Mechanisms for drawdown of floating particles in a laminar stirred tank flow

The authors gratefully acknowledge the financial support from the National Key R&D Program of China (2017YFB0306701) and from the National Natural Science Foundation of China (No.21676007).Peer reviewedPostprin

An evaluation of EQ-5D-3L health utility scores using five country-specific tariffs in a rural population aged 45-69 years in Hua county, Henan province, China.

BACKGROUND: This study aims to compare the performance of the recently developed Chinese (city) tariff of the EQ-5D-3L against the UK, US, Japanese and Korean tariffs in a general rural population in China. METHODS: From November 2015 to September 2016, 12,085 permanent residents aged 45-69 from 257 villages randomly selected from Hua County, Henan Province, China, were interviewed using EQ-5D-3L, and a one-on-one questionnaire investigation was used to collect data on factors associated with HRQOL. The health utility scores were calculated using the UK, US, Japanese, Korean and Chinese (city) tariffs. The agreement, known-groups validity and sensitivity of these five tariffs were evaluated. Transition scores for pairs of observed EQ-5D-3L health states were calculated and compared. RESULTS: The Korean tariff yielded the highest mean health utility score (0.963), followed by the Chinese (city) (0.948), US (0.943), UK (0.930) and Japanese (0.921) tariffs, but the differences in the scores of any two tariffs did not exceed the MCID. The Chinese (city) tariff showed higher ICC values (ICCs> 0.89, 95% CI:0.755-0.964) and narrower limits of agreement (0.099-0.167) than the Korean tariff [(ICCs> 0.71, 95% CI:0.451-0.955); (0.146-0.253)]. The Chinese (city) tariff had a higher relative efficiency and effect size statistics in 10 out of 11 variables as compared to the UK, US and Japanese tariffs. The Chinese (city) tariff (0.215) was associated with moderate mean absolute transition scores compared with the UK (0.342), US (0.230), Japanese (0.149) and Korean (0.189) tariffs for 1485 observed pairs of the EQ-5D-3L health states. CONCLUSIONS: Health utility scores derived from the five tariffs differed. The Chinese (city) tariff was the most suitable of these tariffs and was without obvious weakness. We recommend adopting the Chinese (city) tariff when applying EQ-5D-3L to assess quality of life among the elderly in China's agricultural region with socio-economic status similar to Hua County. Results of this study had provided a crucial basis for health surveys, health promotion projects, health intervention trials, and health economic evaluation taking HRQOL as a target in rural areas of China

Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5

The pacemaker is composed of specialized cardiomyocytes located within the sinoatrial node (SAN), and is responsible for originating and regulating the heart beat. Recent advances towards understanding the SAN development have been made on the genetic control and gene interaction within this structure. Here we report that the Shox2 homeodomain transcription factor is restrictedly expressed in the sinus venosus region including the SAN and the sinus valves during embryonic heart development. Shox2 null mutation results in embryonic lethality due to cardiovascular defects, including an abnormal low heart beat rate (bradycardia) and severely hypoplastic SAN and sinus valves attributed to a significantly decreased level of cell proliferation. Genetically, the lack of Tbx3 and Hcn4 expression, along with ectopic activation of Nppa, Cx40, and Nkx2-5 in the Shox2−/− SAN region, indicates a failure in SAN differentiation. Furthermore, Shox2 overexpression in Xenopus embryos results in extensive repression of Nkx2-5 in the developing heart, leading to a reduced cardiac field and aberrant heart formation. Reporter gene expression assays provide additional evidence for the repression of Nkx2-5 promoter activity by Shox2. Taken together our results demonstrate that Shox2 plays an essential role in the SAN and pacemaker development by controlling a genetic cascade through the repression of Nkx2-5

Oral microbiome and risk of malignant esophageal lesions in a high-risk area of China: A nested case-control study.

OBJECTIVE: We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk. METHODS: We conducted a case-control study nested within a population-based cohort with up to 8 visits of oral swab collection for each subject over an 11-year period in a high-risk area for esophageal cancer in China. The oral microbiome was evaluated with 16S ribosomal RNA (rRNA) gene sequencing in 428 pre-diagnostic oral specimens from 84 cases with esophageal lesions of severe squamous dysplasia and above (SDA) and 168 matched healthy controls. DESeq analysis was performed to identify taxa of differential abundance. Differential oral species together with subject characteristics were evaluated for their potential in predicting SDA risk by constructing conditional logistic regression models. RESULTS: A total of 125 taxa including 37 named species showed significantly different abundance between SDA cases and controls (all P0.84. CONCLUSIONS: The oral microbiome may play an etiological and predictive role in esophageal cancer, and it holds promise as a non-invasive early warning biomarker for risk stratification for esophageal cancer screening programs

A Critical Role for PDGFRα Signaling in Medial Nasal Process Development

<div><p>The primitive face is composed of neural crest cell (NCC) derived prominences. The medial nasal processes (MNP) give rise to the upper lip and vomeronasal organ, and are essential for normal craniofacial development, but the mechanism of MNP development remains largely unknown. PDGFRα signaling is known to be critical for NCC development and craniofacial morphogenesis. In this study, we show that PDGFRα is required for MNP development by maintaining the migration of progenitor neural crest cells (NCCs) and the proliferation of MNP cells. Further investigations reveal that PI3K/Akt and Rac1 signaling mediate PDGFRα function during MNP development. We thus establish PDGFRα as a novel regulator of MNP development and elucidate the roles of its downstream signaling pathways at cellular and molecular levels.</p></div

PI3K signaling mediates PDGFRα regulation on cell proliferation during MNP development.

<p>(A, B) Histological coronal sections of embryos at E13.5. PDGFRα^PI3K/PI3K embryo (B) exhibits a shortened nasal septum (arrow) and hypoplastic mandible and tongue, as compared to the PDGFRα^PI3K/+ control (A). (C, D) PDGFRα^PI3K/PI3K E18.5 embryos develop hypoplastic nasal cartilages and shorter premaxilla bones than control (C). Asterisks refer to defective bones or cartilages. (E, F) At E11.5, BrdU labeling results show a decreased proliferation rate in PDGFRα^PI3K/PI3K MNP mesenchymal cells (F) as compared to the control (E). (G) The ratio of proliferating cells is significantly decreased in PDGFRα^PI3K/PI3K MNP mesenchyme when compared to that of PDGFRα^PI3K/+. The LNP cell proliferation rate in PDGFRα^PI3K/PI3K is not affected. N = 9; asterisk, p<0.01. Als, alisphenoid; bs, basisphenoid; FB, forebrain; MD, mandible; MNP, medial nasal process; MX, maxilla; nc, nasal cartilage; NS, nasal septum; pmx, premaxilla; ptg, pterygoid; so, supraoccipital bone; T, tongue.</p

Tissue specific inactivation of PDGFRα from NCCs causes facial clefting and absence of MNP derived structures.

<p>(A, B) Frontal view of PDGFRα^fl/+; Wnt1Cre (A) and PDGFRα^fl/fl; Wnt1Cre embryo (B) at E11.5. An obvious gap was observed between MNPs in PDGFRα^fl/fl; Wnt1Cre embryo (arrow in B). (C, D) Ventral view of PDGFRα^fl/+; Wnt1Cre (C) and PDGFRα^fl/fl; Wnt1Cre embryo (D) at E13.5. The PDGFRα^fl/fl; Wnt1Cre embryo shows cleft lip and lacks of philtrum and primary palate (asterisk in D). The mandible has been removed for visualization. (E, F) Histological coronal sections of PDGFRα^fl/+; Wnt1Cre (E) and PDGFRα^fl/fl; Wnt1Cre embryo (F) at E13.5. PDGFRα^fl/fl; Wnt1Cre embryo shows a cleft of the nasal septum and lacks the primary palate (asterisk in F). (G, H) Ventral view of skeletal preparation of PDGFRα^fl/+; Wnt1Cre (G) and PDGFRα^fl/fl; Wnt1Cre embryo (H) at E18.5. Note the shortening and clefting of the nasal cartilage in the PDGFRα^fl/fl; Wnt1Cre embryo. Asterisks refer to defective bones or cartilages. Als, alisphenoid; bs, basisphenoid; LNP, lateral nasal process; MNP, medial nasal process; nc, nasal cartilage; NS, nasal septum; P, philtrum; pl, palatine; pmx, premaxilla; PP, primary palate; PS, palatal shelf; ptg, pterygoid.</p

PDGFRα controls chemotaxis and cell motility.

<p>(A) PDGFA (0.5 ng/ml and 5 ng/ml) stimulates chemotaxis of MEPMs in transwell assays. N = 9; asterisk, p<0.01. (B) PDGFA (30 ng/ml) accelerates wound healing in MEPMs in scratch assays. N = 9; asterisk, p<0.01. (C) PDGFRα^PI3K/PI3K MEPMs migrate towards PDGFA at a comparable level to PDGFRα^PI3K/+ MEPMs in transwell assays. N = 9; asterisk, p<0.01. (D) The speed of wound healing in scratch assays is significantly affected in cKO MEPMs, but not in PDGFRα^PI3K/PI3K MEPMs. N = 9; asterisk, p<0.01.</p