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1.
J Hazard Mater ; : 127910, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34863568

RESUMO

A selective separation-recovery process based on tuning organic acid was proposed to the resource recycling of spent lithium-ion batteries (LIBs) for the first time. The low-cost preparation of CoFe2O4, reuse of waste acid and recovery of Li can be realized in this process, simultaneously. Li and Co in spent LIBs can be leached efficiently using citric acid as a leaching agent, and separated effectively from leaching solution by tuning oxalic acid content. The results from the characterizations of the prepared CoFe2O4 (CoFe2O4-LIBs) show that it possesses higher ratio of Co(II)/Co(III) and Fe(II)/Fe(III), larger surface specific area and more number of acid sites in comparison with pure CoFe2O4. Besides, CoFe2O4-LIBs was used to activate peroxymonosulfate (PMS) for the degradation of bisphenol A (BPA). Interestingly, its degradation performance is superior to that of pure CoFe2O4 and the related Co-based catalysts. The excellent degradation performance can be maintained in presence of inorganic ions (e.g., Cl-, HCO3-, H2PO4- and NO3-) with high concentration or humic acid. Moreover, surface-bound SO4∙- is considered as the main reactive species for the degradation of BPA. More importantly, CoFe2O4-LIBs can be readily recycled by using an external magnet and own superior ability of regeneration.

2.
Water Res ; 206: 117732, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34637972

RESUMO

Microplastics (MPs) have been recognized as a global concern due to their potential health effect, as MPs could adsorb and carry various pollutants in aquatic environment. In the present study, a new environmental behavior related to polyvinyl chloride microplastics (PVC-MPs) and the underlying mechanism were described. Our results showed that the photo-aged PVC-MPs could affect the transformation of cephalosporin antibiotics. For instance, the presence of altered PVC-MPs significantly accelerated the hydrolysis of cefazolin (CFZ), but exhibited negligible effect on the degradation of cephalexin (CFX). As indicated by in situ Fourier transform infrared spectra and theoretical calculations, hydrogen bonds could be formed between ß-lactam carbonyl of CFZ and the oxygen-containing moieties on the aged PVC-MP surfaces. The hydrogen-bonding was able to significantly increase the positive atomic Mulliken charge on the ß-lactam carbonyl carbon, thus narrowing the energy gap of CFZ hydrolysis and subsequently enhancing the disruption of ß-lactam ring. While for CFX, instead of the ß-lactam carbonyl, the amide amino group was involved in the hydrogen-bonding due to the structural difference. Therefore, in addition to increasing the adsorption capacity, the aged PVC-MPs could act as the catalyst to mediate the transformation of antibiotics. Our study would help improve the understanding for interactions between contaminants and MPs in natural environments.


Assuntos
Microplásticos , Poluentes Químicos da Água , Adsorção , Cefalosporinas , Plásticos , Cloreto de Polivinila , Poluentes Químicos da Água/análise
3.
Opt Express ; 29(19): 30337-30347, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34614759

RESUMO

A Mach-Zehnder interferometer system based on weak measurement was set up to determinate the concentration variation of molecule by measuring the phase difference change between the two optical paths. The spectrum of the light was recorded to monitor the concentration of trastuzumab (Herceptin), which is a humanised monoclonal antibody, targeted to human epidermal growth factor receptor 2 (HER2). The trastuzumab targeting to HER2 was real-time detected and continuously monitored, the HER2 numbers of COS7 cells on a coverslip was determined at pico-molar level. Our weak measurement enabled method proposes an alternative approach for the concentration detection of molecules, providing a promising functional tool for the quantification of HER2 in cancer cells, possibly promoting fields such as the diagnosis and treatment of cancer.

5.
Stat Med ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34649301

RESUMO

Alzheimer's disease (AD) is a severe neurodegenerative disorder impairing multiple domains, for example, cognition and behavior. Assessing the risk of AD progression and initiating timely interventions at early stages are critical to improve the quality of life for AD patients. Due to the heterogeneous nature and complex mechanisms of AD, one single longitudinal outcome is insufficient to assess AD severity and disease progression. Therefore, AD studies collect multiple longitudinal outcomes, including cognitive and behavioral measurements, as well as structural brain images such as magnetic resonance imaging (MRI). How to utilize the multivariate longitudinal outcomes and MRI data to make efficient statistical inference and prediction is an open question. In this article, we propose a multivariate joint model with functional data (MJM-FD) framework that relates multiple correlated longitudinal outcomes to a survival outcome, and use the scalar-on-function regression method to include voxel-based whole-brain MRI data as functional predictors in both longitudinal and survival models. We adopt a Bayesian paradigm to make statistical inference and develop a dynamic prediction framework to predict an individual's future longitudinal outcomes and risk of a survival event. We validate the MJM-FD framework through extensive simulation studies and apply it to the motivating Alzheimer's Disease Neuroimaging Initiative (ADNI) study.

6.
Front Artif Intell ; 4: 568384, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568811

RESUMO

There is an ever-growing mismatch between the proliferation of data-intensive, power-hungry deep learning solutions in the machine learning (ML) community and the need for agile, portable solutions in resource-constrained devices, particularly for intelligence at the edge. In this paper, we present a fundamentally novel approach that leverages data-driven intelligence with biologically-inspired efficiency. The proposed Sparse Embodiment Neural-Statistical Architecture (SENSA) decomposes the learning task into two distinct phases: a training phase and a hardware embedment phase where prototypes are extracted from the trained network and used to construct fast, sparse embodiment for hardware deployment at the edge. Specifically, we propose the Sparse Pulse Automata via Reproducing Kernel (SPARK) method, which first constructs a learning machine in the form of a dynamical system using energy-efficient spike or pulse trains, commonly used in neuroscience and neuromorphic engineering, then extracts a rule-based solution in the form of automata or lookup tables for rapid deployment in edge computing platforms. We propose to use the theoretically-grounded unifying framework of the Reproducing Kernel Hilbert Space (RKHS) to provide interpretable, nonlinear, and nonparametric solutions, compared to the typical neural network approach. In kernel methods, the explicit representation of the data is of secondary nature, allowing the same algorithm to be used for different data types without altering the learning rules. To showcase SPARK's capabilities, we carried out the first proof-of-concept demonstration on the task of isolated-word automatic speech recognition (ASR) or keyword spotting, benchmarked on the TI-46 digit corpus. Together, these energy-efficient and resource-conscious techniques will bring advanced machine learning solutions closer to the edge.

7.
Science ; 374(6566): 472-478, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34554826
8.
N Engl J Med ; 385(20): 1856-1867, 2021 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-34534429

RESUMO

BACKGROUND: Pembrolizumab has efficacy in programmed death ligand 1 (PD-L1)-positive metastatic or unresectable cervical cancer that has progressed during chemotherapy. We assessed the relative benefit of adding pembrolizumab to chemotherapy with or without bevacizumab. METHODS: In a double-blind, phase 3 trial, we randomly assigned patients with persistent, recurrent, or metastatic cervical cancer in a 1:1 ratio to receive pembrolizumab (200 mg) or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy and, per investigator discretion, bevacizumab. The dual primary end points were progression-free survival and overall survival, each tested sequentially in patients with a PD-L1 combined positive score of 1 or more, in the intention-to-treat population, and in patients with a PD-L1 combined positive score of 10 or more. The combined positive score is defined as the number of PD-L1-staining cells divided by the total number of viable tumor cells, multiplied by 100. All results are from the protocol-specified first interim analysis. RESULTS: In 548 patients with a PD-L1 combined positive score of 1 or more, median progression-free survival was 10.4 months in the pembrolizumab group and 8.2 months in the placebo group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.50 to 0.77; P<0.001). In 617 patients in the intention-to-treat population, progression-free survival was 10.4 months and 8.2 months, respectively (hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P<0.001). In 317 patients with a PD-L1 combined positive score of 10 or more, progression-free survival was 10.4 months and 8.1 months, respectively (hazard ratio, 0.58; 95% CI, 0.44 to 0.77; P<0.001). Overall survival at 24 months was 53.0% in the pembrolizumab group and 41.7% in the placebo group (hazard ratio for death, 0.64; 95% CI, 0.50 to 0.81; P<0.001), 50.4% and 40.4% (hazard ratio, 0.67; 95% CI, 0.54 to 0.84; P<0.001), and 54.4% and 44.6% (hazard ratio, 0.61; 95% CI, 0.44 to 0.84; P = 0.001), respectively. The most common grade 3 to 5 adverse events were anemia (30.3% in the pembrolizumab group and 26.9% in the placebo group) and neutropenia (12.4% and 9.7%, respectively). CONCLUSIONS: Progression-free and overall survival were significantly longer with pembrolizumab than with placebo among patients with persistent, recurrent, or metastatic cervical cancer who were also receiving chemotherapy with or without bevacizumab. (Funded by Merck Sharp and Dohme; KEYNOTE-826 ClinicalTrials.gov number, NCT03635567.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma/mortalidade , Carcinoma/secundário , Método Duplo-Cego , Feminino , Humanos , Análise de Intenção de Tratamento , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Medidas de Resultados Relatados pelo Paciente , Intervalo Livre de Progressão , Análise de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
9.
Nature ; 597(7877): 503-510, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34552257

RESUMO

Large, distributed collections of miniaturized, wireless electronic devices1,2 may form the basis of future systems for environmental monitoring3, population surveillance4, disease management5 and other applications that demand coverage over expansive spatial scales. Aerial schemes to distribute the components for such networks are required, and-inspired by wind-dispersed seeds6-we examined passive structures designed for controlled, unpowered flight across natural environments or city settings. Techniques in mechanically guided assembly of three-dimensional (3D) mesostructures7-9 provide access to miniature, 3D fliers optimized for such purposes, in processes that align with the most sophisticated production techniques for electronic, optoelectronic, microfluidic and microelectromechanical technologies. Here we demonstrate a range of 3D macro-, meso- and microscale fliers produced in this manner, including those that incorporate active electronic and colorimetric payloads. Analytical, computational and experimental studies of the aerodynamics of high-performance structures of this type establish a set of fundamental considerations in bio-inspired design, with a focus on 3D fliers that exhibit controlled rotational kinematics and low terminal velocities. An approach that represents these complex 3D structures as discrete numbers of blades captures the essential physics in simple, analytical scaling forms, validated by computational and experimental results. Battery-free, wireless devices and colorimetric sensors for environmental measurements provide simple examples of a wide spectrum of applications of these unusual concepts.

10.
Front Oncol ; 11: 706448, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476214

RESUMO

Tumor-associated macrophages (TAMs) account for more than 50% of the cells in the tumor immune microenvironment of patients with breast cancer. A high TAM density is associated with a poor clinical prognosis. Targeting TAMs is a promising therapeutic strategy because they promote tumor growth, development, and metastasis. In this study, we found that dimethyl formamide (DMF) significantly inhibited the tumor invasion-promoting ability of TAMs in the co-culture system and further showed that DMF functioned by reducing reactive oxygen species (ROS) production in TAMs. The orthotopic 4T1 cell inoculation model and the spontaneous mouse mammary tumor virus-polyoma middle tumor-antigen tumor model were used to evaluate the antitumor effect of DMF. The results showed that DMF significantly inhibited tumor metastasis and increased T-cell infiltration into the tumor microenvironment. Mechanistically, NRF2 activation was necessary for DMF to exert its function, and DMF can play a role in breast cancer as an anticancer drug targeting TAMs.

11.
Bioresour Technol ; 340: 125701, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34352644

RESUMO

This study investigated the dynamics of ATP synthase activity, phospholipid fatty acid (PLFA) profile, and temporal evolution and spatial distribution of bacterial community to analyze bacterial survival strategies in sludge alkaline fermentation (SAF) for volatile fatty acids (VFAs) production. The results revealed a significant increase in ATP synthase activity at pH 9 and 10 (p < 0.05), which could contribute to proton entry into cells and benefit bacterial survival. PLFA analysis indicated that the unsaturated fatty acids content increased with the increase of pH. Firmicutes were the dominant microorganisms in the running stage of the pH 10 reactor (35.81-62.34%) and might have been the key microbes that influenced VFAs production. Further analysis of the spatial distribution of microbial community suggested that Firmicutes mainly lived inside flocs during SAF. These findings provide an understanding for bacterial survival strategies in SAF, which could help to develop methods to further improve VFAs yield.


Assuntos
Ácidos Graxos Voláteis , Esgotos , Bactérias , Reatores Biológicos , Fermentação , Concentração de Íons de Hidrogênio
12.
Sheng Li Xue Bao ; 73(4): 551-558, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34405211

RESUMO

Nonalcoholic fatty liver disease (NAFLD) and hyperhomocysteinemia (HHcy) both are major health problems worldwide, whose incidence are closely related with each other. We previously reported the mechanism of HHcy-caused hepatic steatosis, but the role of n-3 polyunsaturated fatty acid (n-3 PUFA) in HHcy-induced hepatic steatosis remains unclear. In this study, 6-week-old C57BL/6 male mice were given a high methionine diet (HMD, 2% methionine diet), and plasma homocysteine levels were measured by ELISA to confirm the establishment of an HHcy model. Meantime, mice were fed HMD with or without n-3 PUFA supplement for 8 weeks to determine the role and mechanism of n-3 PUFA in hepatic steatosis induced by HHcy. Results showed that n-3 PUFA significantly improved hepatic lipid deposition induced by HHcy. qRT-PCR analysis demonstrated that n-3 PUFA inhibited the upregulation of Cd36, a key enzyme of fatty acid uptake, caused by HHcy. Further, the inhibition of hepatic Cd36 expression was associated with the inactivation of aryl hydrocarbon receptor (Ahr) induced by n-3 PUFA. Of note, mass spectrometry revealed that hepatic content of lipoxin A5 (LXA5) was significantly increased in HMD+n-3 PUFA-fed mice compared with that in HMD-fed mice. In primary cultured hepatocytes, LXA5 treatment markedly reversed homocysteine-evoked Cd36 upregulation and Ahr activation, which resulted in reduced lipid accumulation. In conclusion, we demonstrate that n-3 PUFA inactivates HHcy-induced Ahr-Cd36 pathway by increasing hepatic LXA5 content, which alleviates hepatic steatosis. Thus, our results may provide a potential strategy for treatment of NAFLD.


Assuntos
Ácidos Graxos Ômega-3 , Fígado Gorduroso , Hiper-Homocisteinemia , Animais , Fígado Gorduroso/tratamento farmacológico , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/tratamento farmacológico , Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL
13.
Matern Child Nutr ; 17(4): e13244, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34258858

RESUMO

Human immunodeficiency virus (HIV)-positive women can breastfeed with minimal risk of mother-to-child transmission if taking antiretrovirals. Guidelines surrounding infant feeding for HIV-positive women have evolved several times over the last two decades. Our review aimed to explore perspectives of breastfeeding with antiretrovirals from HIV-positive women since the World Health Organization (2010) infant feeding and antiretroviral guidelines. HIV-positive pregnant and postnatal women from all countries/settings were eligible. HIV-positive women were either on an antiretroviral regimen at the time of the study, previously on an antiretroviral regimen, not initiated on a regimen yet, or enrolled in prevention of mother-to-child transmission (PMTCT) care. Quality assessment of all included studies were conducted. Four databases (CINAHL, EMBASE, MEDLINE and PsycINFO) were searched for studies conducted from January 2010 to October 2020. Nine papers were included in the review, of which two presented findings from the same study. Five analytical themes were developed via thematic synthesis: (1) awareness of breastfeeding with antiretrovirals, (2) turmoil of emotions, (3) coping mechanisms, (4) the intertwining of secret, stigma and support and (5) support needed. Support from family and health care professionals and coping approaches were important to overcome stigma and the emotional challenges of breastfeeding with antiretrovirals. Health care professionals should be familiar with the most updated national and local guidance surrounding infant feeding and antiretrovirals. Further research into interventions to encourage HIV-positive women to adhere and commit to lifelong antiretroviral treatment (Option B+) for breastfeeding is required.


Assuntos
Infecções por HIV , Complicações Infecciosas na Gravidez , Aleitamento Materno , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/prevenção & controle
14.
Nurs Open ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34198365

RESUMO

AIM: Our study aimed to evaluate the sleep status of psychiatric nurses in Chinese population and analyse the influencing factors. DESIGN: Cross-sectional, correlation design with logistic regression analysis. METHODS: We investigated 1,044 psychiatric nurses from seven psychiatric hospitals in China. Pittsburgh Sleep Quality Index and Maslach Burnout Inventory General Survey were used as main measures. RESULTS: The average Pittsburgh Sleep Quality Index score of 1,044 psychiatric nurses was 7.00 ± 3.59, and 38.63% of nurses had a total Pittsburgh Sleep Quality Index score >7. Our study found that middle-night shift nurses had poor sleep quality and sleep disorders are positively correlated with emotional exhaustion and cynical disregard for job burnout. Middle-night shift nurses showed 1.586 times more likely to suffer from sleep disorders than those non-middle-night shift. The higher the score of emotional exhaustion, the greater the risk of sleep disorders.

15.
Poult Sci ; 100(9): 101310, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34298381

RESUMO

In China, the low egg production rate is a major challenge to Muscovy duck farmers. Hypothalamus and ovary play essential role in egg production of birds. However, there are little or no reports from these tissues to identify potential candidate genes responsible for egg production in White Muscovy ducks. A total of 1,537 laying ducks were raised; the egg production traits which include age at first egg (days), number of eggs at 300 d, and number of eggs at 59 wk were recorded. Moreover, 4 lowest (LP) and 4 highest producing (HP) were selected at 59 wk of age, respectively. To understand the mechanism of egg laying regulation, we sequenced the hypothalamus and ovary transcriptome profiles in LP and HP using RNA-Seq. The results showed that the number of eggs at 300 d and number of eggs at 59 wk in the HP were significantly more (P < 0.001) than the LP ducks. In total, 106.98G clean bases were generated from 16 libraries with an average of 6.68G clean bases for each library. Further analysis showed 569 and 2,259 differentially expressed genes (DEGs) were identified in the hypothalamus and ovary between LP and HP, respectively. The KEGG pathway enrichment analysis revealed 114 and 139 pathways in the hypothalamus and ovary, respectively which includes Calcium signaling pathway, ECM-receptor interaction, Focal adhesion, MAPK signaling pathway, Apoptosis and Apelin signaling pathways that are involved in egg production. Based on the GO terms and KEGG pathways results, 10 potential candidate genes (P2RX1, LPAR2, ADORA1, FN1, AKT3, ADCY5, ADCY8, MAP3K8, PXN, and PTTG1) were identified to be responsible for egg production. Further, protein-protein interaction was analyzed to show the relationship between these candidate genes. Therefore, this study provides useful information on transcriptome of hypothalamus and ovary of LP and HP Muscovy ducks.


Assuntos
Patos , Ovário , Animais , Galinhas , Patos/genética , Feminino , Perfilação da Expressão Gênica/veterinária , Hipotálamo , Óvulo , Transcriptoma
16.
BMC Surg ; 21(1): 300, 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34174862

RESUMO

BACKGROUND: Anastomotic leakage is one of the most serious postoperative complications of rectal cancer. Prophylactic ileostomy has been widely used to reduce the risk and severity of complications of anastomotic leakage. However, prophylactic ileostomy itself has some complications, and ileostomy high output syndrome (HOS) is one of them. This study was performed to explore the risk factors of HOS in ileostomy. METHODS: A total of 114 patients with HOS were screened out from 494 eligible ileostomy patients in the last 5 years. The relationship between HOS and the clinicopathological data was analyzed using the Chi-square test and Fisher's exact probability. Multivariate analysis was performed by logistic regression. RESULTS: The incidence of HOS was 23.07% in this study. Dehydration was the most common symptom of HOS (37.7%). There was no clear correlation between HOS occurrence with sex, age, gross typing, histological grade, tumor location, lymph node metastasis, and TNM stage (p > 0.05). The incidence of HOS was 14/18 in inflammatory bowel disease patients, 18/28 in diabetes mellitus patients, and 23/72 in neoadjuvant chemoradiotherapy patients, 13/17 in total colectomy and abdominal infection patients. Multivariate analysis showed that they are risk factors for HOS (p < 0.05). CONCLUSION: HOS occurred occasionally but rarely studied and lacks attention. Inflammatory bowel disease, diabetes mellitus, neoadjuvant radiotherapy chemotherapy, total colectomy and abdominal infection are the risk factors for HOS.


Assuntos
Ileostomia , Neoplasias Retais , Anastomose Cirúrgica , Fístula Anastomótica , Humanos , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco
17.
Philos Trans R Soc Lond B Biol Sci ; 376(1827): 20200033, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-33938280

RESUMO

This review aimed to synthesize qualitative evidence of views and experiences of partners and other family members who provided breastfeeding support for a relative. The Joanna Briggs Institute (JBI) methodology for systematic reviews of qualitative evidence was followed. Seven databases: CINAHL, MEDLINE, EMBASE, PsycINFO, Scopus, Maternal and Infant Care, and Web of Science were searched. Partners and other family members (e.g. grandmothers, siblings) of women in any countries were included. Included papers were critically appraised. The JBI meta-aggregative approach was used to analyze data and form synthesized findings. Seventy-six papers from 74 studies were included. Five synthesized findings were: (i) spectrum of family members' breastfeeding knowledge, experiences and roles; (ii) the complexity of infant feeding decision making; (iii) the controversy of breastfeeding in front of others; (iv) impact of breastfeeding on family; and (v) it takes more than just family members: support for family members. Partners' and family members' views and experiences of breastfeeding support reflected multi-faceted personal, social, financial, cultural, religious, emotional, psychological, and societal factors of the support they provided (or not). Healthcare professionals should engage them in breastfeeding discussions with the woman, and offer tailored and practical guidance relevant to help them to appropriately support the woman. This article is part of the theme issue 'Multidisciplinary perspectives on social support and maternal-child health'.


Assuntos
Aleitamento Materno/psicologia , Família/psicologia , Humanos , Cônjuges/psicologia
18.
Future Oncol ; 17(22): 2847-2855, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33975465

RESUMO

Current guidelines recommend two-drug cytotoxic chemotherapy with a fluoropyrimidine (fluorouracil or capecitabine) and a platinum-based agent (oxaliplatin or cisplatin) as first-line treatment for advanced gastric cancer. Pembrolizumab monotherapy has demonstrated durable antitumor activity in patients with advanced programmed death ligand 1-positive (combined positive score ≥1) gastric/gastroesophageal junction adenocarcinoma. Accumulating evidence indicates that combining pembrolizumab with standard-of-care chemotherapy for the treatment of advanced or metastatic cancer improves clinical outcomes. We describe the rationale for and the design of the randomized, double-blind, placebo-controlled, Phase III KEYNOTE-859 study, which is investigating pembrolizumab in combination with chemotherapy as first-line treatment for patients with human epidermal growth factor receptor 2-negative advanced unresectable or metastatic gastric/gastroesophageal junction adenocarcinoma. The planned sample size is 1542 patients, and the primary end point is overall survival. Clinical trial registration: NCT03675737 (ClinicalTrials.gov).

19.
Bioorg Med Chem Lett ; 45: 128139, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34048880

RESUMO

Jumonji-C (JmjC) domain-containing 7 (JMJD7), which is a 2-oxoglutarate (2OG)-dependent oxygenase, has been demonstrated to play an important role in the occurrence and development of a number of diseases, particularly cancer. Discovery of JMJD7 inhibitors is thus of great importance. Herein consensus docking/scoring strategy and bioactivity evaluation were used to identify JMJD7 inhibitors from various chemical databases. Seven active compounds were retrieved. The most potent compound, Cpd-3, showed an IC50 value of 6.62 µM against JMJD7. Further biophysical assays confirmed that Cpd-3 could efficiently bind to JMJD7 in vitro. Flexible docking was used to predict the binding mode of Cpd-3 with JMJD7. In a cellular assay, Cpd-3 displayed good inhibitory activity against cancer cell lines expressing a high level of JMJD7. As far as we know, Cpd-3 is the first JMJD7 inhibitor reported so far. Overall, this study established a good starting point for drug discovery targeting JMJD7.

20.
Rapid Commun Mass Spectrom ; 35(10): e9075, 2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-33648023

RESUMO

RATIONALE: Due to isotope fractionations during partial nitrogen release from minerals and rocks, the complete extraction of nitrogen for analysis is crucial to ensure high-quality nitrogen isotopic data. However, the appropriate nitrogen extraction conditions (e.g. temperature, duration) have not been established for most silicate minerals and rocks. METHODS: Nitrogen in a number of common minerals and rocks was extracted using the most robust sealed-tube offline combustion techniques, purified and quantified in a custom-made metal manifold, and carried by helium gas to an isotope ratio mass spectrometer for isotopic measurement at nanomolar nitrogen level. Each mineral or rock was combusted in a variety of temperature and duration conditions to compare the nitrogen yields and isotopic compositions. RESULTS: The nitrogen yields and isotopic compositions of minerals and rocks are strongly affected by combustion temperature and duration. The optimal combustion temperature is lowest for cyclosilicate minerals, followed by phyllosilicate, tectosilicate and inosilicate minerals. Preheating of samples can induce significant nitrogen loss and δ15 N shift. Heating of samples above their optimal temperatures may cause nitrogen re-assimilation by the residual mineral or rock. CONCLUSIONS: Each mineral or rock has a characteristic optimal temperature and duration for complete nitrogen release. Preheating, under-heating or over-heating can cause nitrogen loss and isotopic shift. Therefore, we recommend using the offline combustion techniques and the optimal combustion conditions obtained in this study for nitrogen quantification and isotopic analysis of silicate minerals and rocks.

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