Methylation-mediated silencing of PTPRD induces pulmonary hypertension by promoting pulmonary arterial smooth muscle cell migration via the PDGFRB/PLCγ1 axis

OBJECTIVE: Pulmonary hypertension is a lethal disease characterized by pulmonary vascular remodeling and is mediated by abnormal proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). Platelet-derived growth factor BB (PDGF-BB) is the most potent mitogen for PASMCs and is involved in vascular remodeling in pulmonary hypertension development. Therefore, the objective of our study is to identify novel mechanisms underlying vascular remodeling in pulmonary hypertension. METHODS: We explored the effects and mechanisms of PTPRD downregulation in PASMCs and PTPRD knockdown rats in pulmonary hypertension induced by hypoxia. RESULTS: We demonstrated that PTPRD is dramatically downregulated in PDGF-BB-treated PASMCs, pulmonary arteries from pulmonary hypertension rats, and blood and pulmonary arteries from lung specimens of patients with hypoxic pulmonary arterial hypertension (HPAH) and idiopathic PAH (iPAH). Subsequently, we found that PTPRD was downregulated by promoter methylation via DNMT1. Moreover, we found that PTPRD knockdown altered cell morphology and migration in PASMCs via modulating focal adhesion and cell cytoskeleton. We have demonstrated that the increase in cell migration is mediated by the PDGFRB/PLCγ1 pathway. Furthermore, under hypoxic condition, we observed significant pulmonary arterial remodeling and exacerbation of pulmonary hypertension in heterozygous PTPRD knock-out rats compared with the wild-type group. We also demonstrated that HET group treated with chronic hypoxia have higher expression and activity of PLCγ1 in the pulmonary arteries compared with wild-type group. CONCLUSION: We propose that PTPRD likely plays an important role in the process of pulmonary vascular remodeling and development of pulmonary hypertension in vivo

Gigahertz-rate-switchable wavefront shaping through integration of metasurfaces with photonic integrated circuit

Achieving spatiotemporal control of light at high-speeds presents immense possibilities for various applications in communication, computation, metrology, and sensing. The integration of subwavelength metasurfaces and optical waveguides offers a promising approach to manipulate light across multiple degrees of freedom at high-speed in compact photonic integrated circuit (PICs) devices. Here, we demonstrate a gigahertz-rate-switchable wavefront shaping by integrating metasurface, lithium niobite on insulator (LNOI) photonic waveguide and electrodes within a PIC device. As proofs of concept, we showcase the generation of a focus beam with reconfigurable arbitrary polarizations, switchable focusing with lateral focal positions and focal length, orbital angular momentum light beams (OAMs) as well as Bessel beams. Our measurements indicate modulation speeds of up to gigahertz rate. This integrated platform offers a versatile and efficient means of controlling light field at high-speed within a compact system, paving the way for potential applications in optical communication, computation, sensing, and imaging

Ethan

In a not too distant future, a technologically advanced country faces a serious problem of population replacement as her individualistic and highly educated citizens reject the idea of procreation. After several failed attempts at encouraging its citizens to procreate, the highly efficient government came up with a single magical solution of the Labour Supplementary Program (LSP) to literally grow the Nation’s population. All healthy citizens who do not have children are required to contribute their sperms and ovaries to the LSP. This program uses advanced scientific technology to artificially engineer the entire process of human growth. Humans are treated as mere labour, a product and nothing more. Babies can now be mass- produced within individual Artificial Gestation Units (AGUs) (refer Appendix) –man-made uterus-- and each child is able to grow at an exponential rate relative to a child by natural birth. In a twist of fate, Vogt, a career-driven scientist develops a father-son bond with one of his specimens and is faced with a dilemma of having to choose between saving his genetically defected “son” from extermination and fulfilling his duties as Head of the LSP.Bachelor of Communication Studie

Public acceptance of COVID-19 control measures and associated factors during Omicron-dominant period in China: a cross-sectional survey

Abstract Objectives This study aims to evaluate the public acceptance of coronavirus disease 2019 (COVID-19) control measures during the Omicron-dominant period and its associated factors. Methods A cross-sectional design was conducted and 1391 study participants were openly recruited to participate in the questionnaire survey. Logistic regression model was performed to assess the association between the public acceptance and potential factors more specifically. Results By August 26, 2022, 58.9% of the study participants were less acceptive of the control measures while 41.1% expressed higher acceptance. Factors associated with lower acceptance included young age, such as < 18 (OR = 8.251, 95% CI: 2.009 to 33.889) and 18–29 (OR = 2.349, 95% CI: 1.564 to 3.529), and household per capita monthly income lower than 5000 yuan (OR = 1.512, 95% CI: 1.085 to 2.105). Furthermore, individuals who perceived that the case fatality rate (CFR) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was very low (OR = 6.010, 95% CI: 2.475 to 14.595) and that the restrictions could be eased once the CFR dropped to 2–3 times of the influenza (OR = 2.792, 95% CI: 1.939 to 4.023) showed greater oppositional attitudes. Likewise, respondents who were dissatisfied with control measures (OR = 9.639, 95% CI: 4.425 to 20.998) or preferred fully relaxation as soon as possible (OR = 13.571, 95% CI: 7.751 to 23.758) had even lower acceptability. By contrast, rural residents (OR = 0.683, 95% CI: 0.473 to 0.987), students (OR = 0.510, 95% CI: 0.276 to 0.941), public (OR = 0.417, 95% CI: 0.240 to 0.727) and private (OR = 0.562, 95% CI: 0.320 to 0.986) employees, and vaccinated participants (OR = 0.393, 95% CI: 0.204 to 0.756) were more compliant with control measures. Conclusion More than half of the Chinese public were less supportive of COVID-19 control measures during Omicron-dominant period, which varied based on their different demographic characteristics, cognition and overall attitude towards SARS-CoV-2 infection. Control measures that struck a balance between public safety and individual freedom would be more acceptable during the pandemic

General self-efficacy and social support as mediators of the association between perceived stress and quality of life among rural women with previous gestational diabetes mellitus.

To explore the association between perceived stress and quality of life (QoL) and the mediating role of general self-efficacy and social support in this association. Gestational diabetes mellitus (GDM) is one of the most common metabolic diseases suffered by pregnant women. Women with previous GDM may experience more medical-related stress and have a lower QoL than those without it. A multisite correlational study. Four hundred sixty-five women with previous GDM living in rural areas in China participated in this study from November 2017 to June 2019. The participants completed a set of self-reported socio-demographic questionnaires, the Perceived Stress Scale, the General Self-Efficacy Scale, the Social Support Rating Scale and the World Health Organization QoL assessment (Brief version). STROBE checklist was used as the guideline for this study. The mean QoL score was 13.97 (SD 2.07) for physical health, 13.75 (SD 1.98) for psychological health, 14.96 (SD 1.99) for social relations and 12.49 (SD 1.74) for environmental conditions. About 43.9% of women with previous GDM reported increased stress, which was negatively correlated with each of these QoL domains. Yet, the negative effect of perceived stress on QoL could be completely or partly mediated by better social support or general self-efficacy among this population. Nearly half of the women in the study living in rural China reported increased stress after delivery, and there is room to improve QoL in the environmental domain among women with previous GDM. Increasing general self-efficacy or social support can help these women avoid the negative effects of perceived stress on their QoL. These findings suggest that healthcare providers need to be cognizant of the importance of self-efficacy and social support for women with previous GDM in both enhancing QoL and reducing the negative impact of perceived stress on QoL

MicroRNAs in pulmonary hypertension, from pathogenesis to diagnosis and treatment

Pulmonary hypertension (PH) is a fatal and untreatable disease, ultimately leading to right heart failure and eventually death. microRNAs are small, non-coding endogenous RNA molecules that can regulate gene expression and influence various biological processes. Changes in microRNA expression levels contribute to various cardiovascular disorders, and microRNAs have been shown to play a critical role in PH pathogenesis. In recent years, numerous studies have explored the role of microRNAs in PH, focusing on the expression profiles of microRNAs and their signaling pathways in pulmonary artery smooth muscle cells (PASMCs) or pulmonary artery endothelial cells (PAECs), PH models, and PH patients. Moreover, certain microRNAs, such as miR-150 and miR-26a, have been identified as good candidates of diagnosis biomarkers for PH. However, there are still several challenges for microRNAs as biomarkers, including difficulty in normalization, specificity in PH, and a lack of longitudinal and big sample-sized studies. Furthermore, microRNA target drugs are potential therapeutic agents for PH treatment, which have been demonstrated in PH models and in humans. Nonetheless, synthetic microRNA mimics or antagonists are susceptible to several common defects, such as low drug efficacy, inefficient drug delivery, potential toxicity and especially, off-target effects. Therefore, finding clinically safe and effective microRNA drugs remains a great challenge, and further breakthrough is urgently needed

Effects of Different Processing Methods on Volatile Flavor Components of Zanthoxylum bungeanum Maxim. Extract and Braised Duck Neck

To investigate the effects of crushed water extraction, uncrushed water extraction, crushed alcohol extraction, uncrushed alcohol extraction, pulverized soup post-extraction and unpulverized soup extraction on volatile flavor components of Zanthoxylum bungeanum Maxim. and its ability to confer volatile flavor substances to braised duck neck was studied. Gas chromatography-mass spectrometry (GC-MS) and gas chromatography-ion mobility spectrometry (GC-IMS) were used to determine the differences of main volatile flavor components in brine and braised duck neck under different treatment methods. GC-MS results showed that the main aromatic compounds in Zanthoxylum bungeanum Maxim. were alcohols, hydrocarbons, esters and ethers. Water extraction could improve the dissolution of 4-terpineol and other alcohols, and alcohol extraction could improve the dissolution of pyoletene and other substances. Decoction extraction had a better dissolution effect on ethers, and crushing treatment could effectively promote the dissolution of hydrocarbons and esters, and was not conducive to the retention of volatile components of alcohol and ether in the brine. The main substances in braised duck neck were 4-terpenoid and cineole after brine preparation of Zanthoxylum bungeanum Maxim. extract under different treatment methods. Water extraction could significantly promote the retention of eucalyptol and limonene in braised duck neck. Ethanol extraction improved the effect of anethole in duck neck. Whether Zanthoxylum bungeanum Maxim. was crushed or not had no significant effect on the volatile flavor substances assigned to duck neck by the prepared brine. Based on GC-IMS spectrum analysis, it was found that for the extract, only alcohol extraction showed significant differences. Similarly, only alcohol extraction showed significant difference in braised duck neck. The volatile flavour compounds of different treatments for Zanthoxylum bungeanum Maxim. extract and gives braised duck neck ability has a significant effect of volatile flavor substances