[Pollution Characteristics of Carbonaceous Components in PM10 and PM2.5 of Road Dust Fall and Soil Dust in Xi'an].

To investigate the pollution characteristics of carbonaceous components in PM10 and PM2.5 of road dust fall and soil dust in Xi'an and enrich their source profiles, samples from five sites of road dust fall and 16 sites of soil dust were collected in Xi'an from April to May 2015. The ZDA-CY01 particulate matter resuspension sampler was used to obtain PM10 and PM2.5 samples, and the Model5L-NDIR OC and EC analyzer were used to determine the concentrations of organic carbon (OC) and elemental carbon (EC) in PM10 and PM2.5. The pollution and sources of carbonaceous aerosol in PM10 and PM2.5 were investigated by analyzing OC and EC characteristics, ratio, and the principal component analysis statistical model. The results showed that the proportions of OC in PM10 and PM2.5 at the various dust fall sites differed, ranging from 6.0% to 19.4% and 7.6% to 29.8%, respectively. The ratios of EC in PM10 and PM2.5at the different dust fall sites were relatively small, accounting for 0.6%-2.2% and 0.2%-3.6% in urban sites, respectively; however, EC was almost undetectable in most peripheral soil dust. The proportions of carbonaceous components in PM10 and PM2.5 followed the order of urban road dust fall>external control dust>river beach soil dust>soil dust and urban road dust fall>soil dust>external control dust>river beach soil dust, respectively. OC dominated the carbonaceous aerosols at the different sites, which was relatively low in urban road dust fall. The OC to total carbon (TC) ratios in PM10 and PM2.5 at urban road dust fall were 85.2%-95.3% and 87.9%-98.9%, respectively. The OC to TC ratios in PM10 and PM2.5 of soil dust were relatively high, exceeding 99%. Carbonaceous components were primarily concentrated in fine particles. The pollution distribution of carbonaceous components in the urban road dust fall sites was consistent, whereas that in the different soil dust sites were quite different. The carbonaceous components in urban road dust fall and soil dust were primarily affected by pollutant source emissions such as biomass burning, coal burning, gasoline, and diesel vehicle exhaust. There were differences in the source contribution rates of carbonaceous aerosols in PM10 and PM2.5.

Echocardiographic evaluation of right heart failure which might be associated with DNA damage response in SU5416-hypoxia induced pulmonary hypertension rat model.

Right heart failure is the leading cause of death in pulmonary hypertension (PH), and echocardiography is a commonly used tool for evaluating the risk hierarchy of PH. However, few studies have explored the dynamic changes in the structural and functional changes of the right heart during the process of PH. Previous studies have found that pulmonary circulation coupling right ventricular adaptation depends on the degree of pressure overload and other factors. In this study, we performed a time-dependent evaluation of right heart functional changes using transthoracic echocardiography in a SU5416 plus hypoxia (SuHx)-induced PH rat model. Rats were examined in 1-, 2-, 4-, and 6-week using right-heart catheterization, cardiac echocardiography, and harvested heart tissue. Our study found that echocardiographic measures of the right ventricle (RV) gradually worsened with the increase of right ventricular systolic pressure, and right heart hypofunction occurred at an earlier stage than pulmonary artery thickening during the development of PH. Furthermore, sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2), a marker of myocardial damage, was highly expressed in week 2 of SuHx-induced PH and had higher levels of expression of γ-H2AX at all timepoints, as well as higher levels of DDR-related proteins p-ATM and p53/p-p53 and p21 in week 4 and week 6. Our study demonstrates that the structure and function of the RV begin to deteriorate with DNA damage and cellular senescence during the early stages of PH development.

Oral delivery of biomacromolecules by overcoming biological barriers in the gastrointestinal tract: an update.

INTRODUCTION: Biomacromolecules have proven to be an attractive choice for treating diseases due to their properties of strong specificity, high efficiency, and low toxicity. Besides greatly improving the patient's complaint, oral delivery of macromolecules also complies with hormone physiological secretion, which has become one of the most innovative fields of research in recent years. AREAS COVERED: Oral delivery biological barriers for biomacromolecule, transport mechanisms, and various administration strategies were discussed in this review, including absorption enhancers, targeting nanoparticles, mucoadhesion nanoparticles, mucus penetration nanoparticles, and intelligent bionic drug delivery systems. EXPERT OPINION: The oral delivery of biomacromolecules has important clinical implications; however, these are still facing the challenges of low bioavailability due to certain barriers. Various promising technologies have been developed to overcome the barriers and improve the therapeutic effect of oral biomacromolecules. By considering safety and efficacy comprehensively, the development of intelligent nanoparticles based on the GIT environment has demonstrated some promise in overcoming these barriers; however, a more comprehensive understanding of the oral fate of oral biomacromolecules is still required.

SARS-CoV-2 spike protein receptor-binding domain perturbates intracellular calcium homeostasis and impairs pulmonary vascular endothelial cells.

Exposure to the spike protein or receptor-binding domain (S-RBD) of SARS-CoV-2 significantly influences endothelial cells and induces pulmonary vascular endotheliopathy. In this study, angiotensin-converting enzyme 2 humanized inbred (hACE2 Tg) mice and cultured pulmonary vascular endothelial cells were used to investigate how spike protein/S-RBD impacts pulmonary vascular endothelium. Results show that S-RBD leads to acute-to-prolonged induction of the intracellular free calcium concentration ([Ca2+]i) via acute activation of TRPV4, and prolonged upregulation of mechanosensitive channel Piezo1 and store-operated calcium channel (SOCC) key component Orai1 in cultured human pulmonary arterial endothelial cells (PAECs). In mechanism, S-RBD interacts with ACE2 to induce formation of clusters involving Orai1, Piezo1 and TRPC1, facilitate the channel activation of Piezo1 and SOCC, and lead to elevated apoptosis. These effects are blocked by Kobophenol A, which inhibits the binding between S-RBD and ACE2, or intracellular calcium chelator, BAPTA-AM. Blockade of Piezo1 and SOCC by GsMTx4 effectively protects the S-RBD-induced pulmonary microvascular endothelial damage in hACE2 Tg mice via normalizing the elevated [Ca2+]i. Comparing to prototypic strain, Omicron variants (BA.5.2 and XBB) of S-RBD induces significantly less severe cell apoptosis. Transcriptomic analysis indicates that prototypic S-RBD confers more severe acute impacts than Delta or Lambda S-RBD. In summary, this study provides compelling evidence that S-RBD could induce persistent pulmonary vascular endothelial damage by binding to ACE2 and triggering [Ca2+]i through upregulation of Piezo1 and Orai1. Targeted inhibition of ACE2-Piezo1/SOCC-[Ca2+]i axis proves a powerful strategy to treat S-RBD-induced pulmonary vascular diseases.

Making contract users safer: Towards building a Safe Browsing platform on Ethereum.

There are many papers and tools regarding the detection of unsafe contracts, but few ways for detection results to practically benefit contract users and owners. This paper presents a Blockchain Safe Browsing (BSB) platform to safely disseminate those detection results. An encrypted blacklist will be generated to provide privacy preserving user warning before they make transactions with unsafe contracts. Contract owners will be notified that there are vulnerabilities in their contracts, and they can purchase related reports which record how to exploit the vulnerabilities. The profits inspire the researchers to contribute their update-to-date lists of unsafe contracts. An effective encryption scheme is developed to guarantee that only contract owners can decrypt the encrypted reports. Extensive evaluations demonstrate that our prototype can function as intended without sacrificing user experience.

[Emission Characteristics of Organic Carbon and Elemental Carbon in PM10 and PM2.5 from Vehicle Exhaust and Civil Combustion Fuels].

To study the emission characteristics of carbonaceous aerosol in particulate matter emitted from vehicle exhaust and main civil combustion fuels, organic carbon (OC) and elemental carbon (EC) in PM10 and PM2.5 samples from vehicle sources (gasoline vehicles, light duty diesel vehicles, and heavy duty diesel vehicles), civil coal (chunk coal and briquette coal), and biomass fuels (wheat straw, wood plank, and grape branches) were collected and analyzed by using a multifunctional portable dilution channel sampler and the Model 5L-NDIR OC/EC analyzer. The results showed that there were significant differences in the proportion of carbonaceous aerosols in PM10 and PM2.5from different emission sources. The proportions of total carbon (TC) in PM10 and PM2.5 of different emission sources were 40.8%-68.5% and 30.5%-70.9%, respectively, and the OC/EC were 1.49-31.56 and 1.90-87.57, respectively. The carbon components produced by different emission sources were dominated by OC, and the OC/TC values in PM10 and PM2.5 were 56.3%-97.0% and 65.0%-98.7%, respectively. The proportions of OC in carbonaceous aerosols in PM10and PM2.5 were in the descending order of:briquette coal>chunk coal>gasoline vehicle>wood plank>wheat straw>light duty diesel vehicle>heavy duty diesel vehicle and briquette coal>gasoline car>grape branches>chunk coal>light duty diesel vehicle>heavy duty diesel vehicle, respectively. The main components of carbonaceous aerosols in PM10 and PM2.5 emitted from the various emission sources were different, and source apportionment of carbonaceous aerosols could be accurately distinguished by their ingredient composition profiles.

Airway delivery of Streptococcus salivarius is sufficient to induce experimental pulmonary hypertension in rats.

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.

CSDR Coupling with Exo III for Ultrasensitive Electrochemistry Determination of miR-145.

Recently, miRNAs have become a promising biomarker for disease diagnostics. miRNA-145 is closely related to strokes. The accuracy determination of miRNA-145 (miR-145) in stroke patients still remains challenging due to its heterogeneity and low abundance, as well as the complexity of the blood matrix. In this work, we developed a novel electrochemical miRNA-145 biosensor via subtly coupling the cascade strand displacement reaction (CSDR), exonuclease III (Exo III), and magnetic nanoparticles (MNPs). The developed electrochemical biosensor can quantitatively detect miRNA-145 ranging from 1 × 102 to 1 × 106 aM with a detection limit as low down as 100 aM. This biosensor also exhibits excellent specificity to distinguish similar miRNA sequences even with single-base differences. It has been successfully applied to distinguish healthy people from stroke patients. The results of this biosensor are consistent with the results of the reverse transcription quantitative polymerase chain reaction (RT-qPCR). The proposed electrochemical biosensor has great potential applications for biomedical research on and clinical diagnosis of strokes.

SARS-CoV-2 spike protein induces IL-18-mediated cardiopulmonary inflammation via reduced mitophagy.

Cardiopulmonary complications are major drivers of mortality caused by the SARS-CoV-2 virus. Interleukin-18, an inflammasome-induced cytokine, has emerged as a novel mediator of cardiopulmonary pathologies but its regulation via SARS-CoV-2 signaling remains unknown. Based on a screening panel, IL-18 was identified amongst 19 cytokines to stratify mortality and hospitalization burden in patients hospitalized with COVID-19. Supporting clinical data, administration of SARS-CoV-2 Spike 1 (S1) glycoprotein or receptor-binding domain (RBD) proteins into human angiotensin-converting enzyme 2 (hACE2) transgenic mice induced cardiac fibrosis and dysfunction associated with higher NF-κB phosphorylation (pNF-κB) and cardiopulmonary-derived IL-18 and NLRP3 expression. IL-18 inhibition via IL-18BP resulted in decreased cardiac pNF-κB and improved cardiac fibrosis and dysfunction in S1- or RBD-exposed hACE2 mice. Through in vivo and in vitro work, both S1 and RBD proteins induced NLRP3 inflammasome and IL-18 expression by inhibiting mitophagy and increasing mitochondrial reactive oxygenation species. Enhancing mitophagy prevented Spike protein-mediated IL-18 expression. Moreover, IL-18 inhibition reduced Spike protein-mediated pNF-κB and EC permeability. Overall, the link between reduced mitophagy and inflammasome activation represents a novel mechanism during COVID-19 pathogenesis and suggests IL-18 and mitophagy as potential therapeutic targets.

Poorly Controlled Diabetes Mellitus Increases the Risk of Deaths and Castration-Resistance in Locally Advanced Prostate Cancer Patients.

The association between DM and prostate cancer progression remains controversial. Previous studies mainly focused on early stage prostate cancer patients. We aimed to study the association between DM and prostate cancer progression in locally advanced prostate cancer patients. 598 locally advanced prostate cancer patients in a top tertiary hospital in China between 2012 and 2021 were divided into three groups based on the postoperative average HbA1c level. The follow-up time is 46.96 ± 27.07 months. Three hundred and forty-eight (58.2%) were normal glucose, 175 (29.3%) were moderate glucose, and 75 (12.5%) were high glucose. Higher postoperative-average HbA1c was associated with poorer OS, PCSM, and PSA-RFS. We concluded that poorly controlled DM was correlated with poorer OS, PCSM, and PSA-RFS in locally advanced prostate cancer patients.

The Novel Lysosomal Autophagy Inhibitor (ROC-325) Ameliorates Experimental Pulmonary Hypertension.

BACKGROUND: Autophagy plays an important role in the pathogenesis of pulmonary hypertension (PH). ROC-325 is a novel small molecule lysosomal autophagy inhibitor that has more potent anticancer activity than the antimalarial drug hydroxychloroquine, the latter has been prevalently used to inhibit autophagy. Here, we sought to determine the therapeutic benefit and mechanism of action of ROC-325 in experimental PH models. METHODS AND RESULTS: Hemodynamics, echocardiography, and histology measurement showed that ROC-325 treatment prevented the development of PH, right ventricular hypertrophy, fibrosis, dysfunction, and vascular remodeling after monocrotaline and Sugen5416/hypoxia administration. ROC-325 attenuated high K+ or alveolar hypoxia-induced pulmonary vasoconstriction and enhanced endothelial-dependent relaxation in isolated pulmonary artery rings. ROC-325 treatment inhibited autophagy and enhanced endothelial nitric oxide synthase activity in lung tissues of monocrotaline-PH rats. In cultured human and rat pulmonary arterial smooth muscle cell and pulmonary arterial endothelial cell under hypoxia exposure, ROC-325 increased LC3B (light chain 3 beta) and p62 accumulation, endothelial cell nitric oxide production via phosphorylation of endothelial nitric oxide synthase (Ser1177) and dephosphorylation of endothelial nitric oxide synthase (Thr495) as well as decreased HIF (hypoxia-inducible factor)-1α and HIF-2α stabilization. CONCLUSIONS: These data indicate that ROC-325 is a promising novel agent for the treatment of PH that inhibits autophagy, downregulates HIF levels, and increases nitric oxide production.

Low-Intensity Pulsed Ultrasound Enhanced Adipose-Derived Stem Cell-Mediated Angiogenesis in the Treatment of Diabetic Erectile Dysfunction through the Piezo-ERK-VEGF Axis.

Objectives: Erectile dysfunction is a major comorbidity of diabetes. Stem cell transplantation is a promising method to treat diabetic erectile dysfunction. In this study, we evaluated whether low-intensity pulsed ultrasound (LIPUS) could enhance the efficacy of adipose-derived stem cells (ADSCs) and investigated the underlying molecular mechanism. Materials and methods. Sixty 8-week-old male Sprague-Dawley rats were randomly divided into the normal control (NC) cohort or the streptozocin-induced diabetic ED cohort, which was further subdivided into DM, ADSC, LIPUS, and ADSC+LIPUS groups. Rats in the ADSC or ADSC+LIPUS group received ADSC intracavernosal injection. Rats in the LIPUS or ADSC+LIPUS group were treated with LIPUS. The intracavernous pressure (ICP) and mean arterial pressure (MAP) were recorded at Day 28 after injection. The corpus cavernosum tissues were harvested and subjected to histologic analysis and ELISA. The effects of LIPUS on proliferation and cytokine secretion capacity of ADSCs were assessed in vitro. RNA sequencing and bioinformatic analysis were applied to predict the mechanism involved, and western blotting and ELISA were used for verification. Results: Rats in the ADSC+LIPUS group achieved significantly higher ICP and ICP/MAP ratios than those in the DM, ADSC, and LIPUS groups. In addition, the amount of cavernous endothelium and cGMP level also increased significantly in the ADSC+LIPUS group. In vitro experiments demonstrated that LIPUS promoted proliferation and cell cycle progression in ADSCs. The excretion of cytokines such as CXCL12, FGF2, and VEGF was also enhanced by LIPUS. Bioinformatic analysis based on RNA sequencing indicated that LIPUS stimulation might activate the MAPK pathway. We confirmed that LIPUS enhanced ADSC VEGF secretion through the Piezo-ERK pathway. Conclusion: LIPUS enhanced the curative effects of ADSCs on diabetic erectile dysfunction through the activation of the Piezo-ERK-VEGF pathway. ADSC transplantation combined with LIPUS could be applied as a synergistic treatment for diabetic ED.

Upregulation of mechanosensitive channel Piezo1 involved in high shear stress-induced pulmonary hypertension.

INTRODUCTION: Piezo1 is an important mechanosensitive channel implicated in vascular remodeling. However, the role of Piezo1 in different types of vascular cells during the development of pulmonary hypertension (PH) induced by high shear stress is largely unknown. MATERIALS AND METHODS: We used a rat PH model established by left pulmonary artery ligation (LPAL, for 2-5 weeks), which mimics the high flow and hemodynamic stress, to study Piezo1 contribution to pulmonary vascular remodeling. RESULTS: Right ventricular systolic pressure (RVSP), a surrogate measure for pulmonary arterial systolic pressure, and right ventricular wall thickness, a measure for right ventricular hypertrophy, were significantly increased in LPAL rats compared with Sham-control (SHAM) rats. Rats in LPAL-5w groups developed remarkable pulmonary vascular remodeling, while phenylephrine-induced contraction and acetylcholine-induced relaxation were both significantly inhibited in these rats. Upregulation of Piezo1, in association with increase in cytosolic Ca2+ concentration ([Ca2+]cyt), was observed in pulmonary arterial smooth muscle cells (PASMCs) from LPAL-2w and LPAL-5w rats in comparison to the SHAM controls. Piezo1 upregulation in PASMCs from LPAL rats was directly related to Yes-associated protein (YAP)/ TEA domain transcription factor 4 (TEAD4). Piezo1 expression was also upregulated in the whole-lung tissue of LPAL rats. The endothelial upregulation of Piezo1 was related to transcriptional regulation by RELA (p65) and lung inflammation. CONCLUSION: The upregulation of Piezo1 in both PASMCs and ECs coordinates with each other via different cell signaling pathways to cause pulmonary vascular remodeling in LPAL-PH rats, providing novel insights into the cell-type specific pathogenic roles of Piezo1 in shear stress-associated experimental PH.

Fruchterman-Reingold Hexagon Empowered Node Deployment in Wireless Sensor Network Application.

Internet of Things (IoT) and Big Data technologies are becoming increasingly significant parts of national defense and the military, as well as in the civilian usage. The proper deployment of large-scale wireless sensor network (WSN) provides the foundation for these advanced technologies. Based on the Fruchterman-Reingold graph layout, we propose the Fruchterman-Reingold Hexagon (FR-HEX) algorithm for the deployment of WSNs. By allocating edges of hexagonal topology to sensor nodes, the network forms hexagonal network topology. A comprehensive evaluation of 50 simulations is conducted, which utilizes three evaluation metrics: average moving distance, pair correlation diversion (PCD), and system coverage rate. The FR-HEX algorithm performs consistently, the WSN topologies are properly regulated, the PCD values are below 0.05, and the WSN system coverage rate reaches 94%. Simulations involving obstacles and failed nodes are carried out to explore the practical applicability of the FR-HEX algorithm. In general, the FR-HEX algorithm can take full advantage of sensors' hardware capabilities in the deployment. It may be a viable option for some IoT and Big Data applications in the near future.

Plasma-Catalytic Reforming of Naphthalene and Toluene as Biomass Tar over Honeycomb Catalysts in a Gliding Arc Reactor.

Biomass gasification is a promising and sustainable process to produce renewable and CO2-neutral syngas (H2 and CO). However, the contamination of syngas with tar is one of the major challenges to limit the deployment of biomass gasification on a commercial scale. Here, we propose a hybrid plasma-catalytic system for steam reforming of tar compounds over honeycomb-based catalysts in a gliding arc discharge (GAD) reactor. The reaction performances were evaluated using the blank substrate and coated catalytic materials (γ-Al2O3 and Ni/γ-Al2O3). Compared with the plasma alone process, introducing the honeycomb materials in GAD prolonged the residence time of reactant molecules for collision with plasma reactive species to promote their conversions. The presence of Ni/γ-Al2O3 gave the best performance with the high conversion of toluene (86.3%) and naphthalene (75.5%) and yield of H2 (35.0%) and CO (49.1%), while greatly inhibiting the formation of byproducts. The corresponding highest overall energy efficiency of 50.9 g/kWh was achieved, which was 35.4% higher than that in the plasma alone process. Characterization of the used catalyst and long-term running indicated that the honeycomb material coated with Ni/γ-Al2O3 had strong carbon resistance and excellent stability. The superior catalytic performance of Ni/γ-Al2O3 can be mainly ascribed to the large specific surface area and the in situ reduction of nickel oxide species in the reaction process, which promoted the interaction between plasma reactive species and catalysts and generated the plasma-catalysis synergy.

Porous Se@SiO2 Nanoparticles Enhance Wound Healing by ROS-PI3K/Akt Pathway in Dermal Fibroblasts and Reduce Scar Formation.

Hypertrophic scarring, which is characterized by excessive extracellular matrix deposition and abnormal fibroblast homeostasis, is an undesirable outcome of dermal wound healing. Once formed, the scar will replace the normal function of local skin, and there are few noninvasive clinical treatments that can cure it. Se@SiO2 nanoparticles were synthesized to suppress oxidative stress, which induced the presence and activation of myofibroblasts during wound recovery. The characterization, antioxidant capacity and biological safety of Se@SiO2 NPs were evaluated. A full-thickness excisional wound model was established, and the wounds were divided into three groups. The re-epithelization and distribution of collagen fibers were assessed using hematoxylin and eosin staining and Masson's trichome staining after specific treatments. Our results revealed that the Se@SiO2 NPs accelerated dermal wound healing and suppressed the formation of hypertrophic scars, accompanied by oxidative stress inhibition. Moreover, we found that Se@SiO2 NPs worked by activating the PI3K/Akt pathway and upregulating the phosphorylation of Akt. The findings of our study provide a new method to promote dermal scar-free wound healing by suppressing excessive oxidative stress and through PI3K/Akt pathway activation.

Sodium tanshinone IIA sulfonate enhances the BMP9-BMPR2-Smad1/5/9 signaling pathway in rat pulmonary microvascular endothelial cells and human embryonic stem cell-derived endothelial cells.

BACKGROUND: Recent studies have demonstrated the beneficial effects of STS in treating pulmonary hypertension by inhibiting the pulmonary vascular remodeling and suppressing the abnormally elevated proliferation and migration of PASMCs. However, the roles of STS on pulmonary vascular endothelium remain largely known. METHODS: In this study, we investigated the effects and mechanisms of STS on pulmonary vascular endothelial dysfunction by using a chronic hypoxia-induced pulmonary hypertension (HPH) rat model, as well as in primarily cultured rat PMVECs and human ESC-ECs cell models. RESULTS: Firstly, a 21-day treatment of STS significantly prevents the disease development of HPH by normalizing the right ventricular systolic pressure and right ventricular hypertrophy, improving the cardiac output. Then, STS treatment markedly inhibits the hypoxia-induced medial wall thickening of the distal intrapulmonary arteries. Notably, STS significantly inhibits the hypoxia-induced apoptosis in both the pulmonary endothelium of HPH rats and primarily cultured PMVECs, through the stabilization of BMPR2 protein and protection of the diminished BMP9-BMPR2-Smad1/5/9 signaling pathway. In mechanism, STS treatment retrieves the hypoxic downregulation of BMPR2 by stabilizing the BMPR2 protein, inhibiting the BMPR2 protein degradation via lysosome system, and promoting the plasma membrane localization of BMPR2, all of which together reinforcing the BMP9-induced signaling transduction in both PMVECs and human ESC-ECs. However, these effects are absent in hESC-ECs expressing heterozygous dysfunctional BMPR2 protein (BMPR2+/R899X). CONCLUSION: STS may exert anti-apoptotic roles, at least partially, via induction of the BMP9-BMPR2-Smad1/5/9 signaling transduction in pulmonary endothelium and PMVECs.

Established pulmonary hypertension in rats was reversed by a combination of a HIF-2α antagonist and a p53 agonist.

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.

A Novel 3D Node Deployment Inspired by Dusty Plasma Crystallization in UAV-Assisted Wireless Sensor Network Applications.

With the rapid progress of hardware and software, a wireless sensor network has been widely used in many applications in various fields. However, most discussions for the WSN node deployment mainly concentrated on the two-dimensional plane. In such a case, some large scale applications, such as information detection in deep space or deep sea, will require a good three dimensional (3D) sensor deployment scenario and also attract most scientists' interests. Excellent deployment algorithms enable sensors to be quickly deployed in designated areas with the help of unmanned aerial vehicles (UAVs). In this paper, for the first time, we present a three dimensional network deployment algorithm inspired by physical dusty plasma crystallization theory in large-scale WSN applications. Four kinds of performance evaluation methods in 3D space, such as the moving distance, the spatial distribution diversion, system coverage rate, and the system utilization are introduced and have been carefully tested.Furthermore, in order to improve the performance of the final deployment, we integrated the system coverage rate and the system utilization to analyze the parameter effects of the Debye length and the node sensing radius. This criterion attempts to find the optimal sensing radius with a fixed Debye length to maximize the sensing range of the sensor network while reducing the system redundancy. The results suggest that our 3D algorithm can quickly complete an overall 3D network deployment and then dynamically adjust parameters to achieve a better distribution. In practical applications, engineers may choose appropriate parameters based on the sensor's hardware capabilities to achieve a better 3D sensor network deployment. It may be significantly used in some large-scale 3D WSN applications in the near future.

Upregulation of Piezo1 (Piezo Type Mechanosensitive Ion Channel Component 1) Enhances the Intracellular Free Calcium in Pulmonary Arterial Smooth Muscle Cells From Idiopathic Pulmonary Arterial Hypertension Patients.

[Figure: see text].