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1.
J Control Release ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33157190

RESUMO

The endothelium participates in maintaining vascular hemostasis and is involved in multiple pathological processes. Although it is rarely the targeted tissue, the endothelium interacts intimately with applied therapeutic systems. Carbon nanomaterials (CBNs) with editable physiochemical characteristics and outstanding biosafety are believed to have great prospects in the biomedical field. Before reaching their destination, these materials necessarily enter the blood vessels and interact with the vascular endothelium, which strongly affects the biomedical efficiency. In this work, we start with the changes that CBNs cause to physiological endothelial barriers and then organize the potential mechanisms revealed. Subsequently, we discuss the factors influencing the CBN-endothelium interaction and highlight the importance of balancing therapeutic efficiency and biocompatibility. More importantly, this work introduces the heterogeneity of multiple vascular endothelia under both physiological and pathological conditions and the related applications with the hope of promoting improved accuracy and curative effects of future therapeutic systems. Through this manuscript, we hope to help illuminate the current status quo of CBN-vascular research and inspire further exciting progress via the insights we gained from the current outstanding examples.

2.
Nanotechnology ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33207330

RESUMO

Density functional theory was used to study the Ag-doped Cu@CuO core-shell structure, electronic properties and catalytic properties. Similar to the undoped Cu@CuO clusters, the Ag doped clusters also retain the core-shell structure. Ag doping increases the charge transfer between surrounding O atoms and Cu atoms and reduces the potential of the core-shell structure, thereby increasing its surface activity. The study of its orbital distribution found that the doping of Ag atoms caused the interaction between the inner Cu core and the outer CuO shell, which changed the electron orbital motion inside the shell. The internal chemical stability of the core-shell material is improved. In addition, Ag atom doping accelerates the decomposition of H2O2 on Cu@CuO structure and increases its adsorption of small molecules, which indicates that Ag atom doping improves the catalytic performance of Cu@CuO structure.

3.
J Hazard Mater ; : 124373, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33153788

RESUMO

In recent years, ultraviolet (UV) irradiation coupled with chlor(am)ination process is ubiquitous in secondary water supply systems in many cities of China. However, the disinfection by-products (DBPs) formation in a UV-activated mixed chlorine/chloramine system (MCCS) still remains unclear. In this study, the DBPs formation in a UV-activated MCCS was systematically investigated, considering influencing factors including the mass ratios of free chlorine to NH2Cl, UV irradiation, pH values, NOM types, Br- concentration and toxicity of the DBPs. Results indicated that DBPs formation decreased remarkably as mass ratio of free chlorine to NH2Cl changed from 5:0 to 0:5. The DBPs formation in humic acid (HA)-containing water was the highest, followed by those in fulvic acid (FA) and algal organic matter (AOM). Besides, better control of the DBP-related calculated toxicity can be achieved in acidic conditions regardless of the UV irradiation. Furthermore, in the presence of Br-, a significant reduction of DBPs formation could be achieved in a UV-activated MCCS. The findings also demonstrated that DBPs formation in real water can be effectively reduced at high UV fluence in a MCCS.

4.
Part Fibre Toxicol ; 17(1): 53, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066795

RESUMO

BACKGROUND: Widespread biomedical applications of nanomaterials (NMs) bring about increased human exposure risk due to their unique physicochemical properties. Autophagy, which is of great importance for regulating the physiological or pathological activities of the body, has been reported to play a key role in NM-driven biological effects both in vivo and in vitro. The coexisting hazard and health benefits of NM-mediated autophagy in biomedicine are nonnegligible and require our particular concerns. MAIN BODY: We collected research on the toxic effects related to NM-mediated autophagy both in vivo and in vitro. Generally, NMs can be delivered into animal models through different administration routes, or internalized by cells through different uptake pathways, exerting varying degrees of damage in tissues, organs, cells, and organelles, eventually being deposited in or excreted from the body. In addition, other biological effects of NMs, such as oxidative stress, inflammation, necroptosis, pyroptosis, and ferroptosis, have been associated with autophagy and cooperate to regulate body activities. We therefore highlight that NM-mediated autophagy serves as a double-edged sword, which could be utilized in the treatment of certain diseases related to autophagy dysfunction, such as cancer, neurodegenerative disease, and cardiovascular disease. Challenges and suggestions for further investigations of NM-mediated autophagy are proposed with the purpose to improve their biosafety evaluation and facilitate their wide application. Databases such as PubMed and Web of Science were utilized to search for relevant literature, which included all published, Epub ahead of print, in-process, and non-indexed citations. CONCLUSION: In this review, we focus on the dual effect of NM-mediated autophagy in the biomedical field. It has become a trend to use the benefits of NM-mediated autophagy to treat clinical diseases such as cancer and neurodegenerative diseases. Understanding the regulatory mechanism of NM-mediated autophagy in biomedicine is also helpful for reducing the toxic effects of NMs as much as possible.

5.
Environ Microbiol ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089595

RESUMO

As the most abundant and genetically diverse biological entities, viruses significantly influence ecological, biogeographical and evolutionary processes in the ocean. However, the biogeography of marine viruses and the drivers shaping viral community are unclear. Here, the biogeographic patterns of T4-like viruses and the relative impacts of deterministic (environmental selection) and dispersal (spatial distance) processes were investigated in the northern South China Sea. The dominant viral operational taxonomic units were affiliated with previously defined Marine, Estuary, Lake and Paddy Groups. A clear viral biogeographic pattern was observed along the environmental gradient from the estuary to open sea. Marine Groups I and IV had a wide geographical distribution, whereas Marine Groups II, III and V were abundant in lower-salinity continental or eutrophic environments. A significant distance-decay pattern was noted for the T4-like viral community, especially for those infecting cyanobacteria. Both deterministic and dispersal processes influenced viral community assembly, although environmental selection (e.g. temperature, salinity, bacterial abundance and community, etc.) had a greater impact than spatial distance. Network analysis confirmed the strong association between viral and bacterial community composition, and suggested a diverse ecological relationship (e.g. lysis, co-infection or mutualistic) between and within viruses and their potential bacterial hosts.

6.
Cells ; 9(10)2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33020410

RESUMO

We have previously discovered that HDAC6 regulates the DNA damage response (DDR) via modulating the homeostasis of a DNA mismatch repair protein, MSH2, through HDAC6's ubiquitin E3 ligase activity. Here, we have reported HDAC6's second potential E3 ligase substrate, a critical cell cycle checkpoint protein, Chk1. We have found that HDAC6 and Chk1 directly interact, and that HDAC6 ubiquitinates Chk1 in vivo and in vitro. Specifically, HDAC6 interacts with Chk1 via the DAC1 domain, which contains its ubiquitin E3 ligase activity. During the cell cycle, Chk1 protein levels fluctuate, peaking at the G2 phase, subsequently resolving via the ubiquitin-proteasome pathway, and thereby allowing cells to progress to the M phase. However, in HDAC6 knockdown non-small cell lung cancer (NSCLC) cells, Chk1 is constitutively active and fails to resolve post-ionizing radiation (IR), and this enhanced Chk1 activity leads to preferential G2 arrest in HDAC6 knockdown cells accompanied by a reduction in colony formation capacity and viability. Depletion or pharmacological inhibition of Chk1 in HDAC6 knockdown cells reverses this radiosensitive phenotype, suggesting that the radiosensitivity of HDAC6 knockdown cells is dependent on increased Chk1 kinase activity. Overall, our results highlight a novel mechanism of Chk1 regulation at the post-translational level, and a possible strategy for sensitizing NSCLC to radiation via inhibiting HDAC6's E3 ligase activity.

7.
Artigo em Chinês | MEDLINE | ID: mdl-33040497

RESUMO

Objective:To explore the correlation factors and prognosis of local recurrence of laryngeal squamous cell carcinoma. Method:The clinical data of 69 patients with local recurrence of laryngeal squamous cell carcinoma were analyzed retrospectively. The survival curve was analyzed by Kaplan-Meier method, and the survival rate was compared by chi-square test and log rank test, Cox risk regression model was used to analyze multivariate survival. Result:Patients with local recurrence of laryngeal cancer had DFS and OS at 3 years of 17.4% and 63.8%, at 5 years of 4.3% and 40.6%, respectively. The invasion of the thyroid cartilage plate is significantly related to the prognosis of the patient, and the degree of squamous cell carcinoma differentiation is an independent factor influencing the prognosis, patients with non-invasive thyroid cartilage plate and high differentiated squamous cell carcinoma have better prognosis. Conclusion:Local recurrence of laryngeal carcinoma is common among patients with moderately or poorly differentiated squamous cell carcinoma, invasion of the thyroid cartilage plate, and positive or insufficient resection margins. And the prognosis of above patients is still poor after receiving salvage surgery; comprehensive treatment and closer follow-up should be paid to these patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , Humanos , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Estudos Retrospectivos
8.
Eur J Med Chem ; 207: 112744, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32949955

RESUMO

Due to the critical tumorigenic role of fused NTRK genes in multiple cancers, TRK kinases have attracted extensive attention as a drug discovery target. Starting from an indazole based scaffold, through the type II kinase inhibitor fragments hybrid design approach with a ring closure strategy, we discovered a novel potent type II TRK kinase inhibitor compound 34 (IHMT-TRK-284), which exhibited IC50 values of 10.5 nM, 0.7 nM and 2.6 nM to TRKA, B, and C respectively. In addition, it displayed great selectivity profile in the kinome when tested among 468 kinases and mutants (S score (1) = 0.02 at 1 µM). Importantly, 34 could overcome drug resistant mutants including V573M and F589L in the ATP binding pocket as well as G667C/S in the DFG region. In vivo, 34 exhibited good PK profiles in different species including mice, rats, and dogs. It also displayed good in vivo antitumor efficacies in the TRKA/B/C, TRKA mutants, and KM-12-LUC cells mediated mouse models. The potent activity against clinically important TRK mutants combined with the good in vivo PK and efficacy properties of 34 indicated that it might be a new potential therapeutic candidate for TRK kinase fusion or mutants driven cancers.

9.
J Hazard Mater ; 399: 122809, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32937690

RESUMO

Zinc oxide nanoparticles (ZnO-NPs) have been extensively applied in our daily life. Humans are at high risk of being exposed to ZnO-NPs, which induce potentially adverse health effects. Although a growing number of studies have investigated the toxic effects of ZnO-NPs, the available data concerning ZnO-NP interactions with the blood-milk barrier (BMB) remain highly limited. Herein, we systematically investigated the damage to BMB integrity induced by ZnO-NPs and the mechanisms involved. ZnO-NPs that were intravenously injected into lactating dams accumulated in the mammary gland and entered into the breast milk, inducing disruption to BMB integrity and changes in the tight junction (TJ) and adherens junction (AJ) components. Furthermore, using an in vitro BMB model composed of EpH4-Ev cells, we verified that ZnO-NP-triggered ROS generation and the activation of MKK4 and JNK are the main mechanism of cell-cell junction damage. More interestingly, JNK activation played different roles in inducing changes in the TJ and AJ complex, and these effects did not need to activate the downstream c-Jun. These data provide more information for understanding ZnO-NP interactions with the BMB and raise concern for the daily use and the intravenous use of ZnO-NPs by lactating mothers.

10.
Leukemia ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943751

RESUMO

Limited evidence supports the use of early endpoints to evaluate the success of initial treatment of extranodal NK/T-cell lymphoma (ENKTCL) in the modern era. We aim to analyze progression-free survival at 24 months (PFS24) and subsequent overall survival (OS) in a large-scale multicenter cohort of patients. 1790 patients were included from the China Lymphoma Collaborative Group (CLCG) database. Subsequent OS was defined from the time of PFS24 or progression within 24 months to death. OS was compared with age- and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Patients who did not achieve PFS24 had a median OS of 5.3 months after progression, with 5-year OS rate of 19.2% and the SMR of 71.4 (95% CI, 62.9-81.1). In contrast, 74% patients achieved PFS24, and the SMR after achieving PFS24 was 1.77 (95% CI, 1.34-2.34). The observed OS rate after PFS24 versus expected OS rate at 5 years was 92.2% versus 94.3%. Similarly, superior outcomes following PFS24 were observed in early-stage patients (5-year OS rate, 92.9%). Patients achieving PFS24 had excellent outcome, whereas patients exhibiting earlier progression had a poor survival. These marked differences suggest that PFS24 may be used for study design and risk stratification in ENKTCL.

11.
Vet Res ; 51(1): 125, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32988413

RESUMO

The aim of this study was to investigate the biological characteristics and functions of a Trichinella spiralis serine proteinase (TsSerp) during larval invasion and development in the host. The full-length TsSerp cDNA sequence was cloned and expressed in Escherichia coli BL21. The results of RT-PCR, IFA and western blotting analyses showed that TsSerp was a secretory protein that was highly expressed at the T. spiralis intestinal infective larva and muscle larva stages and primarily located at the cuticle, stichosome and intrauterine embryos of the parasite. rTsSerp promoted the larval invasion of intestinal epithelial cells (IECs) and the enteric mucosa, whereas an anti-rTsSerp antibody impeded larval invasion; the promotion and obstruction roles were dose-dependently related to rTsSerp and the anti-rTsSerp antibodies, respectively. Vaccination of mice with rTsSerp elicited a remarkable humoral immune response (high levels of serum IgG, IgG1/IgG2a, IgE and IgM), and it also triggered both systemic (spleen) and local intestinal mucosal mesenteric lymph node (MLN) cellular immune responses, as demonstrated by a significant elevation in Th1 cytokines (IFN-γ) and Th2 cytokines (IL-4) after the spleen and MLN cells from vaccinated mice were stimulated with rTsSerp. Anti-TsSerp antibodies participated in the killing and destruction of newborn larvae via ADCC. The mice vaccinated with rTsSerp exhibited a 48.7% reduction in intestinal adult worms and a 52.5% reduction in muscle larvae. These results indicated that TsSerp participates in T. spiralis invasion and development in the host and might be considered a potential candidate target antigen to develop oral polyvalent preventive vaccines against Trichinella infection.

12.
Acta Pharmacol Sin ; 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737469

RESUMO

Inhibition of glycolysis process has been an attractive approach for cancer treatment due to the evidence that tumor cells are more dependent on glycolysis rather than oxidative phosphorylation pathway. Preliminary evidence shows that inhibition of phosphoglycerate kinase 1 (PGK1) kinase activity would reverse the Warburg effect and make tumor cells lose the metabolic advantage for fueling the proliferation through restoration of the pyruvate dehydrogenase (PDH) activity and subsequently promotion of pyruvic acid to enter the Krebs cycle in glioma. However, due to the lack of small molecule inhibitors of PGK1 kinase activity to treat glioma, whether PGK1 could be a therapeutic target of glioma has not been pharmacologically verified yet. In this study we developed a high-throughput screening and discovered that NG52, previously known as a yeast cell cycle-regulating kinase inhibitor, could inhibit the kinase activity of PGK1 (the IC50 = 2.5 ± 0.2 µM). We showed that NG52 dose-dependently inhibited the proliferation of glioma U87 and U251 cell lines with IC50 values of 7.8 ± 1.1 and 5.2 ± 0.2 µM, respectively, meanwhile it potently inhibited the proliferation of primary glioma cells. We further revealed that NG52 (12.5-50 µM) effectively inhibited the phosphorylation of PDHK1 at Thr338 site and the phosphorylation of PDH at Ser293 site in U87 and U251 cells, resulting in more pyruvic acid entering the Krebs cycle with increased production of ATP and ROS. Therefore, NG52 could reverse the Warburg effect by inhibiting PGK1 kinase activity, and switched cellular glucose metabolism from anaerobic mode to aerobic mode. In nude mice bearing patient-derived glioma xenograft, oral administration of NG52 (50, 100, 150 mg· kg-1·d-1, for 13 days) dose-dependently suppressed the growth of glioma xenograft. Together, our results demonstrate that targeting PGK1 kinase activity might be a potential strategy for glioma treatment.

13.
J Thorac Cardiovasc Surg ; 160(5): 1331-1345.e1, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32798022

RESUMO

OBJECTIVE: Concern exists regarding surgery after thoracic radiation. We aimed to assess early results of anatomic resection following induction therapy with platinum-based chemotherapy and full-dose thoracic radiation for resectable N2+ stage IIIA non-small cell lung cancer. METHODS: Two prospective trials were recently conducted by NRG Oncology in patients with resectable N2+ stage IIIA non-small cell lung cancer with the primary end point of mediastinal node sterilization following concurrent full-dose chemoradiotherapy (Radiation Therapy Oncology Group trials 0229 and 0839). All surgeons demonstrated postinduction resection expertise. Induction consisted of weekly carboplatin (area under the curve, 2.0) and paclitaxel (50 mg/m2) and concurrent thoracic radiation 60 Gy (0839)/61.2 Gy (0229) in 30 fractions. Patients in study 0839 were randomized 2:1 to weekly panitumumab + chemoradiotherapy or chemoradiotherapy alone during induction. Primary results were similar in all treatment arms and reported previously. Short-term surgical outcomes are reported here. RESULTS: One hundred twenty-six patients enrolled; 93 (74%) had anatomic resection, 77 underwent lobectomy, and 16 underwent extended resection. Microscopically margin-negative resections occurred in 85 (91%). Fourteen (15%) resections were attempted minimally invasively, including 2 converted without event. Grade 3 or 4 surgical adverse events were reported in 26 (28%), 30-day mortality in 4 (4%) and 90-day mortality in 5 (5%). Patients undergoing extended resection experienced similar rates of grade 3 or 4 adverse events (odds ratio, 0.95; 95% confidence interval, 0.42-3.8) but higher 30-day (1.3% vs 18.8%) (odds ratio, 17.54; 95% confidence interval, 1.75-181.8) and 90-day mortality (2.6% vs 18.8%) (odds ratio, 8.65; 95% confidence interval, 1.3-56.9). CONCLUSIONS: Lobectomy was performed safely following full-dose concurrent chemoradiotherapy in these multi-institutional prospective trials; however, increased mortality was noted with extended resections.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Pneumonectomia , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Pneumonectomia/mortalidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos
14.
Water Res ; 184: 116116, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32750585

RESUMO

The conversion mechanisms of chlorine species (including free chlorine, monochloramine (NH2Cl), dichloramine, and total chlorine), nitrogen species (including ammonium (NH4+), nitrate (NO3-), and nitrite (NO2-)) as well as the formation of disinfection by-products (DBPs) in a UV-activated mixed chlorine/chloramines system in water were investigated in this work. The consumption rates of free chlorine and NH2Cl were significantly promoted in a HOCl/NH2Cl coexisting system, especially in the presence of UV irradiation. Moreover, the transformation forms of nitrogen in both ultrapure and HA-containing waters were considerably affected by UV irradiation and the mass ratio of free chlorine to NH2Cl. NO3- and NO2- can be easily produced under UV irradiation, and the removal efficiency of total nitrogen with UV was obvious higher than that without UV when the initial ratio of HOCl/NH2Cl was less than 1. The roles of different radicals in the degradation of free chlorine, NH2Cl and NH4+ were also considered in such a UV-activated mixed chlorine/chloramines system. The results indicated that OH• was important to the consumption of free chlorine and NH2Cl, and showed negligible influence on the consumption of NH4+. Besides, the changes of DOC and UV254 in HA-containing water in UV-activated mixed chlorine/chloramines system indicated that the removal efficiency of DOC (24%) was much lower than that of UV254 (94%). The formation of DBPs in a mixed chlorine/chloramines system was also evaluated. The yields of DBPs decreased significantly as the mass ratio of HOCl/NH2Cl varied from 1 : 0 to 0 : 1. Moreover, compared to the conditions without UV irradiation, higher DBPs yields and DBP-associated calculated toxicity were observed during the UV-activated mixed chlorine/chloramine process.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Cloraminas , Cloro , Desinfecção , Halogenação , Nitrogênio
15.
Artigo em Chinês | MEDLINE | ID: mdl-32791636

RESUMO

Objective:To explore the rule of occult cervical lymph nodes metastasis in clinically node negative(cN0) supraglottic laryngeal carcinoma. Method:The clinical data of 185 patients with cN0 supraglottic laryngeal carcinoma were analyzed retrospectively. All patients received surgical resection of the primary lesions and lateral neck dissection. The survival curve was analyzed by Kaplan-Meier method, and the survival rate was compared by chi-square test and log rank test. Result:The total incidence of occult cervical lymph nodes metastasis in cN0 supraglottic laryngeal carcinoma was 38.9%(72/185), the unilateral and bilateral neck occult metastases were determined in 51 cases(27.6%) and 21 cases(11.4%) respectively. A total of 266 positive nodes were collected, and the distributions of the 266 positive nodes were as follows: 220(82.7%) in level Ⅱ, 42(15.8%) in level Ⅲ, and 4(1.5%) in level Ⅳ. The occult metastasis rates of bilateral cervical lymph nodes with different degrees of differentiation were 37.5%(12/32) for poorly differentiated squamous cell carcinoma, 7.4%(6/81) for moderately differentiated squamous cell carcinoma, and 4.2%(3/72) for high differentiated squamous cell carcinoma; the occult metastasis rates of bilateral cervical lymph nodes at T1, T2, T3, T4 were 0, 2.7%(2/73), 8.1%(6/74), 46.4%(13/28), respectively,and the difference was statistically significant(P<0.01). Conclusion:cN0 supraglottic laryngeal carcinoma has a high rate of occult cervical lymph nodes metastasis, and its metastatic area is mainly located in level Ⅱ-Ⅲ, so the primary tumor of the laryngeal carcinoma and the neck lymph node of level Ⅱ-Ⅲ should be managed at the same time. For the cN0 patients with poorly differentiated squamous cell carcinoma or T4 staging should be treated with bilateral neck dissection.


Assuntos
Neoplasias Laríngeas , Humanos , Linfonodos , Metástase Linfática , Esvaziamento Cervical , Estadiamento de Neoplasias , Estudos Retrospectivos
16.
J Clin Oncol ; 38(31): 3604-3614, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32780661

RESUMO

PURPOSE: No randomized trials have compared hypofractionated radiotherapy (HFRT) with conventional fractionated radiotherapy (CFRT) after breast-conserving surgery in the Asian population. This study aimed to determine whether a 3.5-week schedule of HFRT is noninferior to a standard 6-week schedule of CFRT in China. PATIENTS AND METHODS: Patients from 4 Chinese institutions who had undergone breast-conserving surgery and had T1-2N0-3 invasive breast cancers participated this study. Patients were randomly assigned (1:1) using a computer-generated central randomization schedule, without stratification, to receive whole-breast irradiation with or without nodal irradiation, followed by tumor-bed boost, either at a dose of 50 Gy in 25 fractions over 5 weeks with a boost of 10 Gy in five fractions over 1 week (CFRT) or 43.5 Gy in 15 fractions over 3 weeks with a boost of 8.7 Gy in three daily fractions (HFRT). The primary endpoint was 5-year local recurrence (LR), and a 5% margin of 5-year LR was used to establish noninferiority. RESULTS: Between August 2010 and November 2015, 734 patients were assigned to the HFRT (n = 368) or CFRT (n = 366) group. At a median follow-up of 73.5 months (interquartile range, 60.5-91.4 months), the 5-year cumulative incidence of LR was 1.2% in the HFRT group and 2.0% in the CFRT group (hazard ratio, 0.62; 95% CI, 0.20 to 1.88; P = .017 for noninferiority). There were no significant differences in acute and late toxicities, except that the HFRT group had less grade 2-3 acute skin toxicity than the CFRT group (P = .019). CONCLUSION: CFRT and HFRT with a tumor-bed boost may have similar low LR and toxicity.

17.
ACS Appl Mater Interfaces ; 12(38): 43073-43082, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32851841

RESUMO

Using temporal dimension in optical multiplexing is a promising method to increase the security of data encryption. However, adjusting the fluorescence lifetime of light-emitting material often results in inevitable changes in their fluorescence spectra, which is unfavorable for confidential information protection. Here, we report the preparation of various perovskite quantum dot/polymer nanospheres (PQD/polymer) with tunable and long fluorescence lifetimes but identical fluorescence spectra, which are ideal multidimensional data encryption materials. This new data encryption strategy utilizes the water sensitivity of perovskite and achieves spatial dimension encryption of information using different water stabilities between uncoated perovskite quantum dots and PQD/polymer. The fluorescence lifetime of PQD/polymer is used as the coding element to achieve temporal dimension data encryption, and the data are decrypted by fluorescence lifetime imaging microscopy and time-gated luminescence imaging techniques. This study shows the potential of PQD/polymer as a new class of materials for advanced data encryption.

18.
Anal Chem ; 92(18): 12387-12393, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32809810

RESUMO

A single microbead (MB)-concentrated surface-enhanced Raman scattering (SERS) mapping strategy is proposed for ultrasensitive and multiplexed immunoassay with high precision. In this design, the SERS tags are specifically immobilized on the surface of a plasmonic gold nanoparticle (GNP) layer-coated single MB via target protein-mediated immune coupling. By this means, even ultralow target dosage can bring highly concentrated SERS tags on the confined small zone around the single MB, and the target-induced SERS signals are largely enhanced by the plasmonic layer, endowing the proposed strategy with ultrahigh sensitivity to quantify subpicogram per milliliter levels of proteins. Moreover, the per-pixel averaged SERS intensity is adopted for target quantitation through mapping the SERS signals around the MB's surface, achieving greatly improved reproducibility compared with traditional single-point measurement. Benefiting from the intrinsic merits of SERS mapping, this elegant strategy also enables multiplexed immunoassay on a single MB.

19.
PLoS Comput Biol ; 16(8): e1007920, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32780741

RESUMO

Standard neuroeconomic decision theory assumes that choice is based on a value comparison process, independent from how information about alternative options is collected. Here, we investigate the opposite intuition that preferences are dynamically shaped as options are sampled, through iterative covert pairwise comparisons. Our model builds on two lines of research, one suggesting that a natural frame of comparison for the brain is between default and alternative options, the other suggesting that comparisons spread preferences between options. We therefore assumed that during sequential option sampling, people would 1) covertly compare every new alternative to the current best and 2) update their values such that the winning (losing) option receives a positive (negative) bonus. We confronted this "covert pairwise comparison" model to models derived from standard decision theory and from known memory effects. Our model provided the best account of human choice behavior in a novel task where participants (n = 92 in total) had to browse through a sequence of items (food, music or movie) of variable length and ultimately select their favorite option. Consistently, the order of option presentation, which was manipulated by design, had a significant influence on the eventual choice: the best option was more likely to be chosen when it came earlier in the sequence, because it won more covert comparisons (hence a greater total bonus). Our study provides a mechanistic understanding of how the option sampling process shapes economic preference, which should be integrated into decision theory.


Assuntos
Comportamento de Escolha/fisiologia , Modelos Psicológicos , Adulto , Biologia Computacional , Simulação por Computador , Comportamento do Consumidor , Teoria da Decisão , Feminino , Humanos , Masculino , Motivação , Psicofísica , Adulto Jovem
20.
EBioMedicine ; 57: 102880, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32645614

RESUMO

BACKGROUND: Information regarding risk factors associated with severe coronavirus disease (COVID-19) is limited. This study aimed to develop a model for predicting COVID-19 severity. METHODS: Overall, 690 patients with confirmed COVID-19 were recruited between 1 January and 18 March 2020 from hospitals in Honghu and Nanchang; finally, 442 patients were assessed. Data were categorised into the training and test sets to develop and validate the model, respectively. FINDINGS: A predictive HNC-LL (Hypertension, Neutrophil count, C-reactive protein, Lymphocyte count, Lactate dehydrogenase) score was established using multivariate logistic regression analysis. The HNC-LL score accurately predicted disease severity in the Honghu training cohort (area under the curve [AUC]=0.861, 95% confidence interval [CI]: 0.800-0.922; P<0.001); Honghu internal validation cohort (AUC=0.871, 95% CI: 0.769-0.972; P<0.001); and Nanchang external validation cohort (AUC=0.826, 95% CI: 0.746-0.907; P<0.001) and outperformed other models, including CURB-65 (confusion, uraemia, respiratory rate, BP, age ≥65 years) score model, MuLBSTA (multilobular infiltration, hypo-lymphocytosis, bacterial coinfection, smoking history, hypertension, and age) score model, and neutrophil-to-lymphocyte ratio model. The clinical significance of HNC-LL in accurately predicting the risk of future development of severe COVID-19 was confirmed. INTERPRETATION: We developed an accurate tool for predicting disease severity among COVID-19 patients. This model can potentially be used to identify patients at risks of developing severe disease in the early stage and therefore guide treatment decisions. FUNDING: This work was supported by the National Nature Science Foundation of China (grant no. 81972897) and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2015).


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Índice de Gravidade de Doença , Betacoronavirus , Proteína C-Reativa/análise , Síndrome da Liberação de Citocina/patologia , Feminino , Humanos , Hipertensão/patologia , L-Lactato Desidrogenase/análise , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Pandemias , Prognóstico , Estudos Retrospectivos
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