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1.
Artigo em Inglês | MEDLINE | ID: mdl-33826217

RESUMO

Developing highly efficient electrocatalysts for CO 2 reduction is of critical importance. Good conductivity and abundant catalytic sites feature ideal electrocatalysts. Two-dimensional conductive metal-organic frameworks (2D c -MOFs) are promising candidates in this regard as efficient electrocatalysts for CO 2 reduction reaction (CO 2 RR). Herein, a nitrogen-rich tricycloquinazoline (TQ) based multitopic catechol ligand was employed to coordinate with transition metal ions (Cu 2+ and Ni 2+ ), which therefore, formed 2D graphene-like porous sheets: M 3 (HHTQ) 2 (M = Cu, Ni; HHTQ = 2,3,7,8,12,13-Hexahydroxytricycloquinazoline). M 3 (HHTQ) 2 can be regarded as a single-atom catalyst where Cu or Ni centers are uniformly distributed in the hexagonal lattices. Cu 3 (HHTQ) 2 exhibited superior catalytic activity towards CO 2 RR in which CH 3 OH is the sole product. The Faradic efficiency of CH 3 OH reached up to 53.6% at a small over-potential of -0.4 V vs RHE. Theoretical calculations and experimental results further indicated that, Cu 3 (HHTQ) 2 exhibited larger CO 2 adsorption energies and higher activities over the isostructural Ni 3 (HHTQ) 2 and the reported archetypical Cu 3 (HHTP) 2 . The current work reveals strong dependence of both metal centers and the N -rich ligands on the electrocatalytic performance, and provide new possibilities to develop novel 2D c -MOF-based electrocatalysts toward efficient CO 2 RR.

2.
J Transl Med ; 19(1): 150, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858440

RESUMO

BACKGROUND: Sidedness (right/left) of colorectal cancer (CRC) is essential for treatment. Whether carcinogenesis of tobacco varies by sidedness remains unclear. The present study aims to evaluate the sidedness tendency of cigarette smoking and to explore its impact on prognosis. METHODS: In the multi-center retrospective study, data on 46 166 Chinese CRC patients were extracted from a big-data platform. Logistic regression analyses were performed to evaluate qualitative and quantitative associations between smoking and tumor sidedness. Survival analyses were conducted in metastatic CRC. RESULTS: History of smoking was associated with left-sided CRC (LSCRC; Adjusted odds ratio, 1.25; 95% CI, 1.16 - 1.34; P < .001). The sidedness tendency towards LSCRC increased from non-smokers, to ex-smokers, and to current smokers (P for trend < .001). Longer duration (P for trend < .001) and larger total amount of cigarette smoking (P for trend < .001) were more associated with LSCRC, respectively. The association was confirmed in both left-sided colon cancer and rectal cancer, but was stronger for rectal cancer (P = .016). Alcoholism significantly enhanced the association by 7% (P = .027). Furthermore, prognostic advantage of metastatic LSCRC diminished among ever-smokers, with contrary survival impacts of smoking on either side of CRC. CONCLUSIONS: History of smoking was associated with LSCRC in a positive dose-response relationship, and presented opposite prognostic impacts on right- and left-sided tumors. Smoking potentially plays an instrumental role in the mechanism for sidedness heterogeneity in CRC.

3.
Foods ; 10(3)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807529

RESUMO

Hydroxycinnamic acids are one category of bioactive phenolic acids that are widely distributed in plants. In this study, chitosan (CS) was functionalized with three kinds of hydroxycinnamic acids (p-coumaric acid, caffeic acid and ferulic acid) through the carbodiimide-mediated grafting method. The obtained hydroxycinnamic-acid-grafted CSs (hydroxycinnamic acid-g-CSs) were further fabricated into food packaging films through solvent casting. For the first time, the functionalities of the different hydroxycinnamic acid-g-CS films were compared. Results showed the grafting ratio of p-coumaric acid-g-CS, caffeic acid-g-CS and ferulic acid-g-CS was 73.68, 129.42 and 91.75 mg/g, respectively. Instrumental analyses confirmed hydroxycinnamic acids conjugated with CS through amide and ester bonds. The functionalization of CS film with hydroxycinnamic acids produced a more compact microstructure and higher UV light barrier ability, mechanical strength, water vapor barrier ability, thermal stability and antioxidant and antimicrobial activities. Among the different hydroxycinnamic acid-g-CS films, caffeic acid-g-CS film presented the strongest barrier, mechanical, antioxidant and antimicrobial properties. Moreover, caffeic acid-g-CS film packaging effectively extended the shelf life of pork to 10 days at 4 °C. Our results suggest caffeic acid-g-CS film can be used in the active food packaging field.

4.
Plant Cell Environ ; 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33864643

RESUMO

Efficient root colonization of plant growth-promoting rhizobacteria is critical for their plant-beneficial functions. However, the strategy to overcoming plant immunity during root colonization is not well understood. In particular, how Bacillus strains cope with plant-derived reactive oxygen species (ROS), which function as the first barrier of plant defense, is not clear. In the present study, we found that the homolog of flg22 in Bacillus velezensis SQR9 (flg22SQR9 ) has 78.95% identity to the typical flg22 (flg22P.s. ) and induces a significant oxidative burst in cucumber and Arabidopsis. In contrast to pathogenic or beneficial Pseudomonas, live B. velezensis SQR9 also induced an oxidative burst in cucumber. We further found that B. velezensis SQR9 tolerated higher H2 O2 levels than Pst DC3000, the pathogen that harbors the typical flg22, and that it possesses the ability to suppress the flg22-induced oxidative burst, indicating that B. velezensis SQR9 may exploit a more efficient ROS tolerance system than DC3000. Further experimentation with mutagenesis of bacteria and Arabidopsis showed that the two-component regulatory system, ResDE, in B. velezensis SQR9 is involved in tolerance to plant-derived oxidative stress, thus contributing to root colonization. This study supports a further investigation of the interaction between beneficial rhizobacteria and plant immunity. This article is protected by copyright. All rights reserved.

5.
Neurosci Res ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33887355

RESUMO

The Microbiota-gut-brain axis describes the bidirectional communication between central nervous system and microorganisms in the gastrointestinal tract. Increasing evidence has suggests that the vagus nerve, a major neural connection between the gut and brain, plays a key role in facilitating signaling along the microbiota-gut-brain axis. Much of this evidence has come from studies employing surgical subdiaphragmatic vagotomy. Here we provide a review of the use of vagotomy as a tool to explore the role of the vagus nerve in gut to brain signaling and the knowledge this approach has provided. We also examine how, more recently, vagotomy has contributed to the understanding of the vagus nerve as a bridge for multi-systemic communication; linking microbiota, immune and central nervous systems. Finally, we address limitations to surgical vagotomy and identify such limitations may be mitigated in future studies.

6.
Nano Lett ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33900785

RESUMO

Free-standing crystalline membranes are highly desirable owing to recent developments in heterogeneous integration of dissimilar materials. Van der Waals (vdW) epitaxy enables the release of crystalline membranes from their substrates. However, suppressed nucleation density due to low surface energy has been a challenge for crystallization; reactive materials synthesis environments can induce detrimental damage to vdW surfaces, often leading to failures in membrane release. This work demonstrates a novel platform based on graphitized SiC for fabricating high-quality free-standing membranes. After mechanically removing epitaxial graphene on a graphitized SiC wafer, the quasi-two-dimensional graphene buffer layer (GBL) surface remains intact for epitaxial growth. The reduced vdW gap between the epilayer and substrate enhances epitaxial interaction, promoting remote epitaxy. Significantly improved nucleation and convergent quality of GaN are achieved on the GBL, resulting in the best quality GaN ever grown on two-dimensional materials. The GBL surface exhibits excellent resistance to harsh growth environments, enabling substrate reuse by repeated growth and exfoliation.

7.
Neural Comput Appl ; : 1-14, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33723476

RESUMO

Lumbar spinal stenosis (LSS) is a lumbar disease with a high incidence in recent years. Accurate segmentation of the vertebral body, lamina and dural sac is a key step in the diagnosis of LSS. This study presents an lumbar spine magnetic resonance imaging image segmentation method based on deep learning. In addition, we define the quantitative evaluation methods of two clinical indicators (that is the anteroposterior diameter of the spinal canal and the cross-sectional area of the dural sac) to assist LSS diagnosis. To improve the segmentation performance, a dual-branch multi-scale attention module is embedded into the network. It contains multi-scale feature extraction based on three 3 × 3 convolution operators and vital information selection based on attention mechanism. In the experiment, we used lumbar datasets from the spine surgery department of Shengjing Hospital of China Medical University to evaluate the effect of the method embedded the dual-branch multi-scale attention module. Compared with other state-of-the-art methods, the average dice similarity coefficient was improved from 0.9008 to 0.9252 and the average surface distance was decreased from 6.40 to 2.71 mm.

8.
Animal Model Exp Med ; 4(1): 2-15, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33738432

RESUMO

Background: Cardiovascular diseases (CVDs) and diabetes mellitus (DM) are top two chronic comorbidities that increase the severity and mortality of COVID-19. However, how SARS-CoV-2 alters the progression of chronic diseases remain unclear. Methods: We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in mice. SARS-CoV-2's impacts on pathogenesis of chronic diseases were studied through histopathological, virologic and molecular biology analysis. Results: Pre-existing CVDs resulted in viral invasion, ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 infection. Viral infection increased fasting blood glucose and reduced insulin response in DM model. Bone mineral density decreased shortly after infection, which associated with impaired PI3K/AKT/mTOR signaling. Conclusion: We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic diseases. Pre-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection, which further aggravated the pre-existing diseases. This work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection.

9.
Opt Express ; 29(3): 3596-3608, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33770956

RESUMO

We experimentally demonstrate an improved orthogonal frequency division multiplexing (OFDM) into the pulse width modulation (PWM) scheme for the X-ray communication (XCOM). The scheme is insensitive to the nonlinearity of the grid-controlled X-ray tube with switching 'on' and 'off' between two points. The dependence of this system's bit-error-rate (BER) performances on the data rates and the working parameters including the anode voltage and filament current of the grid-controlled X-ray tube are studied. The OFDM-PWM scheme reaches the data rate of 360 kbps at a BER of the forward error correction threshold of 3.8 × 10-3 over a 5 cm air channel. In addition, an experiment aided by density-based spatial clustering of applications with noise nonlinear compensation is carried out, and the results demonstrate the improvements in Q-factor by 0.62 dB.

10.
J Pharm Pharmacol ; 73(5): 682-691, 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33772297

RESUMO

OBJECTIVES: The expression of interferon regulatory factor 6 (IRF6) has been reported in several cancer types, but its roles underlying the progression of lung cancer have not been detailedly investigated. METHODS: The pairs of lung cancer tissues and para-carcinoma tissues and The Cancer Genome Atlas database were collected to detect IRF6 expression. Cell counting kit-8, transwell and terminal-deoxynucleoitidyl transferase-mediated nick end labelling assays were used to evaluate cell proliferation, migration and apoptosis. KEY FINDINGS: A significant up-regulation of IRF6 in both lung adenocarcinoma and lung squamous cell carcinoma tissues compared with normal non-tumor tissues. Subsequently, Immunostaining also revealed that canceration of lung tissues predisposed to evoke IRF6 expression. In vitro experiments revealed the antitumour effects, including growth and migration inhibition, of IRF6 siRNA transfection. Considering miR-320 as an endogenous inhibitor to IRF6, miR-320 mimics transfection led to the inhibition of proliferation and migration of lung cancer cells. However, overexpressed IRF6 neutralized the antineoplastic activities of miR-320 in lung cancer cells. CONCLUSIONS: The miR-320/IRF6 signalling axis was implicated in pulmonary canceration. miR-320 as an endogenous inhibitor of IRF6 provided a novel therapeutic strategy for the treatment of lung cancer.

11.
Expert Opin Drug Deliv ; : 1-18, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33682562

RESUMO

Introduction: In selected patients with limited peritoneal metastasis (PM), favorable tumor biology, and a good clinical condition, there is an indication for combination of cytoreductive surgery (CRS) and subsequent intravenous (IV) or intraperitoneal (IP) chemotherapy. Compared with IV injection, IP therapy can achieve a high drug concentration within the peritoneal cavity with low systemic toxicity, however, the clinical application of IP chemotherapy is limited by the related abdominal pain, infection, and intolerance.Areas covered:To improve the anti-tumor efficacy and safety of IP therapy, various pharmaceutical strategies have been developed and show promising potential. This review discusses the specialized modification of traditional drug delivery systems and demonstrates the preparation of customized drug carriers for IP therapy, including chemotherapy and gene therapy. IP therapy has important clinical significance in the treatment of PM using novel anti-tumor agents as well as conventional drugs in new applications.Expert opinion: Although IP therapy exhibits good performance both in mouse models and in patients with PM in clinical trials, its clinical application remains limited due to the serious side effects and low acceptability. Further investigations, including pharmaceutical strategies, are needed to develop potential IP therapy, focusing on the efficacy and safety thereof.

12.
Sci Prog ; 104(1): 36850421997286, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33661721

RESUMO

Immune cells have emerged as key regulators in the occurrence and development of multiple tumor types. However, it is unclear whether immune-related genes (IRGs) and the tumor immune microenvironment can predict prognosis for patients with gastric cancer (GC). The mRNA expression data in GC tissues (n = 368) were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed IRGs in patients with GC were determined using a computational difference algorithm. A prognostic signature was constructed using COX regression and random survival forest (RSF) analyses. In addition, datasets related to "gemcitabine resistance" and "trastuzumab resistance" (GSE58118 and GSE77346) were obtained for GEO database, and DEGs associated with drug-resistance were screened. Then, we analyzed correlations between gene expression and cancer immune infiltrates via Tumor Immune Estimation Resource (TIMER) site. The cBioportal database was used to analyze drug-resistant gene mutation status and survival. One hundred and fifty-five differentially expressed IRGs were screened between GC and normal tissues, and a prognostic signature consisting of four IRGs (NRP1, PPP3R1, IL17RA, and FGF16) was closely related to the overall survival (OS). According to cutoff value of risk score, patients were divided into high-risk and low-risk group. Patients in the high-risk group had shorter OS compared to the low-risk group in both the training (p < 0.0001) and testing sets (p = 0.0021). In addition, we developed a 5-IRGs (LGR6, DKK1, TNFRSF1B, NRP1, and CXCR4) signature which may participate in drug resistance processes in GC. Survival analysis showed that patients with drug-resistant gene mutations had shorter OS (p = 0.0459) and DFS (p < 0.001). We constructed four survival-related IRGs and five IRGs related to drug resistance which may contribute to predict the prognosis of GC.

13.
Anticancer Drugs ; 32(4): 469-473, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33587347

RESUMO

Lung cancer is one of the most important and lethal cancers in the world. Human epidermal growth factor 2 (HER2) is a member of the erbB receptor tyrosine kinase family. The incidence of HER2 kinase domain mutations in adenocarcinoma of lung ranges from 1% to 3%. HER2 V659D mutation is located in the trans-membrane domain (TMD) with only a few cases reported before, and importantly, there were no more standard and effective ways for this kind of diseases until now. Afatinib irreversibly blocks all kinase-competent HER family members. Apatinib is one of the small-molecule oral anti-angiogenesis-targeted agents developed firstly in China, and it's a highly selective inhibition of the activity of VEGFR-2. This report presents an advanced lung adenocarcinoma patient with HER2 V659D mutation who was treated with combination of Afatinib and Apatinib. He achieved good efficacy and tolerable adverse reactions.

14.
Plant Cell Environ ; 44(5): 1663-1678, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33548150

RESUMO

Lateral root formation is coordinated by both endogenous and external factors. As biotic factors, plant growth-promoting rhizobacteria can affect lateral root formation, while the regulation mechanism is unclear. In this study, by applying various marker lines, we found that volatile compounds (VCs) from Bacillus amyloliquefaciens SQR9 induced higher frequency of DR5 oscillation and prebranch site formation, accelerated the development and emergence of the lateral root primordia and thus promoted lateral root development in Arabidopsis. We demonstrated a critical role of auxin on B. amyloliquefaciens VCs-induced lateral root formation via respective mutants and pharmacological experiments. Our results showed that auxin biosynthesis, polar transport and signalling pathway are involved in B. amyloliquefaciens VCs-induced lateral roots formation. We further showed that acetoin, a major component of B. amyloliquefaciens VCs, is less active in promoting root development compared to VC blends from B. amyloliquefaciens, indicating the presence of yet uncharacterized/unknown VCs might contribute to B. amyloliquefaciens effect on lateral root formation. In summary, our study revealed an auxin-dependent mechanism of B. amyloliquefaciens VCs in regulating lateral root branching in a non-contact manner, and further efforts will explore useful VCs to promote plant root development.

15.
J Infect Dis ; 223(8): 1313-1321, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33605423

RESUMO

Domestic cats, an important companion animal, can be infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This has aroused concern regarding the ability of domestic cats to spread the virus that causes coronavirus disease 2019. We systematically demonstrated the pathogenesis and transmissibility of SARS-CoV-2 in cats. Serial passaging of the virus between cats dramatically attenuated the viral transmissibility, likely owing to variations of the amino acids in the receptor-binding domain sites of angiotensin-converting enzyme 2 between humans and cats. These findings provide insight into the transmissibility of SARS-CoV-2 in cats and information for protecting the health of humans and cats.


Assuntos
/transmissão , /patogenicidade , Aminoácidos/metabolismo , Animais , Gatos , Linhagem Celular , Chlorocebus aethiops , Feminino , Humanos , Masculino , Células Vero
16.
J Thorac Oncol ; 16(5): 827-839, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33588113

RESUMO

INTRODUCTION: By implementing dynamic circulating tumor DNA (ctDNA) analysis, we explored the impact of TP53 mutations on tumor evolution and resistance mechanisms to ensartinib in patients with ALK-positive NSCLC. METHODS: In a multicenter phase 2 trial, patients with ALK-positive NSCLC who progressed on crizotinib were treated with ensartinib. Blood samples for ctDNA analysis were collected at baseline, cycle 3 day 1, and progression disease (PD) and analyzed with a 212-gene panel. RESULTS: A total of 440 samples were collected from 168 patients. Baseline TP53 mutations (20.2%) significantly correlated with inferior progression-free survival (4.2 mo versus 11.7 mo, p < 0.0001). Patients with TP53 mutations had higher mutation load than those without TP53 mutations at baseline (13.79 ± 3.72 versus 4.67 ± 0.39, p < 0.001). Although there was no significant difference in mutation load between these groups at cycle 3 day 1 (5.89 ± 2.25 versus 3.72 ± 0.62, p = 0.425), patients with mutated TP53 developed more mutations at PD (7.07 ± 1.25 versus 3.20 ± 0.33, p = 0.003). Frequency and abundance of secondary ALK mutations G1269A, G1202R, and E1210K increased markedly at PD than baseline. In patients without secondary ALK mutations, we identified ALK-independent resistance mechanisms including bypass signaling activation, downstream effector protein reactivation, epithelial-mesenchymal transformation, and epigenetic dysregulation. CONCLUSIONS: Our study highlighted the advantage of ctDNA analysis for monitoring tumor evolution. TP53 mutations promoted genetic evolution and accelerated occurrence of resistance. We also unveiled ALK-dependent resistance mechanisms, mainly by G1269A, G1202R, and E1210K mutations, and ALK-independent resistance mechanisms to ensartinib.

17.
Microbiome ; 9(1): 35, 2021 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-33517892

RESUMO

BACKGROUND: The relationship between biodiversity and soil microbiome stability remains poorly understood. Here, we investigated the impacts of bacterial phylogenetic diversity on the functional traits and the stability of the soil microbiome. Communities differing in phylogenetic diversity were generated by inoculating serially diluted soil suspensions into sterilized soil, and the stability of the microbiome was assessed by detecting community variations under various pH levels. The taxonomic features and potential functional traits were detected by DNA sequencing. RESULTS: We found that bacterial communities with higher phylogenetic diversity tended to be more stable, implying that microbiomes with higher biodiversity are more resistant to perturbation. Functional gene co-occurrence network and machine learning classification analyses identified specialized metabolic functions, especially "nitrogen metabolism" and "phosphonate and phosphinate metabolism," as keystone functions. Further taxonomic annotation found that keystone functions are carried out by specific bacterial taxa, including Nitrospira and Gemmatimonas, among others. CONCLUSIONS: This study provides new insights into our understanding of the relationships between soil microbiome biodiversity and ecosystem stability and highlights specialized metabolic functions embedded in keystone taxa that may be essential for soil microbiome stability. Video abstract.


Assuntos
Microbiota/fisiologia , Filogenia , Microbiologia do Solo , Solo , Biodiversidade , Microbiota/genética
18.
Sci Total Environ ; 771: 144800, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33545477

RESUMO

Cation exchange is one of the dominant mechanisms in the adsorption of cationic ammonium nitrogen (NH4+) from water. In this study, we focus on the role of counter cations in cation exchange process of NH4+ to enhance the adsorption capacity. Five amorphous titanates namely lithium titanate (LiT), sodium titanate (NaT), potassium titanate (KT), strontium titanate (SrT) and barium titanate (BaT) with different counter cation were facilely synthesized. The adsorption performance for NH4+ by these samples is in the order of LiT> NaT > KT> > SrT > BaT. The maximum adsorption capacity of LiT calculated by Langmuir is as high as 50.31 mg·g-1. According to the experimental results and theoretical analysis, the electrostatic interaction between counter ions (cations in framework or eternal solution) and charged framework (fixed ions) is the main influence factor during cation exchange process in general. The cation valence and the hydrated ionic radius of the counter ions can inversely affect the ion exchange equilibrium and the affinity of counter ions to titanates. Therefore, a definition of a brief parameter, affinity coefficient Kf (relating to ion valence and distance between opposite charged ions), is introduced and used to explain the difference in adsorption performance of five titanates for NH4+. The conclusion about cation exchange and ions affinity may provide possible strategies for enhancement of cationic contaminant adsorption from water or wastewater.

19.
Arch Microbiol ; 203(4): 1743-1752, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33471134

RESUMO

Beneficial rhizobacteria can inhibit soilborne pathogens by secreting an array of polyketides, lipopeptides and dipeptides, but the effect of polyketides on crown gall disease caused by Agrobacterium tumefaciens C58 is unclear. In this study, the antagonistic compounds of the plant growth-promoting rhizobacterium Bacillus velezensis CLA178 was sorted with different organic phases, purified by high-pressure liquid chromatography, and detected by a liquid chromatography ionization-mass spectrometry system. Macrolactins were found to be the compounds with antagonistic activity against A. tumefaciens C58. When the macrolactin synthesis pathway was disrupted, the mutant △mlnA only showed slight antagonistic activity against A. tumefaciens C58. Transmission electron microscopy showed that the inhibition of C58 cell division by cell-free culture from the mutant △mlnA was weaker than that by cell-free culture from CLA178. The mutant deficient in production of macrolactin showed a weaker transcription of genes involved in attachment of C58 to plant and lower biocontrol of crown gall disease in rose than the wild-type strain CLA178. The effect of macrolactins on pathogen C58 has been also confirmed by the purified macrolactins. These results reveal that macrolactins contribute to the biocontrol activity of C58 by inhibiting cell division and downregulating the transcription of chvB and chvE.

20.
J Clin Oncol ; 39(7): 704-712, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33492986

RESUMO

PURPOSE: As yet, no checkpoint inhibitor has been approved to treat nasopharyngeal carcinoma (NPC). This study was aimed to evaluate the antitumor activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) inhibitor for recurrent or metastatic NPC (RM-NPC) refractory to standard chemotherapy. PATIENTS AND METHODS: In this single-arm, multicenter phase II study, patients with RM-NPC received 3 mg/kg toripalimab once every 2 weeks via intravenous infusion until confirmed disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). The secondary end points included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS: Among all 190 patients, the ORR was 20.5% with median DOR 12.8 months, median PFS 1.9 months, and median OS 17.4 months. Among 92 patients who failed at least two lines of systemic chemotherapy, the ORR was 23.9%. The ORRs were 27.1% and 19.4% in PD-L1+ and PD-L1- patients, respectively (P = .31). Patients with ≥ 50% decrease of plasma Epstein-Barr virus (EBV) DNA copy number on day 28 had significantly better ORR than those with < 50% decrease, 48.3% versus 5.7% (P = .0001). Tumor mutational burden had a median value of 0.95 muts/mega-base in the cohort and had no predictive value for response. Whole-exome sequencing results from 174 patients revealed that the patients with genomic amplification in 11q13 region or ETV6 genomic alterations had poor responses to toripalimab. CONCLUSION: The POLARIS-02 study demonstrated a manageable safety profile and durable clinical response of toripalimab in patients with chemorefractory metastatic NPC. An early decrease in plasma EBV DNA copy number correlated with favorable response.

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