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1.
Signal Transduct Target Ther ; 6(1): 250, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34219129

RESUMO

Triple-negative breast cancer (TNBC) is the most challenging subtype of breast cancer. Various endeavor has been made to explore the molecular biology basis of TNBC. Herein, we reported a novel function of factor Kinectin 1 (KTN1) as a carcinogenic promoter in TNBC. KTN1 expression in TNBC was increased compared with adjacent tissues or luminal or Her2 subtypes of breast cancer, and TNBC patients with high KTN1 expression have poor prognosis. In functional studies, knockdown of KTN1 inhibited the proliferation and invasiveness of TNBC both in vitro and in vivo, while overexpression of KTN1 promoted cancer cell proliferation and invasiveness. RNA-seq analysis revealed that the interaction of cytokine-cytokine receptor, particularly CXCL8 gene, was upregulated by KTN1, which was supported by the further experiments. CXCL8 depletion inhibited the tumorigenesis and progression of TNBC. Additionally, rescue experiments validated that KTN1-mediated cell growth acceleration in TNBC was dependent on CXCL8 both in vitro and in vivo. Furthermore, it was found that KTN1 enhanced the phosphorylation of NF-κB/p65 protein at Ser536 site, and specifically bound to NF-κB/p65 protein in the nucleus and cytoplasm of cells. Moreover, the transcription of CXCL8 gene was directly upregulated by the complex of KTN1 and NF-κB/p65 protein. Taken together, our results elucidated a novel mechanism of KTN1 gene in TNBC tumorigenesis and progression. KTN1 may be a potential molecular target for the development of TNBC treatment.

2.
Huan Jing Ke Xue ; 42(7): 3223-3231, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34212648

RESUMO

The interface between Shengjin Lake and Yangtze River was selected as the study area. The water chemical composition and hydrogen and oxygen isotope values of different types of water bodies were tested, and their seasonal variation characteristics were analyzed to explore the sources of chemical ions in the surface and groundwater. Finally, the contribution of mixed water sources to chemical ions in groundwater was estimated. The results show the following ① The concentration of chemical ions in the surface and groundwater of the study area is higher than that of atmospheric precipitation, and the physical and chemical parameters exhibit seasonal variation. ② Surface water mainly belongs to the Ca-HCO3 type, but the proportion of the Ca-SO4 type in summer is significantly lower than that in other seasons; Groundwater primarily belongs to Ca-HCO3 and Ca-SO4 types, with proportions of 46% and 27%, respectively, and the seasonal difference is not significant. ③ Ca2+ and Mg2+ in the surface and groundwater mainly come from the dissolution of carbonate rocks, carbonic acid and sulfate ions participate in the dissolving process of carbonate minerals. Na+and Cl- are partly derived from atmospheric precipitation and partly sourced from agricultural fertilization and manure sewage. ④ Mixed water sources is also an important source of chemical ions in groundwater, with the average contribution 28% to Cl-, showing a seasonal trend.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Monitoramento Ambiental , Lagos , Rios , Poluentes Químicos da Água/análise
3.
Nutr J ; 20(1): 67, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256749

RESUMO

BACKGROUND: Inconsistent associations between egg consumption and cardiovascular disease (CVD) risk have been observed in previous studies. This study aims to longitudinally investigate the association between egg consumption and altered risk of arterial stiffness, a major pre-clinical pathogenic change of CVD, which was assessed by brachial-ankle pulse wave velocity (baPWV). METHODS: A total of 7315 Chinese participants from the Kailuan Study, free of CVD and cancer were included in this study. Egg consumption was assessed by a semi-quantitative validated food frequency questionnaire in 2014. baPWV was repeatedly measured at baseline and during follow-up (mean follow-up: 3.41 years). General linear regression was used to calculate means of baPWV change rate across different egg consumption groups, adjusting for age, sex, baseline baPWV, healthy eating index, total energy, social-economic status, blood pressure, obesity, smoking, lipid profiles, and fasting glucose concentrations. RESULTS: Compared to the annual baPWV change rate in participants with 0-1.9 eggs/wk. (adjusted mean: 35.9 ± 11.2 cm/s/y), those consuming 3-3.9 eggs/wk. (adjusted mean: 0.2 ± 11.4 cm/s/y) had the lowest increase in baPWV during follow-up (P-difference = 0.002). Individuals with low (0-1.9 eggs/wk) vs. high (5+ eggs /wk) egg intake showed similar changes in baPWV. CONCLUSIONS: In this large-scale longitudinal analysis, we did not find a significant difference in arterial stiffness, as assessed by baPWV level, between low and high egg consumption groups. However, moderate egg consumption (3-3.9 eggs/wk) appeared to have beneficial effects on arterial stiffness.

4.
Clin Nutr ; 40(7): 4538-4550, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34229258

RESUMO

BACKGROUND & AIMS: Previous randomized controlled trials (RCTs) have compared the effects of pure preparations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in reducing metabolic syndrome (MetS) risk factors, but the results were inconsistent. The present study aimed to clarify whether EPA and DHA have differential effects on MetS features in humans. METHODS: A systematic literature search was conducted in CNKI, PubMed, Embase and Scopus updated to February 2021. The mean changes in the characteristics of MetS were calculated as weighted mean differences by using a random-effects model. Thirty-three RCTs were included. RESULTS: The results showed that both EPA and DHA were effective at lowering serum triglycerides (TG) levels. EPA supplementation decreased the serum levels of total cholesterol (TC) (WMD = -0.24 mmol/L; 95% CI, -0.43, -0.05 mmol/L), TG (WMD = -0.77 mmol/L; 95% CI, -1.54, -0.00 mmol/L) and low density lipoprotein-cholesterol (LDL-C) (WMD = -0.13 mmol/L; 95% CI, -0.25, -0.01 mmol/L), while DHA increased the serum levels of TC (WMD = 0.14 mmol/L; 95% CI, 0.03, 0.25 mmol/L), LDL-C (WMD = 0.26 mmol/L; 95% CI, 0.15, 0.38 mmol/L) and high density lipoprotein-cholesterol (HDL-C) (WMD = 0.07 mmol/L; 95% CI, 0.04, 0.09 mmol/L). Moreover, DHA increased the serum levels of insulin compared with EPA, especially in subgroups whose mean age was <60 years (0.43 mU/L; 95% CI: 0.04, 0.81 mU/L) and duration of DHA supplementation < 3 months (0.39 mU/L; 95% CI: 0.01, 0.77 mU/L). CONCLUSIONS: The present meta-analysis provides evidence that EPA and DHA have different effects on risk factors of MetS.

5.
BMJ Open ; 11(7): e046329, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215604

RESUMO

OBJECTIVE: To systematically review and qualitatively evaluate epidemiological evidence on associations between Parkinson's disease (PD) and cancer via meta-analysis. DATA SOURCES: MEDLINE via PubMed, Web of Science and EMBASE, until March 2021. STUDY SELECTION: Included were publications that (1) were original epidemiological studies on PD and cancer; (2) reported risk estimates; (3) were in English. Exclusion criteria included: (1) review/comments; (2) biological studies; (3) case report/autopsy studies; (4) irrelevant exposure/outcome; (5) treated cases; (6) no measure of risk estimates; (7) no confidence intervals/exact p values and (8) duplicates. DATA EXTRACTION AND SYNTHESIS: PRISMA and MOOSE guidelines were followed in data extraction. Two-step screening was performed by two authors blinded to each other. A random-effects model was used to calculate pooled relative risk (RR). MAIN OUTCOMES AND MEASURES: We included publications that assessed the risk of PD in individuals with vs without cancer and the risk of cancer in individuals with vs without PD. RESULTS: A total of 63 studies and 17 994 584 participants were included. Meta-analysis generated a pooled RR of 0.82 (n=33; 95% CI 0.76 to 0.88; p<0.001) for association between PD and total cancer, 0.76 (n=21; 95% CI 0.67 to 0.85; p<0.001) for PD and smoking-related cancer and 0.92 (n=19; 95% CI 0.84 to 0.99; p=0.03) for non-smoking-related cancer. PD was associated with an increased risk of melanoma (n=29; pooled RR=1.75; 95% CI 1.43 to 2.14; p<0.001) but not for other skin cancers (n=17; pooled RR=0.90; 95% CI 0.60 to 1.34; p=0.60). CONCLUSIONS: PD and total cancer were inversely associated. This inverse association persisted for both smoking-related and non-smoking-related cancers. PD was positively associated with melanoma. These results provide evidence for further investigations for possible mechanistic associations between PD and cancer. PROSPERO REGISTRATION NUMBER: CRD42020162103.

6.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(3): 402-405, 2021 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-34238416

RESUMO

Objective To investigate the incidence of surgical site infection(SSI)following conversion from laparoscopic to open cholecystectomy and to analyze the related risk factors. Methods The clinical data of 179 patients who had experienced conversion from laparoscopic to open cholecystectomy in Peking Union Medical College Hospital from January 2014 to August 2019 were analyzed retrospectively.Univariate and multivariate logistic regression analyses were performed to evaluate the associations between clinical variables and SSI. Results The incidence of SSI was 19.0%(34/179)after conversion from laparoscopic to open cholecystectomy.The multivariable analysis demonstrated that preoperative endoscopic retrograde cholangiopancreatography(ERCP)(OR=4.208,95% CI:1.590-11.135,P=0.004)was the only independent risk factor of SSI. Conclusions The incidence of SSI after conversion from laparoscopic to open cholecystectomy increased remarkably,especially in those who had preoperative ERCP.Preventive interventions should be taken to reduce the incidence of SSI.


Assuntos
Laparoscopia , Infecção da Ferida Cirúrgica , Colecistectomia , Humanos , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-34269929

RESUMO

Circular RNA (circRNA) has a closed-loop structure, and its 3' and 5' ends are directly covalently connected by reverse splicing, which is more stable than linear RNA. CircRNAs usually possess microRNA (miRNA) binding sites, which can bind miRNAs and inhibit miRNA function. Many studies have shown that circRNAs are involved in the processes of cell senescence, proliferation and apoptosis and a series of signalling pathways, playing an important role in the prevention and treatment of diseases. CircRNAs are potential biological diagnostic markers and therapeutic targets for cardiovascular diseases (CVDs). To identify biomarkers and potential effective therapeutic targets without toxicity for heart disease, we summarize the biogenesis, biology, characterization and functions of circRNAs in CVDs, hoping that this information will shed new light on the prevention and treatment of CVDs.

8.
Opt Lett ; 46(14): 3476-3479, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264242

RESUMO

Naked-eye 3D micro-LED display combines the 3D characteristics and advantages of micro-LED simultaneously. A conventional micro-LED device emission exhibits Lambertian distribution, and it requires stacking of multiple optical components into a 3D display, resulting in bulky systems, low efficiency, and a limited viewing zone and points. We propose and investigate a single-chip micro-LED with unidirectional emission through an in-situ integrated resonant cavity and metasurface, which has great potential to be used for an efficient naked-eye 3D display with a wide viewing angle and multiple viewpoints. This Letter promotes the application of GaN-based micro-LEDs in a display, especially a 3D display.

9.
IEEE Trans Image Process ; 30: 6168-6183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34214039

RESUMO

3D dynamic point clouds provide a natural discrete representation of real-world objects or scenes in motion, with a wide range of applications in immersive telepresence, autonomous driving, surveillance, etc. Nevertheless, dynamic point clouds are often perturbed by noise due to hardware, software or other causes. While a plethora of methods have been proposed for static point cloud denoising, few efforts are made for the denoising of dynamic point clouds, which is quite challenging due to the irregular sampling patterns both spatially and temporally. In this paper, we represent dynamic point clouds naturally on spatial-temporal graphs, and exploit the temporal consistency with respect to the underlying surface (manifold). In particular, we define a manifold-to-manifold distance and its discrete counterpart on graphs to measure the variation-based intrinsic distance between surface patches in the temporal domain, provided that graph operators are discrete counterparts of functionals on Riemannian manifolds. Then, we construct the spatial-temporal graph connectivity between corresponding surface patches based on the temporal distance and between points in adjacent patches in the spatial domain. Leveraging the initial graph representation, we formulate dynamic point cloud denoising as the joint optimization of the desired point cloud and underlying graph representation, regularized by both spatial smoothness and temporal consistency. We reformulate the optimization and present an efficient algorithm. Experimental results show that the proposed method significantly outperforms independent denoising of each frame from state-of-the-art static point cloud denoising approaches, on both Gaussian noise and simulated LiDAR noise.

10.
Traffic Inj Prev ; : 1-6, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242107

RESUMO

OBJECTIVE: Novice drivers who delay in driving licensure may miss safety benefits of Graduate Driver Licensing (GDL) programs, potentially putting themselves at higher crash-risk. Time to licensure relates their access to independent transportation to potential future economic- and educational-related opportunities. The objective of this study was to explore time to licensure associations with teens' race/ethnicity and GDL restrictions. METHODS: Secondary analysis using all seven annual assessments of the NEXT Generation Health Study, a nationally representative longitudinal study starting with 10th grade (N = 2785; 2009-2010 school year). Data were collected in U.S. public/private schools, colleges, workplaces, and other settings. The outcome variable was interval-censored time to licensure (event = obtained driving licensure). Independent variables included race/ethnicity and state-specific GDL restrictions. Covariates included family affluence, parent education, nativity, sex, and urbanicity. Proportional hazards (PH) models were conducted for interval-censored survival analysis based on stepwise backward elimination for fitting multivariate models with consideration of complex survey features. In the PH models, a hazard ratio (HR) estimates a greater (>1) or lesser (<1) likelihood of licensure at all timepoints. RESULTS: Median time to licensure after reaching legal driving age for Latinos, African Americans, and Non-Latino Whites was 3.47, 2.90, and 0.41 years, respectively. Multivariate PH models showed that Latinos were 46% less likely (HR = 0.54, 95%CI: 0.35-0.72) and African Americans were 56% less likely (HR = 0.44, 95%CI: 0.32-0.56) to have obtained licensure at any time compared to Non-Latino Whites. Only learner minimum age GDL restriction was associated with time to licensure. Living in a state with a required learner driving minimum age of ≥16 years (HR = 0.57, 95%CI: 0.16-0.98) also corresponded with 43% lower likelihood of licensure at legal eligibility compared to living in other states with a required learner driving minimum age of <16 years. CONCLUSION: Latinos and African American teens obtained their license approximately three years after eligibility on average, and much later than Non-Latino Whites. Time to licensure likelihood was associated with race/ethnicity and required minimum age of learner permit, indicating important implications for teens of different racial/ethnic groups in relation to licensure, access to independent transportation, and exposure to GDL programs.

11.
Adv Mater ; : e2102362, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242431

RESUMO

Properties of emulsions highly depend on the interdroplet interactions and, thus, engineering interdroplet interactions at molecular scale are essential to achieve desired emulsion systems. Here, attractive Pickering emulsion gels (APEGs) are designed and prepared by bridging neighboring particle-stabilized droplets via telechelic polymers. In the APEGs, each telechelic molecule with two amino end groups can simultaneously bind to two carboxyl functionalized nanoparticles in two neighboring droplets, forming a bridged network. The APEG systems show typical shear-thinning behaviors and their viscoelastic properties are tunable by temperature, pH, and molecular weight of the telechelic polymers, making them ideal for direct 3D printing. The APEGs can be photopolymerized to prepare APEG-templated porous materials and their microstructures can be tailored to optimize their performances, making the APEG systems promising for a wide range of applications.

12.
Nat Commun ; 12(1): 4233, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244485

RESUMO

The Jahn-Teller effect is an essential mechanism of spontaneous symmetry breaking in molecular and solid state systems, and has far-reaching consequences in many fields. Up to now, to directly image the onset of Jahn-Teller symmetry breaking remains unreached. Here we employ ultrafast ion-coincidence Coulomb explosion imaging with sub-10 fs resolution and unambiguously image the ultrafast dynamics of Jahn-Teller deformations of [Formula: see text] cation in symmetry space. It is unraveled that the Jahn-Teller deformation from C3v to C2v geometries takes a characteristic time of 20 ± 7 fs for this system. Classical and quantum molecular dynamics simulations agree well with the measurement, and reveal dynamics for the build-up of the C2v structure involving complex revival process of multiple vibrational pathways of the [Formula: see text] cation.

13.
Nutr Clin Pract ; 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34245474

RESUMO

BACKGROUND: Conventional treatment for Crohn disease (CD) in pregnancy includes mesalamine, thiopurine, and anti-tumor necrosis factor (TNF)-α agents. However, women may abstain because of complications, nonresponse, or potential adverse outcomes. Peptide-based formula therapy, through oral or nasogastric feeding without other food intake, is an effective and safe therapy for active CD. Herein, We confirmed the effectiveness and safety of peptide-based formula therapy for active CD in pregnant women or those preparing for pregnancy. METHOD: Outcomes of peptide-based formula therapy to induce CD remission during pregnancy preparation and the conception period were evaluated retrospectively among 14 women. Efficacy was evaluated as the change in serum indices and inflammatory markers after 12-week treatment. Pregnancy outcomes were compared between 14 women treated with nutrition therapy and eight women using conventional CD drugs. RESULTS: After 12 weeks, 85.7% (12 of 14) of patients treated with peptide-based formula achieved remission with a significant decrease in the CD activity index (P < .001) and high-sensitivity C-reactive protein level (P = .004). There were no effects of peptide-based formula therapy on pregnancy outcomes compared with conventional CD treatment (P > .05). Among the 12 patients who achieved CD remission with exclusive peptide-based formula therapy, 10 selected to continue total or partial peptide-based formula treatment to maintain CD remission throughout pregnancy. CONCLUSION: Peptide-based formula therapy, without other food intake, may provide a safe and effective alternative to conventional CD drugs to induce disease remission among women during conception and pregnancy.

14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(6): 609-614, 2021 Jun 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34275929

RESUMO

OBJECTIVES: With the increase of people's living standards increasing year by year, Type 2 diabetes has brought great economic and living burden to the society and patients. Bariatric surgery can improve metabolic indicators in patients with diabetes, but specific mechanisms are still under study. This study aims to evaluate the effect of Roux-en-Y gastric bypass (RYGB) on insulin resistance in patients with Type 2 diabetes by hyperinsulinemic-euglycemic clamp. METHODS: The peripheral glucose uptake (M value) of 40 patients undergoing laparoscopic Roux-en-Y gastric bypass surgery before and 6 months after the operation were analyzed hyperinsulinemic euglycemic clamp. Fasting blood glucose, glycosylated hemoglobin, triglycerides, andlow-density lipoprotein cholesterol levels as well as body mass index were also analyzed. RESULTS: M value of patients after laparoscopic Roux-en-Y gastric bypass was significantly higher than that before the operation, while indexes such as fasting blood glucose, glycosylated hemoglobin, triglycerides, and low-density lipoprotein cholesterol levels as well as body mass index were lower than those before the operation (all P<0.05). CONCLUSIONS: Laparoscopic Roux-en-Y gastric bypass surgery significantly improves insulin resistance in patients with Type 2 diabetes, decreases blood sugar and blood lipid, and can exert a positive effect on the treatment of Type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Derivação Gástrica , Resistência à Insulina , Laparoscopia , Glicemia , Diabetes Mellitus Tipo 2/cirurgia , Técnica Clamp de Glucose , Humanos , Insulina , Resultado do Tratamento
15.
Nutrients ; 13(7)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209676

RESUMO

Alcohol consumption may be associated with the risk of rheumatoid arthritis (RA), but potential sex-related differences in this association have not been explored. Thus, we utilized 87,118 participants in the Kailuan Study, a prospective cohort initiated in 2006 to study the risk factors of cardiovascular disease in a Chinese population. We included those that did not have RA at baseline (2006), and performed cox proportional hazard modeling to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of RA according to the levels of alcohol consumption (never or past, light or moderate (<1 serving/day for women, <2 servings/day for men), and heavy (>1 serving/day for women, >2 servings/day for men), adjusting for age, sex, body mass index, and smoking. Diagnoses of RA were confirmed via medical record review by rheumatologists. From 2006 to 2018, we identified 87 incident RA cases. After adjusting for potential confounders, the HR of RA was 1.26 (95% CI: 0.62, 2.56) for participants with light or moderate alcohol consumption and 1.98 (95% CI: 0.93, 4.22) for participants with heavy alcohol consumption) versus non-drinkers. The HR of each 10 g increase in alcohol consumption was 1.11 (95% CI: 0.98, 1.26) (p-trend = 0.09). A significant association between alcohol consumption and RA risk was observed in women, but not in men (p for interaction = 0.06). Among women, each 10 g increase in alcohol consumption was significantly associated with a high risk of RA (HR: 1.56; 95% CI: 1.06, 2.29). In contrast, each 10 g increase in alcohol consumption was not significantly associated with the risk of RA in men (HR: 1.10; 95% CI: 0.97, 1.25). Excluding past drinkers generated similar results. In this prospective Chinese cohort, increasing alcohol consumption was associated with an elevated risk of RA among women, but not in men. These findings highlight the importance of incorporating analysis of sex differences into future studies of alcohol consumption and RA risk.

16.
Ecohealth ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34212260

RESUMO

Chytridiomycosis, a leading cause for the global decline in the number of amphibians, is caused by the fungal pathogen Batrachochytrium dendrobatidis. In this study, global distribution data of B. dendrobatidis were collected from January 2009 to May 2019. Space-time scan statistics and the maximum entropy (MaxEnt) model were used to analyze the epidemic trends and aggregation of the pathogen, and predict B. dendrobatidis distribution through its relationships with climate factors, wind speed, and solar radiation. The results of space-time scan statistics show seven clusters of data for the distribution of B. dendrobatidis. The time was mainly concentrated in 2009, 2013, 2015, and 2016, and the regions were primarily concentrated in southeastern Canada, southwestern France, Nigeria, Cameroon, eastern Brazil, southeastern Brazil, central Madagascar, and central and eastern Australia. MaxEnt showed that annual precipitation had the largest contribution percentage in the model, and annual mean temperature highly influenced the distribution of B. dendrobatidis. The global high-risk areas of B. dendrobatidis distribution were mainly observed in western Canada, southern Brazil, Chile, the United Kingdom, Japan, the Republic of Korea, eastern South Africa, eastern Madagascar, southeastern Australia, and southern China.

17.
Appl Opt ; 60(15): 4335-4339, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34143122

RESUMO

The weak-value-amplification technique has shown great importance in the measurement of tiny physical effects. Here we introduce a polarization-dependent angular velocity measurement system consisting of two Glan prisms and a true zero-order half-wave plate, where a non-Fourier-limited Gaussian pulse acts as the meter. The angular velocities measurements results agree well with theoretical predictions, and its uncertainties are bounded by the Cramér-Rao bound. We also investigate uncertainties of angular velocities for different numbers of detected photons and the smallest reliable postselection probability, which can reach ${3.42*10^{- 6}}$.

18.
BMC Med ; 19(1): 142, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34130689

RESUMO

BACKGROUND: The risk of stroke in individuals with very low low-density lipoprotein cholesterol (LDL-C) concentrations remains high. We sought to prioritize predictive risk factors for stroke in Chinese participants with LDL-C concentrations < 70 mg/dL using a survival conditional inference tree, a machine learning method. METHODS: The training dataset included 9327 individuals with LDL-C concentrations < 70 mg/dL who were free of cardiovascular diseases and did not use lipid-modifying drugs from the Kailuan I study (N = 101,510). We examined the validity of this algorithm in a second Chinese cohort of 1753 participants with LDL-C concentrations < 70 mg/dL from the Kailuan II study (N = 35,856). RESULTS: During a mean 8.5-9.0-year follow-up period, we identified 388 ischemic stroke cases and 145 hemorrhagic stroke cases in the training dataset and 20 ischemic stroke cases and 8 hemorrhagic stroke cases in the validation dataset. Of 15 examined predictors, poorly controlled blood pressure and very low LDL-C concentrations (≤ 40 mg/dL) were the top hierarchical predictors of both ischemic stroke risk and hemorrhagic stroke risk. The groups, characterized by the presence of 2-3 of aforementioned risk factors, were associated with a higher risk of ischemic stroke (hazard ratio (HR) 7.03; 95% confidence interval (CI) 5.01-9.85 in the training dataset; HR 4.68, 95%CI 1.58-13.9 in the validation dataset) and hemorrhagic stroke (HR 3.94, 95%CI 2.54-6.11 in the training dataset; HR 4.73, 95%CI 0.81-27.6 in the validation dataset), relative to the lowest risk groups (presence of 0-1 of these factors). There was a linear association between cumulative average LDL-C concentrations and stroke risk. LDL-C concentrations ≤ 40 mg/dL was significantly associated with increased risk of ischemic stroke (HR 2.07, 95%CI 1.53, 2.80) and hemorrhagic stroke (HR 2.70, 95%CI 1.70, 4.30) compared to LDL-C concentrations of 55-70 mg/dL, after adjustment for age, hypertension status, and other covariates. CONCLUSION: Individuals with extremely low LDL-C concentrations without previous lipid-modifying treatment could still be at high stroke risk. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-TNRC-11001489 . Registered on 24-08-2011.

19.
J Proteomics ; 245: 104292, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34089897

RESUMO

Wheat is one of the most widely grown and important food crops in the world, providing approximately 20% of the food energy and protein produced for human consumption. The progress of wheat breeding is seriously restricted by the narrow genetic basis of common wheat germplasms. Dasypyrum villosum, a wild grass species that is commonly used in wheat improvement, has many excellent traits such as disease resistance, drought resistance, cold resistance, strong tillering ability, and processing quality. In this study, we compared and analyzed the cultivated wheat variety Chinese Spring (CS) and D. villosum using comparative proteomics. A total of 883 different abundant proteins (DAPs) were identified. Some of these different abundant proteins are associated with defense and stress, such as the Gα subunit, zinc finger protein family, PR1, HSP family, LEA protein, and serpin family. And a total of 24 different abundant proteins are gluten proteins. There are also 24 different abundant proteins associated with starch and sucrose metabolism. These results will provide potential candidate genes and a foundation for further research on resistance and quality for wheat genetics and breeding. SIGNIFICANCE: Proteins are the direct functional molecules of living organisms. It is of great significance to study the function of plant related genes from the perspective of protein. In this study, proteomics methods based on iTRAQ were used to compare the proteomic differences between wheat varieties Chinese Spring (CS) and D. villosum. The results provide novel insight into improving the quality of wheat. It is helpful to search for potential candidate genes for improving wheat quality and elucidate the molecular mechanisms associated with these genes.

20.
Drug Deliv ; 28(1): 1342-1355, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34180769

RESUMO

Poly(lactic-co-glycolic acid) (PLGA) has garnered increasing attention as a candidate drug delivery polymer owing to its favorable properties, including its excellent biocompatibility, biodegradability, non-toxicity, non-immunogenicity, and mechanical strength. PLAG are specifically used as microspheres for the sustained/controlled and targeted delivery of hydrophilic or hydrophobic drugs, as well as biological therapeutic macromolecules, including peptide and protein drugs. PLGAs with different molecular weights, lactic acid (LA)/glycolic acid (GA) ratios, and end groups exhibit unique release characteristics, which is beneficial for obtaining diverse therapeutic effects. This review aims to analyze the composition of PLGA microspheres, and understand the manufacturing process involved in their production, from a quality by design perspective. Additionally, the key factors affecting PLGA microsphere development are explored as well as the principles involved in the synthesis and degradation of PLGA and its interaction with active drugs. Further, the effects elicited by microcosmic conditions on PLGA macroscopic properties, are analyzed. These conditions include variations in the organic phase (organic solvent, PLGA, and drug concentration), continuous phase (emulsifying ability), emulsifying stage (organic phase and continuous phase interaction, homogenization parameters), and solidification process (relationship between solvent volatilization rate and curing conditions). The challenges in achieving consistency between batches during manufacturing are addressed, and continuous production is discussed as a potential solution. Finally, potential critical quality attributes are introduced, which may facilitate the optimization of process parameters.

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