profile, while comparable levels of metabolic perturbations were identified at the individual metabolite level. This study provides novel insights into the stereoselective effects of the chiral fungicide EPO, and valuable evidence for soil environmental risk assessments.

8.
Mol Genet Genomics ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36396788

RESUMO

Congenital heart disease (CHD) is a worldwide problem with high morbidity and mortality. Early diagnosis of congenital heart disease is still a challenge in clinical work. In recent years, few studies indicated that placental methylation may be predictors of CHD. More studies are needed to confirm the association between placental methylation and CHD. The aim of this study was to investigate the association between prenatal placental DNA methylation and CHD. Placental tissues were obtained from four fetuses during the second trimester with isolated, non-syndromic congenital heart disease, including three cases with double outlet right ventricle (DORV) and one case with tetralogy of Fallot (TOF), and four unaffected fetuses as controls. The Illumina Infinium Human Methylation 850K BeadChip assay was employed to identify differential methylation sites (DMSs) and differential methylation regions (DMRs). Differential methylation was evaluated by comparing the ß-values for individual CpG loci in cases vs. controls. In addition, the function of genes was assessed through KEGG enrichment analysis, Gene Ontology (GO) analysis and KEGG pathway analysis. Compared with the control group, we identified 9625 differential methylation genes on 26,202 DMSs (p < 0.05), of which 6997 were hyper-methylation and 2628 were hypo-methylation. The top 30 terms of GO biological process and KEGG enrichment analysis of DMSs were connected with multiple important pathways of heart development and disease. Ten differentially methylated regions and the genes related to DMRs, such as TLL1, CRABP1, FDFT1, and PCK2, were identified. The deformity caused by the loss of function of these genes is remarkably consistent with the clinical phenotype of our cases. The DNA methylation level of placental tissue is closely associated with fetal congenital heart disease.

9.
Molecules ; 27(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364345

RESUMO

Malassezia is a genus of commensal and lipid-dependent yeasts in human skin which also have a pathogenic lifestyle associated with several common skin disorders such as atopic dermatitis and eczema. Symptoms include red, itchy, and inflamed skin. We studied the growth characteristics and biochemical analyses of M. furfur which showed that the protein contents were greater in extracts taken at 24 h. These were then used to infect C57BL/6 mice, resulting in skin rupture. Polygalaxanthone III (POL), a more effective anti-inflammatory ingredient in Polygala japonica Houtt., was applied externally to the ulceration and successfully healed the wounds quickly. POL could not inhibit Malassezia activity as tested by the inhibition zone test, but affected the formation of lipid droplets in HaCaT cells. The wound-healing molecular mechanisms may be involved in the STAT3 pathway according to the Western blot results of skin tissues. Malassezia's role in skin health is far from certain, and there is no clear solution, so understanding the development of Malassezia-associated skin diseases in general and seeking solutions are very important.


Assuntos
Dermatite Atópica , Malassezia , Polygala , Camundongos , Animais , Humanos , Camundongos Endogâmicos C57BL , Pele , Fator de Transcrição STAT3
10.
Food Chem ; 405(Pt B): 134962, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36413841

RESUMO

Epoxiconazole is widely used in agriculture to control plant diseases; however, its effect on the nutritional quality of crops is poorly understood. In the present study, the stereoselective effects of epoxiconazole and its enantiomers on leek metabolites and lipids were clarified using metabolomics and lipidomics based on ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Multivariate analysis revealed significant differences in 123 compounds of leek exposed to chiral epoxiconazole compared to the control group. The order of the degree of influence was (+)-epoxiconazole > racemic-epoxiconazole>(-)-epoxiconazole, indicating significant stereoselectivity. The differential expression of metabolites indicated the activation of stress defense systems, including the antioxidant defense system and signaling pathways and phenylpropanoid metabolism. Alterations in the levels of compounds associated with nutritional quality, such as amino acids, vitamins, phenylpropanoids, flavonoids and lipids indicated changes in the nutritional quality of leek. In general, the nutritional quality of leek decreased after exposure to epoxiconazole.

11.
Front Immunol ; 13: 1049164, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439188

RESUMO

Tumor-associated macrophages (TAMs) play a critical role in supporting tumor growth and metastasis, taming host immunosurveillance, and augmenting therapeutic resistance. As the current treatment paradigms for cancers are generally insufficient to exterminate cancer cells, anti-cancer therapeutic strategies targeting TAMs have been developed. Since TAMs are highly heterogeneous and the pro-tumoral functions are mediated by phenotypes with canonical surface markers, TAM-associated materials exert anti-tumor functions by either inhibiting polarization to the pro-tumoral phenotype or decreasing the abundance of TAMs. Furthermore, TAMs in association with the immunosuppressive tumor microenvironment (TME) and tumor immunity have been extensively exploited in mounting evidence, and could act as carriers or accessory cells of anti-tumor biomaterials. Recently, a variety of TAM-based materials with the capacity to target and eliminate cancer cells have been increasingly developed for basic research and clinical practice. As various TAM-based biomaterials, including antibodies, nanoparticles, RNAs, etc., have been shown to have potential anti-tumor effects reversing the TME, in this review, we systematically summarize the current studies to fully interpret the specific properties and various effects of TAM-related biomaterials, highlighting the potential clinical applications of targeting the crosstalk among TAMs, tumor cells, and immune cells in anti-cancer therapy.


Assuntos
Neoplasias , Macrófagos Associados a Tumor , Humanos , Materiais Biocompatíveis/uso terapêutico , Materiais Biocompatíveis/farmacologia , Macrófagos , Neoplasias/patologia , Microambiente Tumoral
12.
Chemosphere ; : 137346, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36442676

RESUMO

When a membrane is used to treat dye wastewater, dye molecules are continually concentrated at the membrane surface over time, resulting in a dramatic decrease in membrane flux. Aside from routine membrane cleaning, the pretreatment of dye wastewater to degrade organic pollutants into tiny molecules is a facile solution to the problem. In this study, the use of layered double hydroxide (LDH) to activate peroxymonosulfate (PMS) for efficient degradation of organic pollutant has been thoroughly investigated. We utilized a simple two-drop co-precipitation process to prepare CoFe-LDH. The transition metal components in CoFe-LDH effectively activate PMS to create oxidative free radicals, and the layered structure of LDH increases the number of active sites, and thereby considerably enhancing the reaction rate. It was found that the reaction process produced non-free and free radicals, including singlet oxygen (1O2), sulfate radicals (SO4•-), and hydroxyl radicals (•OH), with 1O2 being the dominant reactive species. Under the optimal conditions (pH 6.7, PMS dosage 0.2 g/L, catalyst loading 0.1 g/L), the degradation of Acid Red 27 dye in the CoFe-LDH/PMS system reached 96.7% within 15 min at an initial concentration of 200 mg/L. The CoFe-LDH/PMS system also exhibited strong resistance to inorganic ions and pH during the degradation of organic pollutants. This study presents a novel strategy for the synergistic treatment of dye wastewater with free and non-free radicals produced by LDH-activated PMS in a natural environment.

13.
Chemosphere ; 312(Pt 1): 137194, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36372337

RESUMO

The treatment of high-salinity and high-organic wastewater is a tough task, with the removal of organic matter and the separation of salts often mutually restricting. Catalytic wet air oxidation (CWAO) coupled desalination technology (membrane distillation (MD), membrane bioreactor (MBR), ultrafiltration (UF), nanofiltration (NF), etc.) provides an effective method to simultaneously degrade the high-salinity (via desalination) and high-organic matters (via CWAO) in wastewater. In this work, five kinds of RuO2/TiO2 catalysts with different calcination temperatures were prepared for CWAO of maleic acid wastewater with a theoretical chemical oxygen demand (COD) value of 20,000 mg L-1. RuO2/TiO2 series catalysts demonstrated prominent salt resistance, with more than 80% TOC removal rates in the CWAO system containing 5 wt% Na2SO4; while RuO2/TiO2-350 showed the best degradation performance in both non-salinity and Na2SO4-containing conditions. Multiple characterization techniques, such as XRD, BET, XPS, NH3-TPD and TEM etc., verified the physicochemical structure of RuO2/TiO2 catalysts, and their influence on the degradation of pollutants. The calcination temperature was found to have a direct impact on the specific surface area, pore volume, oxygen vacancies and acid sites of catalysts, which in turn affected the ultimate catalytic activity. Furthermore, we also investigated the performance of the RuO2/TiO2-350 catalyst for the treatment of acids, alcohols and aromatic compounds with the addition of NaCl or Na2SO4, proving its good universality and excellent salt resistance in saline wastewater. Meanwhile, the relationship between the structure of three types of organic compounds and the degradation effect in the CWAO system was also explored.

14.
Small ; : e2204348, 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36336632

RESUMO

KVPO4 F is one of the most competitive cathode candidates for potassium-ion batteries (KIBs) because of its high output voltage and energy density. Although the gravimetric energy density of KIBs is intensively discussed in literature, little attention is paid to the volumetric energy density. In view of this, pomegranate-like carbon-coated KVPO4 F microspheres with a high volumetric energy density are designed in this work. The nano-sized primary particles with carbon sheets in KVPO4 F microspheres enable promis rate capability by enhancing the K+ diffusion kinetics, while the micro-sized spheres guarantee the improvement of cycling stability. Owing to the dense hierarchical microspheres, the volumetric energy density of cells is greatly improved compared to bulk materials. This cathode delivers a reversible capacity of 101.5 mA h g-1 at 0.3 C with an average output voltage of 4.0 V and a capacity retention of 85.1% after 200 cycles. The KVPO4 F@C microspheres have a compact density of 2.45 g cm-3 and further offer a high volumetric energy density up to 891.3 Wh L-1 . The overcharge behavior of KVPO4 F in the first three cycles is also revealed. The presented KVPO4 F@C microspheres cathode provides a new sight for developing KIBs with large volumetric energy density.

15.
BMC Gastroenterol ; 22(1): 432, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224557

RESUMO

INTRODUCTION: Functional dyspepsia (FD) is diagnosed based on self-reported symptoms and negative upper gastrointestinal endoscopic findings. The Rome criteria were not adopted as a diagnostic instrument in clinical guidelines due to their complexity. Different guidelines used relatively simple symptom assessment schemes with contents that vary significantly. A previously evaluated short Reference Standard may serve as a more standardised tool for guidelines. We evaluated its diagnostic accuracy against the Rome IV criteria in a cross-sectional study in Hong Kong. METHODS: A total of 220 dyspeptic patients sampled consecutively from a tertiary hospital and the community completed the Rome IV diagnostic questionnaire, which was translated into Cantonese-Chinese, and the Reference Standard. Sensitivity, specificity, positive and negative likelihood ratios (LRs), and area under the receiver operating characteristics curve (AUC), with 95% confidence intervals (CIs), were calculated. RESULTS: Among the participants, 160 (72.7%) fulfilled the Reference Standard with negative upper gastrointestinal endoscopic results. The Reference Standard identified patients with Rome IV-defined FD with 91.1% (95% CI 82.6%-96.4%) sensitivity and 37.6% (95% CI 29.6%-46.1%) specificity. The positive and negative LRs were 1.46 (95% CI 1.26-1.69) and 0.24 (95% CI 0.11-0.49), respectively. The AUC value was 0.64 (95% CI 0.59-0.69). CONCLUSIONS: The Reference Standard can rule out patients without Rome IV-defined FD. It may be used as an initial screening tool for FD in settings where the use of the Rome IV criteria is impractical. It may also provide a uniform definition and diagnostic rule for future updates of clinical guidelines.


Assuntos
Dispepsia , China , Estudos Transversais , Dispepsia/diagnóstico , Endoscopia Gastrointestinal , Humanos , Padrões de Referência , Cidade de Roma , Inquéritos e Questionários
16.
Int J Public Health ; 67: 1604986, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36250153

RESUMO

Objectives: To evaluate the distribution and changes in different obesity metabolic phenotypes, as well as their impact on the incidence of type 2 diabetes mellitus (T2DM) in a northwest Chinese population sample. Methods: Data comes from prospective cohort study (n = 1,393, mean follow up = 9.46 years). Participants were classified into four groups through a combination of the Chinese Diabetes Society (CDS) diagnostic criteria for metabolic syndrome with anthropometric measurements: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO). Cox regression models with time-dependent covariates were used to evaluate changes in obesity metabolic phenotypes and risk of T2DM. Results: Participants in MUO state had the highest risk of developing T2DM, the incidence density was 12.10/1,000 person-year. The MHO and MUO groups showed an increased risk of incident diabetes based on body mass index (BMI) (HR, 1.29; 95% CI, 1.03-1.61; p = 0.026 and HR, 1.20; 95% CI, 1.02-1.40; p = 0.024 respectively.) Besides, the MHO group had an increased risk of incident diabetes based on waist circumference (WC) (HR, 1.41; 95% CI, 1.10-1.80; p = 0.006). Conclusion: Diabetes is more frequent in the MHO and MUO groups and co-occurrence of obesity and metabolic abnormalities (MA) contributes to the development of T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Síndrome Metabólica , Obesidade Metabolicamente Benigna , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Síndrome Metabólica/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Obesidade Metabolicamente Benigna/diagnóstico , Obesidade Metabolicamente Benigna/epidemiologia , Sobrepeso , Fenótipo , Estudos Prospectivos , Fatores de Risco
17.
Cell Cycle ; : 1-14, 2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36310380

RESUMO

This study investigated the effects of ibandronate (IBN) on cardiomyopathy remodeling in diabetic rats. A rat model of diabetic cardiomyopathy (DCM) was established by supplementing them with a high-calorie diet combined with a low dose of streptozotocin (STZ). The diabetic rats received IBN (5 µg/kg per day) or normal saline subcutaneously for 16 weeks. The hematoxylin and eosin (H&E) and Masson's trichrome staining were performed for evaluating the myocardial morphologies of the rats. Echocardiography and cardiac catheter were performed to assess their cardiac functional parameters. The protein levels of connective tissue growth factor (CTGF), farnesyl pyrophosphate synthase (FPPS), and mitogen-activated protein kinase (MAPK) were determined using Western blot analysis. RhoA activation was detected using a small GTP protease-linked immunosorbent assay (GLISA). The diabetic rats showed the development of moderate hyperglycemia, insulin resistance, hyperlipidemia, myocardial fibrosis, FPPS overexpression, cardiac systolic, and diastolic dysfunction. Inhibiting the FPPS could ameliorate myocardial hypertrophy and fibrosis. These anatomical findings were accompanied by a significant improvement in heart function. Furthermore, the inhibition of FPPS, the increased activation of RhoA, and phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2 in DCM decreased significantly with the treatment of IBN. This study for the first time demonstrated that the upregulation of FPPS expression might be involved in diabetic myocardial remodeling in diabetes mellitus (DM). In addition, IBN might exert its inhibitory effects on myocardial tissue remodeling by suppressing the RhoA/ERK1/2 and RhoA/p38 MAPK pathways in DCM.

18.
Clin Cancer Res ; 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36190525

RESUMO

PURPOSE: In many cancers, nivolumab in combination with ipilimumab improves response rates compared to either agent alone, but the combination has not been evaluated in childhood cancer. We conducted a Phase I/II trial of nivolumab plus ipilimumab in children and young adults with recurrent/refractory solid tumors. EXPERIMENTAL DESIGN: ADVL1412, Part C assessed safety of nivolumab plus ipilimumab at two dose levels (DL): DL1 1mg/kg of each drug and DL2 3mg/kg nivolumab plus 1mg/kg Ipilimumab. Part D evaluated response at the recommended phase 2 dose (RP2D) in Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma. Part E tested DL3 (1mg/kg nivolumab plus 3mg/kg Ipilimumab) in Ewing sarcoma and rhabdomyosarcoma. Tumor response was measured using RECIST v1.1. Pharmacokinetics and PD-L1 expression on archival tissues were assessed. RESULTS: Fifty-five eligible patients enrolled. Based upon safety, tolerability and similar drug exposure to the same doses administered in adults, DL2 was defined as the pediatric RP2D. Among 41 patients treated at the RP2D, 2 patients experienced dose-limiting toxicities during Cycle 1 and 4 patients experienced toxicities beyond that period. Two patients had clinically significant sustained partial responses (1 rhabdomyosarcoma, 1 Ewing sarcoma) and 4 had stable disease. Among 8 patients treated at DL3, 3 DLTs occurred, all immune related adverse events; no objective responses were observed. CONCLUSIONS: The RP2D of nivolumab (3mg/kg) plus ipilimumab (1mg/kg) is well-tolerated in children and young adults with solid tumors and shows some clinical activity. Increased dose of ipilimumab (3mg/kg) plus nivolumab (1mg/kg) was associated with increased toxicity without clinical benefit.

19.
Int J Pharm ; 628: 122294, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36252645

RESUMO

The objective of this study was to investigate the feasibility of the bolus administration of PLS via skin by using dissolving microneedles of palonosetron hydrochloride (PLS-DMNs). Tip-loaded PLS-DMNs were fabricated by a casting method using sodium hyaluronate (HA) as DMNs-forming polymer. PLS-DMNs were shown to have a content of 118.5 ± 8.7 µg per piece with sufficient mechanical strength for insertion into pig skin ex vivo. In situ dissolution of PLS-DMNs was achieved within 5 min and 83.2 % of PLS was delivered. In vitro studies showed that PLS-DMNs provided much higher PLS permeation than that after passive permeation using a PLS hydrogel. Moreover, the application of 30 min-iontophoresis at the beginning of PLS-DMNs administration further enhanced PLS delivery. In vivo pharmacokinetic studies were carried out in rats. The area under the curve (AUC) and the time to reach the peak (Tmax) after application of PLS-DMNs was not significantly different compared to those after subcutaneous (S.C.) injection. PLS-DMNs plus 30 min-iontophoresis enabled the pharmacokinetic profile to be even closer to that seen after S.C. administration. These results suggest that application of PLS-DMNs with short-duration iontophoresis exhibits promise as an alternative PLS delivery method that can be painlessly self-administered with rapid onset.


Assuntos
Iontoforese , Agulhas , Ratos , Suínos , Animais , Microinjeções , Administração Cutânea , Palonossetrom , Pele , Sistemas de Liberação de Medicamentos/métodos , Vômito
20.
Adv Colloid Interface Sci ; 309: 102794, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36215901

RESUMO

Fog on a solid surface is prejudicial to its optical properties and will even cause hygienic and safety concerns in some exceptional cases. Thus, antifogging coatings have attracted great interest in fundamental research and industry applications. Superhydrophilic and superhydrophobic coatings have been mainly explored and described in the antifogging field. In recent years, hygroscopic antifogging coatings of hydrophilic and hydrophobic parties have been introduced due to their unique properties. In this review, three antifogging mechanisms are reviewed to provide design strategies for antifogging surfaces. The current techniques for fabricating polymeric antifogging coatings are discussed in depth. The recent progress in materials and structures for antifogging surfaces is briefly summarize. Finally, the practical applications and outlooks related to multifunctional antifogging coatings are mentioned.


Assuntos
Polímeros , Propriedades de Superfície , Interações Hidrofóbicas e Hidrofílicas , Polímeros/farmacologia , Polímeros/química , Molhabilidade
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