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1.
Int Ophthalmol ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34232432

RESUMO

PURPOSE: To compare the morphological and biomechanical properties of normal cornea and keratoconus at different stages. METHODS: A total of 408 patients (517 eyes) with keratoconus were included in this study. According to the Topographic Keratoconus (TKC) grading method, keratoconus was divided into stage I (TKC = 1, 130 eyes), stage II (TKC = 1-2, 2, 164 eyes), stage III (TKC = 2-3, 3, 125 eyes) and stage IV (TKC = 3-4, 4, 98 eyes). A total of 158 normal subjects (158 eyes) were recruited as the normal group. The corneal morphological parameters and biomechanical parameters were obtained with Scheimpflug tomography (Pentacam) and corneal visualization Scheimpflug technology (Corvis ST), and the receiver operating characteristic (ROC) curves were drawn. RESULTS: Each corneal morphological and most biomechanical parameters of the keratoconic eyes were significantly different from those of the normal eyes in this study (p < 0.001). ROC curve demonstrated that most parameters in this study showed high efficiency in diagnosing keratoconus (the area under the ROC (AUC) was > 0.9), with the Belin-Ambrósio deviation (BAD-D) and Tomographic and Biomechanical Index (TBI) showing higher efficiency. The efficiency of BAD-D and TBI was high in differentiating keratoconus at different stages (AUC > 0.963). The comparison of ROC curves of keratoconus at different stages did not reveal statistically significant differences for TBI. CONCLUSION: BAD-D and TBI can effectively diagnose stage I keratoconus. Moreover, the efficiency of TBI is the same in diagnosing keratoconus at all stages, while the diagnostic efficiency of other parameters increases with the increase in keratoconus stages.

2.
CNS Neurosci Ther ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34255932

RESUMO

AIMS: Chronification of postoperative pain is a common clinical phenomenon following surgical operation, and it perplexes a great number of patients. Estrogen and its membrane receptor (G protein-coupled estrogen receptor, GPER) play a crucial role in pain regulation. Here, we explored the role of GPER in the rostral ventromedial medulla (RVM) during chronic postoperative pain and search for the possible mechanism. METHODS AND RESULTS: Postoperative pain was induced in mice or rats via a plantar incision surgery. Behavioral tests were conducted to detect both thermal and mechanical pain, showing a small part (16.2%) of mice developed into pain persisting state with consistent low pain threshold on 14 days after incision surgery compared with the pain recovery mice. Immunofluorescent staining assay revealed that the GPER-positive neurons in the RVM were significantly activated in pain persisting rats. In addition, RT-PCR and immunoblot analyses showed that the levels of GPER and phosphorylated µ-type opioid receptor (p-MOR) in the RVM of pain persisting mice were apparently increased on 14 days after incision surgery. Furthermore, chemogenetic activation of GPER-positive neurons in the RVM of Gper-Cre mice could reverse the pain threshold of pain recovery mice. Conversely, chemogenetic inhibition of GPER-positive neurons in the RVM could prevent mice from being in the pain persistent state. CONCLUSION: Our findings demonstrated that the GPER in the RVM was responsible for the chronification of postoperative pain and the downstream pathway might be involved in MOR phosphorylation.

3.
BMC Cardiovasc Disord ; 21(1): 340, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256698

RESUMO

BACKGROUND: Mobile health-based individualized interventions have shown potential effects in managing cardiovascular risk factors. This study aims to assess whether or not mHealth based individualized interventions delivered by an Individualized Cardiovascular Application system for Risk Elimination (iCARE) could reduce the incidence of major cardiovascular events in individuals with coronary heart disease. METHODS: This study is a large-scale, multi-center, parallel-group, open-label, randomized controlled clinical trial. This study will be conducted from September 2019 to December 2025. A total of 2820 patients with coronary heart disease will be recruited from two clinical sites and equally randomized into three groups: the intervention group and two control groups. All participants will be informed of six-time points (at 1, 3, 6, 12, 24, and 36 months after discharge) for follow-up visits. Over a course of 36 months, patients who are randomized to the intervention arm will receive individualized interventions delivered by a fully functional iCARE that using various visualization methods such as comics, videos, pictures, text to provide individualized interventions in addition to standard care. Patients randomized to control group 1 will receive interventions delivered by a modified iCARE that only presented in text in addition to routine care. Control group 2 will only receive routine care. The primary outcome is the incidence of major cardiovascular events within 3 years of discharge. Main secondary outcomes include changes in health behaviors, medication adherence, and cardiovascular health score. DISCUSSION: If the iCARE trial indeed demonstrates positive effects on patients with coronary heart disease, it will provide empirical evidence for supporting secondary preventive care in this population. Results will inform the design of future research focused on mHealth-based, theory-driven, intelligent, and individualized interventions for cardiovascular risk management. TRIAL REGISTRATION: Trial registered 24th December 2016 with the Chinese Clinical Trial Registry (ChiCTR-INR-16010242). URL: http://www.chictr.org.cn/showproj.aspx?proj=17398 .

4.
Pharm Biol ; 59(1): 884-892, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34219593

RESUMO

CONTEXT: Laurolitsine is an aporphine alkaloid and exhibits potent antihyperglycemic and antihyperlipidemic effects in ob/ob mice. OBJECTIVE: To investigate the pharmacokinetics, tissue distribution and excretion of laurolitsine. MATERIALS AND METHODS: A LC-MS/MS method was established and validated to determine laurolitsine concentrations in the biological matrix of rats (plasma, tissue homogenate, urine and faeces). 10 Sprague-Dawley (SD) rats were used for plasma exposure study: 5 rats were injected with 2.0 mg/kg of laurolitsine via the tail vein, and the other 5 rats were administered laurolitsine (10.0 mg/kg) by gavage. 25 SD rats used for tissue distribution study and 5 SD rats for urine and faeces excretion study: rats administered laurolitsine (10.0 mg/kg) by gavage. After administered, serial blood, tissue, urine and faeces were collected. Analytical quantification was performed by a previous LC-MS/MS method. The pharmacokinetics, bioavailability, tissue distribution and excretion of laurolitsine were described. RESULTS: The pharmacokinetic parameters of oral and intravenous administration with Tmax were 0.47 and 0.083 h, t1/2 were 3.73 and 1.67 h, respectively. Oral bioavailability was as low as 18.17%. Laurolitsine was found at a high concentration in the gastrointestinal tract, liver, lungs and kidneys (26 015.33, 905.12, 442.32 and 214.99 ng/g at 0.5 h, respectively) and low excretion to parent laurolitsine in urine and faeces (0.03 and 1.20% in 36 h, respectively). CONCLUSIONS: This study established a simple, rapid and accurate LC-MS/MS method to determine laurolitsine in different rat samples and successful application in a pharmacokinetic study.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34275621

RESUMO

OBJECTIVES: After surgery, inflammation is a prominent factor influencing postoperative atrial fibrillation. Myeloperoxidase is a major contributor to inflammatory responses after surgical tissue damage. We evaluated whether myeloperoxidase is associated with postoperative atrial fibrillation clinically and in an animal model. METHODS: This prospective cohort study included patients undergoing isolated coronary artery bypass grafting. Myeloperoxidase concentrations in blood and pericardial fluid were determined at baseline and 6, 12, and 18 hours after coronary artery bypass grafting. Myeloperoxidase activity in blood, pericardial fluid, and atrium were also evaluated in a canine coronary artery bypass grafting model. Electrophysiologic, histologic, and immunohistochemistry analyses were performed to explore underlying mechanisms. RESULTS: Postoperative atrial fibrillation occurred in 45 of 137 patients (32.8%). Patients with postoperative atrial fibrillation had significantly higher serum and pericardial myeloperoxidase levels. Individual clinical and surgical factors had moderate predictive value (area under the curve, 0.760) for postoperative atrial fibrillation. Discrimination improved remarkably when myeloperoxidase was combined with other parameters (area under the curve, 0.901). Pericardial myeloperoxidase at 6 hours postoperatively was the strongest independent predictor of postoperative atrial fibrillation (odds ratio, 19.215). The rate of postoperative atrial fibrillation increased exponentially across pericardial myeloperoxidase grades. Compared with controls, coronary artery bypass grafting-treated dogs showed higher atrial fibrillation vulnerability and maintenance, shorter atrial effective refractory period, attenuated connexin 43 expression, and increased myocardial and pericardial myeloperoxidase activity. Connexin 43 expression and atrial effective refractory period were strongly negatively correlated with myocardial and pericardial myeloperoxidase activity. CONCLUSIONS: Myeloperoxidase is linked to postoperative atrial fibrillation, and the ability to predict postoperative atrial fibrillation was remarkably improved by adding pericardial myeloperoxidase. Myeloperoxidase-related atrial structural and electrical remodeling is a physiologic substrate for this arrhythmia.

6.
Microb Ecol ; 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34272992

RESUMO

Mesoscale eddies are common oceanographic processes that can enhance primary productivity by transporting nutrients to the euphotic zone. In the northern South China Sea (SCS), eddies were frequently found to promote the exchange between the nutrient-rich shelf water and the oligotrophic water at the slope area. However, the response of bacterial community to eddy perturbations remains unclear. In the present study, we examined the variation of bacterial community under the impact of eddies in early spring and summer. The results showed that both the summer cyclonic eddy and spring anticyclonic eddy enhanced the bacterial abundance in surface water. The bacterial community composition and their functional potentials of surface samples were also influenced by the summer cyclonic eddy, while no significant change was observed in the case of spring anticyclonic eddy. Salinity and nutrients, which varied between the inside and outside of the eddies, were the significant factors explaining the differentiation of the community composition and related functions. Taken together, the results of our present study reveal the effects of mesoscale eddies on the bacterial community and associated metagenomes, providing a better understanding of the dynamics of bacteria in the slope ecosystem of the SCS.

7.
J Cancer Res Ther ; 17(3): 740-748, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34269308

RESUMO

Context and Aims: The identification of inflammation-related prognostic heterogeneity in intermediate-stage hepatocellular carcinoma (HCC) can reveal more effective first-line treatments. Our study aimed to compare the intermediate-stage HCC patients' different inflammation-based scores in predicting their progression-free survival (PFS) after transarterial chemoembolization (TACE). Materials and Methods: We analyzed retrospectively a total of 128 intermediate-stage HCC patients who received first-line TACE treatment. We used the Cox-proportional hazards modeling to identify the independent prognostic factors. We compared the inflammation-based scores abilities to predict the PFS through the time-dependent receiver operating characteristic curves and area under the curves. Results: The multivariate analysis showed that tumor size and platelet-to-lymphocyte ratio (PLR) were the independent prognostic factors for PFS (P < 0.05). The PLR predicted the intermediate-stage HCC patients' PFS receiving the TACE treatment better than other inflammation-based scores (e.g., the neutrophil-to-lymphocyte ratio, the Glasgow Prognostic Score (GPS), the modified GPS, the Prognostic Index, the Prognostic Nutritional Index, the lymphocyte-to-monocyte ratio, and the systemic immune-inflammation index) (P < 0.05). An easy-to-use novel inflammation score based on tumor size - PLR-size score significantly improved the PFS prediction performance (P < 0.05). Conclusions: As a first-line treatment, TACE was not well suitable for all intermediate-stage HCC patients, while the PLR was a better inflammation-based score than others. Tumor size should be regarded as an essential variable in affecting intermediate-stage HCC patients' first-line treatment strategies.

8.
Peptides ; : 170609, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34242679

RESUMO

Cell pyroptosis, a new type of programmed cell death, has been recently reported to play important roles in the development of cardiac remodeling. How cardiomyocyte pyroptosis is induced remains to be elucidated. Urotensin II (UII) has been known closely related to cardiac remodeling and the development of heart failure. Inhibition of UII receptors has been shown to be effective in the treatment of cardiac hypertrophy and remodeling. However, it is not clear whether UII might induce cardiomyocyte pyroptosis. We here examined the effect of UII treatment on pyroptosis in cultured cardiomyocytes. Treatment of cardiomyocyes of neonatal rats with UII (500 nmol/l) for 48 hours induced a significant pyroptosis as evidenced by not only increased cell death but also upregulated expression levels of NLR family pyrin domain containing 3 (NLRP3), caspase-1, IL-1ß, IL-18 and gasdermin D (GMDSD)-N which are important markers for the identification of cell pyroptosis. All these pyroptosis responses induced by UII were abrogated by an inhibitor of NLRP3. Moreover, the antagonist of UII receptor, Urantide abolished UII- induced cardiomyocyte pyroptosis. Additionally, inhibition of calcineurin by cyclosporin A rather than that of CaMKII by KN93 suppressed the UII-upregulated expression levels of those pyroptosis markers. We therefore demonstrate that UII might induce cardiomyocyte pyroptosis through calcineurin.

9.
Front Endocrinol (Lausanne) ; 12: 672350, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276558

RESUMO

Background: Chronic kidney disease (CKD) is a public health problem largely caused by diabetes. The epidemiology of diabetes mellitus-related CKD (CKD-DM) could provide specific support to lessen global, regional, and national CKD burden. Methods: Data were derived from the GBD 2019 study, including four measures and age-standardized rates (ASRs). Estimated annual percentage changes and 95% CIs were calculated to evaluate the variation trend of ASRs. Results: Diabetes caused the majority of new cases and patients with CKD in all regions. All ASRs for type 2 diabetes-related CKD increased over 30 years. Asia and Middle socio-demographic index (SDI) quintile always carried the heaviest burden of CKD-DM. Diabetes type 2 became the second leading cause of CKD and CKD-related death and the third leading cause of CKD-related DALYs in 2019. Type 2 diabetes-related CKD accounted for most of the CKD-DM disease burden. There were 2.62 million incident cases, 134.58 million patients, 405.99 thousand deaths, and 13.09 million disability-adjusted life-years (DALYs) of CKD-DM worldwide in 2019. Age-standardized incidence (ASIR) and prevalence rate (ASPR) of type 1 diabetes-related CKD increased, whereas age-standardized death rate (ASDR) and DALY rate decreased for females and increased for males. In high SDI quintile, ASIR and ASPR of type 1 diabetes-related CKD remained the highest, with the slowest increase, whereas the ASDR and age-standardized DALY rate remained the lowest there. In high SDI quintile, ASIR of type 2 diabetes-related CKD was the highest, with the lowest increasing rate. In addition, type 2 diabetes-related CKD occurred most in people aged 80-plus years worldwide. The main age of type 2 diabetes-related CKD patients was 55-64 years in Asia and Africa. The prevalence, mortality, and DALY rate of type 2 diabetes-related CKD increased with age. As for incidence, there was a peak at 80 years, and after age of 80, the incidence declined. CKD-DM-related anemia was mainly in mild to moderate grade. Conclusions: Increasing burden of CKD-DM varied among regions and countries. Prevention and treatment measures should be strengthened according to CKD-DM epidemiology, especially in middle SDI quintile and Asia.

10.
J Colloid Interface Sci ; 603: 220-232, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34197982

RESUMO

This work synthesized a novel CuS/KTa0.75Nb0.25O3 (KTN) heterojunction composite and firstly applied it in photocatalytic and piezocatalytic reduction of N2 to NH3. XRD, Raman, XPS, SEM, and TEM analyses indicate that CuS nanoparticles closely adhered to the surface of KTN nanorods, which facilitates the migration of electrons between the two semiconductors. Mott-Schottky and valence band XPS analysis shows that KNbO3 shows a higher conduction band than CuS, indicating that CuS mainly acts as electron trappers to capture the photogenerated electrons from KTN. Because of the great enhanced spatial separation of photogenerated charge carriers, the CuS/KTN presents much higher performance than pure KNT, which is further confirmed by 1H NMR analysis of the reaction solution. An interesting finding is that synthesized CuS/KTN not only performs well under light irradiation but also can work in an ultrasonic bath, indicating its great potential in photo/piezocatalytic conversion of N2 to NH3. The optimal 10 %CuS/KTN shows an NH3 production rate of 36.2 µmol L-1 g-1 h-1 under ultrasonic vibration, which reaches 7.4 times that of KTN. The electrons generated by KTN through the piezoelectric effect can be captured by CuS, which endows the electrons a longer life to participate in the reaction, thereby improving the catalytic reaction performance.

11.
Mult Scler Relat Disord ; 54: 103124, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34243102

RESUMO

BACKGROUND: Susceptibility weighted imaging (SWI) has detected veins in the center of white matter lesions and alterations in veins themselves in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). However, the relationship between SWI-detected venous alterations and disease progression is unclear. The objective of this study was to assess alterations in the lumbar spinal cord veins in EAE mice over the disease course using serial SWI. METHODS: EAE mice (n = 8) underwent imaging for SWI using a 9.4T Bruker Avance console at baseline, 7 days (pre-motor dysfunction), 12 days (typical motor dysfunction onset), and 16-18 days (typical peak disease) post-immunization. Naïve controls were imaged alongside EAE mice (n = 3). SWI hypointensities were counted by two subjects and compared between time points. RESULTS: SWI hypointensities appeared before motor dysfunction onset in most EAE mice. The ratio of SWI hypointensities to baseline was highly variable for EAE mice (0.45-6.75) while less so for controls (0.80-1.31). The time point for the maximum number of SWI hypointensities always preceded or coincided with maximum motor disability. CONCLUSION: Venous alterations are detected before the onset of motor disability in some EAE mice using SWI which may relate to inflammation and/or tissue hypoxia.

12.
Ecotoxicol Environ Saf ; 222: 112475, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34243112

RESUMO

Harmonious ecological environment is a major concern with rising feeding and consumption of ducks, as these waterfowl birds can promote the spread of antibiotic resistant genes (ARGs). Therefore, this study was conducted to know diversity of antimicrobial resistance (AMR), integrons, and mobile genetic elements (MGEs) in Escherichia coli (E. coli) isolated from intestinal contents or pericardial effusion of diseased ducks from 2018 to 2020 in Sichuan, China. The AMR phenotype was determined via disk diffusion test in 165 E. coli isolates. Further, the integrase genes of integron (intI1, intI2 and intI3 genes), gene cassettes (GCs) and MGEs were screened by PCR and sequencing. The results indicated 100% isolates were resistant to at least one antibiotic and 98.8% were multidrug-resistant strains. Highest AMR phenotype was recorded to rifampin (97.0%) followed by ampicillin (95.8%), chloramphenicol (89.7%), trimethoprim-sulfamethoxazole (84.2%), ciprofloxacin (83.0%), cefotaxime (80.0%), streptomycin (75.8%), doxycycline (49.7%), amikacin (10.3%), amoxicillin/clavulanic acid (3.6%), polymyxin B (1.2%) and ertapenem (0.6%). Further, class 1 and 2 integrons were found in 87.3% and 17.6% isolates, respectively. All isolates were negative for intI3 gene. The variable region of class 1 and 2 integrons contained total 13 different GCs, including arr-3+dfrA27, dfrA1+aadA1, dfrA17+aadA5, dfrA12, dfrA1+sat2+aadA1, dfrA12+aadA2, dfrA5, aadA2+ere(A)+dfrA32, aac(6')-Ib-cr, aadA22, aadA5, dfrA17, and dfrA27. Moreover, 13 MGEs in 69 different combinations were observed with predominance of IS26 followed by tnpA/Tn21, trbC, ISEcp1, merA, ISAba1, tnsA, tnsB, tnsC, IS1133, tnsD, ISCR3/14, and tnsE. Thus, the monitoring of integrons, MGEs and ARGs is important to understand the complex mechanism of AMR, which might help to introduce interventions for prevention and control of AMR in duck farms in China.

13.
J Parkinsons Dis ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34250953

RESUMO

BACKGROUND: Genetic studies have indicated that variants in several lysosomal genes are risk factors for idiopathic Parkinson's disease (PD). However, the role of lysosomal genes in PD in Asian populations is largely unknown. OBJECTIVE: This study aimed to analyze rare variants in lysosomal related genes in Chinese population with early-onset and familial PD. METHODS: In total, 1,136 participants, including 536 and 600 patients with sporadic early-onset PD (SEOPD) and familial PD, respectively, underwent whole-exome sequencing to assess the genetic etiology. Rare variants in PD were investigated in 67 candidate lysosomal related genes (LRGs), including 15 lysosomal function-related genes and 52 lysosomal storage disorder genes. RESULTS: Compared with the autosomal dominant PD (ADPD) or SEOPD cohorts, a much higher proportion of patients with multiple rare damaging variants of LRGs were found in the autosomal recessive PD (ARPD) cohort. At a gene level, rare damaging variants in GBA and MAN2B1 were enriched in PD, but in SCARB2, MCOLN1, LYST, VPS16, and VPS13C were much less in patients. At an allele level, GBA p. Leu483Pro was found to increase the risk of PD. Genotype-phenotype correlation showed no significance in the clinical features among patients carrying a discrepant number of rare variants in LRGs. CONCLUSION: Our study suggests rare variants in LRGs might be more important in the pathogenicity of ARPD cases compared with ADPD or SEOPD. We further confirm rare variants in GBA are involve in PD pathogenecity and other genes associated with PD identified in this study should be supported with more evidence.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34197328

RESUMO

This article proposes a fault-tolerant adaptive multigradient recursive reinforcement learning (RL) event-triggered tracking control scheme for strict-feedback discrete-time multiagent systems. The multigradient recursive RL algorithm is used to avoid the local optimal problem that may exist in the gradient descent scheme. Different from the existing event-triggered control results, a new lemma about the relative threshold event-triggered control strategy is proposed to handle the compensation error, which can improve the utilization of communication resources and weaken the negative impact on tracking accuracy and closed-loop system stability. To overcome the difficulty caused by sensor fault, a distributed control method is introduced by adopting the adaptive compensation technique, which can effectively decrease the number of online estimation parameters. Furthermore, by using the multigradient recursive RL algorithm with less learning parameters, the online estimation time can be effectively reduced. The stability of closed-loop multiagent systems is proved by using the Lyapunov stability theorem, and it is verified that all signals are semiglobally uniformly ultimately bounded. Finally, two simulation examples are given to show the availability of the presented control scheme.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34226121

RESUMO

BACKGROUND AND AIMS: Cardiometabolic multimorbidity (CM) is an increasing public health burden. This study aimed to evaluate the association of waist-to-height ratio (WHtR), waist circumference (WC), waist divided by height0.5 (WHT.5R) and body mass index (BMI) with the risk of CM. METHODS AND RESULTS: We used data from the China Health and Retirement Longitudinal Study (CHARLS). A total of 10,521 participants aged 45 years and over were recruited, including 8807 individuals with 0 cardiometabolic diseases at baseline (stage I) and 1714 individuals with 1 cardiometabolic disease at baseline (stage II). CM was defined as self-reporting of two or more of the following conditions: stroke, diabetes and heart disease. Logistic regression was conducted to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). The net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to evaluate the incremental predictive value beyond conventional factors. In stage I, an increased risk of CM was observed among participants with WHtR ≥0.5 (OR: 1.76, 95% CI: 1.05-2.97), WC ≥ 90 cm (men) + WC ≥ 80 cm (women) (OR: 2.06, 95% CI: 1.29-3.27), WHT.5R ≥ 6.54 cm0.5 (OR: 1.81, 95% CI: 1.16-2.83) or BMI ≥24 kg/m2 (OR: 1.48, 95% CI: 0.98-2.24). Furthermore, the NRI and IDI of WHtR, WC and WHT.5R were all higher than those of BMI. In stage II, the adjusted ORs (95% CIs) of WHtR, WC, WHT.5R and BMI were 2.04 (1.24-3.35), 1.89 (1.29-2.77), 1.86 (1.24-2.78) and 1.47 (1.06-2.04), respectively. In addition, WC exhibited the highest NRI and IDI. CONCLUSION: WHtR, WC, WHT.5R and BMI are independent predictors of CM in the middle-aged and older Chinese population. WHtR, WC and WHT.5R show better abilities in predicting CM than BMI.

16.
J Microbiol Biotechnol ; 312021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34226414

RESUMO

The transcriptional capacities of target genes are strongly influenced by promoters, whereas, few studies focus on the development of robust, high-performance and cross-species promoters for widely application in different bacteria. In this work, four novel promoters (Pk.rtufB, Pk.r1, Pk.r2 and Pk.r3) were predicted from Ketogulonicigenium robustum and their inconsistency of -10 and -35 region nucleotide sequences indicated they were different promoters. Their activities were evaluated by using green fluorescent protein (gfp) as reporter in different species bacteria, including K. vulgare SPU B805, Pseudomonas putida KT2440, Paracoccus denitrificans PD1222, Bacillus licheniformis and Raoultella ornithinolytica due to their importance in metabolic engineering. Results showed that the four promoters had different activities, whereas Pk.r1 showed the strongest activity in almost all the experimental bacteria. Comparison with the commonly used promoters of E. coli (tufB, lac, lacUV5), K. vulgare (Psdh, Psndh) and P. putida KT2440 (JE111411), the four promoters showed significantly differences due to only 12.62% nucleotide similarities, and relatively higher ability in regulating target gene expression. Further validation experiments confirmed their ability in initiating the target minCD cassette because of the shape changes under the promoter regulation. The overexpression of sorbose dehydrogenase and cytochrome c551 by Pk.r1, Pk.r2 resulted in a 22.75% enhancement of 2-KGA yield indicating their practices application in metabolic engineering. This study demonstrates an example of applying bioinformatics to find new biological components for gene operation and provides four novel promoters with broad suitability, which enriches the usable range of promoters to realize accurate regulation in different genetic backgrounds.

17.
Nat Genet ; 53(6): 840-860, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34059833

RESUMO

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.


Assuntos
Glicemia/genética , Grupo com Ancestrais do Continente Europeu/genética , Característica Quantitativa Herdável , Alelos , Epigênese Genética , Perfilação da Expressão Gênica , Genoma Humano , Estudo de Associação Genômica Ampla , Hemoglobina A Glicada/metabolismo , Humanos , Herança Multifatorial/genética , Mapeamento Físico do Cromossomo , Locos de Características Quantitativas/genética
18.
J Cell Mol Med ; 25(14): 6679-6694, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34132454

RESUMO

The prethrombotic state (PTS) is a possible cause of recurrent spontaneous abortion (RSA). The aim of this study was to identify serum biomarkers for the detection of RSA with PTS (PSRSA). A Quantibody array 440 was used to screen novel serum-based biomarkers for PSRSA/NRSA (RSA without PTS). Proteins differentially expressed in PSRSA were analysed using bioinformatics methods and subjected to a customized array and enzyme-linked immunosorbent assay (ELISA) validation. We used receiver operating characteristic to calculate diagnostic accuracy, and machine learning methods to establish a biomarker model for evaluation of the identified targets. 20 targets were selected for validation using a customized array, and seven targets via ELISA. The decision tree model showed that IL-24 was the first node and eotaxin-3 was the second node distinguishing the PSRSA and NRSA groups (an accuracy rate of 100% and an AUC of 1). Epidermal growth factor (EGF) as the node distinguished the PSRSA and NC groups (an accuracy rate of 100% and an AUC of 1). EGF as the node distinguished the NRSA and NC groups (an accuracy rate of 96.5% and an AUC of 0.998). Serum DNAM-1, BAFF, CNTF, LAG-3, IL-24, Eotaxin-3 and EGF represent a panel of promising diagnostic biomarkers to detect the PSRSA.

19.
Poult Sci ; 100(8): 101251, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34175799

RESUMO

Previously, we isolated a novel strain of goose pegivirus (GPgV) that infects geese and shows high levels of lymphotropism. This novel pegivirus strain is phylogenetically distinct from previously known Pegivirus species, Pegivirus A-K, and qualifies as a candidate new Pegivirus species, GPgV. GPgV is tentatively named Pegivirus M. Here, to better understand the epidemic of GPgV infection and the coinfection of this virus with other viruses in Southwest China, 25 geese in poor health from Sichuan Province and 24 geese in poor health from the municipality of Chongqing were collected. The geese were tested for 9 types of goose viruses (goose hemorrhagic polyomavirus, GPgV, astrovirus, parvovirus, circovirus, reovirus, coronavirus, paramyxovirus, and avian influenza virus) by RT-PCR or nested RT-PCR. GPgV RNA was detected in 2 out of 25 monoinfections and 8 out of 25 coinfections with other viruses on Sichuan farms and 2 out of 24 monoinfections and 10 out of 24 coinfections on Chongqing farms. Overall, 22 of the 49 (44.9%) geese were positive for GPgV, which indicated a high infection rate. To the best of our knowledge, this is the first report of GPgV coinfection with other epidemic viruses. This study enhances our understanding of the emergence and epidemiology of Pegivirus.

20.
Clin Chim Acta ; 520: 95-100, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34107314

RESUMO

BACKGROUND: Breast malignancy is the most frequently diagnosed malignancy in women worldwide, and the diagnosis relies on invasive examinations. However, most clinical breast changes in women are benign, and invasive diagnostic approaches cause unnecessary suffering for the patients. Thus, a novel noninvasive approach for discriminating malignant breast lesions from benign lesions is needed. METHODS: We performed cell-free DNA (cfDNA) sequencing on plasma samples from 173 malignant breast lesion patients, 158 benign breast lesion patients, and 102 healthy women. We then analyzed the cfDNA-based nucleosome profiles, which reflect the various tissues of origin and transcription factor activities. Moreover, by using machine learning classifiers along with the cfDNA sequencing data, we built classifiers for discriminating benign from malignant breast lesions. Receiver operating characteristic curve analyses were used to evaluate the performance of the classifiers. RESULTS: cfDNA-based nucleosome profiles reflected the various tissues of origin and transcription factor activities in benign and malignant breast lesions. The cfDNA-based transcription factor activities and breast malignancy-specific transcription factor-binding site accessibility profiles could accurately distinguish benign and malignant breast lesions, with area under the curve values of 0.777 and 0.824, respectively. CONCLUSIONS: Our proof-of-principle study established a methodology for noninvasively discriminating benign from malignant breast lesions.


Assuntos
Neoplasias da Mama , Ácidos Nucleicos Livres , Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Ácidos Nucleicos Livres/genética , Diagnóstico Diferencial , Feminino , Humanos , Nucleossomos/genética , Curva ROC
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