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1.
Artigo em Inglês | MEDLINE | ID: mdl-33422666

RESUMO

BACKGROUND: Ultrafast ultrasound imaging has been demonstrated to be an effective method to evaluate carotid stiffness through carotid pulse-wave velocity (PWV) with high reproducibility, but a lack of reference values has precluded its widespread use in clinical practice. The aims of this study were to establish reference values of PWV for ultrafast ultrasound imaging in a prospective, multicenter, population-based cohort study and to investigate the main determinants of carotid PWV. METHODS: A total of 1,544 healthy Han Chinese volunteers (581 men [38%]; age range, 18-95 years) were enrolled from 32 collaborating laboratories in China. The participants were categorized by age, blood pressure (BP), and body mass index (BMI). Basic clinical parameters and carotid PWV at the beginning of systole (BS) and at end-systole (ES) were measured using ultrafast ultrasound imaging techniques. RESULTS: PWV at both BS and ES was significantly higher in the left carotid artery than in the right carotid artery. PWV at BS was significantly higher in men than in women; however, no significant difference was noted in PWV at ES between men and women. Multiple linear regression analyses revealed that age, BP, and BMI were independently correlated with PWV at both BS and ES. PWV at BS and ES progressively increased with increases in age, BP, and BMI. Furthermore, age- and sex-specific reference values of carotid PWV for ultrafast ultrasound imaging were established. CONCLUSIONS: Reference values of carotid PWV for ultrafast ultrasound imaging, stratified by sex and age, were determined for the first time. Age, BP, and BMI were the dominant determinants of carotid PWV for ultrafast ultrasound imaging, which should be considered in clinical practice for assessing arterial stiffness.

2.
Carbohydr Polym ; 255: 117475, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33436239

RESUMO

Extraintestinal pathogenic Escherichia coli (ExPEC) has presented a major clinical infection emerged in the past decades. O-polysaccharide (OPS)-based glycoconjugate vaccines produced using the bacterial glycosylation machinery can be utilized to confer protection against such infection. However, constructing a low-cost microbial cell factory for high-efficient production of OPS-based glycoconjugate vaccines remains challenging. Here, we engineered a glyco-optimized chassis strain by reprogramming metabolic network. The yield was enhanced to 38.6 mg L-1, the highest level reported so far. MS analysis showed that designed glycosylation sequon was modified by target polysaccharide with high glycosylation efficiency of 90.7 % and 76.7 % for CTB-O5 and CTB-O7, respectively. The glycoconjugate vaccines purified from this biosystem elicited a marked increase in protection against ExPEC infection in mouse model, compared to a non-optimized system. The glyco-optimized platform established here is broadly suitable for polysaccharide-based conjugate production against ExPEC and other surface-polysaccharide-producing pathogens.

3.
Am J Hum Genet ; 108(2): 337-345, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33434492

RESUMO

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/genética , Anormalidades Congênitas/genética , Ductos Paramesonéfricos/anormalidades , Ductos Paramesonéfricos/crescimento & desenvolvimento , Mutação , Ductos Mesonéfricos/crescimento & desenvolvimento , Adulto , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 7/genética , Códon sem Sentido , Feminino , Estudos de Associação Genética , Pleiotropia Genética , Proteínas Homeobox A10/genética , Proteínas de Homeodomínio/genética , Humanos , Fator de Transcrição PAX8/genética , Herança Paterna , Penetrância , Proteínas com Domínio T/genética , Fatores de Transcrição/genética , Proteínas Wnt/genética , Ductos Mesonéfricos/anormalidades
4.
Mol Med Rep ; 23(1): 1, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33179114

RESUMO

Calcitonin gene­related peptide (CGRP) is the predominant neurotransmitter located in sensory nerves. This peptide is extensively distributed in central and peripheral tissues. CGRP causes relaxation of cardiovascular smooth muscle cells and confers protection against ischaemic myocardium and cardiac remodeling. The pharmacological effects of nitroglycerine and rutaecarpine have been demonstrated to be associated with an increase in the synthesis and release of CGRP. In the gastrointestinal tissues, CGRP participates in the regulation of gastrointestinal function, and exerts protective effects on gastric mucosa. Rutaecarpine, capsaicin and its derivatives, such as evodiamine, decrease gastric mucosal damage induced by several factors, including increased synthesis and release of CGRP. Taken together, this review focuses on the pharmacological effects of several CGRP related canonical drugs and suggests that synthesis and secretion of CGRP exhibit significant therapeutic effects in the occurrence and development of cardiovascular and gastrointestinal diseases.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 1998-2003, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33283732

RESUMO

OBJECTIVE: To evaluate the proformance of multiplex PCR and capillary electrophoresis(MPCE) in the detection of JAK2V617F and CALR mutation in myeloproliferative neoplasms(MPN). METHODS: The specificity primers of JAK2617F gene mutation and the primers of CALR gene were designed at the same time. The JAK2V617F and CALR gene primers were labeled with Cy5 fluorescence, all the primers were mixed in one tube for multiplex PCR and the PCR prodcuts were analysised by capillary electrophoresis. Then detection limit and sensitivity of MPCE were evaluated, and compared with comercial diagnostic kit. RESULTS: JAK2V617F and CALR gene mutations could be detect by MPCE in one PCR test. JAK2V617F mutation could be detected at 0.01 ng genomic DNA, double positive JAK2V617F and CLAR gene mutations could be detected at 0.1 ng genomic DNA, at least 0.1% JAK2V617F positive mutation could be detected. The consistency between MPCE and commercial diagnostic gene mutation kit was 100%. CONCLUSION: It is developed that a new gene mutation detection method of JAK2 V617F and CLAR gene based on MPCE in our experiment and it can be used as a new reagent for molecular diagnosis of MPN patients.

6.
Am J Clin Nutr ; 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33381807

RESUMO

BACKGROUND: Although adherence to healthful dietary patterns has been associated with a lower risk of kidney function decline in Western populations, evidence in Asian populations remains scanty. OBJECTIVES: We examined predefined dietary patterns, namely, the Alternate Healthy Eating Index-2010 (AHEI-2010), the Dietary Approaches to Stop Hypertension (DASH), and the alternate Mediterranean diet (aMED), in relation to risk of end-stage kidney disease (ESKD). METHODS: We included 56,985 Chinese adults (aged 45-74 y) in the Singapore Chinese Health Study who were free of cancer, stroke, coronary artery disease, and ESKD at recruitment (1993-1998). Dietary pattern scores were calculated based on a validated 165-item FFQ. AHEI-2010 and aMED scores were modified by excluding the alcohol intake component because daily drinking has been associated with a higher risk of ESKD in our study population. We identified 1026 ESKD cases over a median follow-up of 17.5 y via linkage with the nationwide Singapore Renal Registry. Multivariable Cox regression models were used to compute HRs and their 95% CIs. RESULTS: Higher scores of all 3 dietary patterns were associated with lower ESKD risk in a dose-dependent manner. Compared with the lowest quintiles, the multivariable-adjusted HRs (95% CIs) of ESKD were 0.75 (0.61, 0.92) for the highest quintile of AHEI-2010, 0.67 (0.54, 0.84) for DASH, and 0.73 (0.59, 0.91) for aMED (all P-trend ≤ 0.004). These inverse associations were stronger with increasing BMI (in kg/m2), and the HRs for the diet-ESKD association were lowest in the obese (BMI ≥ 27.5), followed by the overweight (BMI = 25 to <27.5) participants, compared with those in lower BMI categories; the P-interaction values between BMI and diet scores were 0.03 for AHEI-2010, 0.004 for aMED, and 0.06 for DASH. CONCLUSIONS: Adherence to healthful dietary patterns was associated with a lower ESKD risk in an Asian population, especially in overweight or obese individuals.

7.
Int J Cancer ; 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33326609

RESUMO

Associations of coffee and tea consumption with lung cancer risk have been inconsistent, and most lung cancer cases investigated were smokers. Included in this study were over 1.1 million participants from 17 prospective cohorts. Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Potential effect modifications by sex, smoking, race, cancer subtype and coffee type were assessed. After a median 8.6 years of follow-up, 20 280 incident lung cancer cases were identified. Compared with noncoffee and nontea consumption, HRs (95% CIs) associated with exclusive coffee drinkers (≥2 cups/d) among current, former and never smokers were 1.30 (1.15-1.47), 1.49 (1.27-1.74) and 1.35 (1.15-1.58), respectively. Corresponding HRs for exclusive tea drinkers (≥2 cups/d) were 1.16 (1.02-1.32), 1.10 (0.92-1.32) and 1.37 (1.17-1.61). In general, the coffee and tea associations did not differ significantly by sex, race or histologic subtype. Our findings suggest that higher consumption of coffee or tea is associated with increased lung cancer risk. However, these findings should not be assumed to be causal because of the likelihood of residual confounding by smoking, including passive smoking, and change of coffee and tea consumption after study enrolment.

8.
J Adv Nurs ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33231300

RESUMO

AIMS: Nurses are at the forefront of public health emergencies facing psychological pressures ensuing from the loss of patients and potential risk of infection while treating the infected. This study examines whether inclusive leadership has a causal relationship with psychological distress and to assess the mediation effect of psychological safety on this relationship in the long run. The hypotheses are developed and interpreted with the help of theoretical underpinnings from job demands resources theory and the theory of shattered assumptions. DESIGN: Three-wave longitudinal study. METHODS: Questionnaire was used to carry out three waves of data collection from 405 nurses employed at five hospitals in Wuhan during the COVID-19 outbreak between the months of January-April 2020. Partial least square structural equation modelling (PLS-SEM) was used to analyze data while controlling for age, gender, education, experience, and working hours. RESULTS: Results supported the hypothesized relationships where inclusive leadership indicated significant inverse causal relationship with psychological distress and a positive causal relationship with psychological safety. Mediation effect of psychological safety was found significant, while the model explained 73.9% variance in psychological distress. CONCLUSION: Inclusive leadership, through its positive and supportive characteristics, can pave way for such mechanisms that improve the psychological safety of employees in the long run and curbs psychological distress. IMPACT: This is the first longitudinal study to examine the relationship between inclusive leadership and psychological distress in health care and also examines the mediating mechanism of psychology safety. There is scarcity of empirical research on factors that determine and affect behavioural mechanism of healthcare workers during traumatic events and crisis. Clinical leaders and healthcare policy makers must invest in and promote inclusive and supportive environment characterized with open and accessible leaders at workplace to improve psychological safety; it helps reduce levels of psychological distress.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33187965

RESUMO

BACKGROUND: While the associations between individual lifestyle factors and risk of hepatocellular carcinoma (HCC) have been previously described, their combined impact on HCC risk is unknown. METHODS: The association of a composite score of healthy lifestyle factors, including body mass index, alcohol consumption, cigarette smoking, alternative Mediterranean diet, and sleep duration, and HCC risk was examined in the Singapore Chinese Health Study, an on-going prospective cohort study of 63,257 Chinese. Cox proportional hazard regression method was used to estimate hazard ratio (HR) and its 95% confidence interval (CI). Conditional logistic regression method was used to evaluate this composite lifestyle score-HCC risk association among a subset of individuals who tested negative for hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody. RESULTS: After a mean follow-up of 17.7 years, 561 participants developed HCC. Individuals with higher composite scores representing healthier lifestyles (range 0-8) were at significantly lower risk of HCC. Compared to the lowest composite score category (0-4), the HRs (95% CIs) for the composite scores of 5, 6, 7, and 8 were 0.67 (0.62-0.85), 0.61 (0.48-0.77), 0.49 (0.37-0.65), and 0.13 (0.06-0.30), respectively (Ptrend<0.0001). A similar inverse association was observed in participants with negative HBsAg and anti-HCV negative serology (HR=0.38, 95% CI: 0.19-0.79; for the highest versus the lowest category of the composite scores (Ptrend=0.001). CONCLUSION: Healthy lifestyles protects against HCC development, especially for individuals without hepatitis B virus and hepatitis C infections. IMPACT: Our current study highlight the importance of a comprehensive lifestyle modification strategy for HCC primary prevention.

10.
Exp Neurol ; : 113525, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33161049

RESUMO

A pivotal neuropathological manifestation of synucleinopathies, like Parkinson's disease (PD), is the aggregation of α-synuclein. In a recent cell-to-cell transmission model of α-synuclein, α-synuclein propagation was demonstrated to resemble that of prion proteins in the central nervous system. Furthermore, exosomes, as biomolecule carriers, have been shown to transmit α-synuclein from neuron to neuron. However, the mechanisms underlying exosomal α-synuclein transmission have not been well understood. The NLR family pyrin domain containing 3 protein (NLRP3) inflammasome activation in microglia, and the subsequent release of proinflammatory cytokines, are two crucial pathological events involved in neuroinflammation and PD progression. Research has revealed that the NLRP3 inflammasome may facilitate the secretion of extracellular vesicles, as well as exosomal transmission of proteins like aggregated α-synuclein. However, only a few reports have evaluated these pathogenic mechanisms. Herein we evaluate for the first time the current evidence for the involvement of the NLRP3 inflammasome in microvesicle generation by microglial cells, and the various mechanisms regarding the production, shedding, and content of exosomes in relation to α-synuclein transmission from neuron to neuron. Furthermore, we propose a model of microglial NLRP3 inflammasome-dependent exosome secretion and exosomal α-synuclein transmission in PD. This knowledge may lead to the identification of novel potential targets for drug development and stimulate further research in PD.

11.
J Am Med Dir Assoc ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33218913

RESUMO

OBJECTIVE: To examine the associations between dietary patterns in midlife and likelihood of future healthy ageing in Chinese older adults. DESIGN: Prospective population-based study. SETTING AND PARTICIPANTS: We included 14,159 participants aged 45-74 years who were free from cancer, cardiovascular disease, or diabetes at baseline (1993-1998) from the Singapore Chinese Health Study. METHODS: Dietary intakes in midlife were assessed by a validated food frequency questionnaire at baseline. Diet quality was scored according to the alternate Mediterranean diet (aMED), the Dietary Approaches to Stop Hypertension (DASH) diet, the alternative Healthy Eating Index (AHEI)-2010, overall plant-based diet index (PDI), and healthful plant-based diet index (hPDI). Healthy ageing was assessed at the third follow-up visit (2014-2016), which occurred about 20 years after the baseline visit, and was defined as the absence of 10 chronic diseases, no impairment of cognitive function, no limitations in instrumental activities of daily living, no clinical depression at screening, good overall self-perceived health, good physical functioning, and no function-limiting pain among participants who had survival to at least 65 years of age. Multivariable-adjusted logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each dietary pattern score and healthy ageing. RESULTS: About 20.0% of participants met the healthy ageing criteria. The OR (95% CI) for healthy ageing comparing the highest with the lowest quartile of diet quality scores was 1.52 (1.31-1.77) for aMED, 1.53 (1.35-1.73) for DASH, 1.39 (1.23-1.57) for AHEI-2010, 1.34 (1.18-1.53) for PDI, and 1.45 (1.27-1.65) for hPDI (all P-trend < .001). Each standard deviation increment in different diet quality scores was associated with 12% to 18% higher likelihood of healthy ageing. CONCLUSIONS AND IMPLICATIONS: In this Chinese population, adherence to various healthy dietary patterns at midlife is associated with higher likelihood of healthy ageing at later life.

12.
Metallomics ; 12(11): 1834-1840, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33151228

RESUMO

Cisplatin and oxaliplatin are widely used anti-tumour chemotherapeutic agents with different spectra of activity. The therapeutic efficacy of such platinum-based drug is believed to, at least in part, result from formation of Pt-DNA adducts, followed by DNA damage response and ultimately apoptosis. However, it remains unclear whether these DNA lesions caused by cisplatin and oxaliplatin elicit distinct reactions in cellular signaling pathways. Here, a label-free comparative proteomic study was performed to profile the protein phosphorylation patterns using Pt-DNA probes with different ligand identities and geometries. Phosphorylated proteins recognizing different cisplatin- and oxaliplatin-DNA lesions were enriched and analyzed on LC-MS/MS. Proteomic analysis revealed that cisplatin mainly affected proteins involved in mRNA processing, while chromatin organization and rRNA processing are two major biological processes influenced by oxaliplatin. Changes to site-specific phosphorylation levels of two proteins YBX1 and UBF1 were also validated by Western blotting. In particular, platinum drug treatment in colon and liver cancer cell lines down-regulated S484 phosphorylation of UBF1, which is an essential transcription factor responsible for ribosomal DNA transcription activation, implying that inhibition of ribosome biogenesis might be involved in the cytotoxic mechanism of platinum drugs. Collectively, these results directly reflected distinct protein phosphorylation patterns triggered by cisplatin and oxaliplatin, and could also provide valuable resources for future mechanistic studies of platinum-based anti-tumour agents.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33203693

RESUMO

BACKGROUND: Interleukin-27 mRNA is highly enriched in the tissue of hepatocellular carcinoma. Overexpression of interleukin-27 gene has been found to increase T cell expression of inhibitory receptors, an immunosuppressive feature in tumor microenvironment, that promotes the development of hepatocellular carcinoma. METHODS: Two parallel case-control studies of hepatocellular carcinoma, each with 100 case-control pairs were conducted in the Singapore Chinese Health Study and the Shanghai Cohort Study to examine the association between serum interleukin-27 levels and risk of developing hepatocellular carcinoma. The interleukin-27 concentrations were significantly elevated in sera collected from study participants 4-5 years prior to the diagnosis of hepatocellular carcinoma in both cohort studies. RESULTS: Compared with the lowest tertile of interleukin-27, odds ratios (ORs)of hepatocellular carcinoma for the highest tertile of interleukin-27 was 46.08 [95% confidence interval (CI): 4.68-453.86] in the Singapore Chinese Health Study and 19.09 (95% CI: 3.81-95.57) in the Shanghai Cohort Study (both ptrend <0.001). The corresponding ORs in both cohort studies were 42.47 (95% CI: 8.30-217.40) among individuals negative for hepatitis B surface antigen (HBsAg) and 242.46 (95% IC: 38.42-1529.01) among those positive for HBsAg compared with the lowest tertile of interleukin-27 and negative HBsAg. CONCLUSION: Levels of interleukin-27 in prediagnostic sera were significantly associated with increased risk of hepatocellular carcinoma development. IMPACT: Interleukin-27 through its immunosuppressive property may play a significant role in the development of hepatocellular carcinoma. Serum levels of interleukin-27 may be used as a biomarker for prediction of hepatocellular carcinoma development.

14.
Int J Cancer ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33210298

RESUMO

2,456 lung cancer cases and 5,342 controls were evaluated in this International Lung Cancer Consortium (ILCCO) pooled analysis on estrogen-related hormonal factors and lung cancer in Asian women. Random effect of study site and fixed effect of age, smoking status, comprehensive smoking index, and family history of lung cancer were adjusted for in the multivariable logistic regression models. We found that late onset of menarche conferred elevated odds of lung cancer with adjusted odds ratio (OR) of 1.24 (95% confidence interval, CI=1.05 , 1.45) for 17 years or older, compared with 14 years or younger. Late onset of menopause at 55 years old or older was associated with lung cancer with OR=1.24 (95% CI=1.02 , 1.51). Non-natural menopause was associated with an OR of 1.39 (95%CI=1.13 , 1.71). More live births showed reversed association with lung cancer (ORs of 5 or more live births: 0.71 (95%CI=0.60 , 0.84), compared with 0-2 live births (Ptrend <0.001). A later first child delivery seemed associated with an increased susceptibility: OR of 21-25 years old: 1.23 (95% CI=1.06 , 1.40), 26 or older: 1.27 (95%CI=1.06, 1.52), Ptrend =0.010). Oral contraceptives use appeared to be protective with an OR of 0.69 (95% CI=0.57, 0.83). Stronger for adenocarcinoma than squamous cell carcinoma, these relationships were not clearly modified by smoking status, probably because of lower prevalence of smoking. This is a first and largest pooling study of lung cancer among Asian women and the results suggested potential roles of hormone-related pathways in the etiology of this disease. This article is protected by copyright. All rights reserved.

15.
J Thorac Oncol ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33137463

RESUMO

RATIONALE: The workup and longitudinal monitoring for subjects presenting with pulmonary nodules is a pressing clinical problem. A blood-based biomarker panel potentially has utility for identifying subjects at higher risk for harboring a malignant nodule for whom additional work-up would be indicated or subjects at reduced risk for whom imaging based follow-up would be indicated. OBJECTIVES: To assess whether a previously described four-protein biomarker panel, previously reported to improve assessment of lung cancer risk compared to a smoking-based lung cancer risk model, can provide discrimination between benign and malignant indeterminate pulmonary nodules. METHODS: A previously validated multiplex enzyme linked immunoassay was performed on matched case and control samples from each cohort. MEASUREMENTS: The biomarker panel was tested in two case-control cohorts of patients presenting with indeterminate pulmonary nodules at the University of Pittsburgh Medical Center and The University of Texas Southwestern. MAIN RESULTS: In both cohorts, the biomarker panel resulted in improved prediction of lung cancer risk over a model based on nodule size alone. Of particular note, the addition of the marker panel to nodule size greatly improved sensitivity at a high specificity in both cohorts. CONCLUSIONS: A four-marker biomarker panel, previously validated to improve lung cancer risk prediction, also shows utility in distinguishing benign from malignant indeterminate pulmonary nodules. Its performance in improving sensitivity at a high specificity indicates potential utility of the marker panel in assessing likelihood of malignancy in otherwise indeterminate nodules.

16.
Materials (Basel) ; 13(22)2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33203049

RESUMO

Extended end-plate (EP) bolted connections are widely used in steel structures as moment-resisting connections. Most of these connections are semi-rigid or in other words flexible. The paper aims to study the behavior of such connections under the effect of column top-side cyclic loading using the finite element (FE) method. For semi-rigid connections, it is very vital to determine the moment-rotation relationship as well as the connection stiffness. These beam-column connections have been parametrically studied, the effect of joint type, shear forces, diameter of bolt, thickness of end-plate, and end-plate style were studied. Parametric studies show that the panel zone shear force is the key factor and has a significant effect on the connection stiffness. Finally, based on the component method, the stiffness of the bending component is improved, and the initial stiffness calculation model of the connection under column top-side cyclic loadings is established. The results show that the calculation model is in good agreement with the finite element analyses, and this proves that the calculation model proposed in this study could act as a reference method.

17.
Environ Technol ; : 1-27, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33251967

RESUMO

The environmental prevalence and potential toxicity of dibutyl phthalate (DBP) motivate the attempt to develop feasible strategies to deal with DBP contamination. In this study, a strain of endphytic bacteria HB-T2 was isolated from sorrel roots and identified as Bacillus sp. by analyzing its morphology, physiology, biochemistry and 16S rDNA sequence. The degradation efficiency of DBP by HB-T2 was almost identical under the temperature of 30∼40 °C, but was significantly enhanced as the culture pH and inoculum size increases from 6.0 to 8.0, and 1% to 5% respectively. The degradation kinetics of DBP could be well described by the first-order kinetic model, with the degradation half-life ranging from 1.59 to 7.61 h when the initial concentrations of DBP were in the range of 5 to 20 mg/L. LC-MS analysis of the culture samples taken at varying intervals revealed monobutyl phthalate, phthalic acid and protocatechuic acid as the major metabolic intermediates during the degradation process. HB-T2 exhibited an excellent capability to degrade a wide range of phthalate esters (PAEs), especially butyl benzyl phthalate (BBP), dipentyl phthalate (DPP), and diisobutyl phthalate (DIBP). Inoculation of HB-T2 into Chinese cabbage (Brassica chinensis L.) growing in DBP-contaminated soils could significantly reduce the DBP levels in plant tissues and relieve the phytotoxic effects of DBP. Results of this study highlighted the great potential of this novel endophytic Bacillus subtilis strain HB-T2 for bioremediation of PAEs contamination and improvement of agricultural product safety by reducing PAEs accumulation in edible crops.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33051982

RESUMO

AIM: Radium-223, a targeted alpha therapy, is approved widely for the treatment of patients with metastatic castrate-resistant prostate cancer, based on a pivotal phase 3 study in predominantly white patients. We investigated the efficacy and safety of radium-223 in Asian patients with castrate-resistant prostate cancer and metastatic bone disease. METHODS: This multicenter, prospective, single-arm, open-label phase 3 trial evaluated the efficacy and safety of the standard radium-223 regimen (55 kBq/kg every 4 weeks for six cycles) in patients from Asian countries. The primary endpoints were the safety and overall survival. RESULTS: A total of 226 patients were enrolled and received at least one dose of radium-223. Median overall survival was 14.0 months (95% confidence interval [CI], 11.2-17.4). Median time to total alkaline phosphatase and prostate-specific antigen progression were 7.5 (95% CI, 6.8-7.7) and 3.6 (95% CI, 3.1-3.7) months, respectively. Median skeletal-related event-free survival was 26.0 months (95% CI, 12.6-not reached). Grade ≥3 treatment-emergent adverse events were reported in 103 (46%) of 226 patients, with anemia being the most common event (34 [15%] patients). Grade ≥3 drug-related treatment-emergent adverse events occurred in 39 (17%) of 226 patients. Serious treatment-emergent adverse events were reported in 65 (29%) of 226 patients. Seven (3%) patients had an adverse event leading to death; none were considered to be related to radium-223. CONCLUSION: The results of this study support the use of the standard radium-223 regimen for the treatment of Asian patients with castrate-resistant prostate cancer and symptomatic bone metastases.

19.
J Phys Chem B ; 124(44): 9829-9839, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33104345

RESUMO

The thermodynamics and kinetics of protein folding and protein aggregation in vivo are of great importance in numerous scientific areas including fundamental biophysics research, nanotechnology, and medicine. However, these processes remain poorly understood in both in vivo and in vitro systems. Here we extend an established model for protein aggregation that is based on the kinetic equations for the moments of the polymer size distribution by introducing macromolecular crowding particles into the model using scaled-particle and transition-state theories. The model predicts that the presence of crowders can either speed up, cause no change to, or slow down the progress of the aggregation compared to crowder-free solutions, in striking agreement with experimental results from nine different amyloid-forming proteins that utilized dextran as the crowder. These different dynamic effects of macromolecular crowding can be understood in terms of the change of excluded volume associated with each reaction step.

20.
Zhongguo Gu Shang ; 33(10): 970-4, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33107263

RESUMO

OBJECTIVE: To investigate therapeutic effect of minimally invasive percutaneous plate internal fixation (MIPPO) through a single incision in treating open distal tibiofibula fractures. METHODS: From March 2015 to February 2019, 10 patients with open distal tibiofibula fractures were treated with MIPPO technique through single anterolateral incision, including 8 males and 2 females, aged from 31 to 68 years old. According to Gustilo classification, 6 patients were typeⅠ, 3 patients were typeⅡand 1 patient was type ⅢA. Operative time, intraoperative blood loss and fracture healing were observed, Mazur ankle joint scoring was used to evaluate clinical effect. RESULTS: All patients were followed up from 9 to 24 months. Operative time ranged from 85 to 120 min, intraoperative blood loss ranged from 80 to 200 ml, fracture healing time ranged from 18 to 30 weeks. Nine patients with Gustilo typeⅠandⅡachieved satisfactory healing wound, original wound of 1 patient with Gustilo type ⅢA was poor, and healed by skin flap transplantation at stageⅡ. No steel exposed and infection occurred. According to Mazur ankle scoring at the final following-up, total score was from 61 to 97, and 8 patients got excellent result, 1 good and 1 poor. CONCLUSION: MIPPO technique through anterolateral single incision for the treatment of open distal tibiofibula fractures could protect original medial wound in opertaion, avoid plate exposed through anterolateral extensor tendon to cover internal fixation, and MIPPO technique could protect fracture end blood flow to improve fracture healing rate, and it is a kind of choice.


Assuntos
Placas Ósseas , Fraturas Expostas , Adulto , Idoso , Feminino , Fixação Interna de Fraturas , Consolidação da Fratura , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos
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