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1.
J Am Chem Soc ; 146(19): 13607-13616, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38709316

RESUMO

Materials exhibiting aggregation-induced emission (AIE) are both highly emissive in the solid state and prompt a strongly red-shifted emission and should therefore pose as good candidates toward emerging near-infrared (NIR) applications of organic semiconductors (OSCs). Despite this, very few AIE materials have been reported with significant emissivity past 700 nm. In this work, we elucidate the potential of ortho-carborane as an AIE-active component in the design of NIR-emitting OSCs. By incorporating ortho-carborane in the backbone of a conjugated polymer, a remarkable solid-state photoluminescence quantum yield of 13.4% is achieved, with a photoluminescence maximum of 734 nm. In contrast, the corresponding para and meta isomers exhibited aggregation-caused quenching. The materials are demonstrated for electronic applications through the fabrication of nondoped polymer light-emitting diodes. Devices employing the ortho isomer achieved nearly pure NIR emission, with 86% of emission at wavelengths longer than 700 nm and an electroluminescence maximum at 761 nm, producing a significant light output of 1.37 W sr-1 m-2.

2.
Ann Rheum Dis ; 83(3): 324-334, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37977819

RESUMO

OBJECTIVES: This study aimed to identify the types and heterogeneity of cells within the spinal enthesis and investigate the underlying mechanisms of osteogenesis. METHODS: Single-cell RNA sequencing was used to identify cell populations and their gene signatures in the spinal enthesis of five patients with ankylosing spondylitis (AS) and three healthy individuals. The transcriptomes of 40 065 single cells were profiled and divided into 7 clusters: neutrophils, monocytic cells, granulomonocytic progenitor_erythroblasts, T cells, B cells, plasma cells and stromal cells. Real-time quantitative PCR, immunofluorescence, flow cytometry, osteogenesis induction, alizarin red staining, immunohistochemistry, short hairpin RNA and H&E staining were applied to validate the bioinformatics analysis. RESULTS: Pseudo-time analysis showed two differentiation directions of stromal cells from the mesenchymal stem cell subpopulation MSC-C2 to two Cxcl12-abundant-reticular (CAR) cell subsets, Osteo-CAR and Adipo-CAR, within which three transcription factors, C-JUN, C-FOS and CAVIN1, were highly expressed in AS and regulated the osteogenesis of mesenchymal stem cells. A novel subcluster of early-stage neutrophils, CD99_G1, was elevated in AS. The proinflammatory characteristics of monocyte dendritic cell progenitor-recombinant adiponectin receptor 2 monocytic cells were explored. Interactions between Adipo-CAR cells, CD99_G1 neutrophils and other cell types were mapped by identifying ligand-receptor pairs, revealing the recruitment characteristics of CD99_G1 neutrophils by Adipo-CAR cells and the pathogenesis of osteogenesis induced in AS. CONCLUSIONS: Our results revealed the dynamics of cell subpopulations, gene expression and intercellular interactions during AS pathogenesis. These findings provide new insights into the cellular and molecular mechanisms of osteogenesis and will benefit the development of novel therapeutic strategies.


Assuntos
Células-Tronco Mesenquimais , Espondilite Anquilosante , Humanos , Diferenciação Celular , Células Cultivadas , Neutrófilos/metabolismo , Osteogênese/genética , Espondilite Anquilosante/patologia
3.
Int J Mol Sci ; 25(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38255916

RESUMO

Chicoric acid (CA) has been reported to exhibit biological activities; it remains unclear, however, whether CA could regulate colitis via modulation of the gut microbiota and metabolites. This study aimed to assess CA's impact on dextran sulfate sodium (DSS)-induced colitis, the gut microbiota, and metabolites. Mice were induced with 2.5% DSS to develop colitis over a 7-day period. CA was administered intragastrically one week prior to DSS treatment and continued for 14 days. The microbial composition in the stool was determined using 16S rRNA sequencing, while non-targeted metabolomics was employed to analyze the metabolic profiles of each mouse group. The results show that CA effectively alleviated colitis, as evidenced by an increased colon length, lowered disease activity index (DAI) and histological scores, and decreased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels. CA intervention restored the structure of gut microbiota. Specifically, it decreased the abundance of Bacteroidetes and Cyanobacteria at the phylum level and Bacteroides, Rosiarcus, and unclassified Xanthobacteraceae at the genus level, and increased the abundance of unclassified Lachnospiraceae at the genus level. Metabolomic analysis revealed that CA supplementation reversed the up-regulation of asymmetric dimethylarginine, N-glycolylneuraminic acid, and N-acetylneuraminic acid, as well as the down-regulation of phloroglucinol, thiamine, 4-methyl-5-thiazoleethanol, lithocholic acid, and oxymatrine induced by DSS. Our current research provides scientific evidence for developing CA into an anti-colitis functional food ingredient. Further clinical trials are warranted to elucidate the efficacy and mechanism of CA in treating human inflammatory bowel disease (IBD).


Assuntos
Ácidos Cafeicos , Colite , Microbioma Gastrointestinal , Succinatos , Humanos , Animais , Camundongos , Camundongos Endogâmicos BALB C , Sulfato de Dextrana/toxicidade , RNA Ribossômico 16S/genética , Colite/induzido quimicamente , Colite/tratamento farmacológico
4.
Int J Cancer ; 153(4): 792-802, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-36919366

RESUMO

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).


Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Antígeno Prostático Específico , Tioidantoínas/efeitos adversos , Antagonistas de Receptores de Andrógenos , Resultado do Tratamento
5.
J Transl Med ; 21(1): 573, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37626378

RESUMO

BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disease with a genetic correlation and is characterized by inflammation in the axial skeleton and sacroiliac joints. Many AS patients also have inflammatory bowel diseases (IBD), but the underlying causes of intestinal inflammation and osteoporosis in AS are not well understood. CX3CL1, a protein involved in inflammation, has been found to be up-regulated in AS patients and AS-model mice. METHODS: The authors investigated the effects of CX3CL1 on AS by studying its impact on macrophage polarization, inflammation factors, and osteoclast differentiation. Furthermore, the effects of inhibiting the NF-κB pathway and blocking CX3CL1 were assessed using BAY-117082 and anti-CX3CL1 mAb, respectively. AS model mice were used to evaluate the effects of anti-CX3CL1 mAb on limb thickness, spine rupture, and intestinal tissue damage. RESULTS: The authors found that CX3CL1 increased the expression of M1-type macrophage markers and inflammation factors, and promoted osteoclast differentiation. This effect was mediated through the NF-κB signaling pathway. Inhibition of the NF-κB pathway prevented M1-type macrophage polarization, reduced inflammation levels, and inhibited osteoclast differentiation. Injection of anti-CX3CL1 mAb alleviated limb thickness, spine rupture, and intestinal tissue damage in AS model mice by inhibiting M1-type macrophage polarization and reducing intestinal tissue inflammation. CONCLUSIONS: The study demonstrated that up-regulated CX3CL1 promotes M1-type macrophage polarization and osteoclast differentiation through the NF-κB signaling pathway. Inhibition of this pathway and blocking CX3CL1 can alleviate inflammation and bone destruction in AS. These findings contribute to a better understanding of the pathogenesis of AS and provide a basis for clinical diagnosis and treatment.


Assuntos
NF-kappa B , Espondilite Anquilosante , Animais , Camundongos , Inflamação , Osteoclastos , Transdução de Sinais
6.
Pharmacol Res ; 197: 106942, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37775021

RESUMO

The design of chimeric antigen receptors (CAR) significantly enhances the antitumor efficacy of T cells. Although some CAR-T products have been approved by FDA in treating hematological tumors, adoptive immune therapy still faces many difficulties and challenges in the treatment of solid tumors. In this study, we reported a new strategy to treat solid tumors using a natural killer-like T (NKT) cell line which showed strong cytotoxicity to lyse 15 cancer cell lines, safe to normal cells and had low or no Graft-versus-host activity. We thus named it as universal NKT (UNKT). In both direct and indirect 3D tumor-like organ model, UNKT showed efficient tumor-killing properties, indicating that it could penetrate the microenvironment of solid tumors. In mesothelin (MSLN)-positive tumor cells (SKOV-3 and MCF-7), MSLN targeting CAR modified-UNKT cells had enhanced killing potential against MSLN positive ovarian cancer compared with the wild type UNKT, as well as MSLN-CAR-T cells. Compared with CAR-T, Single-cell microarray 32-plex proteomics revealed CAR-UNKT cells express more effector cytokines, such as perforin and granzyme B, and less interleukin-6 after activation. Moreover, our CAR-UNKT cells featured in more multifunctionality than CAR-T cells. CAR-UNKT cells also demonstrated strong antitumor activity in mouse models of ovarian cancer, with the ability to migrate and infiltrate the tumor without inducing immune memory. The fast-in and -out, enhanced and prolonged tumor killing properties of CAR-UNKT suggested a novel cure option of cellular immunotherapy in the treatment of MSLN-positive solid tumors.


Assuntos
Neoplasias Hematológicas , Neoplasias Ovarianas , Receptores de Antígenos Quiméricos , Animais , Feminino , Humanos , Camundongos , Linhagem Celular , Mesotelina , Neoplasias Ovarianas/terapia , Microambiente Tumoral
7.
Eur Radiol ; 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37981590

RESUMO

OBJECTIVES: To compare prostate-specific membrane antigen (PSMA) PET with multiparametric MRI (mpMRI) in the diagnosis of pretreatment prostate cancer (PCa). METHODS: Pubmed, Embase, Medline, Web of Science, and Cochrane Library were searched for eligible studies published before June 22, 2022. We assessed risk of bias and applicability by using QUADAS-2 tool. Data synthesis was performed with Stata 17.0 software, using the "midas" and "meqrlogit" packages. RESULTS: We included 29 articles focusing on primary cancer detection, 18 articles about primary staging, and two articles containing them both. For PSMA PET versus mpMRI in primary PCa detection, sensitivities and specificities in the per-patient analysis were 0.90 and 0.84 (p<0.0001), and 0.66 and 0.60 (p <0.0001), and in the per-lesion analysis they were 0.79 and 0.78 (p <0.0001), and 0.84 and 0.82 (p <0.0001). For the per-patient analysis of PSMA PET versus mpMRI in primary staging, sensitivities and specificities in extracapsular extension detection were 0.59 and 0.66 (p =0.005), and 0.79 and 0.76 (p =0.0074), and in seminal vesicle infiltration (SVI) detection they were 0.51 and 0.60 (p =0.0008), and 0.93 and 0.96 (p =0.0092). For PSMA PET versus mpMRI in lymph node metastasis (LNM) detection, sensitivities and specificities in the per-patient analysis were 0.68 and 0.46 (p <0.0001), and 0.91 and 0.90 (p =0.81), and in the per-lesion analysis they were 0.67 and 0.36 (p <0.0001), and 0.99 and 0.99 (p =0.18). CONCLUSION: PSMA PET has higher diagnostic value than mpMRI in the detection of primary PCa. Regarding the primary staging, mpMRI has potential advantages in SVI detection, while PSMA PET has relative advantages in LNM detection. CLINICAL RELEVANCE STATEMENT: The integration of prostate-specific membrane antigen (PSMA) PET into the diagnostic pathway may be helpful for improving the accuracy of prostate cancer detection. However, further studies are needed to address the cost implications and evaluate its utility in specific patient populations or clinical scenarios. Moreover, we recommend the combination of PSMA PET and mpMRI for cancer staging. KEY POINTS: • Prostate-specific membrane antigen PET has higher sensitivity and specificity for primary tumor detection in prostate cancer compared to multiparametric MRI. • Prostate-specific membrane antigen PET also has significantly better sensitivity and specificity for lymph node metastases of prostate cancer compared to multiparametric MRI. • Multiparametric MRI has better accuracy for extracapsular extension and seminal vesicle infiltration compared to ate-specific membrane antigen PET.

8.
Appl Microbiol Biotechnol ; 107(21): 6641-6653, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37682300

RESUMO

This study aimed to evaluate the antibacterial activities of α-terpineol against common foodborne pathogenic bacteria by agar well diffusion, broth microdilution, and colony counting assay. Propulsive research was conducted to reveal the antibacterial mechanisms, including morphology, infrared spectroscopy, membrane fluidity, membrane permeability, proton motive force, and oxidative phosphorylation. Results indicated that the antibacterial activity of α-terpineol decreased in the following order: Escherichia coli O157:H7, Salmonella typhimurium, Listeria monocytogenes, and Staphylococcus aureus. With an initial cell count of 8 log CFU/mL, α-terpineol at 0.8% (v/v) reduced E. coli O157:H7 and S. aureus by approximately 5.6 and 3.9 log CFU/mL within 1 h, respectively. Remarkable destruction in cell envelopes and intracellular organizations was observed. The hydroxyl of α-terpineol might form glycosidic bonds with carbohydrates and hydrogen bonds with PO2- and COO- via infrared spectroscopy analysis. Generalized polarization of Laurdan revealed that the polar head groups of phospholipids transformed into close packed. The anisotropy variations of trimethyl amino-diphenylhexatriene (TMA-DPH) and DPH suggested membrane fluidity decreased. The N-phenyl-1-naphthylamine intake assay indicated that α-terpineol impaired the cell wall. Propidium iodide staining was indicative of damaged plasma membranes. Electron transport in the cytoplasmic membrane was impaired, inducing reactive oxygen species accumulation. Both membrane electrical potential and membrane pH gradient collapsed. The disruption of proton motive force and the leakage of ATP resulted in a deficit of intracellular ATP. Our research revealed the interaction between the hydroxyl group of α-terpineol and bacteria affects membrane function contributing to the bacteria's death. KEY POINTS: • α-Terpineol hydroxy formed glycosidic bonds and hydrogen bonds with bacteria • α-Terpineol increased the membrane gelation and reduced the membrane fluidity • Proton motive force and oxidative phosphorylation were impaired.


Assuntos
Escherichia coli O157 , Listeria monocytogenes , Microbiologia de Alimentos , Staphylococcus aureus , Contagem de Colônia Microbiana , Antibacterianos/farmacologia , Trifosfato de Adenosina
9.
Postgrad Med J ; 99(1177): 1138-1147, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37689998

RESUMO

Ankylosing spondylitis (AS) is a rheumatic bone and joint disease caused by inflammation, erosion, and pathological bone formation. The pathological features of chronic inflammation, bone destruction, and pathological ossification occur due to the disruption of the body's immune regulation and altered bone remodeling balance. Mesenchymal stem cells (MSCs) have multidirectional differentiation potential and immunomodulatory functions and play an important role in immune regulation and bone formation. The immune regulation and osteogenic capacity of MSCs in AS are altered by factors such as genetic background, internal environment, infection, and mechanical forces that drive disease development. This review further evaluates the role of MSCs dysfunction in inflammation and pathological bone formation by analyzing the effects of the above-mentioned factors on MSCs function and also looks forward to the prospects of MSCs in treating AS, providing some ideas for an in-depth study of inflammation and ectopic ossification.

10.
Acta Biochim Biophys Sin (Shanghai) ; 55(6): 956-973, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37294106

RESUMO

The distinct tumor microenvironment (TME) of prostate cancer (PCa), which promotes tumor proliferation and progression, consists of various stromal cells, immune cells, and a dense extracellular matrix (ECM). The understanding of the prostate TME extends to tertiary lymphoid structures (TLSs) and metastasis niches to provide a more concise comprehension of tumor metastasis. These constituents collectively structure the hallmarks of the pro-tumor TME, including immunosuppressive, acidic, and hypoxic niches, neuronal innervation, and metabolic rewiring. In combination with the knowledge of the tumor microenvironment and the advancement of emerging therapeutic technologies, several therapeutic strategies have been developed, and some of them have been tested in clinical trials. This review elaborates on PCa TME components, summarizes various TME-targeted therapies, and provides insights into PCa carcinogenesis, progression, and therapeutic strategies.


Assuntos
Neoplasias , Neoplasias da Próstata , Masculino , Humanos , Próstata , Microambiente Tumoral , Neoplasias da Próstata/terapia , Carcinogênese
11.
Sensors (Basel) ; 23(18)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37765931

RESUMO

To reduce the risks and challenges faced by frontline workers in confined workspaces, accurate real-time health monitoring of their vital signs is essential for improving safety and productivity and preventing accidents. Machine-learning-based data-driven methods have shown promise in extracting valuable information from complex monitoring data. However, practical industrial settings still struggle with the data collection difficulties and low prediction accuracy of machine learning models due to the complex work environment. To tackle these challenges, a novel approach called a long short-term memory (LSTM)-based deep stacked sequence-to-sequence autoencoder is proposed for predicting the health status of workers in confined spaces. The first step involves implementing a wireless data acquisition system using edge-cloud platforms. Smart wearable devices are used to collect data from multiple sources, like temperature, heart rate, and pressure. These comprehensive data provide insights into the workers' health status within the closed space of a manufacturing factory. Next, a hybrid model combining deep learning and support vector machine (SVM) is constructed for anomaly detection. The LSTM-based deep stacked sequence-to-sequence autoencoder is specifically designed to learn deep discriminative features from the time-series data by reconstructing the input data and thus generating fused deep features. These features are then fed into a one-class SVM, enabling accurate recognition of workers' health status. The effectiveness and superiority of the proposed approach are demonstrated through comparisons with other existing approaches.


Assuntos
Comércio , Dispositivos Eletrônicos Vestíveis , Humanos , Coleta de Dados , Nível de Saúde
12.
Nano Lett ; 22(3): 979-988, 2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35061402

RESUMO

Antisolvent-assisted spin coating has been widely used for fabricating metal halide perovskite films with smooth and compact morphology. However, localized nanoscale inhomogeneities exist in these films owing to rapid crystallization, undermining their overall optoelectronic performance. Here, we show that by relaxing the requirement for film smoothness, outstanding film quality can be obtained simply through a post-annealing grain growth process without passivation agents. The morphological changes, driven by a vaporized methylammonium chloride (MACl)-dimethylformamide (DMF) solution, lead to comprehensive defect elimination. Our nanoscale characterization visualizes the local defective clusters in the as-deposited film and their elimination following treatment, which couples with the observation of emissive grain boundaries and excellent inter- and intragrain optoelectronic uniformity in the polycrystalline film. Overcoming these performance-limiting inhomogeneities results in the enhancement of the photoresponse to low-light (<0.1 mW cm-2) illumination by up to 40-fold, yielding high-performance photodiodes with superior low-light detection.

13.
Molecules ; 28(23)2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38067533

RESUMO

The flower of Syringa pubescens Turcz. is used in Chinese folk medicine and also as a flower tea for healthcare. The effects of five drying methods on the active compound contents, the antioxidant abilities, anti-inflammatory properties and enzyme inhibitory activities were evaluated. The plant materials were treated using shade-drying, microwave-drying, sun-drying, infrared-drying and oven-drying. The seven active compounds were simultaneously determined using an HPLC method. Furthermore, the chemical profile was assessed using scanning electron microscopy, ultraviolet spectroscopy and infrared spectroscopy. The antioxidant capacities and protective effects on L02 cells induced with hydrogen peroxide were measured. The anti-inflammatory effects on lipopolysaccharide-induced RAW264.7 cells were investigated. The enzyme inhibitory activities were determined against α-amylase, α-glucosidase cholinesterases and tyrosinase. The results indicated that drying methods had significant influences on the active compound contents and biological properties. Compared with other samples, the OD samples possessed low IC50 values with 0.118 ± 0.004 mg/mL for DPPH radical, 1.538 ± 0.0972 for hydroxyl radical and 0.886 ± 0.199 mg/mL for superoxide radical, while the SHD samples had stronger reducing power compared with other samples. The SHD samples could be effective against H2O2-induced injury on L02 cells by the promoting of T-AOC, GSH-PX, SOD and CAT activities and the reducing of MDA content compared with other samples. Furthermore, SPF samples, especially the SHD sample, could evidently ameliorate inflammation through the inhibition of IL-6, IL-1ß and TNF-α expression. All the studied SPF samples exhibited evidently inhibitory effects on the four enzymes. The IC50 values of inhibitory activity on α-glucosidase and α-amylase from SHD sample were 2.516 ± 0.024 and 0.734 ± 0.034 mg/mL, respectively. SD samples had potential inhibitory effects on cholinesterases and tyrosinase with IC50 values of 3.443 ± 0.060 and 1.732 ± 0.058 mg/mL. In consideration of active compound contents and biological activities, it was recommended that SHD and SD be applied for drying SPF at an industrial scale.


Assuntos
Antioxidantes , Syringa , Antioxidantes/farmacologia , Antioxidantes/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Monofenol Mono-Oxigenase , alfa-Glucosidases , Peróxido de Hidrogênio , Anti-Inflamatórios/farmacologia , Flores , alfa-Amilases , Colinesterases
14.
Prostate ; 82(2): 276-285, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34807458

RESUMO

BACKGROUND: Preclinical studies showed that HC-1119, a deuterated version of enzalutamide, could competitively inhibit androgen binding to androgen receptor by blocking the transmission of androgen receptor signaling pathway as enzalutamide, inducing apoptosis of prostate cancer cells and reducing the proliferation of prostate cancer cells. Animal pharmacokinetic studies also show that deuterization of enzalutamide as HC-1119 could retain the basic properties of mother drug, increases the stability of compounds to metabolic enzymes and the drug exposure in vivo, prolong the half-life and reduce the production of metabolites, which may lead to a better efficacy and safety of HC-1119 compared with enzalutamide. METHODS: To evaluate the pharmacokinetics and safety of HC-1119 and the effects of food on pharmacokinetics in healthy adult Chinese men after single-dose administration of HC-1119. A total of 47 Chinese healthy adult male subjects received HC-1119 soft capsule at a single oral dose of 40, 80, or 160 mg followed on fasting or 160 mg after high-fat meal respectively. HC-1119 prototype and its metabolites M1 and M2 in plasma were collected individually in a total 23 time points. Pharmacokinetics were determined by sensitive LC/MS/MS for dose-proportionality study. RESULTS: In subjects taking HC-1119 soft capsules on fasting, Cmax of HC-1119 prototype increased dose-dependently. Either Cmax and AUC0-∞ of M1 or Cmax of M2 showed statistically significant difference. Dose-proportionality evaluation showed linear pharmacokinetic characteristics in Cmax of HC-1119 prototype, Cmax and AUC0-∞ of M2 in dose range of 40-160 mg. Cmax of HC-1119 was significantly different between the two groups as 160 mg HC-1119 on fasting or after a high-fat diet respectively, while the other parameter were not. HC-1119 and its metabolites M1 and M2 showed a linear dynamic trend. CONCLUSIONS: HC-1119 is expected to have lower clinical dose than the similar drug enzalutamide. The absorption of HC-1119 and the main pharmacokinetic parameters of HC-1119 and its metabolites M1 and M2 were not affected by high-fat diet. The clinical application of HC-1119 soft capsule in the later stage can be recommended for both fasting and postprandial. The safety and tolerance were good in this population.


Assuntos
Benzamidas , Proliferação de Células/efeitos dos fármacos , Estabilidade de Medicamentos , Interações Alimento-Droga , Nitrilas , Feniltioidantoína , Neoplasias da Próstata , Receptores Androgênicos/metabolismo , Administração Oral , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Benzamidas/farmacocinética , Biomarcadores Farmacológicos/análise , Cápsulas , China , Relação Dose-Resposta a Droga , Meia-Vida , Voluntários Saudáveis , Humanos , Masculino , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Nitrilas/farmacocinética , Feniltioidantoína/administração & dosagem , Feniltioidantoína/efeitos adversos , Feniltioidantoína/farmacocinética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Transdução de Sinais/efeitos dos fármacos
15.
Nat Mater ; 20(1): 10-21, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32929252

RESUMO

Metal halide perovskites have shown promising optoelectronic properties suitable for light-emitting applications. The development of perovskite light-emitting diodes (PeLEDs) has progressed rapidly over the past several years, reaching high external quantum efficiencies of over 20%. In this Review, we focus on the key requirements for high-performance PeLEDs, highlight recent advances on materials and devices, and emphasize the importance of reliable characterization of PeLEDs. We discuss possible approaches to improve the performance of blue and red PeLEDs, increase the long-term operational stability and reduce toxicity hazards. We also provide an overview of the application space made possible by recent developments in high-efficiency PeLEDs.

16.
World J Urol ; 40(6): 1413-1418, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35325307

RESUMO

OBJECTIVES: To investigate the safety profile and short-term outcome of super-veil nerve-sparing extraperitoneal single-port robotic-assisted radical prostatectomy (espRARP) on da Vinci Si platform. METHODS: From December 2018 to March 2021, 106 consecutive patients with treatment-naive prostate cancer were prospectively included. espRARP was performed on da Vinci Si surgical platform. Operative time, estimated blood loss, Clavien-Dindo complication classification, continence, potency recovery, quality-of-life scores, and postoperative prostate-specific antigen (PSA) were documented. RESULTS: Patients aged 52-79 years (mean ± SD, 64.8 ± 6.15 yrs), with a median PSA of 9.2 ng/ml (IQR: 6.70, 16.83) and median prostate volume of 31.9 ml (IQR: 30.01, 38.54). 95.28% (101/106) were clinically localized. All patients underwent espRARP successfully with no open conversions. Operative time was 94.2 ± 30.26 min with an estimated blood loss of 68.5 ml (range, 50-120 ml). No Grade III complications or above were documented. Positive surgical margin was 17.9% (19/106). Median pain score at discharge was 0 (IQR: 0, 1.75) without use of opioid narcotics. Postoperative length of stay was 3 days (IQR: 1, 3), in which 28 patients were discharged within 24 h. Instant, 1-, 3-, and 6 month continence recovery was 18.9, 45.3, 79.2, 93.4, and 96.4%, respectively. Of the 43 patients who received nerve-sparing procedures, 13 (30.23%) resumed potency 6 months postoperatively. 12 month biochemical recurrence-free survival was 92.77% (77/83). CONCLUSIONS: Extraperitoneal single-port robotic-assisted radical prostatectomy is a safe and feasible technique. Combined with super-veil nerve-sparing procedures, it may provide satisfactory outcome in short-term functional recovery.


Assuntos
Próstata , Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Idoso , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/inervação , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Resultado do Tratamento
17.
J Stroke Cerebrovasc Dis ; 31(12): 106841, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36332524

RESUMO

OBJECTIVES: To identify the morphologic and hemodynamic risk factor of mirror middle cerebral artery (MCA) aneurysms. METHODS: We conducted a retrospective analysis of 40 paired mirror MCA aneurysms. Aneurysms were divided into ruptured and unruptured groups. Seventeen morphological and nine hemodynamic parameters were measured using computer-assisted semiautomated measurement (CASAM) and computer flow dynamic (CFD) simulation. We performed a paired t-test (for normally distributed data) or a paired Wilcoxon rank-sum (for non-normally distributed data) to analyze all parameters between the groups. Multivariate conditional logistic regression analysis identified independent risk factors. The receiver operating characteristic curve was analyzed to acquire the area under the curve (AUC) and the cutoff values of the independent risk factors. RESULTS: There were significant differences in morphological and hemodynamic parameters between the ruptured and unruptured mirror aneurysms. The multivariate logistic analysis showed that the greater size (odds ratio [OR] = 9.807, p = 0.003), smaller neck diameter (OR = 0.285, p = 0.018) and maximum oscillatory shear index (OSI) (OR = 0.000001, p = 0.046) were independently correlated with aneurysm rupture. AUCs for size, N. and maximum OSI were 0.794, 0.695, and 0.701, respectively. The cutoff values of the size, neck diameter, and maximum OSI were 6.30, 5.07, and 0.356437, respectively. CONCLUSIONS: Morphology and hemodynamics can help predict aneurysm rupture risks. The more significant size, smaller neck diameter and maximum OSI were independent risk factors for the rupture of MCA aneurysms. The variables could aid practical risk evaluation.


Assuntos
Aneurisma Roto , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Angiografia Cerebral , Estudos Retrospectivos , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/etiologia , Hemodinâmica , Fatores de Risco , Artéria Cerebral Média/diagnóstico por imagem
18.
Compr Rev Food Sci Food Saf ; 21(4): 3647-3672, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35794726

RESUMO

Fish is one of the highly demanded aquatic products, and its quality and safety play a pivotal role in daily diet. However, the possible hazardous substance in perishable fish both in pre- and postharvest periods may decrease their values and pose a threat to public health. Laborious and expensive traditional methods drive the need of developing effective tools for detecting fish quality and safety properties in a rapid, nondestructive, and effective manner. Recent advances in Raman spectroscopy (RS) and surface-enhanced Raman scattering (SERS) have shown enormous potential in various aspects, which largely boost their applications in fish quality and safety evaluation. They have incomparable merits such as providing molecule fingerprint information and allowing for rapid, sensitive, and noninvasive detection with simple sample preparation. This review provides a comprehensive overview focusing on the applications of RS and SERS for fish quality assessment and safety inspection, highlighting the hazardous substance and illegal behavior both in preharvest (veterinary drug residues and environmental pollutants) and postharvest (freshness and illegal behavior) particularly. Moreover, challenges and prospects are also proposed to facilitate the vigorous development of RS and SERS. This review is aimed to emphasize potential opportunities for applying RS and SERS as promising techniques for routine food quality and safety detection. PRACTICAL APPLICATION: With these applications, it can be clearly indicated that RS and SERS are promising and powerful in fish quality and safety surveillance, thereby reducing the occurrence of commercial fraud and food safety issues. More efforts still should be concentrated on exploiting the high-performance Raman instruments, establishing a universal Raman database, developing reproducible SERS substrates and combing RS with other versatile spectral techniques to promote these technologies from laboratory to practice. It is hoped that this review should arouse more research interests in RS and SERS technologies for fish quality and safety surveillance, as well as provide more insights to make a breakthrough.


Assuntos
Poluentes Ambientais , Análise Espectral Raman , Animais , Qualidade dos Alimentos , Substâncias Perigosas , Análise Espectral Raman/métodos
19.
Compr Rev Food Sci Food Saf ; 21(2): 1568-1597, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35075750

RESUMO

Cutting is an imperative operation in the food-manufacturing factory, separating food into a predefined geometry. A broad range of solid foods, with various components, textures, and structures, pose enormous challenges to conventional cutting strategies. Additionally, the cutting performance is significantly impacted by the processing parameters, wherein trial-and-error or empirical methods are often used to select the parameters in source-wasting and time-consuming ways. Hence, there is a need to accelerate the development of advanced cutting techniques and novel modeling approaches in the food-manufacturing industry. Recently, advanced cutting techniques (ultrasonic vibration-assisted [UVA], laser, and waterjet cutting) are seen to be superior in processing foods of various textures, with the advantages of high cutting quality, low contamination, and easy operation. Compared with conventional cutting, advanced cutting techniques can dramatically reduce cutting force and energy consumption, resulting in high efficiency, energy-and-source saving, and low carbon footprint. Additionally, the finite element (FE) model does simulate the cutting process well, and artificial intelligence (AI) technology is competent to optimize the cutting parameters. This review is perhaps the first one focusing on the advanced cutting techniques applied in the food industry, serving as a summary of the cutting mechanisms, critical influence factors, and applications of conventional and advanced cutting techniques including UVA, laser, and waterjet cutting. In addition, the modeling approaches with respect to FE and AI models are emphasized. Finally, the challenges and future perspectives of advanced cutting techniques combined with modeling approaches are highlighted, and those approaches are promising in the future intelligent food-manufacturing industry. PRACTICAL APPLICATION: The review clearly demonstrates that advanced cutting techniques as having advantages such as high efficiency, energy-and-source saving, and low damages, thus exhibiting great potential in processing food of various textures with high cutting quality, low contamination, and easy operation. Additionally, the FE model does simulate the cutting process well and AI is competent in optimizing the cutting parameters, which possesses great potential in providing comprehensive cutting information and selecting the optimal combination of cutting parameters.


Assuntos
Inteligência Artificial , Indústria Alimentícia
20.
Angew Chem Int Ed Engl ; 61(37): e202209337, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-35856900

RESUMO

Additive engineering with organic molecules is of critical importance for achieving high-performance perovskite optoelectronic devices. However, experimentally finding suitable additives is costly and time consuming, while conventional machine learning (ML) is difficult to predict accurately due to the limited experimental data available in this relatively new field. Here, we demonstrate a deep learning method that can predict the effectiveness of additives in perovskite light-emitting diodes (PeLEDs) with a high accuracy up to 96 % by using a small dataset of 132 molecules. This model can maximize the information of the molecules and significantly mitigate the duplicated problem that usually happened with previous models in ML for molecular screening. Very high efficiency PeLEDs with a peak external quantum efficiency up to 22.7 % can be achieved by using the predicated additive. Our work opens a new avenue for further boosting the performance of perovskite optoelectronic devices.

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