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1.
J Integr Plant Biol ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34850567

RESUMO

Although the genetic basis for endosperm development in maize (Zea mays) has been well studied, the mechanism for coordinating grain filling with increasing kernel size remains elusive. Here, we report that increased kernel size was selected during modern breeding and identify a novel DELLA-like transcriptional regulator, ZmGRAS11, that positively regulates kernel size and kernel weight in maize. We find that Opaque2, a core transcription factor for zein protein and starch accumulation, transactivates the expression of ZmGRAS11. Our data suggest that the Opaque2-ZmGRAS11 module mediates synergistic endosperm enlargement with grain filling. This article is protected by copyright. All rights reserved.

2.
Biomaterials ; 279: 121234, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34736152

RESUMO

Extracellular vesicles (EVs) have been emerged as versatile drug delivery vehicles due to their outstanding biocompatibility and long-term circulation, yet are constrained with low targeting property and inefficient loading capacity from post-synthetic passive EVs encapsulation. Herein, we report a simple and feasible in situ biosynthetic approach to encapsulate tumor-targeting folate (FA)-modified EVs with intracellularly produced protoporphyrin X (PpIX) and doxorubicin (DOX). As compared with the traditional directly drug-incubated or drug-electroporated EVs, these biosynthesized EVs revealed high drug-loading efficiency with minimized structural and functional perturbations. Our multifunctional EVs revealed the enhanced accumulation and penetration into deep tumor parenchyma, as well as the strengthened immune response to ablate orthotopic and metastatic tumors, thus realizing the more reliable photochemotherapy. As an intelligent multi-mode therapeutic system, our biosynthetic EVs could be engineered with more therapeutic agents and show great promise for biomedicine applications.

3.
Immunotherapy ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34845913

RESUMO

Aim: To compare the efficacy of single- and double-species mite allergen immunotherapy. Materials and methods: An open, pseudo-randomized, controlled study was conducted (n = 125 allergic rhinitis patients). The primary end point involved the visual analogue scale. Secondary end points included a basophil activation test and serum specific IgE and IgG4 assays. Results: Visual analogue scale analysis indicated considerable reductions in both groups. Both treatments improved quality of life and induced sIgG4 antibody production. Basophil activation and serum IgE inhibition were not evident in either treatment. Neither treatment displayed an early stage immune synergistic effect on cross-allergens. Conclusions: Both treatments were effective against allergic rhinitis, and statistical differences were not observed. Future studies may require long-term, large-scale research.

4.
Environ Res ; : 112321, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34748777

RESUMO

BACKGROUND: Pulmonary embolism (PE) is a life-threatening condition. Few studies have evaluated the relationship between air pollution and PE, and these results have been inconsistent. Therefore, our study aimed to investigate the association between air pollutant exposure and the risk of hospitalization due to PE. MATERIALS AND METHODS: Daily PE admissions, meteorological data, and ambient pollution data from January 1, 2015, to December 31, 2018, were collected in Beijing. A quasi-Poisson regression model combined with time-stratified case-crossover design and a distributed lag nonlinear model was used to determine the effect of air pollutant exposure on PE admission. To examine the stability of air pollutants' effects, multi-pollutant analyses were performed. Stratified analyses by age and sex were further conducted. RESULTS: There were 5060 PE admissions during the study period, with an estimated incidence of 6.5 per 100,000. PM2.5, PM10, SO2, O3 and CO exposures were significantly associated with elevated risk of PE hospitalization. The highest cumulative risks were observed at a lag of 0-28 days for PM2.5 (relative risk [RR] = 1.056, 95% confidence intervals [CI]: 1.015-1.098), PM10 (RR = 1.042, 95%CI: 1.010-1.075), and CO (RR = 1.466, 95%CI: 1.127-1.906), at a lag of 0-27 days for SO2 (RR = 1.674, 95%CI: 1.200-2.335), and at a lag of 0-4 days for O3 (RR = 1.019, 95%CI: 1.001-1.038). All associations mentioned above except O3 remained significant in multi-pollutant models. Stratified analyses showed that women and those aged ≥65 years people were more sensitive to PM10 and CO exposure than men and those aged <65 years. The effect of PM2.5 exposure was statistically significant in all subgroups. CONCLUSIONS: Exposure to PM2.5, PM10, SO2, and CO showed a positive association with PE hospitalization. High-risk PE groups should take special precautions on days with poor air quality.

5.
Biosens Bioelectron ; : 113819, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34836711

RESUMO

Personal glucose meter (PGM) is one of the most commercially available POC (point-of-care) devices for monitoring the level of glucose reliably, yet its non-glucose quantification ability is limited since such strategy needs ingenious interface design and tedious enzyme conjugation. Herein, we constructed a portable and sensitive platform that can detect non-glucose target by combining enzyme-encapsulated zeolitic imidazole framework-90 (ZIF-90) with personal glucose meter. ZIF-90 is an ideal carrier and susceptor due to the extraordinary capability of packaging enzyme and stimuli-responsiveness. We selected adenosine-5'-triphosphate (ATP) as the target model of non-glucose analytes. Upon ATP-induced decomposition of MOF, the released enzyme (glucose oxidase or invertase) catalyzed substrate and gave rise to the change of the glucose concentration for PGM assay. This method determined ATP with a remarkably sensitivity of 233 nM and effective recovery in real serum samples. Our strategy provides a facile and practical approach for measuring the non-glucose target using PGM, and could potentially be applied in bimolecular detection in point-of-care diagnosis.

6.
Sci Total Environ ; : 151962, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34843770

RESUMO

UiO-66, as one of the most stable metal-organic frameworks (MOFs), has attracted a lot of attention in the field of adsorption and photocatalysis. However, this application of UiO-66 is still limited due to either the low accessibility of micropores or the poor electron-hole charge separation capability. This study aims to promote UiO-66 accessibility of micropores and charge separation through the construction of oxygen vacancies (OVs) and mesopore defects as well as copper incorporation. Herein, mesopore Cu doped UiO-66 with rich OVs was synthesized by a one-pot method and demonstrated high efficiency for the removal of ciprofloxacin (CIP) from the aquatic system. First of all, denatured mesopore defects were produced in Cu doped UiO-66 which possessed a 58% increase in specific surface area compared to UiO-66, facilitating the adsorption of molecular oxygen. Secondly, e- was preferentially trapped by OVs under light irradiation. Electron (e-) reacted rapidly with the surface adsorbed oxygen to generate superoxide radical (O2-). Meanwhile, copper incorporation increased the photocurrent and reduced the interfacial charge transfer resistance, thereby improving the charge separation efficiency. As a result, the adsorption efficiency and photocatalytic performance of mesopore Cu doped UiO-66 with OVs were 8.1 and 3.7 times higher than those of UiO-66, respectively. This study paved a way for the one-step synthesis of MOFs containing OVs and broadened the possibilities of practical applications for photo-induced removal of antibiotics from effluent.

7.
Animals (Basel) ; 11(11)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34827793

RESUMO

Total dissolved gas (TDG) supersaturation, which can be caused by flood discharge, results in gas bubble disease (GBD) in fish and threatens their survival downstream of dams. TDG supersaturation has become a serious environmental problem in the Yangtze River. Few studies have evaluated the effect of TDG supersaturation on fish in natural rivers during periods of flood discharge. To estimate fish tolerance to TDG supersaturation under natural conditions, juvenile Myxocyprinus asiaticus and juvenile Procypris rabaudi were exposed to TDG-supersaturated water for 96 h at various depths (0-0.3 m, 0.3-1.3 m, 1.3-2.3 m and 0-2.3 m) during periods of flood discharge of Dagangshan hydropower station. The results showed that juvenile Procypris rabaudi and juvenile Myxocyprinus asiaticus exhibited obvious GBD signs. An increase in exposure time decreased survival probability of the two species. Deeper water depths can increase the tolerance of juvenile Procypris rabaudi to TDG supersaturation in natural rivers during periods of flood discharge while it cannot improve the survival of juvenile Myxocyprinus asiaticus. Compared with juvenile Myxocyprinus asiaticus, juvenile Procypris rabaudi showed weaker tolerance of TDG supersaturation in shallow water, and juvenile Procypris rabaudi were more vulnerable to TDG supersaturation than juvenile Myxocyprinus asiaticus even if the TDG level (116%) was low.

8.
mSystems ; : e0110921, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726485

RESUMO

Hypoxia signaling is a key regulator in the development and progression of many types of human malignancies, including viral cancers. The latency-associated nuclear antigen (LANA), encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) during latency, is a multifunctional protein that plays an essential role in viral episome maintenance and lytic gene silencing for inducing tumorigenesis. Although our previous studies have shown that LANA contains a SUMO-interacting motif (LANASIM), and hypoxia reduces SUMOylated KAP1 association with LANASIM, the physiological proteomic network of LANASIM-associated cellular proteins in response to hypoxia is still unclear. In this study, we individually established cell lines stably expressing wild-type LANA (LANAWT) and its SIM-deleted mutant (LANAdSIM) and treated them with or without hypoxia, followed by coimmunoprecipitation and mass spectrometry analysis to systemically identify the hypoxia-responsive profile of LANASIM-associated cellular proteins. We found that in hypoxia, the number of cellular proteins associated with LANAWT instead of LANAdSIM was dramatically increased. Functional network analysis revealed that two major pathways, which included cytoskeleton organization and DNA/RNA binding and processing pathways, were significantly enriched for 28 LANASIM-associated proteins in response to hypoxia. HNRNPU was one of the proteins consistently identified that interacted with LANASIM in different proteomic screening systems and responded to hypoxia. This study provides a proteomic profile of LANASIM-associated proteins in hypoxia and facilitates our understanding of the role of the collaboration between viral infection and the hypoxia response in inducing viral persistence and tumorigenesis. IMPORTANCE Kaposi's sarcoma-associated herpesvirus (KSHV) has been reported to be involved in the regulation of host proteins in response to hypoxic stress. LANA, one of the key latent proteins, contains a SUMO-interacting motif (LANASIM) and reduces the association with SUMOylated KAP1 upon hypoxic treatment. However, the physiological systematic network of LANASIM-associated cellular proteins in hypoxia is still unclear. Here, we revealed two major pathways, which included cytoskeleton organization and DNA/RNA binding and processing pathways, that were significantly enriched for 28 LANASIM-associated proteins in hypoxia. This discovery not only provides a proteomic profile of LANASIM-associated proteins in hypoxia but also facilitates our understanding of the collaboration between viral infection and hypoxic stress in inducing viral persistence and tumorigenesis.

9.
Clin Cancer Res ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740925

RESUMO

PURPOSE: To establish RP2D in Phase 1 and evaluate safety and efficacy of abivertinib in EGFR T790M+ NSCLC patients with disease progression from prior EGFR inhibitors in Phase 2. PATIENTS AND METHODS: This multicenter, open-label study included 367 adult Chinese patients. Abivertinib at doses of 50mg BID to 350 mg BID was evaluated in Phase 1 in continual 28-day cycles, and the RP2D of 300 mg BID was used in Phase 2 in continual 21-day cycles. Primary endpoints include RP2D in phase 1 and objective response rate (ORR) at RP2D in phase 2. RESULTS: The RP2D of 300 mg BID for abivertinib was established based on pharmacokinetics, efficacy and safety profiles across doses in Phase 1. In Phase 2, 227 patients received RP2D for a median treatment duration of 24.6 weeks (0.43-129). Among 209 response evaluable patients, confirmed ORR was 52.2% (109/209; 95% CI: 45.2%, 59.1%). Disease control rate (DCR) was 88.0% (184/209, 95% CI: 82.9%, 92.1%). The median duration of response (DoR) and progression-free survival (PFS) was 8.5 months (95% CI: 6.1, 9.2) and 7.5 months (95% CI: 6.0, 8.8), respectively. The median OS was 24.9 months (95% CI: 22.4, NR). All (227/227) patients reported at least 1 AE, with 96.9% (220/227) of treatment-related AE. Treatment-related serious AEs were reported in 13.7% (31/227) of patients. Death was reported in 4.4% (10/227) of patients, and none was deemed as treatment related. CONCLUSION: Abivertinib of 300 mg BID demonstrated favorable clinical efficacy with manageable side-effects in patients with EGFR T790M+NSCLC.

10.
Emerg Microbes Infect ; : 1-36, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34753408

RESUMO

Evidence of active tuberculosis (ATB) in patients with rheumatic diseases are research priorities but limited data from China have been reported. Research targeting patients not taking anti-TNF biologics are especially insufficient. We aimed to investigate the prevalence and risk factors of ATB in this at-risk population. We conducted a tertiary hospital-based, multi-center, cross-sectional study by using stratified multi-stage cluster sampling strategy to screen ATB in patients with rheumatic diseases. We estimated the prevalence of ATB in patients with rheumatic diseases and identified risk factors among those who were not taking anti-TNF biologic. A total of 13,550 patients with rheumatic diseases were enrolled, and the result showed the standardized prevalence of ATB according to the composition ratio of various types of rheumatic disease was 882/100000 (95% confidence interval (CI): 706-1057). Multivariable logistic regression analysis in patients not taking anti-TNF biologics showed that the independent risk factors of ATB were having systemic lupus erythematosus (SLE) (OR=2.722, 95% CI: 1.437-5.159, p=0.002), having Behcet's disease (BD) (OR= 5.261, 95% CI: 2.071-13.365, p<0.001), taking azathioprine(AZA) within the past two years (OR=2.095, 95% CI: 0.986-4.450, p=0.054), exposing to glucocorticoids ≥30mg/d for more than four weeks within the past two years (OR=2.031, 95% CI: 1.247-3.309, p=0.004) and having evidences of previous TB (OR= 6.185, 95% CI: 3.487-10.969, p<0.001). The prevalence of ATB was higher in patients with rheumatic diseases compared to the general population. Patients with SLE or BD, prolonged exposure to moderate to high dose of glucocorticoids and previous TB were independent risk factors for ATB.

11.
ACS Nano ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797050

RESUMO

To achieve high solar energy utilization efficiency, photothermal materials with broadband absorption of sunlight and high conversion efficiency are becoming a fast-growing research focus. Inspired by the forest structure with efficient sunlight utilization, we designed and fabricated a graphene film consisting of densely arranged porous graphene though laser scribing on polybenzoxazine resin (poly(Ph-ddm)). This hierarchical structure significantly reduced the light reflection of graphene as a 2D material. With a combination of advanced photothermal conversion properties of graphene, the 3D structured graphene film, named forest-like laser-induced graphene (forest-like LIG), was endowed with a very high light absorption of 99.0% over the whole wavelength range of sunlight as well as advanced light-to-heat conversion performance (reaching up to 87.7 °C within 30 s under the illumination of simulated sunlight and showing an equilibrium temperature of 90.7 ± 0.4 °C). As a further benefit of its superhydrophobicity, a photothermal actuator with quick actuated response and high motion velocity, as well as a solar-driven interfacial desalination membrane with durable salt-rejecting properties and high solar evaporation efficiencies, was demonstrated.

12.
Chin Med J (Engl) ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34802023

RESUMO

BACKGROUND: Differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) has been a challenge for clinicians in high TB burden countries. The purpose of this study was to improve the accuracy of differential diagnosis of ATB and LTBI by using fluorescent immunospot (FluoroSpot) assay to detect specific Th1 cell immune responses. The novel mycobacterium tuberculosis (MTB) latency-associated antigens Rv1733c and synthetic long peptides derived from Rv1733c (Rv1733c SLP) were used based on virulence factors early secreting antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10). METHODS: Fifty-seven ATB cases, including 20 pathogen-confirmed ATB and 37 clinically diagnosed ATB, and 36 LTBI cases, were enrolled between January and December 2017. FluoroSpot assay was used to detect the interferon γ (IFN-γ) and interleukin 2 (IL-2) secreted by the specific T cells after being stimulated with MTB virulence factors ESAT-6 and CFP-10, MTB latency-associated antigens Rv1733c and Rv1733c SLP. The receiver operating characteristic (ROC) curve was used to define the best cutoff value of latency-associated antigens in the use of differentiating ATB and LTBI. The sensitivity, specificity, predictive value, and likelihood ratio of ESAT-6 and CFP-10-FluoroSpot combined with latency-associated antigen in the differential diagnosis of ATB and LTBI were also calculated. RESULTS: Following the stimulation with Rv1733c and Rv1733c SLP, the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP had the largest area under the ROC curve, which was 0.766. With a cutoff value of 1 (spot-forming cells [SFCs]/2.5 × 105 peripheral blood mononuclear cells) for frequency, the sensitivity and specificity of distinguishing ATB from LTBI were 72.2% and 73.7%, respectively. ESAT-6 and CFP-10-FluoroSpot detected the frequency and proportion of single IFN-γ-secreting T cells; the sensitivity and specificity of distinguishing ATB from LTBI were 82.5% and 66.7%, respectively. Combined with the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP on the basis of ESAT-6 and CFP-10-FluoroSpot, the sensitivity and specificity increased to 84.2% and 83.3%, respectively. CONCLUSION: Rv1733c SLP, combined with ESAT-6 and CFP-10, might be used as a candidate antigen for T cell-based tuberculosis diagnostic tests to differentiate ATB from LTBI.

13.
Small ; 17(46): e2104178, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34636139

RESUMO

High-energy electrodes at high mass loadings (usually >8.0 mg cm-2 ) are desired for aqueous pseudocapacitors. Yet, how to overcome the thickness-dependent resistance increase of ion/electron transport in pseudocapacitive materials is still challenging. Herein, a high-performance electrode (denoted as AMC) adapted to high mass loading is achieved by promoting the Li-ion affinity of 3D MoO2 /carbon fabric. The experimental results and corresponding computational results reveal that the oxygen-activated surface of AMC, combined with the wettability and conductivity superiority of 3D graphite network, significantly facilitates the Li-ion adsorption and diffusion at the electrode/electrolyte interface, even at large thicknesses. Consequently, even at a high mass loading up to 8.1 mg cm-2 , the AMC electrode also displays an impressive specific capacity (567.5 C g-1 at 2.5 A g-1 ), substantially superior to most advanced pseudocapacitive electrodes. The strategy of boosting energy characteristic by enhancing the affinity of charge carriers is applicable to other pseudocapacitive electrodes.

14.
BMC Public Health ; 21(1): 1961, 2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715823

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide with continuous rise. Limited studies indicate that COPD was associated with major storms and related power outages (PO). However, significant gaps remain in understanding what PO's role is on the pathway of major storms-COPD. This study aimed to examine how PO mediates the major storms-COPD associations. METHODS: In this time-series study, we extracted all hospital admissions with COPD as the principal diagnosis in New York, 2001-2013. Using distributed lag nonlinear models, the hospitalization rate during major storms and PO was compared to non-major storms and non-PO periods to determine the risk ratios (RRs) for COPD at each of 0-6 lag days respectively after controlling for time-varying confounders and concentration of fine particulate matter (PM2.5). We then used Granger mediation analysis for time series to assess the mediation effect of PO on the major storms-COPD associations. RESULTS: The RRs of COPD hospitalization following major storms, which mainly included flooding, thunder, hurricane, snow, ice, and wind, were 1.23 to 1.49 across lag 0-6 days. The risk was strongest at lag3 and lasted significantly for 4 days. Compared with non-outage periods, the PO period was associated with 1.23 to 1.61 higher risk of COPD admissions across lag 0-6 days. The risk lasted significantly for 2 days and was strongest at lag2. Snow, hurricane and wind were the top three contributors of PO among the major storms. PO mediated as much as 49.6 to 65.0% of the major storms-COPD associations. CONCLUSIONS: Both major storms and PO were associated with increased hospital admission of COPD. PO mediated almost half of the major storms-COPD hospitalization associations. Preparation of surrogate electric system before major storms is essential to reduce major storms-COPD hospitalization.

15.
BMC Infect Dis ; 21(1): 1026, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592936

RESUMO

BACKGROUND: Cytomegalovirus (CMV) reactivation is associated with adverse prognoses of critically ill patients. However, the epidemiology and predictors of CMV reactivation in immunocompetent patients receiving mechanical ventilation (MV) are not clear. The aim of this study was to investigate the epidemiology and predictors of CMV reactivation in immunocompetent patients requiring MV. METHODS: A single-center, prospective observational study (conducted from June 30, 2017 to July 01, 2018) with a follow-up of 90 days (September 29, 2018) that included 71 CMV-seropositive immunocompetent patients with MV at a 37-bed university hospital general intensive care unit (ICU) in China. Routine detection of CMV DNAemia was performed once a week for 28 days (Days 1, 7, 14, 21, and 28). CMV serology, laboratory findings, and clinical data were obtained during hospitalization. RESULTS: Among 71 patients, 13 (18.3%) showed CMV reactivation within 28 days in the ICU. The median time to reactivation was 7 days. CMV reactivation was related to various factors, including body mass index (BMI), sepsis, N-terminal pro-b-type natriuretic peptide (NT-proBNP), blood urea nitrogen (BUN), and hemoglobin (Hb) levels (P < 0.05). In the multivariate regression model, BMI, Hb level, and sepsis were independently associated with CMV reactivation patients (P < 0.05). Moreover, the area under the receiver operating characteristic (AUROC) of BMI, Hb, and BMI combined with Hb was 0.69, 0.70, and 0.76, respectively. The duration of MV, hospitalization expense, length of ICU stay, and 90 day all-cause mortality rate in patients with CMV reactivation was significantly higher than in those without CMV reactivation (P < 0.05). CONCLUSIONS: Among immunocompetent patients with MV, the incidence of CMV reactivation was 18.3%. CMV reactivation was associated with several adverse prognoses. BMI, Hb, and sepsis were independent risk factors for CMV reactivation. BMI and Hb may predict CMV reactivation.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Estado Terminal , Infecções por Citomegalovirus/epidemiologia , Humanos , Respiração Artificial/efeitos adversos , Ativação Viral
16.
Signal Transduct Target Ther ; 6(1): 355, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34650034

RESUMO

This multicenter phase-II trial aimed to investigate the efficacy, safety, and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC. Patients who failed from first-line EGFR-TKIs and did not harbor T790M mutation were enrolled. Toripalimab plus carboplatin and pemetrexed were administrated every three weeks for up to six cycles, followed by the maintenance of toripalimab and pemetrexed. The primary endpoint was objective-response rate (ORR). Integrated biomarker analysis of PD-L1 expression, tumor mutational burden (TMB), CD8 + tumor-infiltrating lymphocyte (TIL) density, whole-exome, and transcriptome sequencing on tumor biopsies were also conducted. Forty patients were enrolled with an overall ORR of 50.0% and disease-control rate (DCR) of 87.5%. The median progression free survival (PFS) and overall survival were 7.0 and 23.5 months, respectively. The most common treatment-related adverse effects were leukopenia, neutropenia, anemia, ALT/AST elevation, and nausea. Biomarker analysis showed that none of PD-L1 expression, TMB level, and CD8 + TIL density could serve as a predictive biomarker. Integrated analysis of whole-exome and transcriptome sequencing data revealed that patients with DSPP mutation had a decreased M2 macrophage infiltration and associated with longer PFS than those of wild type. Toripalimab plus chemotherapy showed a promising anti-tumor activity with acceptable safety profiles as the second-line setting in patients with EGFR-mutant NSCLC. DSPP mutation might serve as a potential biomarker for this combination. A phase-III trial to compare toripalimab versus placebo in combination with chemotherapy in this setting is ongoing (NCT03924050).

17.
Artigo em Inglês | MEDLINE | ID: mdl-34665490

RESUMO

Modulation of A-site defects is crucial to the redox reactions on ABO3 perovskites for both clean air application and electrochemical energy storage. Herein we report a scalable one-pot strategy for in situ regulation of La vacancies (VLa ) in LaMnO3.15 by simply introducing urea in the traditional citrate process, and further reveal the fundamental relationship between VLa creation and surface lattice oxygen (Olatt ) activation. The underlying mechanism is shortened Mn-O bonds, decreased orbital ordering, promoted MnO6 bending vibration and weakened Jahn-Teller distortion, ultimately realizing enhanced Mn-3d and O-2p orbital hybridization. The LaMnO3.15 with optimized VLa exhibits order of magnitude increase in toluene oxidation and ca. 0.05 V versus RHE (reversible hydrogen electrode) increase of half-wave potential in oxygen reduction reaction (ORR). The reported strategy can benefit the development of novel defect-meditated perovskites in both heterocatalysis and electrocatalysis.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34613925

RESUMO

Segmentation of hepatic vessels from 3D CT images is necessary for accurate diagnosis and preoper-ative planning for liver cancer. However, due to the low contrast and high noises of CT images, automatic hepatic vessel segmentation is a challenging task. Hepatic vessels are connected branches containing thick and thin blood vessels, showing an important structural characteristic or a prior: the connectivity of blood vessels. However, this is rarely applied in existing methods. In this paper, we segment hepatic vessels from 3D CT images by utilizing the connectivity prior. To this end, a graph neural network (GNN) used to describe the connectivity prior of hepatic vessels is integrated into a general convolutional neu-ral network (CNN). Specifically, a graph attention network (GAT) is first used to model the graphical connectivity information of hepatic vessels, which can be trained with the vascular connectivity graph constructed directly from the ground truths. Second, the GAT is integrated with a lightweight 3D U-Net by an efficient mechanism called the plug-in mode, in which the GAT is incorporated into the U-Net as a multi-task branch and is only used to supervise the training procedure of the U-Net with the connectivity prior. The GAT will not be used in the inference stage, and thus will not increase the hardware and time costs of the inference stage compared with the U-Net. Therefore, hepatic vessel segmentation can be well improved in an efficient mode. Extensive experiments on two public datasets show that the proposed method is superior to related works in accuracy and connectivity of hepatic vessel segmentation.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34668977

RESUMO

BACKGROUND: This phase II study evaluated camrelizumab in different PD-L1 expression cohorts of patients with previously treated advanced/metastatic non-small cell lung cancer (NSCLC; NCT03085069, registered March 21, 2017). METHODS: Patients who progressed during/after chemotherapy were enrolled and divided into four cohorts based on PD-L1 tumor proportion score (TPS). Patients with EGFR/ALK alterations and PD-L1 TPS ≥ 50% were also eligible. All enrolled patients received camrelizumab at 200 mg IV Q2W. The primary endpoint was objective response rate. RESULTS: A total of 146 patients were enrolled. As of data cutoff on Aug 20, 2020, the median follow-up was 29.5 months (95% CI 27.4-30.8). Objective response rate was 17.8% (95% CI 12.0-25.0) and improved with the increasing PD-L1 TPS (TPS < 1%, 12.2% [95% CI 5.7-21.8]; ≥ 1-< 25%, 19.4% [95% CI 7.5-37.5]; ≥ 25-< 50%, 36.4% [95% CI 10.9-69.2]; ≥ 50%, 23.3% [95% CI 9.9-42.3]). No response was observed in the five patients harboring EGFR mutations. Median progression-free survival was 3.2 months (95% CI 2.0-3.4), and patients with positive PD-L1 TPS had longer progression-free survival. Median overall survival was 14.8 months (95% CI 10.2-18.7). Treatment-related adverse events (TRAEs) of any grade occurred in 87.7% of patients, and 21.2% had grade ≥ 3 TRAEs. CONCLUSION: Camrelizumab showed improved efficacy compared with historical data of the second-line chemotherapy in pre-treated advanced/metastatic NSCLC. Patients with positive PD-L1 expression derived greater benefit from camrelizumab. Camrelizumab has a manageable safety profile.

20.
Chem Commun (Camb) ; 57(85): 11205-11208, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34622901

RESUMO

A versatile approach for the fine control of DNA-based hierarchical assembly via dual stimuli and two assembly strategies is developed. Moreover, with a reasonable design of functional thrombin aptamer structures on the formed DNA nanoassembly, it can achieve precise regulation of thrombin activity.

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