Numerical simulation and experimental study of gas cyclone–liquid jet separator for fine particle separation

To address the shortcomings of existing particulate matter trapping technology,especially the low separation efficiency of fine particles,herein,a novel gas cyclone-liquid jet separator was developed to research fine particle trapping.First,numerical simulation methods were used to investigate the flow field characteristics and dust removal efficiency of the separator under different working conditions,and to determined suitable experimental conditions for subsequent dust removal experiments.Afterward,the separation efficiency of the separator against five kinds of common particles,including g-C_(3)N_(4),TiO_(2),SiC,talc,and SiO_(2),was experimentally studied.A maximum separation efficiency of 99.48%was achieved for particles larger than 13.1μm,and 96.55%efficiency was achieved for particles larger than 2μm.The best crushing atomization effect was achieved for the separator when uGwas 10 m·s^(-1)and uLwas 3 m·s^(-1),while the best separation effect was achieved when uGwas 10 m·s^(-1)and uLwas 3.75 m·s^(-1).Studies have shown that the gas cyclone-liquid jet separator has excellent applicability in the separation of fine particles.

Machine learning modeling identifies hypertrophic cardiomyopathy subtypes with genetic signature

Previous studies have revealed that patients with hypertrophic cardiomyopathy(HCM)exhibit differences in symptom severity and prognosis,indicating potential HCM subtypes among these patients.Here,793 patients with HCM were recruited at an average follow-up of 32.78±27.58 months to identify potential HCM subtypes by performing consensus clustering on the basis of their echocardiography features.Furthermore,we proposed a systematic method for illustrating the relationship between the phenotype and genotype of each HCM subtype by using machine learning modeling and interactome network detection techniques based on whole-exome sequencing data.Another independent cohort that consisted of 414 patients with HCM was recruited to replicate the findings.Consequently,two subtypes characterized by different clinical outcomes were identified in HCM.Patients with subtype 2 presented asymmetric septal hypertrophy associated with a stable course,while those with subtype 1 displayed left ventricular systolic dysfunction and aggressive progression.Machine learning modeling based on personal whole-exome data identified 46 genes with mutation burden that could accurately predict subtype propensities.Furthermore,the patients in another cohort predicted as subtype 1 by the 46-gene model presented increased left ventricular end-diastolic diameter and reduced left ventricular ejection fraction.By employing echocardiography and genetic screening for the 46 genes,HCM can be classified into two subtypes with distinct clinical outcomes.

Effects of Shuanghuanglian oral liquids on patients with COVID-19:a randomized,open-label,parallel-controlled,multicenter clinical trial

We conducted a randomized,open-label,parallel-controlled,multicenter trial on the use of Shuanghuanglian(SHL),a traditional Chinese patent medicine,in treating cases of COVID-19.A total of 176 patients received SHL by three doses(56 in low dose,61 in middle dose,and 59 in high dose)in addition to standard care.The control group was composed of 59 patients who received standard therapy alone.Treatment with SHL was not associated with a difference from standard care in the time to disease recovery.Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group(93.4%vs.73.9%,P=0.006).Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia,which was evaluated by density reduction of inflammatory focus from baseline,at day 7(mean difference(95%CI),−46.39(−86.83 to−5.94)HU;P=0.025)and day 14(mean difference(95%CI),−74.21(−133.35 to−15.08)HU;P=0.014).No serious adverse events occurred in the SHL groups.This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.

MYH7B variants cause hypertrophic cardiomyopathy by activating the Ca MK-signaling pathway

Hypertrophic cardiomyopathy(HCM) is a common genetic disease, predominantly caused by mutations in cardiac sarcomere genes;however, whether MYH7 B causes HCM is not known. In this study, 549 unrelated patients with HCM and 500 healthycontrols were screened using targeted sequencing and whole exome sequencing together. We observed seven variants in MYH7 B causing HCM in 8/549 patients, which accounted for 1.46% of HCM cases. Of these seven variants, three likely pathogenic variants in MYH7 B co-segregating with 5 HCM patients were identified in three HCM pedigrees without other HCM-associated variants. Myh7 b knockout rats were generated and cardiac functions were detected by Millar pressure-volume catheterization and echocardiography. Spontaneous HCM phenotypes, cellular disarray and cardiac fibrosis were observed in both Myh7 b^+/–/Myh7 b^–/–rats. Transcriptome sequencing showed that calcium is the key mediator of cardiac hypertrophy in Myh7 b knockout. Subsequent analysis confirmed over-activation of Ca MK-signaling pathway in cardiomyocytes of Myh7 b^–/–rats.Furthermore, MYH7 B expression in human and rat hearts was identified and micro RNA-208 a and micro RNA-499 levels are unchanged in HCM patients and Myh7 b^+/–/Myh7 b^–/–rats. This study is the first to identify MYH7 B variants as cause of HCM,which account for 1.46% of pathogenesisin HCM patients. Activation of Ca MK-signaling pathway may be involved in its pathophysiology.

Erratum to:MYH7B variants cause hypertrophic cardiomyopathy by activating the CaMK-signaling pathway

In the original manuscript,the value of DBP in WT group was recorded as 128.0±7.6 mm Hg by mistake,which should be the value of SBP in Myh7b;group.And the correct DBP value in WT group should be 88.8±5.3 mm Hg.The corrected Table 3should be as follows.

A targeted sequencing approach to find novel pathogenic genes associated with sporadic aortic dissection

Aortic dissection(AD) is a heterogeneous genetic disease of the aorta with high mortality and poor prognosis. However, only few genetic causes of AD have been explored till date. After conducting a broad literature review focused on identifying potential pathogenic pathways, we designed a panel containing 152 AD-associated genes to conduct massively parallel targeted nextgeneration sequencing of 702 sporadic aortic dissection patients and 163 matched healthy controls. After validation by Sanger sequencing, we identified 21 definitely pathogenic and 635 likely pathogenic variants in 61.25%(430/702) of patients. In these patients, 34.88%(150/430) harbored more than one variant that was either definitely or likely to be pathogenic. Among the candidate genes, we identified 546 likely pathogenic variants in 47.72%(335/702) of patients. Importantly, we identified 94 lossof-function(LOF) variants in 45 genes in AD patients, but only five LOF variants in the controls(P=1.34×10^(-4)). With a burden test, we highlighted RNF213 as an important new gene for AD pathogenesis. We also performed transcriptome sequencing of human aorta tissues to evaluate the expression levels of these newly identified genes. Our study has compiled a comprehensive genetic map of sporadic AD in the Han Chinese population. We believe it will facilitate risk predicting and genetic diagnosis of this severe disease in the future.

Variants of genes encoding collagens and matrix metalloproteinase system increased the risk of aortic dissection

Aortic dissection （AD） is a devastating, heterogeneous condition of aorta. The homeostasis between collagens and matrix metalloproteases （MMPs）/tissue inhibitors of MMPs （TIMPs） system in the extracellular matrix plays an important role for structure and functions of aorta. However, our knowledge on association between variants of genes in this system and pathogenesis of AD is very limited. We analyzed all yet known coding human genes of collagens （45 genes）, MMPs/TIMPs （27 genes） in 702 sporadic AD patients and in 163 matched healthy controls, by using massively targeted next-generation and Sanger sequencing. To define the pathogenesis of potential disease-causing candidate genes, we performed transcriptome sequencing and pedigree co-segregation analysis in some genes and generated Col5a2 knockout rats. We identified 257 pathogenic or likely pathogenic variants which involved 88.89% （64/72） genes in collagens-MMPs/TIMPs system and accounted for 31.05% （218/702） sporadic AD patients. In them, 84.86% patients （185/218） carried one variant, 12.84% two variants and 2.30% more than two variants. Importantly, we identified 52 novel probablY pathogenic loss-of-function （LOF） variants （20 nonsense, 16 frameshift, 14 splice sites, one stop-loss, one initiation codon） in 11.06% （50/452） AD patients, which were absent in 163 controls （P=2.5-10-5）. Transcriptome sequencing revealed that identified variants induced dyshomeostasis in expression of collagens-TIMPs/MMPs systems. The Col5a2-/- rats manifested growth retardation and aortic dysplasia. Our study provides a first comprehensive map of genetic alterations in collagens-MMPs/TIMPs system in sporadic AD patients and suggests that variants of these genes contribute largely to AD pathogenesis.

Resistance of large caisson in floating transport considering the influence of air

This paper deals with the floating resistance of super large caisson by numerical simulation,and the influence of air resistance on the caisson,which is often ignored by previous researchers,is considered.The floating caisson of Taizhou Highway Bridge’s middle tower pier is investigated,and the software package FLUENT is used to simulate the floating process of largescale rounded rectangular steel caisson.This simulation adopts the volume of fluid(VOF)model with water-air two-phase flow,which can take both the hydraulic resistance and air resistance into account.Subsequently,the analyses on hydraulic resistance and air resistance under different working conditions,such as different flow velocities and different draughts of water are performed,and the results are compared with those calculated by related empirical formula.The comparison shows that the air resistance takes up notable portion in the total resistance on the floating caisson,and the effect of air resistance on the safety of caisson should be paid sufficient attention to rather than be ignored.

Identification of COL3A1 variants associated with sporadic thoracic aortic dissection: a case-control study

Thoracic aortic dissection(TAD)without familial clustering or syndromic features is known as sporadic TAD(STAD).So far,the genetic basis of STAD remains unknown.Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population(N=637).After population structure and genetic relationship and ancestry analyses,we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD.We found that COL3A1 was significantly relevant to STAD(P=7.35×10^(−6))after 10000 times permutation test(P=2.49×10^(−3)).Moreover,another independent cohort,including 423 cases and 734 non-STAD subjects(N=1157),replicated our results(P=0.021).Further bioinformatics analysis showed that COL3A1 was highly expressed in dissected aortic tissues,and its expression was related to the extracellular matrix(ECM)pathway.Our study identified a profile of known heritable TAD genes in the Chinese STAD population and found that COL3A1 could increase the risk of STAD through the ECM pathway.We wanted to expand the knowledge of the genetic basis and pathology of STAD,which may further help in providing better genetic counseling to the patients.