Epidemiological Trends in Cardiovascular Disease Mortality Attributable to Modifiable Risk Factors and Its Association with Sociodemographic Transitions across BRICS-Plus Countries

BRICS-Plus countries (Brazil, Russia, India, China, South Africa, and 30 other countries) is a group of 35 countries with emerging economies making up more than half of the world's population. We explored epidemiological trends of cardiovascular disease (CVD) mortality attributable to modifiable risk factors and its association with period and birth cohort effects and sociodemographic index (SDI) across BRICS-Plus countries by using joinpoint regression and age-period-cohort modeling from 1990 to 2019. Between 1990 and 2019, the all-ages CVD deaths increased by 85.2% (6.1 million to 11.3 million) across BRICS-Plus countries. The CVD age-standardized mortality rate attributable to dietary risks and smoking significantly decreased across BRICS-Plus countries, with some exceptions. However, four-fifths of BRICS-Plus countries observed a remarkable increasing trend of high body mass-index (BMI)-related CVD deaths, in particular, among younger adults (25-49 years). Early birth cohorts and individuals aged greater than 50 years showed a higher risk of CVD mortality. Both the China-ASEAN FTA and Mercosur regions stand out for their successful sociodemographic transition, with a significant reduction in CVD mortality over the study period. Singapore and Brazil achieved great progress in CVD mortality reduction and the other BRICS-Plus countries should follow their lead in adopting public health policies and initiatives into practice

Facile Fabrication of Reduction-Responsive Supramolecular Nanoassemblies for Co-delivery of Doxorubicin and Sorafenib toward Hepatoma Cells

Combination of doxorubicin with sorafenib (SF) was reported to be a promising strategy for treating hepatocellular carcinoma (HCC). In this study, we designed a reduction-responsive supramolecular nanosystem based on poly (ethylene glycol)-β-cyclodextrin (PEG-CD) and a disulfide-containing adamantine-terminated doxorubicin prodrug (AD) for efficient co-delivery of doxorubicin and sorafenib. PEG-CD/AD supramolecular amphiphiles were formed through host-guest interaction between cyclodextrin and adamantine moieties, and then self-assembled into regular spherical nanoparticles with a uniform size of 166.4 nm. Flow cytometry analysis and confocal laser scanning microscopy images showed that PEG-CD/AD nanoparticles could be successfully taken up by HepG2 cells and then released doxorubicin into the cell nuclei. Moreover, sorafenib could be facilely encapsulated into the hydrophobic cores to form PEG-CD/AD/SF nanoparticles with a slightly larger size of 186.2 nm. PEG-CD/AD/SF nanoparticles sequentially released sorafenib and doxorubicin in a reduction-response manner. In vitro cytotoxicity assay showed that PEG-CD/AD/SF nanoparticles had an approximately 4.7-fold decrease in the IC50 value compared to that of PEG-CD/AD and SF physical mixtures, indicating stronger inhibitory effect against HepG2 cells by co-loading these two drugs. In summary, this novel supramolecular nanosystem provided a simple strategy to co-deliver doxorubicin and sorafenib toward hepatoma cells, which showed promising potential for treatment of HCC

FATIGUE RELIABILITY ANALYSIS OF TOWER CRANE UNDER DYNAMIC LOADS BASE ON STOCHASTIC FINITE ELEMENT METHOD

In order to calculate the fatigue reliability of tower crane under random dynamic loads, this paper consider the distribution of the input parameters affect the tower crane reliability, such as distribution of maneuver load parameters, using stochastic finite element method to calculate stress-time history of tower crane fatigue check points, using rain flow counting method to get the load spectrum of the check points, the residual strength is calculated based on Miner linear fatigue cumulative damage theory. Considering the complexity of the structure of tower crane, it is unable to get the explicit expression of the reliability function. Based on stress-strength interference theory, this paper uses stochastic finite element method to calculate the tower crane reliability, and. the influence of overload on reliability is analyzed quantitatively. The results show that with the use of tower crane, its reliability decreased gradually and due to the cumulative fatigue damage there is a sharp decline of the reliability after a certain period of time, and overload has a great effect to the tower crane reliability. Due to the distribution of all input parameters influence the reliability of the tower crane were considered, and all possible conditions in the work of the tower crane were simulated, the results are more consistent with the actual than existing methods, which can provide reference for the evaluation of fatigue reliability of tower crane

Characterization of recombinant expression of Bombyx mori bidensovirus ns1 using a modified vector

ns1 gene of Bombyx mori bidensovirus (BmBDV) consisted of 951 nucleotides encoding a deduced 316-amino aicd protein. In this study, the gene was cloned and fused in frame with a N-terminal 6×His tag under control of the polyhedrin promoter, which was transposed into the mini-attTn7 locus of a modified baculovirus vector. Transfection of Sf-9 cells with the resulting recombinant DNA was performed to prepare recombinant virus and the resultant supernatant of transfection with fluorescent signal was harvested. Western blot analysis revealed that NS1 protein was successfully expressed in Sf9 cells infected with the recombinant virus and was confirmed by LC-MS/MS analysis. Moreover, the expressed NS1 is a phosphorylated protein and the phosphorylation site is Thr-184. These results showed that the activity of BmBDV NS1 may be regulated by phosphorylation

The auxin response factor gene family in allopolyploid Brassica napus.

Auxin response factor (ARF) is a member of the plant-specific B3 DNA binding superfamily. Here, we report the results of a comprehensive analysis of ARF genes in allotetraploid Brassica napus (2n = 38, AACC). Sixty-seven ARF genes were identified in B. napus (BnARFs) and divided into four subfamilies (I-IV). Sixty-one BnARFs were distributed on all chromosomes except C02; the remaining were on Ann and Cnn. The full length of the BnARF proteins was highly conserved especially within each subfamily with all members sharing the N-terminal DNA binding domain (DBD) and the middle region (MR), and most contained the C-terminal dimerization domain (PBI). Twenty-one members had a glutamine-rich MR that may be an activator and the remaining were repressors. Accordingly, the intron patterns are highly conserved in each subfamily or clade, especially in DBD and PBI domains. Several members in subfamily III are potential targets for miR167. Many putative cis-elements involved in phytohormones, light signaling responses, and biotic and abiotic stress were identified in BnARF promoters, implying their possible roles. Most ARF proteins are likely to interact with auxin/indole-3-acetic acid (Aux/IAA) -related proteins, and members from different subfamilies generally shared many common interaction proteins. Whole genome-wide duplication (WGD) by hybridization between Brassica rapa and Brassica oleracea and segmental duplication led to gene expansion. Gene loss following WGD is biased with the An-subgenome retaining more ancestral genes than the Cn-subgenome. BnARFs have wide expression profiles across vegetative and reproductive organs during different developmental stages. No obvious expression bias was observed between An- and Cn-subgenomes. Most synteny-pair genes had similar expression patterns, indicating their functional redundancy. BnARFs were sensitive to exogenous IAA and 6-BA treatments especially subfamily III. The present study provides insights into the distribution, phylogeny, and evolution of ARF gene family

Functional Studies of MLC1 Mutations in Chinese Patients with Megalencephalic Leukoencephalopathy with Subcortical Cysts

Megalencephalic leukoencephalopathy with subcortical cysts (MLC, MIM # 604004) is an autosomal recessive inherited disease mostly resulting from MLC1 mutations. In this study, we finished the functional analysis of MLC1 mutations identified recently in Chinese patients, including five newly described missense mutations (R22Q, A32V, G73E, A275T, Y278H), one known nonsense mutation (Y198X), and two known missense mutations (S69L, T118M). We found MLC1 wt was localized to the cell periphery, whereas mutant R22Q, A32V, G73E, S69L and T118M were trapped in the lumen of endoplasmic reticulum (ER) when we transfected the wild-type and mutant MLC1 in U373MG cells. Compared to wild type, the mutant G73E, T118M, Y198X and A275T transcript decreased and all mutants except R22Q had lower protein expression in transfected U373MG cells. Therefore, we propose that all these eight MLC1 mutations had functional effect either on thei