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The heterogeneous land surface spanning the Yellow River irrigated oasis and the adjacent Kubuqi and Ulan Buh Desert (Hetao area) in Inner Mongolia, China, has been noted to frequently generate planetary boundary layer convergence line (BLCL), providing an important source of low-level lifting for convection initiation (CI). As the first field experiment to collect comprehensive observations of vegetation-contrast-resulting thermal circulations that consistently generate BLCLs and lead to CI, the Desert-Oasis Convergence Line and Deep Convection Experiment (DECODE) was conducted from 5 July to 9 August 2022 in the Hetao area. Two oasis and four desert observation sites were set up in the region that exhibits the highest frequency of BLCL and CI occurrences, equipped with a suite of advanced instruments probing land-atmosphere interactions, planetary boundary layer processes, and evolution of BLCLs and their associated CI, including Doppler lidars, microwave radiometers, soil temperature and moisture sensors, eddy covariance systems, portable radiosondes, C-band polarimetric Doppler radar, aircraft, and Geostationary High-speed Imager onboard FY-4B satellite. DECODE captured 29 BLCLs (16 with CI), 66 gust fronts, 12 horizontal convective rolls, and one tornado. The observations unveiled full thermal circulations spanning the desert-oasis boundary characterized by a horizontal width of ~25 km, a convergence height of ~1 km above ground level (AGL), and divergence from 2 to ~3.5 km AGL, with vertical wind speeds of up to 2 m [s.sup.-1]. Future publications stemming from DECODE will delve into a spectrum of scientific inquiries, including but not limited to land surface and boundary layer processes, BLCL dynamics, CI mechanisms, convective organization, predictability, and model evaluation. SIGNIFICANCE STATEMENT: The purpose of Desert-Oasis Convergence Line and Deep Convection Experiment (DECODE) is to collect intensive observations around desert-oasis divide to better understand the physical processes of boundary layer convergence lines (BLCLs), their associated thermal circulations, convection initiation (CI), and organization over heterogeneous land surfaces. This is important because deep convection initiation poses a major challenge for weather forecasting over heterogeneous land surfaces due to limited understanding of land-atmosphere interactions. In addition, the targeting divide between a desert and an irrigated oasis facilitates a unique situation where human activities can change the weather. This campaign captured 29 BLCLs (16 with CI), which provided a rich dataset for studies not only on convection dynamics and microphysics but also on land-atmosphere interactions, boundary layer processes, and even interdisciplinary studies such as wind farm impact and convective dust storms. KEYWORDS: Complex terrain; Convection lines; Convective-scale processes; Boundary layer; Vegetation; Orographic effects, 1. Background In early October 2016, by fortuitously clicking on a radar image folder labeled 'Linhe' on a computer at the Training Center of the China Meteorological Administration, the first [...]

Poor medication adherence of patients with bipolar affective disorder is associated with stigma, drug adverse reactions and family economic burden. However, high-quality studies about n medication adherence in patients with bipolar affective disorder are relatively scarce. This paper reviewed studies on influencing factors, assessment tools and interventions of medication adherence in patients with bipolar affective disorder. Efforts should be made to investigate the intelligent tele-healthcare system and tele-healthcare-based interventions, and provide reference for establishment of a long-term accessible extended care. (双相情感障碍患者因病耻感、药物不良反应、家庭经济因素等原因, 其用药依从性水平较低。目前国内针对双相障碍服药依从性的高质量研究仍较少。本文对双相情感障碍服药依从性现状进行综述, 包括影响因素、评估工具及干预措施等。建议未来进一步探索适合我国的远程智能医疗系统、开展基于远程医疗的护理干预, 为患者提供更加便捷、远期的延续护理干预。)

Background and purposeTetramethylpyrazine (TMP) was originally isolated from the traditional Chinese herb ligusticum and the fermented Japanese food natto and has since been synthesized. TMP has a long history of beneficial effects in the treatment of many cardiovascular diseases. Here we have evaluated the therapeutic effects of TMP on pulmonary hypertension (PH) in animal models and in patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH).Experimental approachThree well-defined models of PH -chronic hypoxia (10% O2 )-induced PH (HPH), monocrotaline-induced PH (MCT-PH) and Sugen 5416/hypoxia-induced PH (SuHx-PH) - were used in Sprague-Dawley rats, and assessed by echocardiography, along with haemodynamic and histological techniques. Primary cultures of rat distal pulmonary arterial smooth muscle cells (PASMCs) were used to study intracellular calcium levels. Western blots and RT-qPCR assays were also used. In the clinical cohort, patients with PAH or CTEPH were recruited. The effects of TMP were evaluated in all systems.Key resultsTMP (100 mg·kg-1 ·day-1 ) prevented rats from developing experimental PH and ameliorated three models of established PH: HPH, MCT-PH and SuHx-PH. The therapeutic effects of TMP were accompanied by inhibition of intracellular calcium homeostasis in PASMCs. In a small cohort of patients with PAH or CTEPH, oral administration of TMP (100 mg, t.i.d. for 16 weeks) increased the 6-min walk distance and improved the 1-min heart rate recovery.Conclusion and implicationsOur results suggest that TMP is a novel and inexpensive medication for treatment of PH. Clinical trial is registered with www.chictr.org.cn (ChiCTR-IPR-14005379).

Background and Purpose: The causal relationship between altered host microbiome composition, especially the respiratory tract microbiome, and the occurrence of pulmonary hypertension (PH) has not yet been studied. An increased abundance of airway streptococci is seen in patients with PH compared with healthy individuals. This study aimed to determine the causal link between elevated airway exposure to Streptococcus and PH. Experimental Approach: The dose‐, time‐ and bacterium‐specific effects of Streptococcus salivarius (S. salivarius), a selective streptococci, on PH pathogenesis were investigated in a rat model established by intratracheal instillation. Key Results: Exposure to S. salivarius successfully induced typical PH characteristics, such as elevated right ventricular systolic pressure (RVSP), right ventricular hypertrophy (Fulton's index) and pulmonary vascular remodelling, in a dose‐ and time‐dependent manner. Moreover, the S. salivarius‐induced characteristics were absent in either the inactivated S. salivarius (inactivated bacteria control) treatment group or the Bacillus subtilis (active bacteria control) treatment group. Notably, S. salivarius‐induced PH is characterized by elevated inflammatory infiltration in the lungs, in a pattern different from the classic hypoxia‐induced PH model. Moreover, in comparison with the SU5416/hypoxia‐induced PH model (SuHx‐PH), S. salivarius‐induced PH causes similar histological changes (pulmonary vascular remodelling) but less severe haemodynamic changes (RVSP, Fulton's index). S. salivarius‐induced PH is also associated with altered gut microbiome composition, suggesting potential communication of the lung‐gut axis. Conclusion and Implications: This study provides the first evidence that the delivery of S. salivarius in the respiratory tract could cause experimental PH in rats. [ABSTRACT FROM AUTHOR]

Background and Purpose: Recent studies reported therapeutic effects of monotherapy with either tumour suppressor p53 (p53) agonist or hypoxia‐inducible factor 2α (HIF‐2α) antagonist for pulmonary hypertension (PH). This study investigated whether a combined treatment of p53 agonist, Nutlin3a, and HIF‐2α antagonist, PT2385, would be more effective than monotherapy, based on the cell type‐divergent regulation of p53 in pulmonary arterial smooth muscle cells (PASMC) and endothelial cells (PAEC) in patients and animals with PH. Experimental Approach: The SU5416/hypoxia‐induced PH (SuHx‐PH) rat model was used, along with cultured human PASMC and PAEC. Western blot, RT‐PCR, siRNA and immunohistochemical methods were used along with echocardiography and studies with isolated pulmonary arteries. Key Results: Hypoxia‐induced proliferation of PASMC is associated with decreased p53, whereas hypoxia‐induced PAEC apoptosis is associated with increased p53, via a HIF‐2α‐dependent mechanism. Combined treatment with Nutlin3a and PT2385 is more effective by simultaneously inhibiting the hypoxia‐induced PASMC proliferation and PAEC apoptosis, overcoming the side‐effects of monotherapy. These are (i) Nutlin3a exacerbates hypoxia‐induced PAEC apoptosis by inducing p53 in PAEC and (ii) PT2385 inhibits PAEC apoptosis because HIF‐2α is predominantly expressed in PAEC but lacks direct effects on the hypoxia‐induced PASMC proliferation. In rats, combination treatment is more effective than monotherapy in reversing established SuHx‐PH, especially in protecting pulmonary arterial vasculature, by normalizing smooth muscle thickening, protecting against endothelial damage and improving function. Conclusion and Implications: Combination treatment confers greater therapeutic efficacy against PH through a selective modulation of p53 and HIF‐2α in PASMC and PAEC. [ABSTRACT FROM AUTHOR]

Background and Purpose: Pulmonary hypertension related to pulmonary fibrosis is classed as WHO Group III, one of the most common groups which lacks effective treatment options. In this study, we aimed to uncover the underlying mechanisms, particularly the involvement of the BMP9/BMPR2/SMAD signalling pathway, in this subtype of pulmonary hypertension. Experimental Approach Male Sprague Dawley rats were used to establish a model of pulmonary hypertension with pulmonary fibrosis, induced by bleomycin. Haemodynamic and lung functions were measured, along with histological and immunohistochemical examinations. Primary cultures of rat pulmonary microvascular endothelial cells (PMVECs) were analysed with western blots, apoptosis assays and immunohistochemistry. Key Results: Early (7 days) after bleomycin treatment of rats, pulmonary arterial thickening and severe loss of pulmonary arterial endothelium were observed, followed (14 days) by increased right ventricular systolic pressure and right ventricular hypertrophy. Marked down‐regulation of the BMP9/BMPR2/SMAD signalling pathway was markedly down‐regulated in lung tissues from bleomycin‐treated rats (throughout the 7‐ to 35‐day treatment period) and bleomycin‐treated rat PMVECs, along with excessive cell apoptosis and loss of pulmonary arterial endothelium. Treatment with recombinant human bone morphogenetic protein 9 (rhBMP9) attenuated these aspects of bleomycin‐induced pulmonary hypertension, by restoring disrupted BMP9/BMPR2/SMAD signalling. Conclusion and Implications: In bleomycin‐treated rats, early and persisting suppression of the BMP9/BMPR2/SMAD signalling pathway triggered severe loss of pulmonary arterial endothelium and subsequent pulmonary arterial vascular remodelling, contributing to the development of pulmonary hypertension. Therapeutic approaches reinforcing BMP9/BMPR2/SMAD signalling might be ideal strategies for this subtype of pulmonary hypertension. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc [ABSTRACT FROM AUTHOR]

Background and Purpose: Pulmonary veno-occlusive disease (PVOD) is a rare disease characterized by the obstruction of small pulmonary veins leading to pulmonary hypertension. However, the mechanisms underlying pulmonary vessel occlusion remain largely unclear.Experimental Approach: A mitomycin C (MMC)-induced PVOD rat model was used as in vivo animal model, and primarily cultured rat pulmonary microvascular endothelial cells (PMVECs) were used as in vitro cell model.Key Results: Our data suggested an endothelial-to-mesenchymal transition (EndoMT) may be present in the pulmonary microvessels isolated from either PVOD patients or MMC-induced PVOD rats. In comparison to the control vessels, vessels from both PVOD patients and PVOD rats had co-localized staining of specific endothelial marker von Willebrand factor (vWF) and mesenchymal marker α-smooth muscle actin (α-SMA), suggesting the presence of cells that co-express endothelial and mesenchymal markers. In both the lung tissues of MMC-induced PVOD rats and MMC-treated rat PMVECs there were decreased levels of endothelial markers (e.g. VE-cadherin and CD31) and increased mesenchymal markers (e.g. vimentin, fibronectin and α-SMA) were detected indicating EndoMT. Moreover, MMC-induced activation of the TGFβ/Smad3/Snail axis, while blocking this pathway with either selective Smad3 inhibitor (SIS3) or small interfering RNA (siRNA) against Smad3, dramatically abolished the MMC-induced EndoMT. Notably, treatment with SIS3 remarkably prevented the pathogenesis of MMC-induced PVOD in rats.Conclusions and Implications: Our data indicated that targeted inhibition of Smad3 leads to a potential, novel strategy for PVOD therapy, likely by inhibiting the EndoMT in pulmonary microvasculature. [ABSTRACT FROM AUTHOR]

N6-Methyladenosine (m6A), a pervasive posttranscriptional modification which is reversible, has been among hotspot issues in the past several years. The balance of intracellular m6A levels is dynamically maintained by methyltransferase complex and demethylases. Meanwhile, m6A reader proteins specifically recognize modified residues and convey messages so as to set up an efficient and orderly network of m6A regulation. The m6A mark has proved to affect every step of RNA life cycle, from processing in nucleus to translation or degradation in cytoplasm. Subsequently, disorders in m6A methylation are directly related to aberrant RNA metabolism, which results in tumorigenesis and altered drug response. Therefore, uncovering the underlying mechanism of m6A in oncogenic transformation and tumor progression seeks opportunities for novel targets in cancer therapy. In this review, we conclude the extensive impact of m6A on RNA metabolism and highlight its relevance with human cancer, implicating the far-reaching value in clinical application. [ABSTRACT FROM AUTHOR]