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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.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.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 Casup2+/supconcentration ([Casup2+/sup]subcyt/sub), 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.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.

Plastid genomes (plastomes) of angiosperms are well known for their relative stability in size, structure, and gene content. However, little is known about their heredity and variations in wide crossing. To such an end, the plastomes of five representative rice backcross inbred lines (BILs) developed from crosses of O. glaberrima/O. sativa were analyzed. We found that the size of all plastomes was about 134,580 bp, with a quadripartite structure that included a pair of inverted repeat (IR) regions, a small single-copy (SSC) region and a large single-copy (LSC) region. They contained 76 protein genes, 4 rRNA genes, and 30 tRNA genes. Although their size, structure, and gene content were stable, repeat-mediated recombination, gene expression, and RNA editing were extensively changed between the maternal line and the BILs. These novel discoveries demonstrate that wide crossing causes not only nuclear genomic recombination, but also plastome variation in plants, and that the plastome plays a critical role in coordinating the nuclear–cytoplasmic interaction.

Venous cystic adventitial disease (VCAD) is a rare vascular anomaly located in the common femoral vein in most cases. We describe the case of a 59-year-old female patient with right leg edema who was misdiagnosed with deep vein thrombosis of the lower extremity at another hospital. Magnetic resonance angiography revealed a round mass in the popliteal vein, with a narrow lumen. Considering the location of the lesion, absence of a history of deep venous thrombosis and trauma, and clinical manifestations, the diagnosis is likely a popliteal vein adventitial cyst. Segmental popliteal vein resection and reconstruction were performed using a cylindrical great saphenous vein graft. No joint connection was found during the operation, and the postoperative pathology confirmed VCAD.

Aims Most crops are supplemented with selenium (Se) through the exogenous addition of inorganic Se fertilizer. There is a lack of in-depth research on organic Se fertilizers. Meanwhile, the dosage range between human Se deficiency and Se toxicity is narrow, so the Se content of agricultural products needs to be controlled within a reasonable interval. Methods Se accumulation and speciation in rice were analyzed and compared during three different growth stages (late tillering stage, initiate heading stage, and full heading stage) using three Se fertilizers: selenite, fermented Se, and potassium selenocyanoacetate (Se-AAF) via the foliar application. Results The Se content in rice sprayed with organic Se fertilizer was controlled in the relatively safe range and met the human Se supplement requirement compared to the sprayed sodium selenite, which was too high of a dose. The percentage of organic Se and protein Se in brown rice was found to be similar in all three Se fertilizers. The highest organic Se content of 91.57% was found in the grain of rice at the full heading stage by spraying Se-AAF. The main Se species in the grain was selenomethionine (SeMet), which reached 80% of the total Se. Se-methyl selenocysteine(SeMeCys) was found only in Se-AAF. The grain quality showed that all three Se fertilizers increased the consistency of gelatinization. Conclusions Appropriately delaying the spraying time and selecting organic Se fertilizer as the Se source can help to produce green and safe selenium-rich rice.

To screen and validate differential proteins as novel biomarkers in active Takayasu's arteritis (TAK).Plasma samples from 40 active, 40 inactive patients, and 40 healthy controls were collected. Protein profiles of plasma were mapped by two-dimensional gel electrophoresis. Differential protein spots were detected and identified by image analysis and mass spectrometry. Plasma concentrations of proteins were measured to validate candidate biomarkers. The area under the receiver operating characteristic (ROC) curve (AUC) of circulating plasma concentrations of candidate biomarkers were calculated to assess diagnostic value.With a total of 1507 matched gel spots, there were 170 differential expression spots between active and inactive TAK, including 139 up-regulated and 31 downregulated. Only 11 proteins could be identified by mass spectrometry. Serum amyloid A(SAA), fibrinogen, complement C4a, complement C3c, complement C4b binding protein(C4bp), recombination acting gene protein 1(RAG1), alpha-1-acid glycoprotein, alpha-1-microglobulin, complement C7, complement factor H related protein-1 were up-regulated in active patients, while serum amyloid P was down-regulated. Active patients had higher circulating levels of RAG1(P0.001), C4bp (p=0.012) and SAA (p0.001), compared to inactive patients, while inactive patients had higher levels than controls (RAG1, p=0.011; C4bp, p=0.012; SAA, p=0.005). The composite AUC with SAA, RAG1, and C4bp was 0.94 (95%CI 0.86-0.98) for discriminating activity, larger than 0.71(95% CI 0.60-0.80) for ESR (p=0.0004) or 0.75(95%CI 0.64-0.84) for CRP (p=0.0014), respectively.Some acute-phase and immunology-related proteins may serve as novel biomarkers of TAK. Further study of these proteins may be helpful to elucidate the pathologic mechanism.

The aim of the study was to review the outcomes of femoral-popliteal artery (FPA) interventions using an ultrasound (US)-guided retrograde infrapopliteal artery access after the failure of an antegrade recanalization.From Jan 2016 to Jan 2019, 37 patients with chronic total occlusion (CTO) of the FPA underwent ultrasound (US)-guided retrograde infrapopliteal artery access after failure of an antegrade procedure. Treated limbs were classified as Rutherford class 5 or 6 (29.7%) and class 4 (62.2%). Data collected included success rate and time to access using US. Immediate in-hospital and follow-up outcomes were also documented.US-guided retrograde infrapopliteal artery access was successful in 100% of the patients (anterior tibial = 11, posterior tibial = 19, Peroneal = 4, Dorsalis pedis = 3). Retrograde revascularization was achieved in all 37 patients (100%) using balloon angioplasty (17/37, 45.9%) and additional stent placement (20/37, 54.1%). Ankle-brachial index (ABI) measurements changed from 0.25 ± 0.1 preinterventionally to 0.75 ± 0.07 at 1 day postinterventionally (0.001). Minor complications occurred in 2/37 patients (5.4%) including one bleeding and vasospasm at the posterior tibial artery, both of which were treated conservatively. No patient experienced access-related thrombosis, aneurysm, compartment syndrome or death. Thirty of 37 (81%) patients completed for at least 12 months of follow-up. None of the successful revascularized patients had major or minor amputations during the follow-up period.US-guided retrograde infrapopliteal artery access is a safe and successful technique, which expands revascularization options after the failure of conventional endovascular antegrade approaches.

Emerging studies have reported the mechanosensitive Piezo1 (piezo type mechanosensitive ion channel component 1) plays essential roles in regulating the vascular tone through mechanistic actions on intracellular calcium homeostasis. However, the specific roles of Piezo1 in pulmonary vessels remain incompletely understood. We aim to investigate whether and how Piezo1 regulates the intracellular calcium homeostasis in human pulmonary arterial smooth muscle cells (PASMCs) under normal and pulmonary arterial hypertension (PAH) conditions. Cultured human PASMCs isolated from both control donors and idiopathic PAH patients were used as cell models. Fura-2 based intracellular calcium imaging was performed to measure the intracellular free calcium concentration ([Ca 2+ ] i ). Results showed that activation of Piezo1 by Yoda1 increases [Ca 2+ ] i by inducing both intracellular calcium release from internal calcium stores through the intracellular (intra-) Piezo1 localized at the subcellular organelles, including endoplasmic reticulum/sarcoplasmic reticulum, mitochondria, and nucleus; as well as extracellular calcium influx through the plasma membrane-localized Piezo1 in a mechanism independent of the store-operated calcium entry. Moreover, the Piezo1-mediated increase of [Ca 2+ ] i is linked to increased contraction and proliferation of PASMCs. Yoda1 induces dose-dependent vasocontraction in endothelium-denuded rat intrapulmonary arteries. Significant upregulation and increased activity of Piezo1 were observed in idiopathic PAH-PASMCs versus donor-PASMCs, contributing to the increased [Ca 2+ ] i and excessive proliferation of idiopathic PAH-PASMCs. In summary, Piezo1 mediates the increase of [Ca 2+ ] i by triggering both intracellular calcium release and extracellular influx. The enhanced Piezo1 expression and activity accounts, at least partially, for the abnormally elevated [Ca 2+ ] i and proliferation in idiopathic PAH-PASMCs.

Endothelial progenitor cells-released extracellular vesicles (EPCs-EVs) have previously been reported to promote the dissolution of deep venous thrombosis (DVT) through delivery of microRNA (miR). Given that, this research was projected to search the relative action of EPCs-EVs transferring of miR-136-5p in DVT.From EPCs transfected with miR-136-5p agomir or antagomir, EVs were extracted and then injected into DVT mice. Meanwhile, based on the treatment with EPCs-EVs loading miR-136-5p antagomir, silenced thioredoxin-interacting protein (TXNIP) lentivirus was injected into DVT mice to perform the rescue experiments. Afterwards, the length and weight of venous thrombosis, EPC apoptosis and inflammatory factors, plasmin, fibrinogen, and thrombin-antithrombin were measured. miR-136-5p and TXNIP expression in DVT mice, and their targeting relationship were evaluated.miR-136-5p expression was suppressed and TXNIP expression was elevated in DVT mice. EPCs-EV reduced the length and weight of venous thrombosis, suppressed cell apoptosis and inflammatory reaction, as well as elevated level of plasmin, and reduced levels of fibrinogen and thrombin-antithrombin in DVT mice. Restored miR-136-5p loaded by EPCs-EV further attenuated DVT but EPCs-EV transfer of depleted miR-136-5p resulted in the opposite consequences. miR-136-5p targeted TXNIP and silenced TXNIP rescued the effect of EPCs-EV transfer of depleted miR-136-5p on DVT.miR-136-5p from EPCs-EV suppresses TXNIP expression to reduce the thrombus size in DVT, offering a promising treatment target for DVT.

This study aimed to improve γ-aminobutyric acid (GABA) content and sensory characteristics of brown rice (BR) cake by static magnetic field (SMF)-assisted germination. BR was pre-treated by SMF (10 mT, 60 min, 25 °C), germinated for 36 h, and then germinated BR (GBR) was used to prepare rice cake. The optimal formula was: 60 % GBR, 40 % white rice, 1 % yeast, 20 % sugar, and 55 % water. SMF significantly increased the GABA content by stimulating glutamate decarboxylase, with the values increasing from 28.17 to 32.43 mg/100 g and from 2.50 to 6.27 mg/100 g in GBR (36 h) and GBR cake, respectively. SMF also altered the swelling power and water solubility of GBR flour by promoting the hydrolysis of starch, protein, and fiber, thus improving the texture, flavor, and storage stability of GBR cake. Overall, SMF could be a prospective technique for improving the nutritional and sensory qualities of whole-grain food.

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.

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.

Pulmonary hypertension (PH) is responsible for premature death caused by progressive and severe heart failure. A simple, feasible, and reproducible animal model of PH is essential for the investigation of the pathogenesis and treatment of this condition. Previous studies have demonstrated that the vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor SU5416 combined with hypoxia could establish an animal model of PH. Here, we investigated whether SU5416 itself could induce PH in rats. The effects of SU5416 treatment followed by 5 weeks of normoxia were examined. Hemodynamic measurements and histological assessments of the pulmonary vasculature and the heart were conducted to evaluate the physiological and pathophysiological characteristics of PH. Compared with the control rats, the SU5416-treated rats showed significantly increased right ventricle systolic pressure, right ventricle mass, total pulmonary vascular resistance, and total pulmonary vascular resistance index, while the cardiac output and cardiac index were substantially decreased. Moreover, the degree of occlusion and the muscularization levels of the distal small pulmonary vessels and the medial wall thickness of larger vessels (OD > 50 μm) simultaneously increased. SU5416 inhibited pulmonary vascular endothelial cell apoptosis in rats, as shown by immunostaining of cleaved caspase-3. Furthermore, changes in the right ventricle, myocardial hypertrophy, myocardial edema, myocardial necrosis, striated muscle cell atrophy, vessel muscularization, neointimal occlusion, and increased collagen deposition were observed in the SU5416 group compared with the control group. Thus, treatment with SU5416 alone plus 5 weeks of normoxia could be sufficient to induce PH in rats, which may provide a good and convenient model for future investigation of PH.

Aggregation-induced emission (AIE) molecules have been widely utilized for fluorescence imaging in many biomedical applications, benefited from large Stokes shift, high quantum yield, good biocompatibility, and resistance to photobleaching. And visualization of mitochondria is almost investigated in vitro and ex vivo, but in vivo study of mitochondria is more essential for systematic biological research, especially during embryogenesis. Therefore, suitable and time-saving alternatives with simple operation based on AIE molecules are urgently needed compared with traditional transgenic approach.Five tetraphenylethylene isoquinolinium (TPE-IQ)-based molecules with AIE characteristics and their ability of mitochondrial visualization in vitro and in vivo and mitochondrial tracking during embryogenesis on zebrafish model were investigated. The biosafety of these AIE molecules was also evaluated systematically in vitro and in vivo.All these five AIE molecules could image mitochondria in vitro with good biocompatibility. In them, TPE-IQ1 exhibited excellent imaging quality for in vivo visualization and tracking of mitochondria during the 4-day embryogenesis in zebrafish, in comparison with the conventional transgenic fluorescent protein. Furthermore, TPE-IQ1 could visualize mitochondrial damage induced by chemicals in real time on 24-h post fertilization (hpf) embryos.This study indicated TPE-IQ-based AIE molecules had the potential for mitochondrial imaging and tracking during embryogenesis and mitochondrial damage visualization in vivo.

During the past several decades, numerous studies have provided insights into biological characteristics of cancer cells and identified various hallmarks of cancer acquired in the tumorigenic processes. However, it is still challenging to image these distinctive traits of cancer to facilitate the management of patients in clinical settings. The rapidly evolving field of positron emission tomography (PET) imaging has provided opportunities to investigate cancer's biological characteristics in vivo. This article reviews the current status of PET imaging on characterizing hallmarks of cancer and discusses the future directions of PET imaging strategies facilitating in vivo cancer phenotyping.

The study aimed to explore the stimulating effect of static magnetic field (SMF) treatment on germinated brown rice (GBR) by monitoring changes in α-amylase activity and structural and functional properties of starch. Brown rice was exposed to SMF (10 mT, 60 min, 25 °C) and then germinated for 0 h -72 h at 30 °C. Compared with the control, SMF treatment improved α-amylase activity (15.2%), leading to the hydrolysis of starch into reducing sugar (8.2%) and increasing the germination rate (9.7% -158.8%), shoot length (9.1% -87.3%), root length (19.2% -110.0%), and fresh weight (0.9% -16.5%). In view of the properties of starch, SMF treatment also altered the surface microstructure, induced partial losses of birefringence, exerted no significant effect on the crystalline type, slightly increased the gelatinization temperatures, and significantly decreased the peak viscosity. This study suggested that SMF could serve as a prospective technique for GBR products processing.

Aims Most crops are supplemented with selenium (Se) through the exogenous addition of inorganic selenium fertilizer. There is a lack of in-depth research on organic selenium fertilizers. Meanwhile, the dosage range between human selenium deficiency and selenium toxicity is narrow, so the selenium content of agricultural products needs to be controlled within a reasonable interval. Methods W e analyzed and compared the Se accumulation and speciation in rice during three different growth stages (late tillering stage, initiate heading stage, and full heading stage) using three selenium fertilizers, selenite, fermented Se, and potassium Selenocyanoacetate (Se-AAF) via the foliar application. Results The selenium content in rice sprayed with organic selenium fertilizer was controlled in the relatively safe range and met the human selenium supplement requirement compared to the sprayed sodium selenite, which was too high of a dose. The percentage of organic Se and protein Se in brown rice was found to be similar in all three Se fertilizers. The highest organic selenium content of 91.57% was found in the grain of rice at the full heading stage by spraying Se-AAF. The main Se species in the grain was selenomethionine (SeMet), which reached 80% of the total selenium. Se-methyl selenocysteine(SeMeCys) was found only in Se-AAF. The grain quality showed that all three Se fertilizers increased the consistency of gelatinization. Conclusions Appropriately delaying the spraying time and selecting organic Se fertilizer as the Se source can help to produce green and safe selenium-rich rice.

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.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.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 (BMPR2STS may exert anti-apoptotic roles, at least partially, via induction of the BMP9-BMPR2-Smad1/5/9 signaling transduction in pulmonary endothelium and PMVECs.

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.

Nitrogen (N) is an essential nutrient for plant growth and development. The root system architecture is a highly regulated morphological system, which is sensitive to the availability of nutrients, such as N. Phenotypic characterization of roots from LY9348 (a rice variety with high nitrogen use efficiency (NUE)) treated with 0.725 mM NH4NO3 (1/4N) was remarkable, especially primary root (PR) elongation, which was the highest. A comprehensive analysis was performed for transcriptome and proteome profiling of LY9348 roots between 1/4N and 2.9 mM NH4NO3 (1N) treatments. The results indicated 3908 differential expression genes (DEGs, 2569 upregulated and 1339 downregulated) and 411 differential abundance proteins (DAPs, 192 upregulated and 219 downregulated). Among all DAPs in the proteome, glutamine synthetase (GS2), a chloroplastic ammonium assimilation protein, was the most upregulated protein identified. The unexpected concentration of GS2 from the shoot to the root in the 1/4N treatment indicated that the presence of an alternative pathway of N assimilation regulated by GS2 in LY9348 corresponded to the low N signal, which was supported by GS enzyme activity and glutamine/glutamate (Gln/Glu) contents analysis. In addition, N transporters (NRT2.1, NRT2.2, NRT2.3, NRT2.4, NAR2.1, AMT1.3, AMT1.2, and putative AMT3.3) and N assimilators (NR2, GS1, 1,&nbsp, GS1, 2,&nbsp, 3, NADH-GOGAT2, and AS2) were significantly induced during the long-term N-deficiency response at the transcription level (14 days). Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that phenylpropanoid biosynthesis and glutathione metabolism were significantly modulated by N deficiency. Notably, many transcription factors and plant hormones were found to participate in root morphological adaptation. In conclusion, our study provides valuable information to further understand the response of rice roots to N-deficiency stress.

Sulfate transporters (SULTRs), also known as H+/SO42− symporters, play a key role in sulfate transport, plant growth and stress responses. However, the evolutionary relationships and functional differentiation of SULTRs in Gramineae crops are rarely reported. Here, 111 SULTRs were retrieved from the genomes of 10 Gramineae species, including Brachypodium disachyon, Hordeum vulgare, Setaria italica, Sorghum bicolor, Zea mays, Oryza barthii, Oryza rufipogon, Oryza glabbermia and Oryza sativa (Oryza sativa ssp. indica and Oryza sativa ssp. japonica). The SULTRs were clustered into five clades based on a phylogenetic analysis. Syntheny analysis indicates that whole-genome duplication/segmental duplication and tandem duplication events were essential in the SULTRs family expansion. We further found that different clades and orthologous groups of SULTRs were under a strong purifying selective force. Expression analysis showed that rice SULTRs with high-affinity transporters are associated with the functions of sulfate uptake and transport during rice seedling development. Furthermore, using Oryza sativa ssp. indica as a model species, we found that OsiSULTR10 was significantly upregulated under salt stress, while OsiSULTR3 and OsiSULTR12 showed remarkable upregulation under high temperature, low-selenium and drought stresses. OsiSULTR3 and OsiSULTR9 were upregulated under both low-selenium and high-selenium stresses. This study illustrates the expression and evolutionary patterns of the SULTRs family in Gramineae species, which will facilitate further studies of SULTR in other Gramineae species.

Coronavirus disease 2019 (COVID-19) has become a major public health problem worldwide since its outbreak in 2019. Currently, the spread of COVID-19 is far from over, and various complications have roused increasing awareness of the public, calling for novel techniques to aid at diagnosis and treatment. Based on the principle of molecular imaging, positron emission tomography (PET) is expected to offer pathophysiological alternations of COVID-19 in the molecular/cellular perspectives and facilitate the clinical management of patients. A number of PET-related cases and research have been reported on COVID-19 over the past one year. This article reviews the current studies of PET in the diagnosis and treatment of COVID-19, and discusses potential applications of PET in the development of management strategy for COVID-19 patients in the pandemic era.

Alteration in microbiota composition of respiratory tract has been reported in the progression of many chronic lung diseases, yet, the correlation and causal link between respiratory tract microbiota and the disease development of pulmonary hypertension (PH) remain largely unknown. This study aims to define and compare the respiratory microbiota composition in pharyngeal swab samples between patients with PH and reference subjects. A total of 118 patients with PH and 79 reference subjects were recruited, and the pharyngeal swab samples were collected to sequence the 16S ribosomal RNA (16S rRNA) V3-V4 region of respiratory microbiome. The relative abundances in patients with PH were profoundly different from reference subjects. The Ace and Sobs indexes indicated that the microbiota richness of pharynx value is significantly higher; while the community diversity value is markedly lower in patients with PH, comparing to those of the reference subjects. The microbiota on pharynx showed a different profile between the 2 groups by principal component analysis. The linear discriminant analysis effect size also revealed a significantly higher proportion of Streptococcus , Lautropia , and Ralstonia in patients with PH than reference subjects. The linear discriminant analysis effect size output, which represents the microbial gene functions, suggest genes related to bacterial invasion of epithelial cells, bacterial toxins were enhanced, while genes related to energy metabolism, protein digestion and absorption, and cell division pathways were attenuated in patients with PH versus reference subjects. In summary, our study reports the first systematic definition and divergent profile of the upper respiratory tract microbiota between patients with PH and reference subjects.

Background The iliac occlusive disease is usually treated with endovascular procedures in recent years. The effectiveness of different crossing approaches for these occlusions is not precisely known. We performed a retrospective study to explore the optimal crossing approach (antegrade versus retrograde) for iliac artery chronic total occlusions (CTOs) and to examine the long-term outcomes. Materials and methods We performed a study on 107 patients (116 iliac occlusive lesions, mean age 64.0 ± 11.1, 88 men) who underwent an iliac CTO endovascular intervention attempted with the use of both crossing strategies but were managed with one final crossing approach between August 2012 and August 2018. Baseline data, procedural characteristics, and outcomes were described. A Cox proportional hazard model and Kaplan-Meier method were developed to assess the differences in the two crossing approaches in terms of the 1-year and 5-year primary patency rates, target lesion revascularization (TLR) and major adverse limb events (MALEs). Results Common iliac artery (CIA) lesions were more likely to be crossed successfully in the retrograde direction (6.8% for antegrade vs. 20.9% for retrograde, p = 0.005), while lesions in the CIA/ external iliac artery (EIA) were more prone to be crossed successfully in the antegrade direction (58.9% for antegrade vs. 39.5% for retrograde, p = 0.016). There were no significant differences in the crossing approach for EIA lesions between the two groups. The two crossing approaches were associated with similar estimates of 1- and 5-year primary patency, TLR and MALE rates. Conclusion The antegrade approach was associated with a higher rate of successful crossing in CIA/EIA CTO lesions, while the CIA-only CTOs were more likely to be crossed successfully with the retrograde approach.

Purpose To explore the optimal crossing approach (antegrade versus retrograde) for iliac artery chronic total occlusions (CTOs) and to examine the long-term outcomes. Materials and Methods We performed a study on 107 patients (116 iliac occlusive lesions, mean age 64.0±11.1, 88 men) who underwent an iliac CTO endovascular intervention attempted with the use of both crossing strategies but were managed with one final crossing approach between August 2012 and August 2018. Baseline data, procedural characteristics, and outcomes were described. A Cox proportional hazard model and Kaplan-Meier method were developed to assess the differences in the two crossing approaches in terms of the 1-year and 5-year primary patency rates, TLR (target lesion revascularization) and MALEs (major adverse limb events). Results CIA (common iliac artery) lesions were more likely to be crossed successfully in the retrograde direction (6.8% for antegrade vs. 20.9% for retrograde, p=0.005), while lesions in the CIA/EIA (external iliac artery) were more prone to be crossed successfully in the antegrade direction (58.9% for antegrade vs. 39.5% for retrograde, p=0.016). Considering EIA lesions, there were no significant differences in the crossing approach between the two groups. The two crossing approaches were associated with similar estimates of 1- and 5-year primary patency, TLR and MALE rates. Conclusion The antegrade approach was associated with a higher rate of successful crossing in CIA/EIA CTO lesions, while the CIA-only CTOs were more likely to be crossed successfully with the retrograde approach.

Iliac vein compression (IVC) is a common condition in patients with varicose veins (VVs) of the legs. IVC has been classified into three grades in previous studies. Grade II IVC is defined by50% stenosis without the development of collateral circulation. The purpose of the present study was to investigate the outcomes of radiofrequency ablation (RFA) for patients with VVs combined with grade II IVC.A retrospective analysis was conducted of 339 patients who had undergone RFA for VVs of the left leg from March 2017 to January 2019. Duplex ultrasonography, computed tomography venography, and venography were performed to evaluate for grade II IVC. All the patients were divided into two groups. Group 1 included patients with VVs only, and group 2, patients with VVs combined with grade II IVC. Propensity score matching was used to ensure an even distribution of confounding factors between groups. The venous clinical severity score (VCSS) and chronic venous insufficiency questionnaire (CIVIQ) score were recorded during the 12-month follow-up. Occlusion of the truncal veins was evaluated using duplex ultrasound scans.Using 1:1 propensity score matching, 50 pairs of patients were enrolled in the present analysis. The average age of groups 1 and 2 was 58.7 ± 13.1 and 60.1 ± 7.1 years, respectively. The VCSS had decreased significantly from baseline to 12 months postoperatively (group 1, from 5 to 1; group 2, from 4 to 1; P .01). A significant increase in the CIVIQ score was found between the baseline and 12-month evaluations for both groups (group 1, from 62.5 to 69; group 2, from 63 to 70; P .01). The truncal occlusion rate was 98% in both groups at 12 months. No significant differences were found between the two groups in the VCSS, CIVIQ score, procedure complications, or occlusion rate during the 12-month follow-up.RFA is effective for patients with VVs combined with grade II IVC.

Additional file 10: Table S1. Summary of sequencing nuclear genomes by Illumina. Table S2. Summary of sequencing mitogenomes by Illumina. Table S3. Summary of sequencing mitogenomes by PacBio. Table S4. Multi-copy genes in mitogenomes of the BIL lines. Table S5. Rearrangement types and recombination manners in BIL mitogenomes. Table S6. Variation of some representative gene clusters in mitogenome of BIL lines. Table S7. Special mitogenome sequences in 93–11. Table S8. Homologous region boundaries of BIL lines relative to O. glaberrima. Table S9. All repeats detected in O. glaberrima mitogenome. Table S10. Category of multi-copy repeats in O. glaberrima mitogenome. Table S11. RNA editing events detected in mitochondria of BIL lines. Table S12. Confirmation of RNA editing using Sanger sequencing

For decades, stem cell therapies for pulmonary hypertension (PH) have progressed from laboratory hypothesis to clinical practice. Promising preclinical investigations have laid both a theoretical and practical foundation for clinical application of mesenchymal stem cells (MSCs) for PH therapy. However, the underlying mechanisms are still poorly understood. We sought to study the effects and mechanisms of MSCs on the treatment of PH. For in vivo experiments, the transplanted GFP(+) MSCs were traced at different time points in the lung tissue of a chronic hypoxia–induced PH (CHPH) rat model. The effects of MSCs on PH pathogenesis were evaluated in both CHPH and sugen hypoxia–induced PH models. For in vitro experiments, primary pulmonary microvascular endothelial cells were cultured and treated with the MSC conditioned medium. The specific markers of endothelial-to-mesenchymal transition (EndMT) and cell migration properties were measured. MSCs decreased pulmonary arterial pressure and ameliorated the collagen deposition, and reduced the thickening and muscularization in both CHPH and sugen hypoxia–induced PH rat models. Then, MSCs significantly attenuated the hypoxia-induced EndMT in both the lungs of PH models and primary cultured rat pulmonary microvascular endothelial cells, as reflected by increased mesenchymal cell markers (fibronectin 1 and vimentin) and decreased endothelial cell markers (vascular endothelial cadherin and platelet endothelial cell adhesion molecule-1). Moreover, MSCs also markedly inhibited the protein expression and degradation of hypoxia-inducible factor-2α, which is known to trigger EndMT progression. Our data suggest that MSCs successfully prevent PH by ameliorating pulmonary vascular remodeling, inflammation, and EndMT. Transplantation of MSCs could potentially be a powerful therapeutic approach against PH.

NEW FINDINGS What is the central question of this study? In this study, by using motor vehicle exhaust (MVE) exposure with or without lipopolysaccharide (LPS) instillation, we established, evaluated and compared MVE, LPS and MVE+LPS treatment-induced chronic obstructive pulmonary disease (COPD) models in mice. What is the main finding and its importance? Our study demonstrated that the combination of chronic exposure to MVE with early LPS instillation can establish a mouse model with some features of COPD, which will allow researchers to investigate the underlying molecular mechanisms linking air pollution and COPD pathogenesis. ABSTRACT Although it is well established that motor vehicle exhaust (MVE) has a close association with the occurrence and exacerbation of chronic obstructive pulmonary disease (COPD), very little is known about the combined effects of MVE and intermittent or chronic subclinical inflammation on COPD pathogenesis. Therefore, given the crucial role of inflammation in the development of COPD, we wanted to establish an animal model of COPD using both MVE exposure and airway inflammation, which could mimic the clinical pathological changes observed in COPD patients and greatly benefit the study of the molecular mechanisms of COPD. In the present study, we report that mice undergoing chronic exposure to MVE and intratracheal instillation of lipopolysaccharide (LPS) successfully established COPD, as characterized by persistent air flow limitation, airway inflammation, inflammatory cytokine production, emphysema and small airway remodelling. Moreover, the mice showed significant changes in ventricular and vascular pathology, including an increase in right ventricular pressure, right ventricular hypertrophy and remodelling of pulmonary arterial walls. We have thus established a new mouse COPD model by combining chronic MVE exposure with early intratracheal instillation of LPS, which will allow us to study the relationship between air pollution and the development of COPD and to investigate the underlying molecular mechanisms.

Background We sought to compare the effects of clopidogrel combined with warfarin with clopidogrel alone in the prevention of restenosis after endovascular treatment (EVT) of the femoropopliteal artery. Methods Between June 2008 and May 2009, 88 consecutive patients referred for EVT were randomly divided into a clopidogrel group (42 cases) and a clopidogrel combined with warfarin group (46 cases) before the procedure. Examinations including staging of peripheral arterial disease by Rutherford, ankle-brachial index, and color duplex ultrasonography were performed at baseline, 1 week, 3 months, 6 months, and 12 months after procedure. At the same time, bleeding complications were observed. Results Fifty patients (63 limbs) were included after 12 months of follow-up, in which 25 patients (30 limbs) were from the clopidogrel group and 25 patients (33 limbs) were from the combination group. At 3 months, the rates of restenosis on duplex ultrasonography were 17% in the clopidogrel group and 18% in the combination group ( P = 1.0). At 6 months, the accumulated restenosis rates were 37% and 36% ( P = 0.98), respectively. At 12 months, the accumulated restenosis rates were 53% and 42% ( P = 0.523), respectively. The rate of clinical bleeding events was 21% (6/29) in the combination group compared with 7% (2/27) in the clopidogrel group, and there was no statistical difference ( P = 0.3). Conclusions The combination of clopidogrel with warfarin was not more effective than clopidogrel alone in restenosis prevention for patients who underwent EVT. Instead, the combination of antiplatelet and anticoagulation therapy was inclined to increase the clinical bleeding events.

ObjectiveTakayasu arteritis (TA) is an autoimmune disease with an unclear etiology and pathophysiology. An antibody-mediated inflammatory response is a known feature of this disease, however, the role of circulating B-lymphocyte production of such antibodies is not known. The objective of this study is to characterize in vitro production of autoimmune antibodies by B-lymphocytes from patients with TA and to examine differences related to disease activity.MethodsPeripheral blood samples were taken from 72 patients with TA and 50 age-matched controls. Among the patients with TA, 42 had active disease while 31 had inactive disease. The Sharma modified criteria were used for diagnosis, and the National Institutes of Health criteria were used for TA activity assessment. Levels of autoantibodies in culture supernatant of circulating B-lymphocytes, including anti-endothelial cell antibody (AECA), anti-cardiolipin antibody (ACA), anti-beta2 glycoprotein-I antibody (aβ2GPI), and anti-annexin V antibody (AAVA), were assayed by enzyme-linked immunosorbent assay (ELISA) in each participant.ResultsIn vitro levels of AECA, ACA, aβ2GPI, and AAVA from circulating B-lymphocytes were significantly increased in TA patients compared with controls (AECA: 0.6 ± 0.36 vs 0.18 ± 0.09, P < .001; ACA: 0.69 ± 0.22 vs 0.54 ± 0.13, P < .001; aβ2GPI: 0.99 ± 0.19 vs 0.83 ± 0.07, P< .001; AAVA: 0.62 ± 0.26 vs 0.41 ± 0.44, P < .001). In vitro levels of AECA, ACA, and AAVA from circulating B-lymphocytes in active TA were higher than those in inactive TA (AECA: 0.85 ± 0.29 vs 0.28 ± 0.10, P < .001; ACA: 0.79 ± 0.21 vs 0.56 ± 0.15, P < .001; AAVA: 0.82 ± 0.16 vs 0.36 ± 0.06, P < .001). No difference was found in the in vitro level of aβ2GPI between active TA and inactive TA (1.01 ± 0.17 vs 0.96 ± 0.22, P = .115). In vitro levels of AECA, ACA, and AAVA from circulating B-lymphocytes in inactive TA showed no statistic difference with those in controls (AECA: 0.28 ± 0.10 vs 0.18 ± 0.09, P = .096; ACA: 0.56 ± 0.15 vs 0.54 ± 0.13, P = .699; AAVA: 0.36 ± 0.06 vs 0.41 ± 0.44, P = .200). In vitro levels of aβ2GPI in inactive TA were higher than those in controls (0.96 ± 0.22 vs 0.83 ± 0.07, P < .001).ConclusionsThis study characterizes in vitro production of autoantibodies by circulating B-lymphocytes from patients with TA. Differences in production from those with active versus inactive disease suggest that phenotypic alterations in this cell type may play an important role in pathogenesis.Clinical RelevanceTakayasu arteritis (TA) is a rare and autoimmune vasculitis with unclear pathogenesis. It has a high incidence in young females in Asia and Africa. The natural course of TA consists of an active phase and an inactive phase, which reflects the different inflammatory states of the arterial lesions. In the active phase, immunosuppressive and cytotoxic agents are usually used to control the inflammation development, release the symptoms, and restrict the extent of affected arteries. The treatment aim of the inactive phase is to avoid the disease activity, and if necessary, it is preferable to perform vascular reconstructive operations or endovascular interventions. It is very important that an effective therapy should be found to shorten the active phase of TA and lengthen the inactive stage, which can not only perform the surgery operation as early as possible, but also reduce inflammatory injury of arteries. In recent years, we have been working on the diagnosis and surgical treatment of TA. Our advance study, “Circulation levels of acute phase proteins in patients with Takayasu arteritis” published in “J Vasc Surg 2010;51:700-6”, contributed to the judgment of disease phase and showed the pivotal role of B cells and humoral immunity in TA.In this study, we found that circulating B-lymphocytes, producing autoantibodies to endothelial cells, played an important role in the pathogenesis of TA. It means that part/all of the circulating B-lymphocytes in TA patients can be activated and excrete autoantibodies to endothelial cells. If these abnormal circulating B-lymphocytes can be differentiated and separated from peripheral blood, the active phase could be shorten, the inactive stage could be lengthened, the disease could even be prevented. It might lessen the autoimmune injury of artery wall, lower the difficulty of the operation and shorten the time which TA patients should wait for vascular reconstructive operations or endovascular repair. Therefore, we regarded this study as a foundation of B-cell depletion therapy and/or immunological tolerance therapy for TA. The feasible therapeutic methods will be explored in our future research.

To identify the risk factors associated with the severity of pulmonary embolism among patients with deep venous thrombosis of lower extremities.This prospective study enrolled 208 patients with acute deep venous thrombosis to screen for pulmonary embolism between July 2010 and July 2012 in Beijing Shijitan Hospital. There were 101 male and 107 female patients, with a mean age of (59 ± 16) years. Gender, age, extension, side of lower extremities of deep venous thrombosis was analyzed by χ² test. Ordinal Logistic regression was used to determine risk factors associated with severity of pulmonary embolism.There were 83 patients with iliofemoral deep venous thrombosis, 102 patients with femoropopliteal and 23 patients with calf deep venous thrombosis. Pulmonary embolism was detected in 70 patients with the incidence of 33.7%. Pulmonary embolism was significantly correlated with extension (χ² = 17.286, P = 0.004) and sides (χ² = 15.602, P = 0.008) of deep venous thrombosis, not with age (χ² = 7.099, P = 0.260), gender (χ² = 7.014, P = 0.067), thrombotic risk factors (χ² = 3.335, P = 0.345) in univariate analysis. Results of multivariate ordinal logistic regression showed that iliofemoral vein thrombosis (OR = 6.172, 95% CI: 1.590 to 23.975, P = 0.009) and bilateral venous thrombosis (OR = 7.140, 95% CI: 2.406 to 24.730, P = 0.001) are associated with more serious pulmonary embolism.Incidence of pulmonary embolism is still high in patients with deep venous thrombosis. Extensive iliofemoral and bilateral vein thrombosis may increase risk of severity of pulmonary embolism. Clinicians should pay more attention to these high-risk patients.

Our aim was to describe the technical aspects and clinical outcomes of an open surgical approach to retrograde transtibial endovascular therapy for recanalization of chronic total occlusions (CTOs) of peripheral arteries because of inability to acquire antegrade intravascular access across the occlusion. Between January 2011 and May 2014, conventional antegrade revascularization failed in 15 limbs of 15 patients (11 males, 4 females) with complex CTOs. The mean age of the patients was 74 years (range 48–83 years). Five patients had severe claudication (Rutherford Category 3), and 10 patients had critical limb-threatening ischemia (Rutherford Categories 4–5). For each of these cases of antegrade failure, an open surgical exposure of the tibial or dorsalis pedis artery was used to allow a safe retrograde transtibial endovascular approach to recanalize the CTO. Surgical retrograde access from the tibial artery was achieved successfully in 14 of the 15 patients. In the 14 successful retrograde endovascular approaches, surgical retrograde transtibial access was achieved from the dorsalis pedis artery in 8 patients and from the posterior tibial artery in 6. The average time to obtain retrograde access was 5 min (range 2–11 min). No stenosis or occlusion occurred in the tibial or dorsalis pedis arteries used for the retrograde access sites during follow-up. Routine surgical exposure can be a safe and an effective method for retrograde transtibial access to the more proximal occluded arterial segments in selected patients with CTO.

Thrombolysis is an appropriate treatment for acute arterial occlusion. There remains controversy as to whether thrombolysis before angioplasty helps to identify the underlying lesion and improve results for chronic ischemia of the lower extremity. We sought to investigate the feasibility of catheter-directed thrombolysis-assisted angioplasty for chronic lower limb ischemia.Between July 2008 and December 2009, the data of patients with chronic lower limb ischemia undergoing catheter-directed thrombolysis-assisted angioplasty were retrospectively analyzed.Twenty consecutive patients (18 men with a mean age of 56.35 ± 8.5 years) underwent thrombolysis-assisted angioplasty for occlusion of a native artery (n = 18) or bypass graft (n = 2). The median duration of symptoms was 19 months (range: 3-48 months). Symptoms included disabling claudication in 12 patients, rest pain in 5 patients, and gangrene of the toes in 3 patients. Urokinase or recombinant tissue plasminogen activator as a thrombolytic agent was used before angioplasty. The mean length of occlusive lesions decreased significantly from 150 mm to 30 mm after thrombolysis (P0.01). Four patients had no change in their lesions. Improvement of Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) classification was achieved in 16 patients, with 14 TASC IIA lesions and 2 TASC IIB lesions after thrombolysis. Subsequent stenting was successfully performed in all patients. The ankle-brachial index increased significantly from 0.33 to 0.63 (P0.01). No perioperative deaths occurred. Morbidity included access site bleeding in 1 patient and distal embolization in 2 patients without further intervention. The primary patency rate at 1 year was 95%, with a median follow-up time of 19 months.Catheter-directed thrombolysis-assisted angioplasty is a safe and effective treatment in some patients with chronic lower limb ischemia. It may reduce the magnitude of the lesion and simplify the expected intervention procedures.

Purpose. A novel technique using the reversed iliac leg of a Zenith device has been reported. This study reports a complicated isolated iliac artery aneurysm (IIAA) using this novel technique and reviews the relative literature to discuss current treatment modalities. Case report. A 46-year-old man presented with a mass in the left lower quadrant accompanied by abdominal pain for 60 days. Computer tomography angiography (CTA) revealed a complicated IIAA and a massive retroperitoneal hematoma. Percutaneous puncture and drainage at the hematoma was done. Enterococcus faecium was isolated from the hematoma. The infection was controlled after 2 weeks of drainage and anti-infection treatment. The IIAAs were successfully excluded using the novel technique. The 12-month CTA follow-up was unremarkable. Conclusion. Using inverted Zenith device legs is safe and effective even in complicated IIAAs. Further studies are warranted before it can become a widely acceptable definitive treatment option.

The longest launching range is a very important index for the ground test of missile, which need optimal methods to design multi-disciplines such as engine, aerodynamic and control synchronously. Firstly, supposed that parameters of aerodynamic and engine have been fixed, so short periodic flight quality is analyzed according to flight equations, and root locus method is used to design controller parameters of missile. Secondly, genetic algorithm (GA) is utilized to optimize pitch angle command. Lastly, different launching ranges due to different disturbances are analyzed with simulation results, and the most distinct influence is pointed out at different flight stages, so dynamic analysis of missile can be achieved.