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1.
NEJM Evid ; 3(4): EVIDoa2300236, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38771994

RESUMO

BACKGROUND: Certain populations have been historically underrepresented in clinical trials. Broadening eligibility criteria is one approach to inclusive clinical research and achieving enrollment goals. How broadened trial eligibility criteria affect the diversity of eligible participants is unknown. METHODS: Using a nationwide electronic health record-derived deidentified database, we identified a retrospective cohort of patients diagnosed with 22 cancer types between April 1, 2013 and December 31, 2022 who received systemic therapy (N=235,234) for cancer. We evaluated strict versus broadened eligibility criteria using performance status and liver, kidney, and hematologic function around first line of therapy. We performed logistic regression to estimate odds ratios for exclusion by strict criteria and their association with measures of patient diversity, including sex, age, race or ethnicity, and area-level socioeconomic status (SES); estimated the impact of broadening criteria on the number and distribution of eligible patients; and performed Cox regression to estimate hazard ratios for real-world overall survival (rwOS) comparing patients meeting strict versus broadened criteria. RESULTS: When applying common strict cutoffs for eligibility criteria to patients with complete data and weighting each cancer type equally, 48% of patients were eligible for clinical trials. Female (odds ratio, 1.30; 95% confidence interval [CI], 1.25 to 1.35), older (age 75+ vs. 18 to 49 years old: odds ratio, 3.04; 95% CI, 2.85 to 3.24), Latinx (odds ratio, 1.46; 95% CI, 1.39 to 1.54), non-Latinx Black (odds ratio, 1.11; 95% CI, 1.06 to 1.16), and lower-SES patients were more likely to be excluded using strict eligibility criteria. Broadening criteria increased the number of eligible patients by 78%, with the strongest impact for older, female, non-Latinx Black, and lower-SES patients. Patients who met only broadened criteria had worse rwOS versus those with strict criteria (hazard ratio, 1.31; 95% CI, 1.27 to 1.34). CONCLUSIONS: Data-driven evaluation of clinical trial eligibility criteria may optimize the eligibility of certain historically underrepresented groups and promote access to more inclusive trials. (Sponsored by Flatiron Health.).


Assuntos
Ensaios Clínicos como Assunto , Definição da Elegibilidade , Neoplasias , Seleção de Pacientes , Humanos , Feminino , Neoplasias/terapia , Neoplasias/etnologia , Neoplasias/mortalidade , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Adulto , Adolescente , Adulto Jovem
2.
Chem Commun (Camb) ; 60(10): 1313-1316, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38197169

RESUMO

S-doped nickel molybdate nanorods grown on nickel foam (S-NiMoO4/NF) were fabricated by a two-step hydrothermal method. The resultant S-NiMoO4/NF exhibited remarkable bifunctional electrocatalytic activity, with overpotentials of 235 mV for the hydrogen evolution reaction and 150 mV for the oxygen evolution reaction at a current density of 50 mA cm-2. Assembled into the two-electrode S-NiMoO4/NF electrolyzer in alkaline electrolytes for overall water splitting, it required only low cell voltages of 1.55 V and 1.63 V to drive 50 mA cm-2 and 100 mA cm-2, respectively. No significant performance degradation occurred during the water electrolysis process. The experimental results confirmed that S-doping induced the increase of the oxygen vacancies, accelerating the reaction kinetics and thus improving the electrocatalytic performance. Meanwhile, more active sites exposure on the surface of S-NiMoO4/NF enhanced the reactivity. This work may guide the development of efficient bifunctional catalysts in alkaline electrolysis through oxygen vacancy regulation.

3.
Chemosphere ; 350: 141104, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38171400

RESUMO

The loss of active components, weak acid resistance, and low recover efficiency of common Ca-based catalysts limited its further development and application. In this study, to effectively produce biodiesel from waste cooking oil (WCO), a green and recyclable magnetic acid-base bifunctional CoFe/biochar/CaO catalyst was prepared from sargassum and river snail shell waste via hydrothermal method. The catalysts' structure and properties were investigated by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), CO2/NH3 temperature programmed desorption (CO2/NH3 TPD), etc., The prepared catalyst mainly consisted of the carbon skeleton, CoFe alloy, and CaO. CoFe alloy provided catalyst's ferromagnetism for magnetic separation as well as acid sites for transesterification of WCO. Ca and other metal species with nanoscale (∼5.64 nm) were dispersively anchored on sargassum biochar surface, thereby leading to good catalytic activity (99.21% biodiesel yield) and stability (91.70% biodiesel yield after the 5th cycle). In addition, response surface methodology-Box-Behnken design (RSM-BBD) revealed the optimal operational conditions were 16:1 methanol/oil molar ratio, 3 wt% catalyst dosage, 73 °C for 157 min. The maximum biodiesel yield predicted value was 98.29% and the experimental value was 99.21%, indicating good satisfaction of the established model. Moreover, the quality of WCO biodiesel met the ASTM D6751 standards. This study benefits magnetic waste-derived acid-base bifunctional catalysts for the disposal of WCO towards sustainable biodiesel production.


Assuntos
Biocombustíveis , Carvão Vegetal , Óleos de Plantas , Óleos de Plantas/química , Biocombustíveis/análise , Dióxido de Carbono , Esterificação , Culinária , Catálise , Ligas , Fenômenos Magnéticos
4.
Fa Yi Xue Za Zhi ; 39(2): 129-136, 2023 Apr 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-37277375

RESUMO

OBJECTIVES: To investigate the reliability and accuracy of deep learning technology in automatic sex estimation using the 3D reconstructed images of the computed tomography (CT) from the Chinese Han population. METHODS: The pelvic CT images of 700 individuals (350 males and 350 females) of the Chinese Han population aged 20 to 85 years were collected and reconstructed into 3D virtual skeletal models. The feature region images of the medial aspect of the ischiopubic ramus (MIPR) were intercepted. The Inception v4 was adopted as the image recognition model, and two methods of initial learning and transfer learning were used for training. Eighty percent of the individuals' images were randomly selected as the training and validation dataset, and the remaining were used as the test dataset. The left and right sides of the MIPR images were trained separately and combinedly. Subsequently, the models' performance was evaluated by overall accuracy, female accuracy, male accuracy, etc. RESULTS: When both sides of the MIPR images were trained separately with initial learning, the overall accuracy of the right model was 95.7%, the female accuracy and male accuracy were both 95.7%; the overall accuracy of the left model was 92.1%, the female accuracy was 88.6% and the male accuracy was 95.7%. When the left and right MIPR images were combined to train with initial learning, the overall accuracy of the model was 94.6%, the female accuracy was 92.1% and the male accuracy was 97.1%. When the left and right MIPR images were combined to train with transfer learning, the model achieved an overall accuracy of 95.7%, and the female and male accuracies were both 95.7%. CONCLUSIONS: The use of deep learning model of Inception v4 and transfer learning algorithm to construct a sex estimation model for pelvic MIPR images of Chinese Han population has high accuracy and well generalizability in human remains, which can effectively estimate the sex in adults.


Assuntos
Aprendizado Profundo , Adulto , Feminino , Humanos , Masculino , Imageamento Tridimensional , Pelve , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
5.
ACS Macro Lett ; 12(3): 395-400, 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36877004

RESUMO

Cyclic olefin copolymer (COC) is one of the most promising optical materials; however, the brittle COC suffers from issues including a low refractive index. In this contribution, by the introduction of high refractive index comonomers including phenoxy substituted α-olefin (C4OAr), p-tolylthio substituted α-olefin (C4SAr) and carbazolyl substituted α-olefins (C4NAr, C3NAr, and C2NAr), the zirconocene mediated terpolymerization of ethylene (E) and tetracyclododecene (TCD) produces the preferred E-TCD-CnNAr (n = 2, 3, and 4) cyclic olefin terpolymers (COT) with tunable compositions (TCD: 11.5- 35.8 mol %, CnNAr: 1.2-5.0 mol %), high molecular weights and high glass transition temperatures (up to 167 °C) in high catalytic activities. Compared to the E-TCD copolymer (COC) material, these COT materials show the comparable thermal decomposition temperature (Td,5% = 437 °C), slightly higher strain at break value (up to 7.4%) and higher tensile strength (up to 60.5 MPa). In particular, these noncrystalline optical COT materials have significantly higher refractive indices of 1.550-1.569 and are more transparent (transmittance: 93-95%), relative to the COC materials, indicative of an excellent optical material.

6.
J Biopharm Stat ; 33(6): 770-785, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36843283

RESUMO

Pediatric patients should have access to medicines that have been appropriately evaluated for safety and efficacy through revised labelling. Given this goal, the adequacy of the pediatric clinical development plan and resulting safety database are critical factors to inform a favorable benefit-risk assessment for the intended use of the medicinal product. While extrapolation from adults can be used to support efficacy of drugs in children, there may be a reluctance to use the same approach in safety assessments, wiping out potential gains in trial efficiency through a reduction of sample size. To address this issue, we explore safety review in pediatric trials, including specific types of safety assessments and precision on the estimation of event rates for specific adverse events (AEs) that can be achieved. In addition, we discuss the assessments which can provide a benchmark for the use of extrapolation of safety that focuses on on-target effects. Finally, we explore a unified approach for understanding precision using Bayesian approaches as the most appropriate methodology to describe or ascertain risk in probabilistic terms for the estimate of the event rate of specific AEs.


Assuntos
Teorema de Bayes , Adulto , Humanos , Criança , Tamanho da Amostra , Bases de Dados Factuais , Medição de Risco
7.
J Biopharm Stat ; 33(6): 681-695, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36751009

RESUMO

The regulatory standards of the United States Food and Drug Administration (FDA) require substantial evidence of effectiveness from adequate and well-controlled trials, for drugs developed in both adults and children. However, when scientifically justified, relying on extrapolation may be acceptable. Historically, the FDA's extrapolation approach was based on draft guidance published in 2014, which introduced the categories of full, partial, and no extrapolation. The European Medicines Agency (EMA) took a different view on pediatric extrapolation. To better understand the use of extrapolation to support pediatric drug development and approval, we reviewed the pediatric labeling changes published by the FDA, focusing on the labeling updates between 1/1/2015 and 7/31/2021, the period where the extrapolation approach is in transition to harmonize with the EMA. Within this time window, among the 265 drugs and biological products with pediatric labeling changes, 169 (63.8%) were identified where extrapolation was used. This includes 64 (24.2%) labeling changes, where full extrapolation was used, and 105 (39.6%) labeling changes, where partial extrapolation was used. The major disease areas that extrapolation was used include neuroscience (40/53, 75.5%) and infectious disease (20/28, 71.4%). The extrapolation approach was identified in terms of source population beyond the use of adult as well as extrapolation from clinical trials conducted in the same drug class. The use of extrapolation increased the rates of new and expanded pediatric indication in the period. This review gives the most recent landscape of pediatric labeling changes using extrapolation. With the released ICH (International Council for Harmonization) E11A guidance in April 2022, the paper also provides insights for future pediatric drug development programs.


Assuntos
Aprovação de Drogas , Desenvolvimento de Medicamentos , Criança , Humanos , Preparações Farmacêuticas , Estados Unidos , United States Food and Drug Administration
8.
JAMA Oncol ; 9(4): 455-456, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36757717

RESUMO

This Viewpoint discusses the need for thoughtful, modernized eligibility criteria with equity prioritization in clinical trials.


Assuntos
Definição da Elegibilidade , Humanos , Seleção de Pacientes
9.
Ann Otol Rhinol Laryngol ; 132(3): 259-265, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35403442

RESUMO

OBJECTIVE: To analyze the factors related to postoperative recurrence in patients with localized laryngeal amyloidosis (LocLA) and to construct a nomogram prediction model (NPM). METHODS: We collected the data for LocLA patients diagnosed from March 2000 to May 2019 and clinical characteristics data were extracted. Factors related to recurrence were analyzed using multivariate logistic regression. The NPM was constructed for predicting the recurrence risk of LocLA. The receiver operating characteristic (ROC) curve evaluated the distinguishing ability using the area under curve (AUC). The calibration curve was created to evaluate the consistency of the NPM. RESULTS: A total of 226 confirmed LocLA cases were included. One hundred seventy-five cases (77.4%) had localized single nodule, and 51 cases had more than one lesions. Sixty-three (27.9%) cases had no multinucleated giant cell (MGC) around amyloid, and 163 (72.1%) cases had MGC around amyloid. Multivariate logistic regression analysis showed that more than one lesions (odds ratio [OR] = 3.206 and 95% confidence interval [CI]: 1.492-6.888; P value: .003), subglottic involvement (OR = 2.926 and 95% CI: 1.300-6.585; P = .010), and no multinucleated giant cell (MGC) around amyloid (OR = 2.503 and 95% CI: 1.173-5.342; P = .018) had a statistically significant effect on postoperative LocLA recurrence (P < .05). The AUC of the ROC curve was 0.753 (95% CI: 0.667-0.832). The bias-corrected curve approached the ideal curve, with an average absolute error of 0.037. CONCLUSIONS: More than one lesions, subglottic involvement, and no MGC around amyloid are risk factors for postoperative recurrence of LocLA. The NPM constructed has good applicability.


Assuntos
Amiloidose , Doenças da Laringe , Humanos , Nomogramas , Estudos Retrospectivos , Doenças da Laringe/diagnóstico , Doenças da Laringe/cirurgia , Curva ROC , Amiloidose/diagnóstico
10.
Biomater Sci ; 11(1): 119-127, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36367293

RESUMO

Photodynamic therapy (PDT) has been widely used in preclinical trials for treating various tumors. However, the hypoxic environment of tumors and the limited penetration depth of ultraviolet light severely weaken the PDT effect. To solve the above problems, a near-infrared (NIR) light-triggered oxygen (O2) self-supplied phototherapeutic platform (UCNPs/CeO2/Ce6/BSA) for amplified PDT performance against solid tumors by alleviating tumor hypoxia has been rationally developed. The platform has excellent stability and can continuously decompose H2O2 for sustained O2 supply to synergize 1O2 generation, thus inducing an enhanced mortality rate (59%) of ID8 cells in vitro under hypoxic + H2O2 conditions. The growth of solid tumors was effectively inhibited and the mouse survival rate was dramatically enhanced via a superior PDT therapeutic performance. This reported study facilitated the positive development of multifunctional diagnosis and treatment platforms under long-wavelength excitation for O2 self-supplied tumor treatments.


Assuntos
Nanopartículas , Fotoquimioterapia , Camundongos , Animais , Linhagem Celular Tumoral , Peróxido de Hidrogênio , Nanopartículas/uso terapêutico , Oxigênio , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
11.
Opt Express ; 30(8): 12387-12396, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35472875

RESUMO

Surface-enhanced Raman scattering (SERS) is a powerful analytical method that is especially suitable for the detection of protein molecules. Detection sensitivity of SERS is directly related to the enhancement factor of the substrate, which is dependent on the strength of a local surface electric field generated by surface plasmonic resonance from substrate. In this study, an electromagnetic induced transparency like (EIT-like) metamaterial was used as the SERS substrate. The corresponding plasmonic resonance structure not only produces stronger optical near field but also reduces the spectral line broadening due to radiation damping. This is very beneficial for SERS process, which is strongly dependent on electric field intensity, to improve the sensitivity of SERS detection. Compared with the single resonance mode substrate, the enhancement factor for SERS with the double-mode substrate was increased by an order of magnitude. The obtained EIT-like substrate was used as a SERS-active substrate to detect Lens culinaris agglutinin (LCA)-reactive fraction of AFP (AFP-L3), a hepatocellular carcinoma (HCC)-specific maker. Experimental results are in good agreement with the clinical diagnosis, which demonstrates the potential application of metamaterials in the SERS-based diagnosis and biosensing.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Fenômenos Eletromagnéticos , Humanos , Neoplasias Hepáticas/diagnóstico , Prata/química , Análise Espectral Raman/métodos , alfa-Fetoproteínas
12.
Opt Lett ; 47(9): 2137-2140, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35486743

RESUMO

Fluorescence lifetime imaging microendoscopy (FLIME) has been reported to investigate the physicochemical microenvironment in biological tissue. In this work, we designed a two-photon (TP) FLIME system based on a fiber-bundle glued with an achromatic mini-objective with 1.4-mm diameter, which was coupled to a standard TP microscope containing a dispersion precompensation module in the laser source. With 840 nm excitation, the field of view and lateral resolution of our system are 390 µm and 1.55 µm, respectively. To examine the capability of imaging in vivo, we obtained Z-stack (0-130 µm) TP-FLIME images from the intestine's surface of a mouse injected with squaraine dye. Further, we utilized the TP-FLIME system to image the kidney, liver, and xenografted tumor at 100-µm depth in vivo with cellular resolution, which features the distribution of cells and tissue structures with better contrast than intensity images. These results demonstrated that the proposed system is capable of measuring fluorescence lifetime in situ and provides a powerful tool to research the deep tissue microenvironment naturally.


Assuntos
Rim , Fótons , Animais , Lasers , Camundongos , Imagem Óptica
13.
Bioelectrochemistry ; 146: 108142, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35487143

RESUMO

In this work, a toxicity monitoring microbial system (TMMS) with a nitrifying biofilm as a sensing element and cathode oxygen reduction as an electrical signal was successfully constructed for trichloroacetaldehyde (TCAL) detection. The current and nitrification rate showed a linear relationship with TCAL concentration from 0 to 100 µg/L (R2current = 0.9892, R2nitrification = 0.9858), indicating that the target substrate concentration can be directly obtained from an electrical signal without further sample concentration. High-throughput sequencing revealed that the TMMS was composed of autotrophic/heterotrophic nitrifying and denitrifying microorganisms. Further analysis via a symbiotic relationship network demonstrated that unclassified_Comamonadaceae and unclassified_Xanthobacteraceae were the core nodes for maintaining the interaction between autotropic and heterotrophic nitrifying bacteria. Kyoto Encyclopedia of Genes and Genomes analysis showed that the electron transfer process primarily relied on ferredoxin and cytochromes under TCAL stress, and the abundance of functional enzymes involved in the process of nitrification was decreased, resulting in changes in electrical signal output. This work explored a visual signal sensor combined with electrochemistry and autotrophic/heterotrophic nitrification, which provided new insights into recognition and response mechanisms for microbial monitoring of toxic substances.


Assuntos
Desnitrificação , Nitrificação , Reatores Biológicos/microbiologia , Hidrato de Cloral/análogos & derivados , Nitrogênio
14.
Biomaterials ; 276: 121017, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34280826

RESUMO

Activatable phototherapeutic agents (PTA) in one system with synergistic gas therapy (GT) and photothermal therapy (PTT) hold great promise for highly efficient tumor treatments. In this study, an activatable multifunctional platform with photothermal conversion "turn on" features via nitric oxide (NO) release for synergistic GT and PTT was rationally designed using an aryl N-nitrosamine (NO-donating unit) functionalized aza-BODIPY framework (S-NO). As expected, after NO release from S-NO, the product (Red-S) showed obviously enhanced heat production performance under a longer excited wavelength via improved near-infrared light absorption and decreased fluorescence emission. Furthermore, water-soluble and biocompatible S-NO nanoparticles (S-NO NPs) with negligible dark cytotoxicity successfully suppressed tumor growth and enhanced the survival rate of mice via synergistic GT and PTT under the guidance of multimode imaging. The study offered rational guidance to design better platforms for synergistic tumor treatments and validated that S-NO NPs can act as potential PTAs in biological applications.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Camundongos , Neoplasias/tratamento farmacológico , Óxido Nítrico/uso terapêutico , Fototerapia
15.
Biomed Opt Express ; 12(4): 1962-1973, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33996210

RESUMO

Precise and efficient cell-to-cell communication is critical to the growth and differentiation of organisms, the formation of various organism, the maintenance of tissue function and the coordination of their various physiological activities, especially to the growth and invasion of cancer cells. Tunneling nanotubes (TNTs) were discovered as a new method of cell-to-cell communication in many cell lines. In this paper, we investigated TNTs-like structures in ovarian cancer cells and proved their elements by fluorescent staining, which showed that TNTs are comprised of natural lipid bilayers with microtubules as the skeleton that can transmit ions and organelles between adjacent cells. We then used fluorescence resonance energy transfer (FRET) based on two-photon excitation fluorescence lifetime imaging microscopy (FLIM) (TP-FLIM-FRET) to detect material transport in TNTs. The experimental results showed that the number of TNTs have an impact on the drug treatment of cancer cells, which provided a new perspective for TNTs involvement in cancer treatment. Our results also showed that TP-FLIM-FRET would potentially become a new optical method for TNTs study.

16.
Adv Biol (Weinh) ; 5(1): e2000184, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33724734

RESUMO

Stimulated Raman scattering (SRS) microscopy is a nonlinear optical imaging method for visualizing chemical content based on molecular vibrational bonds. Featuring high speed, high resolution, high sensitivity, high accuracy, and 3D sectioning, SRS microscopy has made tremendous progress toward biochemical information acquisition, cellular function investigation, and label-free medical diagnosis in the biosciences. In this review, the principle of SRS, system design, and data analysis are introduced, and the current innovations of the SRS system are reviewed. In particular, combined with various bio-orthogonal Raman tags, the applications of SRS microscopy in cell metabolism, tumor diagnosis, neuroscience, drug tracking, and microbial detection are briefly examined. The future prospects for SRS microscopy are also shared.


Assuntos
Microscopia , Microscopia Óptica não Linear , Análise Espectral Raman , Vibração
17.
J Proteomics ; 236: 104123, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33540063

RESUMO

Lampreys, one of the most basal jawless vertebrates, are an excellent animal model for investigating vertebrate evolution, embryonic development, and the origin of adaptive immunity. Gut-derived Shewanella strain was isolated and then proved to induce adaptive immunity response in lampreys. Using Shewanella as the antigen, the effect of gut-derived Shewanella on lamprey leukocyte proteome was investigated via label-free liquid chromatography-tandem mass spectrometry for quantitative proteomics analysis. Twenty-five differentially expressed proteins in lamprey leukocytes were identified with significant differences. The differentially expressed proteins were associated with several biological processes. Among these proteins, the signal transducer and activator of transcription 3 (STAT3) was significantly upregulated in leukocytes after Shewanella immunization, indicating that lamprey STAT3 (L-STAT3) was involved in Shewanella-lamprey interactions. Expression pattern analysis revealed that L-STAT3 was mainly distributed in the cytoplasm and upregulated in other tissues after Shewanella immunization. Moreover, L-STAT3 overexpression could promote HEK-293 T and HeLa cell proliferation. However, the functions of L-STAT3 in the adaptive immune response of lamprey induced by gut-derived Shewanella remain to be explored. Overall, the identification of leukocyte proteins involved in Shewanella-lamprey interactions provides important information for understanding the variable lymphocyte receptor-based adaptive immune signal pathways in lampreys. SIGNIFICANCE: Lampreys are considered to be an excellent animal model for studying the origin and development of adaptive immune systems in vertebrates. Lampreys use variable lymphocyte receptors (VLRs) in recognizing antigens. However, the understanding of the VLR-based adaptive immune signal pathways in lampreys remains unclear. Intestinal bacteria could regulate the development of host immune systems. The attempts of inducing lamprey leukocyte differentially expressed proteins using the gut bacterial as the antigen will supply an promising avenue to explore the molecular mechanism of the intestinal bacteria interaction with it's host. Also, the identification of differentially expressed proteins involved in interactions between gut-derived Shewanella and lamprey will supply clues for understanding the variable lymphocyte receptor-based adaptive immune signal pathways in lampreys.


Assuntos
Shewanella , Animais , Células HEK293 , Células HeLa , Humanos , Lampreias , Leucócitos
18.
J Nanobiotechnology ; 19(1): 37, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541369

RESUMO

BACKGROUND: The aim to develop a highly stable near-infrared (NIR) photoinduced tumor therapy agent stems from its considerable potential for biological application. Due to its long wavelength, biological imaging exhibits a high signal-to-background ratio, deep tissue penetration and maximum permissible light power, which can minimize damage to an organism during photoinduced tumor therapy. RESULTS: A class of stable NIR-II fluorophores (NIR998, NIR1028, NIR980, NIR1030, and NIR1028-S) based on aza-boron-dipyrromethene (aza-BODIPY) dyes with donor-acceptor-donor structures have been rationally designed and synthesized by harnessing the steric relaxation effect and intramolecular photoinduced electron transfer (IPET). These fluorophores exhibit an intense range of NIR-II emission, large Stokes shift (≥ 100 nm), excellent photothermal conversion performance, and superior stability against photobleaching. Among the NIR-II fluorophores, NIR998 possesses better NIR-II emission and photothermal conversion performance. NIR998 nanoparticles (NIR998 NPs) can be encapsulated by liposomes. NIR998 NPs show superior stability in the presence of light, heat, and reactive oxygen nitrogen species than that of indocyanine green NPs, as well as a higher photothermal conversion ability (η = 50.5%) compared to other photothermal agents. Finally, under the guidance of photothermal imaging, NIR998 NPs have been proven to effectively eliminate tumors via their excellent photothermal conversion performance while presenting negligible cytotoxicity. CONCLUSIONS: Utilizing IPET and the steric relaxation effect can effectively induce NIR-II emission of aza-BODIPY dyes. Stable NIR998 NPs have excellent photothermal conversion performance and negligible dark cytotoxicity, so they have the potential to act as photothermal agents in biological applications.


Assuntos
Compostos de Boro/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/terapia , Terapia Fototérmica/métodos , Animais , Compostos de Boro/análise , Compostos de Boro/farmacocinética , Linhagem Celular Tumoral , Feminino , Corantes Fluorescentes/análise , Corantes Fluorescentes/farmacocinética , Humanos , Raios Infravermelhos , Camundongos , Nanopartículas/análise , Neoplasias/diagnóstico por imagem , Nanomedicina Teranóstica , Termografia
19.
J Biophotonics ; 14(6): e202000498, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33624930

RESUMO

The mortality of high-grade serous ovarian cancer (HGSOC) accounts for 70% to 80% of all ovarian cancer deaths and overall mortality rate has not declined in the last decade. Recently, many studies have demonstrated that HGSOC originates from the fallopian tubes. The extracellular matrix (ECM) is present in all tissues, its remodeling and interaction with cells are crucial for regulating cell proliferation, migration, and differentiation. In this paper, we used label-free nonlinear optical microscopy to image tissues of the fallopian tube and ovary. Combining a set of image processing algorithms, we monitored the remodeling of ECM in the fallopian tube and ovary during the invasion of primary serous fallopian tube tumor into the ovary in microscopic dimension. With this approach, we can obtain physiological information of HGSOC at the early stage, which provided useful data for auxiliary clinical diagnosis.


Assuntos
Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Matriz Extracelular , Feminino , Humanos , Microscopia Óptica não Linear , Neoplasias Ovarianas/diagnóstico por imagem
20.
Lancet Psychiatry ; 8(3): 191-201, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33610228

RESUMO

BACKGROUND: Cognitive impairment associated with schizophrenia predicts poor functional outcomes, but currently no approved pharmacotherapy is available. This study investigated whether the glycine transporter-1 inhibitor BI 425809 improves cognition in patients with schizophrenia. METHODS: This phase 2, randomised, double-blind, placebo-controlled, parallel-group trial (81 centres, 11 countries), randomly assigned outpatients (aged 18-50 years) with schizophrenia on stable treatment to add-on once-daily oral BI 425809 2 mg, 5 mg, 10 mg, or 25 mg or placebo (1:1:1:1:2) for 12 weeks. Treatment was assigned in blocks using interactive response technology; patients, investigators, and all trial personnel were masked to group assignment. The primary endpoint was change from baseline in MATRICS Consensus Cognitive Battery (MCCB) overall composite T-score at week 12. Six predefined dose-response models were evaluated using a multiple comparison procedure and modelling approach with mixed model repeated measures to assess evidence for a non-flat dose-response relationship for cognitive improvements with BI 425809. Adverse events were monitored. Safety analyses included all randomly allocated patients who received one or more doses of trial medication; efficacy analyses included patients from this set who also had available baseline data and at least one post-baseline on-treatment measurement for the primary or secondary endpoint. This study is registered with ClinicalTrials.gov, number NCT02832037. FINDINGS: 509 patients were randomly assigned between April 25, 2018, and Oct 4, 2019 (BI 425809 2 mg, n=85; 5 mg, n=84; 10 mg, n=85; 25 mg, n=85; placebo, n=170 444 (87%) completed the 12-week treatment. Five of six dose-response models showed a statistically significant benefit of BI 425809 over placebo (linear [t=2·55, p=0·015], linear in log [t=2·56, p=0·015]; Emax [t=2·75, p=0·0089], sigmoid Emax [t=2·98, p=0·0038], logistic [t=2·77, p=0·0085]). Pairwise comparisons showed greater mean improvement from baseline in MCCB overall composite T-score at week 12 with BI 425809 10 mg and 25 mg versus placebo (adjusted mean difference 1·98 [95% CI 0·43-3·53] for 10 mg and 1·73 [0·18-3·28] for 25 mg; standardised effect size 0·34 for 10 mg and 0·30 for 25 mg). Adverse events were balanced across groups, reported in 50 (59%) of 85 patients on BI 425809 2 mg, 44 (52%) of 84 on 5 mg, 35 (41%) of 85 on 10 mg, 36 (42%) of 85 on 25 mg, and 74 (44%) of 170 on placebo. INTERPRETATION: BI 425809 improved cognition after 12 weeks in patients with schizophrenia; doses of 10 mg and 25 mg showed the largest separation from placebo. If these encouraging results are confirmed in phase 3 trials, BI 425809 could provide an effective treatment for cognitive impairment associated with schizophrenia. FUNDING: Boehringer Ingelheim.


Assuntos
Cognição/efeitos dos fármacos , Proteínas da Membrana Plasmática de Transporte de Glicina/antagonistas & inibidores , Compostos Orgânicos/administração & dosagem , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Disfunção Cognitiva/tratamento farmacológico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , Compostos Orgânicos/efeitos adversos , Resultado do Tratamento , Adulto Jovem
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