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1.
Appl Spectrosc ; : 37028211009973, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33825543

RESUMO

Fluorescence-based single molecule techniques, mainly including fluorescence correlation spectroscopy (FCS) and single-molecule fluorescence resonance energy transfer (smFRET), are able to analyze the conformational dynamics and diversity of biological macromolecules. They have been applied to analysis of the dynamics of membrane proteins, such as membrane receptors and membrane transport proteins, due to their superior ability in resolving spatio-temporal heterogeneity and the demand of trace amounts of analytes. In this review, we first introduced the basic principle involved in FCS and smFRET. Then we summarized the labelling and immobilization strategies of membrane protein molecules, the confocal-based and TIRF-based instrumental configuration, and the data processing methods. The applications to membrane protein dynamics analysis are described in detail with the focus on how to select suitable fluorophores, labelling sites, experimental setup and analysis methods. In the last part, the remaining challenges to be addressed and further development in this field are also briefly discussed.

2.
BMC Cancer ; 21(1): 341, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789616

RESUMO

BACKGROUND: To evaluate the efficacy and safety of recombinant human serum albumin /granulocyte colony-stimulating factor (rHSA/G-CSF) in breast cancer following receipt of cytotoxic agents. METHODS: The phase 1b trial assessed the pharmacokinetics, pharmacodynamics, and safety of dose-escalation, ranging from rHSA/G-CSF 1800 µg, 2100 µg, and 2400 µg. Randomized controlled phase 2b trial was further conducted to ensure the comparative efficacy and safety of rHSA/G-CSF 2400 µg and rhG-CSF 5 µg/kg. In multicenter, randomized, open-label, parallel, phase 2 study, participants treated with anthracycline-containing chemotherapy were assigned in a ratio 1:1:1 to receive double delivery of rHSA/G-CSF 1200 µg, 1500 µg, and continuous rhG-CSF 5 µg/kg. RESULTS: Between December 16, 2014, to July 23, 2018, a total of 320 patients were enrolled, including 25 individuals in phase 1b trial, 80 patients in phase 2b trial, and 215 participants in phase 2 study. The mean duration of agranulocytosis during the first chemotherapeutic intermission was observed as 1.14 ± 1.35 days in rHSA/G-CSF 1500 µg, which was comparable with that of 1.07 ± 0.97 days obtained in rhG-CSF control (P = 0.71). Safety profiles were assessed to be acceptable ranging from rHSA/G-CSF 1800 µg to 2400 µg, while the double delivery of HSA/G-CSF 2400 µg failed to meet the noninferiority in comparison with rhG-CSF. CONCLUSION: The prospective randomized controlled trials demonstrated that rHSA/G-CSF was efficacious and well-tolerated with an approachable frequency and expense of application for prophylactic management of agranulocytosis. The double delivery of rHSA/G-CSF 1500 µg in comparisons with paralleling G-CSF preparations is warranted in the phase 3 trial. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02465801 (11/17/2014), NCT03246009 (08/08/2017), NCT03251768 (08/07/2017).

3.
BMC Bioinformatics ; 22(1): 188, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849444

RESUMO

BACKGROUND: The genomics data analysis has been widely used to study disease genes and drug targets. However, the existence of missing values in genomics datasets poses a significant problem, which severely hinders the use of genomics data. Current imputation methods based on a single learner often explores less known genomic data information for imputation and thus causes the imputation performance loss. RESULTS: In this study, multiple single imputation methods are combined into an imputation method by ensemble learning. In the ensemble method, the bootstrap sampling is applied for predictions of missing values by each component method, and these predictions are weighted and summed to produce the final prediction. The optimal weights are learned from known gene data in the sense of minimizing a cost function about the imputation error. And the expression of the optimal weights is derived in closed form. Additionally, the performance of the ensemble method is analytically investigated, in terms of the sum of squared regression errors. The proposed method is simulated on several typical genomic datasets and compared with the state-of-the-art imputation methods at different noise levels, sample sizes and data missing rates. Experimental results show that the proposed method achieves the improved imputation performance in terms of the imputation accuracy, robustness and generalization. CONCLUSION: The ensemble method possesses the superior imputation performance since it can make use of known data information more efficiently for missing data imputation by integrating diverse imputation methods and learning the integration weights in a data-driven way.

4.
Cancer Biol Med ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710812

RESUMO

OBJECTIVE: Anlotinib is a novel tyrosine kinase inhibitor blocking angiogenesis. This study was performed to assess the efficacy and safety of anlotinib in patients with metastatic breast cancer. METHODS: Patients with HER2-negative breast cancer, who were pre-treated with anthracycline or taxanes in a neoadjuvant, adjuvant, or metastatic setting, and had treatment failure after at least one prior chemotherapy regimen in the metastatic setting were enrolled. Anlotinib was administered at 12 mg daily for 14 days in a 21-day cycle until disease progression or unacceptable toxicity occurred. Simultaneously, 5-10 mL of venous blood was collected to perform circulating tumor DNA (ctDNA) testing every 2 treatment cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), overall survival, safety, and biomarkers. RESULTS: Twenty-six eligible patients were enrolled, with a median age of 56 (30-75) years. The median follow-up time was 10.5 months. The ORR was 15.4%, the DCR was 80.8%, and the median PFS was 5.22 months (95% confidence interval 2.86-6.24). Fourteen (53.8%) patients survived for more than 10 months. The changes in the detectable ctDNA variant allele frequency were consistent with the tumor response. The most common treatment-related adverse events were hypertension (57.7%), thyroidstimulating hormone elevation (34.6%), and hand-foot syndrome (23.1%). CONCLUSIONS: Anlotinib showed objective efficacy with tolerable toxicity in heavily pre-treated, metastatic HER2-negative breast cancer. The dynamic changes in the ctDNA variant allele fraction may be predictive of the tumor response.

5.
Int J Cancer ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33783821

RESUMO

Biological evidence suggests that vitamin D has numerous anticancer functions, but the associations between vitamin D status and colorectal cancer (CRC) risk and survival remain inconclusive. Based on UK Biobank, we prospectively evaluated the associations of season-standardized 25-hydroxyvitamin D (25(OH)D) concentrations with CRC risk among 360 061 participants, and with survival among 2509 CRC cases. We observed an inverse linear relationship between 25(OH)D concentrations and CRC risk (P for linearity = .01; HR per 1-SD increment, 0.95; 95% CI, 0.91-0.99). Compared to the lowest quartile of 25(OH)D, the highest quartile was associated with a 13% (HR, 0.87; 95% CI, 0.77-0.98) lower risk of CRC. For CRC survival, compared to those in the lowest quartile of 25(OH)D, cases in the highest quartile had a 20% (HR, 0.80; 95% CI, 0.65-0.99) lower risk for overall death. Our findings indicate that higher concentrations of serum 25(OH)D are associated with lower incidence and improved survival of CRC, suggesting a role of vitamin D in the pathogenesis of CRC.

6.
Eur J Endocrinol ; 184(5): 723-732, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33690154

RESUMO

Objective: Testosterone is a critical determinant of health in both genders. However, the relationship between circulating levels of testosterone and mortality remains undetermined. Methods: We examined the associations of serum total testosterone (TT) and free testosterone (FT) with all-cause and cause-specific mortality in 154 965 men and 93 314 postmenopausal women from UK Biobank. Cox regression models were used to calculate the hazard ratios (HR) and 95% CIs. Given multiple testing, P < 0.005 was considered statistically significant. Results: Over a median follow-up of 8.9 (inter-quartile range: 8.3-9.5) years, we documented 5754 deaths in men, including 1243 (21.6%) from CVD and 2987 (51.9%) from cancer. In postmenopausal women, 2435 deaths occurred, including 346 (14.2%) from CVD and 1583 (65.0%) from cancer. TT and FT concentrations were inversely associated with all-cause mortality in men, with the multivariable HR of 0.82 (95% CI: 0.75-0.91) and 0.80 (95% CI: 0.73-0.87) for the highest (Q5) vs the lowest quintile (Q1), respectively. In postmenopausal women, TT concentrations showed a positive association with all-cause mortality (HR for Q5 vs Q1 = 1.20, 95% CI: 1.06-1.37). Furthermore, higher TT and FT concentrations were associated with a lower risk of cancer mortality in men (both P for trend = 0.001), whereas TT concentrations were suggestively associated with a higher risk of cancer mortality in postmenopausal women (P for trend = 0.03). Conclusions: Our findings suggest that high levels of circulating testosterone may be beneficial for all-cause and cancer mortality in men but detrimental in postmenopausal women.

7.
Biomed Res Int ; 2021: 6692815, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628809

RESUMO

Objectives: Our study will investigate the effect of ultrasound-guided thoracic paravertebral block (UG-TPVB) on postoperative pain, quality of life, and enhanced recovery in patients with non-small-cell lung cancer (NSCLC) undergoing lobectomy surgery. Methods: Our study included 100 patients aged 52 to 75 years who underwent lobectomy surgery with pathological diagnosis of NSCLC. Patients received ultrasound-guided thoracic paravertebral block or general anesthesia with tracheal intubation. Patients' pain score was recorded on a numeric rating scale (NRS) 24 hours post operation. The total postoperative dosage of tramadol hydrochloride, length of hospitalization, quality of life (QoL), and inflammation levels were recorded. Results: Compared with patients who received general anesthesia with tracheal intubation, patients in the UG-TPVB group had lower postoperative NRS scores at 24 h (1.8 vs. 3.5, P = 0.035); the average 24 h postoperative NRS score of the UG-TPVB group is lower than that of the general anesthesia with tracheal intubation (4.6 vs. 5.3, P = 0.012), thus receiving less dosage of tramadol hydrochloride (221 ± 45 vs. 250 ± 38 mg, P < 0.01). Patients in the UG-TPVB group had better EORTC QLQ-C30 scores compared with patients in the general anesthesia with tracheal intubation group. The difference of length of hospitalization, hs-CRP, and IL-6 between two groups did not reach statistical difference (length of hospitalization 6.2 vs. 6.9 days, P = 0.055; hs-CRP: 7.1 ± 1.9 vs. 10.4 ± 6.6, P = 0.095; and IL-6: 71.3 ± 7.2 vs. 68.9 ± 8.7, P = 0.529). Discussion. NSCLC patients undergoing lobectomy surgery who received UG-TPVB had less postoperative pain, used less dosage of tramadol hydrochloride, and had better QoL.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33572116

RESUMO

Measuring activities of daily living (ADLs) using wearable technologies may offer higher precision and granularity than the current clinical assessments for patients after stroke. This study aimed to develop and determine the accuracy of detecting different ADLs using machine-learning (ML) algorithms and wearable sensors. Eleven post-stroke patients participated in this pilot study at an ADL Simulation Lab across two study visits. We collected blocks of repeated activity ("atomic" activity) performance data to train our ML algorithms during one visit. We evaluated our ML algorithms using independent semi-naturalistic activity data collected at a separate session. We tested Decision Tree, Random Forest, Support Vector Machine (SVM), and eXtreme Gradient Boosting (XGBoost) for model development. XGBoost was the best classification model. We achieved 82% accuracy based on ten ADL tasks. With a model including seven tasks, accuracy improved to 90%. ADL tasks included chopping food, vacuuming, sweeping, spreading jam or butter, folding laundry, eating, brushing teeth, taking off/putting on a shirt, wiping a cupboard, and buttoning a shirt. Results provide preliminary evidence that ADL functioning can be predicted with adequate accuracy using wearable sensors and ML. The use of external validation (independent training and testing data sets) and semi-naturalistic testing data is a major strength of the study and a step closer to the long-term goal of ADL monitoring in real-world settings. Further investigation is needed to improve the ADL prediction accuracy, increase the number of tasks monitored, and test the model outside of a laboratory setting.

9.
Innate Immun ; 27(3): 260-265, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33593148

RESUMO

Matrix metalloproteinase-9 (MMP-9) has been shown to participate in the pathogenesis of sepsis. In this study, we recruited 312 sepsis patients and 413 controls to explore the relationship between sepsis risk and the MMP-9 -1562 C/T polymorphism in Han Chinese. The PCR restriction fragment length polymorphism method was used for genotyping. Our data indicated that the MMP-9 -1562 C/T polymorphism was related with the risk of sepsis (CT vs. CC: P = 0.033, odds ratio (OR) = 1.45, 95% confidence interval (CI) 1.03-2.05; TT+CT vs. CC: P = 0.019, OR = 1.49, 95% CI 1.07-2.07). Stratified analyses demonstrated that this effect was more evident in smokers, drinkers, females and overweight individuals. Furthermore, cross-over analyses suggested that the combined effect of smoking and CT genotype of -1562 C/T polymorphism contributed to the risk of sepsis. In addition, MMP-9 serum levels were significantly lower in sepsis patients than in controls. The MMP-9 -1562 C/T polymorphism was significantly associated with decreased MMP-9 serum levels. Lastly, we observed that this polymorphism was connected to the mortality of sepsis. In conclusion, the interaction between the MMP-9 -1562 C/T polymorphism and smoking correlated with the risk of sepsis in Han Chinese. This polymorphism may serve as a diagnostic marker for sepsis patients.

10.
Eur J Epidemiol ; 36(3): 311-318, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33420872

RESUMO

Coronavirus disease 2019 (COVID-19) deteriorates suddenly primarily due to excessive inflammatory injury, and insulin-like growth factor-1 (IGF-1) is implicated in endocrine control of the immune system. However, the effect of IGF-1 levels on COVID-19 prognosis remains unknown. Using UK Biobank resource, we investigated the association between circulating IGF-1 concentrations and mortality risk (available death data updated on 07 Sep 2020) among COVID-19 patients who had pre-diagnostic serum IGF-1 measurements at baseline (2006-2010). Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of mortality. Among 1670 COVID-19 patients, 415 deaths occurred due to COVID-19. Compared to the lowest quartile of IGF-1 concentrations, the highest quartile was associated with a 41% lower risk of mortality (OR = 0.59, 95% CI 0.41-0.86, P-trend = 0.01). In the continuous model, per 1-standard deviation increment in log-transformed IGF-1 was associated with a 15% reduction in the risk (intraclass correlation coefficients corrected OR = 0.85, 95% CI 0.73-0.99). The association was largely consistent in the various stratified and sensitivity analyses. In conclusion, our data suggest that higher IGF-1 concentrations are associated with a lower risk of COVID-19 mortality. Further studies are required to determine whether and how targeting IGF-1 pathway might improve COVID-19 prognosis.

11.
J Cell Mol Med ; 25(4): 2136-2147, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33393205

RESUMO

Trophoblasts are important parts of the placenta and exert vital roles in the maternal-foetal crosstalk, and sufficient trophoblasts migration and invasion is critical for embryo implantation and normal pregnancy. Macrophages, as the major components of decidual microenvironment at maternal-foetal interface, can interact with trophoblasts to participate in the regulation of normal pregnancy. Previously, our group have demonstrated that trophoblasts could induce macrophages polarization to M2 subtype by secreting interleukin-6 (IL-6); however, the understanding of macrophages regulating the migration and invasion of trophoblasts is limited. In the present study, we used the co-cultured model to further investigate the effects of macrophages on trophoblasts migration and invasion. Our results showed that co-culture with macrophages promoted epithelial-to-mesenchymal transition (EMT) of trophoblasts, thereby enhancing their migrative and invasive abilities. Further experiments revealed that M2 macrophage-derived G-CSF was a key factor, which promoted the EMT, migration and invasion of trophoblasts via activating PI3K/Akt/Erk1/2 signalling pathway. Clinically, G-CSF was highly expressed in placental villous tissues of normal pregnancy patients compared to patients with recurrent spontaneous abortion, and its expression level was significantly correlation with EMT markers. Taken together, these findings indicate the important role of M2 macrophages in regulating trophoblasts EMT, migration and invasion, contributing to a new insight in concerning the crosstalk between macrophages and trophoblasts in the establishment and maintenance of normal pregnancy.

12.
Sci Total Environ ; 769: 144489, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33465632

RESUMO

Cyanobacterial harmful algal blooms (CyanoHABs) bring economic loss, damage aquatic ecosystems, and produce cyanobacterial toxins that threaten human health. Algicidal bacteria as pathogens can expediate the decline of CyanoHABs. In this study, a Streptomyces globisporus strain (designated G9), isolated from soil near a eutrophic pond, showed high algicidal activity against Microcystis aeruginosa. Experimental results show that G9 preyed on Microcystis through cell-to-cell contact: (1) the hyphae of G9 killed cyanobacterial cells by twining around them, while cells beyond the reach of G9 hyphae were in normal shapes; (2) No algicides were detectable in the supernatant of G9 cultures or G9-Microcystis cocultures. The algicidal ratio of G9 to M. aeruginosa reached 96.7% after 6 days. G9 selectively killed the tested cyanobacterial strains, while it had only minor impacts on the growth of tested Chlorophyceae. Differential gene expression studies show that G9 affected the expression of key genes of M. aeruginosa involved in photosynthesis, microcystin synthesis and cellular emergency responses. Further, the microcystin-LR content decreased gradually with G9 treatment. As the first reported Streptomyces sp. with algicidal (predation) activity requiring cell-to-cell contact with target prey, G9 is a good candidate for the exploration of additional cyanobacteria-bacteria interactions and the development of novel strategies to control CyanoHABs.


Assuntos
Microcystis , Streptomyces , Ecossistema , Proliferação Nociva de Algas , Humanos , Microcistinas
13.
J Agric Food Chem ; 69(1): 112-125, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33353295

RESUMO

The growth and development of plants are dependent on the interaction between carbon and nitrogen metabolism. Essential information about the metabolic regulation of carbon-nitrogen metabolism is still lacking, such as possible interactions among nitrogen metabolism, photosynthesis, and photorespiration. This study shows that higher photorespiration consumes more CO2 fixed by photosynthesis, making the high photosynthetic efficiency mutant fail to increase production. In order to clarify the effects of photosynthesis and photorespiration on carbon and nitrogen metabolism in high photosynthetic efficiency mutant, a yellow-green leaf mutant (ygl53) was isolated from rice (Oryza sativa L.). Its chlorophyll (Chl) content decreased, but chloroplast development was not affected. Genetic analysis demonstrated that YGL53 encodes the magnesium chelatase D subunit (ChlD). The ygl53 mutant showed an increased net assimilation rate (An) and electron transport flux efficiency and catalase (CAT) activity, and it also had a higher photorespiration rate (Pr), lower H2O2, and reduced nitrogen uptake efficiency (NUpE); however, there was no loss in yield. The higher activities of glutamate synthase (GOGAT) and glutamine synthetase (GS) ensure the α-ketoglutaric acid (2-OG) and ammonia (NH3) availabilities, which are produced from photorespiration in the ygl53 mutant. These have an important function for carbon and nitrogen metabolism homeostasis in ygl53. Further analysis indicated that the energy and substances derived from carbon metabolism supplemented nitrogen metabolism in the form of photorespiration to ensure its normal development when the An of photosynthesis was increased in the ygl53 mutant with reduced NUpE.


Assuntos
Carbono/metabolismo , Liases/metabolismo , Nitrogênio/metabolismo , Oryza/enzimologia , Proteínas de Plantas/metabolismo , Dióxido de Carbono/metabolismo , Clorofila/metabolismo , Luz , Liases/genética , Mutação , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Oryza/efeitos da radiação , Fotossíntese/efeitos da radiação , Proteínas de Plantas/genética , Respiração/efeitos da radiação
14.
Breast ; 55: 30-36, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33310633

RESUMO

PURPOSE: To characterize the incidence, risk factors and survival of patients with brain metastases at initial diagnosis of metastatic breast cancer (MBC) in China. METHODS: The China National Cancer Center database was used to identify 2087 MBC patients diagnosed between 2003 and 2015. Clinicopathological features, treatment and survival information were extracted. Multivariable logistic and Cox regression were performed to determine factors predictive of brain metastases at MBC diagnosis and survival, respectively. RESULTS: Brain metastases occurred in ninety patients (4.3%) at MBC diagnosis, and in 27 patients (2.5%), 42 patients (7.2%) and 21 patients (5.2%) with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR + HER2-), HER2-positive and triple negative breast cancer (TNBC), respectively. HER2-positive subtype (OR = 2.38; 95% CI 1.40-4.04; p < 0.0001), TNBC subtype (OR = 1.89; 95% CI 1.02-3.51; p = 0.005), and metastases to all three sites of bone, liver and lungs (OR = 3.23; 95% CI 1.52-6.87; p = 0.002) were shown to increase the risk of BM at MBC diagnosis. Median survival after BM was 23.7 months. First-line tyrosine kinase inhibitors (TKI) improved survival compared to trastuzumab-based regimen (44.9 vs 35.4 months, p = 0.09). Factors that independently decreased BM death risk were ECOG<2, brain metastases only and multidisciplinary treatment. CONCLUSION: HER2-positive and TNBC subtypes have a higher incidence of BM at initial MBC diagnosis. Brain screening might be considered in patients with HER2-positive disease at MBC diagnosis, and further prospective randomized study is warranted.

15.
BMC Vet Res ; 16(1): 467, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33256712

RESUMO

BACKGROUND: It has been widely accepted that there is a significant difference in peripheral blood oxygen between arteries and veins. Therefore, arterial blood has been collected for blood gas analysis, and venous blood, because it is convenient to collect, has been used for most laboratory examinations. However, venous blood is always difficult to collect in rabbits; in contrast, arterial blood is easier to obtain, and research on whether arterial blood can be used instead of venous blood for routine biochemical parameter examination is rare. Therefore, the present study was designed to explore whether arterial blood can be used as a substitute for venous blood for routine biochemistry parameter examination in rabbits. RESULTS: Three venous blood samples with gross hemolysis were excluded. Venous and arterial blood samples were obtained from forty-two rabbits. Arterial blood samples correlate well with venous blood in alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), total protein (TP), globulin (GLB), serum total cholesterol (TC), serum triglyceride (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), urea (Ur) and creatinine (Cr) levels by Deming regression analysis with slopes ranging from 0.893 to 1.176 and intercepts ranging from - 4.886 to 5.835. Bland-Altman analysis showed that the two sample parameters had 93%-98% of the points within the 95% consistency limits. There were significant differences between venous blood and arterial blood in ALP, TP, TC, TG, HDL, LDL and Cr, while AST, ALT, GGT, GLB and Ur showed no significant differences. CONCLUSIONS: Arterial blood can be a substitute for venous blood in routine biochemistry parameter examinations in rabbits, especially in situations where venous blood is difficult to collect.

16.
Acc Chem Res ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33284599

RESUMO

ConspectusEmerging solar cells that convert clean and renewable solar energy to electricity, such as organic solar cells (OSCs) and perovskite solar cells (PSCs), have attracted increasing attention owing to some merits such as facile fabrication, low cost, flexibility, and short energy payback time. The power conversion efficiencies (PCEs) of OSCs and PSCs have exceeded 18% and 25%, respectively.Fullerene derivatives have high electron affinity and mobility with an isotropic transport feature. Fullerene-based OSCs yielded superior PCEs to other acceptors and have dominated electron acceptor materials from 1995 to 2015. However, some drawbacks of fullerenes, such as weak visible absorption, limited tunability of electronic properties, laborious purification, and morphological instability, restrict further development of OSCs toward higher PCEs and practical applications. The theoretical PCE of fullerene-based OSCs is limited to ∼13% due to the relatively large energy losses. Many efforts have been dedicated to developing new acceptor systems beyond fullerenes, and some successful systems such as rylene diimides have achieved PCEs up to ca. 11%.In 2015, our group pioneered a new class of electron acceptors, fused-ring electron acceptor (FREA), as represented by the star molecule ITIC. The chemical features of FREAs include: (1) a modular structure, consisting of an electron-donating core, electron-withdrawing end groups, π-bridges, and side chains, which benefits molecular tailoring; (2) facile synthesis, purification, and scalability. The physical features of FREAs include: (1) a broad modulation range of absorption and energy levels; (2) strong absorption, especially in the 700-1000 nm region; (3) high electron mobility. The device features of FREAs include: (1) low voltage loss; (2) high efficiency; (3) good stability. The FREAs boosted PCEs of the OSCs up to 18% and initiated the transformation from the fullerene to nonfullerene era of this field. FREAs can also be used in PSCs as interfacial layers, electron transport layers, or active layers, improving both efficiency and stability of the devices. Beyond photovoltaic applications, FREAs can also be used in photodetectors, field-effect transistors, two-photon absorption, photothermal therapy, solar water splitting, etc.In this Account, we review the development of the FREAs and their applications in OSCs, PSCs, and other related fields. Molecular design, device engineering, photophysics, and applications of FREAs are discussed in detail. Future research directions toward performance optimization and commercialization of FREAs are also proposed.

17.
Int J Mol Sci ; 21(23)2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33287214

RESUMO

Prostate cancer (PCa) is a reproductive system cancer in elderly men. We investigated the effects of betel nut arecoline on the growth of normal and cancerous prostate cells. Normal RWPE-1 prostate epithelial cells, androgen-independent PC-3 PCa cells, and androgen-dependent LNCaP PCa cells were used. Arecoline inhibited their growth in dose- and time-dependent manners. Arecoline caused RWPE-1 and PC-3 cell cycle arrest in the G2/M phase and LNCaP cell arrest in the G0/G1 phase. In RWPE-1 cells, arecoline increased the expression of cyclin-dependent kinase (CDK)-1, p21, and cyclins B1 and D3, decreased the expression of CDK2, and had no effects on CDK4 and cyclin D1 expression. In PC-3 cells, arecoline decreased CDK1, CDK2, CDK4, p21, p27, and cyclin D1 and D3 protein expression and increased cyclin B1 protein expression. In LNCaP cells, arecoline decreased CDK2, CDK4, and cyclin D1 expression; increased p21, p27, and cyclin D3 expression; had no effects on CDK1 and cyclin B1 expression. The antioxidant N-acetylcysteine blocked the arecoline-induced increase in reactive oxygen species production, decreased cell viability, altered the cell cycle, and changed the cell cycle regulatory protein levels. Thus, arecoline oxidant exerts differential effects on the cell cycle through modulations of regulatory proteins.

18.
Clin Breast Cancer ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33277191

RESUMO

BACKGROUND: Different clinicopathologic characteristics could contribute to inconsistent prognoses of small breast neoplasms (T1a/T1b). This study was done to conduct a retrospective analysis and establish a clinical prediction model to predict individual survival outcomes of patients with small carcinomas of the breast. MATERIALS AND METHODS: Based on the Surveillance, Epidemiology, and End Results (SEER) database, eligible patients with small breast carcinomas were analyzed. Univariate analysis and multivariate analysis were performed to clarify the indicators of overall survival. Pooling risk factors enabled nomograms to be constructed and further predicted 3-year, 5-year, and 10-year survival of patients with small breast cancer. The model was internally validated for discrimination and calibration. RESULTS: A total of 17,543 patients with small breast neoplasms diagnosed between 2013 and 2016 were enrolled. Histologic grade, lymph node stage, estrogen receptor or progesterone receptor status, and molecular subtypes of breast cancer were regarded as the risk factors of prognosis in a Cox proportional hazards model (P < .05). A nomogram was constructed to give predictive accuracy toward individual survival rate of patients with small breast neoplasms. CONCLUSIONS: This prognostic model provided a robust and effective method to predict the prognosis of patients with small breast cancer.

19.
Comput Methods Programs Biomed ; : 105864, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33280937

RESUMO

BACKGROUND AND OBJECTIVE: Pathological lung segmentation as a pretreatment step in the diagnosis of lung diseases has been widely explored. Because of the complexity of pathological lung structures and gray blur of the border, accurate lung segmentation in clinical 3D computed tomography images is a challenging task. In view of the current situation, the work proposes a fast and accurate pathological lung segmentation method. The following contributions have been made: First, the edge weights introduce spatial information and clustering information, so that walkers can use more image information during walking. Second, a Gaussian Distribution of seed point set is established to further expand the possibility of selection between fake seed points and real seed points. Finally, the pre-parameter is calculated using original seed points, and the final results are fitted with new seed points. METHODS: This study proposes a segmentation method based on an improved random walker algorithm. The proposed method consists of the following steps: First, a gray value is used as the sample distribution. Gaussian mixture model is used to obtain the clustering probability of an image. Thus, the spatial distance and clustering result are added as new weights, and the new edge weights are used to construct a random walker map. Second, a large number of marked points are automatically selected, and the intermediate results are obtained from the newly constructed map and retained only as pre-parameters. When new seed points are introduced, the probability value of the walker is quickly calculated from the new parameters and pre-parameters, and the final segmentation result can be obtained. RESULTS: The proposed method was tested on 65 sets of CT cases. Quantitative evaluation with different methods confirms the high accuracy on our dataset (98.55%) and LOLA11 dataset (97.41%). Similarly, the average segmentation time (10.5s) is faster than random walker (1,332.5s). CONCLUSIONS: The comparison of the experimental results show that the proposed method can accurately and quickly obtain pathological lung processing results. Therefore, it has potential clinical applications.

20.
Front Aging Neurosci ; 12: 582674, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33250764

RESUMO

Postoperative delirium (POD) is the most common postoperative complication affecting elderly patients, yet the underlying mechanism is elusive, and effective therapies are lacking. The neuroinflammation hypothesis for the pathogenesis of POD has recently emerged. Accumulating evidence is supporting the role of specialized proresolving lipid mediators (SPMs) in regulating inflammation. Neuroprotectin D1 (NPD1), a novel docosahexaenoic acid (DHA)-derived lipid mediator, has shown potent immunoresolvent and neuroprotective effects in several disease models associated with inflammation. Here, using a mouse model of POD, we investigated the role of NPD1 in postoperative cognitive impairment by assessing systemic inflammatory changes, the permeability of the blood-brain barrier (BBB), neuroinflammation, and behavior in aged mice at different time points. We report that a single dose of NPD1 prophylaxis decreased the expression of tumor necrosis factor alpha TNF-α and interleukin (IL)-6 and upregulated the expression of IL-10 in peripheral blood, the hippocampus, and the prefrontal cortex. Additionally, NPD1 limited the leakage of the BBB by increasing the expression of tight junction (TJ)-associated proteins such as ZO-1, claudin-5, and occludin. NPD1 also abolished the activation of microglia and astrocytes in the hippocampus and prefrontal cortex, which is associated with improved general and memory function after surgery. In addition, NPD1 treatment modulated the inflammatory cytokine expression profile and improved the expression of the M2 marker CD206 in lipopolysaccharide (LPS)-stimulated macrophages, which may partly explain the beneficial effects of NPD1 on inflammation. Collectively, these findings shed light on the proresolving activities of NPD1 in the pro-inflammatory milieu both in vivo and in vitro and may bring a novel therapeutic approach for POD.

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