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1.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802922

RESUMO

Enhancers are short genomic regions exerting tissue-specific regulatory roles, usually for remote coding regions. Enhancers are observed in both prokaryotic and eukaryotic genomes, and their detections facilitate a better understanding of the transcriptional regulation mechanism. The accurate detection and transcriptional regulation strength evaluation of the enhancers remain a major bioinformatics challenge. Most of the current studies utilized the statistical features of short fixed-length nucleotide sequences. This study introduces the location information of each k-mer (SeqPose) into the encoding strategy of a DNA sequence and employs the attention mechanism in the two-layer bi-directional long-short term memory (BD-LSTM) model (spEnhancer) for the enhancer detection problem. The first layer of the delivered classifier discriminates between enhancers and non-enhancers, and the second layer evaluates the transcriptional regulation strength of the detected enhancer. The SeqPose-encoded features are selected by the Chi-squared test, and 45 positions are removed from further analysis. The existing studies may focus on selecting the statistical DNA sequence descriptors with large contributions to the prediction models. This study does not utilize these statistical DNA sequence descriptors. Then the word vector of the SeqPose-encoded features is obtained by using the word embedding layer. This study hypothesizes that different word vector features may contribute differently to the enhancer detection model, and assigns different weights to these word vectors through the attention mechanism in the BD-LSTM model. The previous study generously provided the training and independent test datasets, and the proposed spEnhancer is compared with the three existing state-of-the-art studies using the same experimental procedure. The leave-one-out validation data on the training dataset shows that the proposed spEnhancer achieves similar detection performances as the three existing studies. While spEnhancer achieves the best overall performance metric MCC for both of the two binary classification problems on the independent test dataset. The experimental data shows that the strategy of removing redundant positions (SeqPose) may help improve the DNA sequence-based prediction models. spEnhancer may serve well as a complementary model to the existing studies, especially for the novel query enhancers that are not included in the training dataset.

2.
Pest Manag Sci ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33798270

RESUMO

BACKGROUND: In Drosophila, the sex peptide receptor (SPR) in females to detect male sex peptide (SP) and trigger changes in female behavior including mating rejection and oviposition. In moths, the SPR had been identified and investigated the limited function by using RNAi. However, the detailed function of SPR after a normal mating in moths, especially the role in female sexual receptivity, remains to be elucidated. RESULTS: In this study, we use Helicoverpa armigera, an economically important pest worldwide, as a case study to verify the function of SPR in vivo by CRISPR/Cas9 gene editing system. Analyzing the post-mating behaviors in mutant females, we investigated that HarmSPR could mediate the long-term sexual receptivity (remating, sex pheromone production and calling behavior) switch in female, but not affect the short-term sexual receptivity and the duration time of remating. The oviposition of mated HarmSPR-/- females was significantly decreased by ~70% comparing to WT mated females and there were more eggs staying in the ovary of mutant females. SPR also showed effect on female longevity, which is that the mated HarmSPR-/- females showed longer longevity than mated WT females. CONCLUSION: The results detailedly demonstrated the functional role of SPR in female post-mating behaviors and we could propose a pest control strategy in which developing a antagonist of SPR to reduce the oviposition of female. This article is protected by copyright. All rights reserved.

3.
Polymers (Basel) ; 13(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799695

RESUMO

With the rapid development of economic construction, styrene-butadiene-styrene (SBS)-modified asphalt is being more and more widely used in highway engineering, but there are still many deficiencies in the process of its use. In order to further improve its performance for use, nano-organic palygorskite (A-Pal) and star-shaped SBS were compounded to obtain modified asphalt in this study. The high-temperature stability of SBS-modified asphalt was enhanced after incorporation with A-Pal for the high-temperature stability test by a dynamic shear rheometer. The A-Pal should improve the surface free energy and adhesion of SBS-modified asphalt by the water stability test analysis. The aging test shows that A-Pal can reduce the thermal oxygen decomposition of SBS and improve the anti-aging performance and the fatigue resistance of SBS-modified asphalt. A-Pal has a certain improvement effect on the low temperature performance of SBS-modified asphalt as shown by a low temperature crack resistance test. A-Pal-compounded SBS-modified asphalt features good storage stability in normal temperatures with the lowest critical compatibility temperature.

4.
Sensors (Basel) ; 21(7)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33805129

RESUMO

The design of compact hyperspectral cameras with high ground resolution and large field of view (FOV) is a challenging problem in the field of remote sensing. In this paper, the time-delayed integration (TDI) of the digital domain is applied to solve the issue of insufficient light energy brought by high spatial resolution, and a hyperspectral camera with linear variable filters suitable for digital domain TDI technology is further designed. The camera has a wavelength range of 450-950 nm, with an average spectral resolution of 10.2 nm. The paper also analyzed the effects of digital domain TDI on the signal-noise ratio (SNR) and the spectral resolution. During its working in orbits, we have obtained high-SNR images with a swath width of 150 km, and a ground sample distance (GSD) of 10 m @ 500 km. The design of the hyperspectral camera has an improved spatial resolution while reducing the cost.

5.
Sensors (Basel) ; 21(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33805882

RESUMO

Snapshot spectral imaging technology plays an important role in many fields. However, most existing snapshot imaging spectrometers have the shortcomings of a large volume or heavy computational burden. In this paper, we present a novel snapshot imaging spectrometer based on the pixel-level filter array (PFA), which can simultaneously obtain both spectral and spatial information. The system is composed of a fore-optics, a PFA, a relay lens, and a monochromatic sensor. The incoming light first forms an intermediate image on the PFA through the fore-optics. Then, the relay lens reimages the spectral images on the PFA onto the monochromatic sensor. Through the use of the PFA, we can capture a three-dimensional (spatial coordinates and wavelength) datacube in a single exposure. Compared with existing technologies, our system possesses the advantages of a simple implementation, low cost, compact structure, and high energy efficiency by removing stacked dispersive or interferometric elements. Moreover, the characteristic of the direct imaging mode ensures the low computational burden of the system, thus shortening the imaging time. The principle and design of the system are described in detail. An experimental prototype is built and field experiments are carried out to verify the feasibility of the proposed scheme.

6.
Reprod Biol Endocrinol ; 19(1): 53, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33820565

RESUMO

BACKGROUND: To minimize the rate of in vitro fertilization (IVF)- associated multiple-embryo gestation, significant efforts have been made. Previous studies related to machine learning in IVF mainly focused on selecting the top-quality embryos to improve outcomes, however, in patients with sub-optimal prognosis or with medium- or inferior-quality embryos, the selection between SET and DET could be perplexing. METHODS: This was an application study including 9211 patients with 10,076 embryos treated during 2016 to 2018, in Tongji Hospital, Wuhan, China. A hierarchical model was established using the machine learning system XGBoost, to learn embryo implantation potential and the impact of double embryos transfer (DET) simultaneously. The performance of the model was evaluated with the AUC of the ROC curve. Multiple regression analyses were also conducted on the 19 selected features to demonstrate the differences between feature importance for prediction and statistical relationship with outcomes. RESULTS: For a single embryo transfer (SET) pregnancy, the following variables remained significant: age, attempts at IVF, estradiol level on hCG day, and endometrial thickness. For DET pregnancy, age, attempts at IVF, endometrial thickness, and the newly added P1 + P2 remained significant. For DET twin risk, age, attempts at IVF, 2PN/ MII, and P1 × P2 remained significant. The algorithm was repeated 30 times, and averaged AUC of 0.7945, 0.8385, and 0.7229 were achieved for SET pregnancy, DET pregnancy, and DET twin risk, respectively. The trend of predictive and observed rates both in pregnancy and twin risk was basically identical. XGBoost outperformed the other two algorithms: logistic regression and classification and regression tree. CONCLUSION: Artificial intelligence based on determinant-weighting analysis could offer an individualized embryo selection strategy for any given patient, and predict clinical pregnancy rate and twin risk, therefore optimizing clinical outcomes.

7.
BMC Neurol ; 21(1): 144, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789600

RESUMO

BACKGROUND: Lewy body dementia (LBD), consisting of dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is the second most common type of neurodegenerative dementia in older people. The current study aimed to investigate the clinical characteristics of LBD in Chinese memory clinics. METHODS: A total of 8405 dementia medical records were reviewed, revealing 455 patients with LBD. Demographic data, neuropsychological scores, and the scale for Medial Temporal lobe Atrophy (MTA) were then analyzed from nine memory clinics in the China Lewy Body Disease Collaborative Alliance. RESULTS: The clinical proportion of LBD among the subjects and among all dementia types was 5.4% (4.9-5.9%) and 7.3% (6.7-8.0%), respectively, with a mean onset age of 68.6 ± 8.4 years. Patients with DLB comprised 5.6% (n = 348, age of onset 69.1 ± 8.3), while PDD comprised 1.7% (n = 107, age of onset 66.7 ± 8.8) of all dementia cases. There were slightly more males than females with DLB (n = 177, 50.9%) and PDD (n = 62, 57.9%). Patients with DLB had a poorer performance compared to those with PDD on the MMSE (16.8 ± 7.1 vs. 19.5 ± 5.7, p = 0.001), the MoCA (11.4 ± 6.6 vs. 14.0 ± 5.8, p<0.001), the CDR (1.8 ± 0.7 vs. 1.6 ± 0.7, p = 0.002), and the MTA (1.8 ± 0.7 vs. 1.2 ± 0.6, p = 0.002). Diagnostic differences for LBD exist among the centers; their reported proportions of those with DLB ranged from 0.7 to 11.4 and those with PDD ranged from 0.0 to 2.9%. CONCLUSIONS: Variations of diagnoses exists in different regions and the clinical proportion of LBD is likely to be underestimated in China and other regions.

8.
Acta Biomater ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33813093

RESUMO

The most significant challenge in designing wound dressings is to mimic the tissue microenvironment because of the pro-regenerative structural and functional properties of skin. Herein, we developed a type of bionic extracellular matrix (ECM) hydrogels based on thiol-modified poly (γ-glutamic acid) (γ-PGA-SH) and oxidized hyaluronic acid (HA-CHO). The rapid and reversible thiol-aldehyde addition reaction of thiols in γ-PGA-SH and aldehyde groups in HA-CHO provided hydrogels with a dynamic covalent network and endowed them with properties of adaptability and self-healing capability, which are conducive for initial wound coverage and for prolonging the lifespan of the dressing. Interestingly, these hydrogels also showed typical viscoelastic characteristics similar to those of natural ECM, degradation property in vitro and in vivo, and free radical scavenging capability. In addition, the gelation time, rheological behavior, mechanical property, porous structure, and degradation process of the hydrogels could be tuned by adjusting polymer content. Furthermore, the ECM-inspired hydrogels significantly enhanced the wound healing process in vivo in a full-thickness skin defect model compared to those by commercial dressing (Tegaderm™) by facilitating angiogenesis and promoting collagen deposition. The successful application of the multifunctional hydrogel as an antioxidant wound dressing for wound treatment significantly exhibited its great application potential for biomedical areas. STATEMENT OF SIGNIFICANCE: The application of tissue engineering techniques to repair full-thickness skin wounds remains a great challenge in clinical trials. Among the recent approaches used for wound healing, in situ forming injectable hydrogels have gained much attention, and few of them have shown satisfactory overall performance, such as integration into the wound bed, biodegradability, immunocompatibility, vascularization, and recapitulation of the structure and function of skin. In the present study, we designed a simple and convenient in situ forming injectable, adaptable, self-healing hydrogels with biodegradability and antioxidative properties, which could substantially improve wound healing quality at an affordable cost. The hydrogel-based wound dressing is expected to solve the abovementioned problems and help in promoting cutaneous wound healing.

9.
Medicine (Baltimore) ; 100(13): e25343, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787634

RESUMO

ABSTRACT: This study was carried out to estimate the incidence and to determine socio-demographic risk factors for dementia among individuals residing in rural northern China.The current prospective, population-based study was conducted between 2011 and 2016. Follow-up interviews were conducted annually from 2014 to 2016. The study involved 1511 dementia-free individuals aged 60 years or above from rural China. Standard criteria were used to make diagnoses for dementia and Alzheimer disease (AD).At least one follow up survey was completed with 1181 study participants. At the 5-year follow-up, 127 individuals had developed dementia, 75 had developed AD, and 32 had developed vascular dementia (VaD). With a total of 5649.2 risk years for the sample, the estimated incidence rates per 1000 person-years were 22.48 (95% CI: 18.62, 26.35) for dementia and 13.28 (95% CI: 10.29, 16.26) for AD. Incidence rates for dementia and AD increased with age across the 10-year age groups. Poor education (illiteracy) was an independent risk factor for both AD and VaD. Being engaged in social activities was an independent protective factor for VaD.The incidence of dementia in rural China was found to be higher than previously reported. Incidence of dementia increased with age, and AD was the most frequent type of dementia. Poor education was associated with a higher risk of VaD and AD. Engagement in social activities was an independent protective factor for VaD.

10.
J Psychiatr Res ; 137: 393-400, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33765451

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has imposed both physical and psychological burdens on healthcare workers (HCWs). What is more, few studies have focused on the gender differences in mental health problems (MHPs) among HCWs during such an outbreak. Thus, the current study investigated the prevalence and gender differences of various MHPs among HCWs in China during the COVID-19 outbreak. This nationwide survey was conducted online from January 29 to February 3, 2020. General information was collected by questions about socio-demographics, work-related factors, and living situations. Depressive, anxiety, stress, and insomnia symptoms were assessed by the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Impact of Event Scale-Revised, and the Insomnia Severity Index, respectively. Among the 2198 contacted HCWs, 1563 (71.1%) responded with valid data, of whom 1293 (82.7%) were females. The prevalences of depressive, anxiety, stress, and insomnia symptoms in participants were 50.7%, 44.7%, 52.5%, and 36.1%, respectively. Female HCWs had significantly higher scores in all four scales (p < 0.001) and higher prevalences in all MHPs involved (range, odds ratio [OR] 1.55-1.97). After adjusting for potential confounders, female HCWs still had higher risks for all MHPs involved than males (range, adjusted OR 1.36-1.96). HCWs present high prevalences of depressive, anxiety, stress, and insomnia symptoms during the COVID-19 outbreak. Furthermore, female HCWs are more vulnerable to all MHPs involved. These findings highlight the need for timely, special care and support for HCWs during the outbreak, especially for females.

11.
Int J Biol Macromol ; 181: 275-290, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33781811

RESUMO

Nanocellulose is a promising "green" nanomaterial that has recently gained scientific interest because of its excellent characteristics, such as less risks of toxicity, biocompatibility, biodegradability, recyclability, and tunable surface features. Initially, three nanocellulose types (i.e., bacterial nanocellulose, nanocrystals, and nanofibers) and their potential biotechnological production routes have been discussed in detail. Contemporary studies are discussed in the development of nanocellulose aerogels, responsive hydrogels, injectable hydrogels/implants, and magnetic nanocellulose. Moreover, the development of hydrogels and potential crosslinking agents for the induction of desired properties has been described. Studies have revealed that the release kinetics of nanocellulosic gels/hydrogels varies from few minutes to several days depending on the given physicochemical conditions. However, such systems provide sustained drug release properties, so they are considered "smart" systems. Recent studies on controlled drug delivery systems have demonstrated their considerable potential for the next-generation transport of therapeutic drugs to target sites via various administration routes. This review presents the selection of appropriate sources and processing methodologies for the development of target nanocellulose types. It explains the potential challenges and opportunities and recommends future research directions about the smart delivery of therapeutic drugs.

12.
Nat Prod Bioprospect ; 2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33719014

RESUMO

Euphopepluanones F - K (1 - 4), four new jatrophane type diterpenoids were isolated from the seeds of Euphorbia peplus, along with eight known diterpenoids (5 - 12). Their structures were established on the basis of extensive spectroscopic analysis and X-ray crystallographic experiments. The new compounds 1 - 4 were assessed for their activities to induce lysosomal biogenesis through LysoTracker Red staining. Compound 2 significantly induced lysosomal biogenesis. In addition, compound 2 could increase the number of LC3 dots, indicating that it could activate the lysosomal-autophagy pathway.

13.
In Vitro Cell Dev Biol Anim ; 57(3): 350-358, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33748908

RESUMO

This study aims to investigate the inhibitory effect of microRNA-337 (miR-337) on osteogenic differentiation in bone marrow mesenchymal stem cells and its action of mechanisms. Overexpression and knockdown of miR-337 were performed in bone marrow mesenchymal stem cells (BMSCs). Cell proliferation was assessed by using a cell counting kit-8 (CCK-8), mineralization assay was performed by alizarin red staining, and alkaline phosphatase activity was then measured. Luciferase reporter assay was applied to verify miR-337 binding to Ras-related protein 1A (Rap1A) mRNA. Reverse transcription and quantitative polymerase chain reaction (RT-qPCR) was applied to measure the expressions of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), bone morphogenetic protein (BMP2), and miR-337. Then the protein level of Rap1A was determined by western blot analysis. High glucose inhibited osteogenic differentiation but increased the level of miR-337. Overexpression of miR-337 inhibited osteogenic differentiation in high glucose-treated BMSCs, while the knockdown of miR-337 reversed this process. Luciferase reporter assay confirmed that the presumed pairing binding site of miRNA-337 was in the 3'-UTR of the Rap1A WT. In addition, the knockdown of Rap1A distinctly repressed osteogenic differentiation, which blocked the effect of miR-337-knockdown on osteogenic differentiation in high glucose-treated BMSCs. MiR-337 could repress osteogenic differentiation in high glucose-treated BMSCs directly targeting Rap1A, thus provide a potential therapeutic strategy for patients with diabetic osteoporosis in clinic.

14.
Alzheimers Res Ther ; 13(1): 62, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731209

RESUMO

BACKGROUND: New therapies are urgently needed for Alzheimer's disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. METHODS: We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. RESULTS: A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was - 2.15 points (95% confidence interval, - 3.07 to - 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. CONCLUSIONS: GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0229391 5. Registered on November 19, 2014.

15.
Biomed Res Int ; 2021: 9409836, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688504

RESUMO

Background: Hepatocellular carcinoma (HCC), one of the most common primary malignancies, is theoretically an epitope candidate for immune checkpoint inhibitors, and therefore, the identification of HCC biomarkers is important. Structure-specific recognition protein 1 (SSRP1) is involved in almost all chromatin-related processes, including DNA replication, repair, and transcription. However, its role in HCC remains to be elucidated. Methods: This study investigated the expression of SSRP1 in HCCDB, Oncomine, HPA, and other databases. The prognostic value of SSRP1 in HCC and its relationship with clinical characteristics were then explored using Kaplan-Meier plotter. At the same time, SSRP1 coexpression genes were explored and functionally annotated in the LinkedOmics database. Finally, the correlation between the SSRP1 expression and HCC immune cell infiltration was explored in TIMER and online single-cell sequencing database. Results: Significantly elevated transcriptional and proteomic SSRP1 expressions were found in HCC. Increased SSRP1 mRNA expression was significantly correlated with relevant clinicopathological parameters such as immune cells. Notably, the SSRP1 expression was positively correlated with the infiltration levels of Treg and CD8+ T cells, especially exhausted CD8+ T cells. Interestingly, the SSRP1 expression was higher in both tumor Treg and exhausted CD8+ T cells than in adjacent tissues. Conclusion: SSRP1, as a new prognostic marker for HCC, promotes HCC development by influencing the infiltration of depleted CD8+ T cells and may influence the effect of immunotherapy.

17.
BMC Cardiovasc Disord ; 21(1): 121, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658008

RESUMO

BACKGROUND: Myocardial ischemia reperfusion injury (MIRI) is defined as tissue injury in the pathological process of progressive aggravation in ischemic myocardium after the occurrence of acute coronary artery occlusion. Research has documented the involvement of microRNAs (miRs) in MIRI. However, there is obscure information about the role of miR-130a-5p in MIRI. Herein, this study aims to investigate the effect of miR-130a-5p on MIRI. METHODS: MIRI mouse models were established. Then, the cardiac function and hemodynamics were detected using ultrasonography and multiconductive physiological recorder. Functional assays in miR-130a-5p were adopted to test the degrees of oxidative stress, mitochondrial functions, inflammation and apoptosis. Hematoxylin and eosin (HE) staining was performed to validate the myocardial injury in mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression patterns of miR-130a-5p, high mobility group box (HMGB)2 and NF-κB. Then, dual-luciferase reporter gene assay was performed to elucidate the targeting relation between miR-130a-5p and HMGB2. RESULTS: Disrupted structural arrangement in MIRI mouse models was evident from HE staining. RT-qPCR revealed that overexpressed miR-130a-5p alleviated MIRI, MIRI-induced oxidative stress and mitochondrial disorder in the mice. Next, the targeting relation between miR-130a-5p and HMGB2 was ascertained. Overexpressed HMGB2 annulled the protective effects of miR-130a-5p in MIRI mice. Additionally, miR-130a-5p targets HMGB2 to downregulate the nuclear factor kappa-B (NF-κB) axis, mitigating the inflammatory injury induced by MIRI. CONCLUSION: Our study demonstrated that miR-130a-5p suppresses MIRI by down-regulating the HMGB2/NF-κB axis. This investigation may provide novel insights for development of MIRI treatments.

18.
Diagnostics (Basel) ; 11(2)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669819

RESUMO

The incidence and mortality rates of lung cancers are different between females and males. Therefore, sex information should be an important part of how to train and optimize a diagnostic model. However, most of the existing studies do not fully utilize this information. This study carried out a comparative investigation between sex-specific models and sex-independent models. Three feature selection algorithms and five classifiers were utilized to evaluate the contribution of the sex information to the detection of early-stage lung cancers. Both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) showed that the sex-specific models outperformed the sex-independent detection of early-stage lung cancers. The Venn plots suggested that females and males shared only a few transcriptomic biomarkers of early-stage lung cancers. Our experimental data suggested that sex information should be included in optimizing disease diagnosis models.

19.
Chin Med J (Engl) ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33655897

RESUMO

BACKGROUND: Cumulative blood pressure (BP), a measure incorporating the level and duration of BP exposure, is associated with the risk of cardiovascular disease (CVD). However, the level at which cumulative BP could significantly increase the risk remains unclear. This study aimed to investigate the association of 15-year cumulative BP levels with the long-term risk of CVD, and to examine whether the association is independent of BP levels at one examination. METHODS: Data from a 26-year follow-up of the Chinese Multi-provincial Cohort Study-Beijing Project were analyzed. Cumulative BP levels between 1992 and 2007 were calculated among 2429 participants free of CVD in 2007. Cardiovascular events (including coronary heart disease and stroke) occurring from 2007 to 2018 were registered. Adjusted hazard ratios (HRs) for CVD incidence associated with quartiles of cumulative systolic blood pressure (SBP) and diastolic blood pressure (DBP) were calculated. RESULTS: Of the 2429 participants, 42.9% (1042) were men, and the mean age in 2007 was 62.1 ±â€Š7.9 years. Totally, 207 CVD events occurred during the follow-up from 2007 to 2018. Participants with higher levels of cumulative SBP or DBP exhibited a higher incidence rate of CVD (P < 0.0001). Compared with the lowest quartile of cumulative SBP, the HR for CVD was 1.03 (95% confidence interval [CI]: 0.59-1.81), 1.69 (95% CI: 0.99-2.87), and 2.20 (95% CI: 1.21-3.98) for the second to the fourth quartile of cumulative SBP, and 1.46 (95% CI: 0.86-2.48), 1.99 (95% CI: 1.18-3.35), and 2.08 (95% CI: 1.17-3.71) for the second to the fourth quartile of cumulative DBP, respectively. In further cross-combined group analyses with BP measurements in 2007, 15-year cumulative BP levels higher than the median, that is, 1970.8/1239.9 mmHg·year for cumulative SBP/DBP, which were equivalent to maintaining SBP/DBP levels of 131/83 mmHg or above on average in 15 years, were associated with higher risk of CVD in subsequent years independent of BP measurements at one-time point. CONCLUSION: Cumulative exposure to moderate elevation of BP is independently associated with increased future cardiovascular risk.

20.
Eur J Med Chem ; 217: 113359, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33725632

RESUMO

A series of highly active CF3-containing 3'-(nitroisoxazole)spiro[pyrrolidin-3,2'-oxindoles] were synthesized and found to be novel glutathione peroxidase 4 (GPX4)/mouse double minute 2 (MDM2) dual inhibitors. Bioactive spirooxindole and isoxazole skeletons were combined, and the resulting compounds exhibited strong activities against both targets. In particular, compound 3d displayed excellent activity in the suppression of MDM2-mediated degradation of p53, as well as levels of GPX4, in MCF-7 breast cancer cells. Moreover, 3d also exhibited inhibitory effects on MDM2 and GPX4 in MCF-7 xenograft model to trigger ferroptotic and apoptotic cell death in in vivo experiments, which was consistent with the results of in vitro experiments.

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