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Mangrove-derived actinobacteria strains are well-known for producing novel secondary metabolites. The polycyclic tetramate macrolactam (PTM), ikarugamycin (IKA) isolated from Streptomyces xiamenensis 318, exhibits antiproliferative activities against pancreatic ductal adenocarcinoma (PDAC) in vitro. However, the protein target for bioactive IKA is unclear. In this study, whole transcriptome-based profiling revealed that the glycolysis pathway is significantly affected by IKA. Metabolomic studies demonstrated that IKA treatment induces a significant drop in glucose-6-phosphate and a slight increase in intracellular glucose level. Analysis of glucose consumption, lactate production, and the extracellular acidification rate confirmed the inhibitory role of IKA on the glycolytic flux in PDAC cells. Surface plasmon resonance (SPR) experiments and docking studies identified the key enzyme of glycolysis, hexokinase 2 (HK2), as a molecular target of IKA. Moreover, IKA reduced tumor size without overt cytotoxicity in mice with PDAC xenografts and increased chemotherapy response to gemcitabine in PDAC cells in vitro. Taken together, IKA can block glycolysis in pancreatic cancer by targeting HK2, which may be a potential drug candidate for PDAC treatment.

The eyeball distortions caused by eye diseases, such as myopia and strabismus, can lead to the deviations of eye-tracking data. In this paper, a model-based method with geometric solutions is proposed for gaze correction. The deviations of estimated gaze points are geometrically analyzed based on the individual eyeball models with considerations of the distortions caused by myopia and strabismus. A set of integrated geometric solutions is derived from the varied situations including the case of strabismus and the case of myopia and strabismus, and then used for gaze correction in eyetracking. The experimental results demonstrate that this model-based method is effective to reduce deviations in estimated gaze points, and can be used to correct the modeling error in eye-tracking. Moreover, the proposed method has the potential to provide a simple approach to correct the eyetracking data for various populations with eye diseases.

Objective To compare outcomes between intensivist-directed and cardiac surgeon-directed care delivery models. Design This retrospective, historical-control study was performed in a cohort of adult cardiac surgical patients at Zhongshan Hospital (Fudan University, China). During the first phase (March to August 2015), cardiac surgeons were in charge of postoperative care while intensivists were in charge during the second phase (September 2015–June 2016). Both phases were compared regarding successful extubation rate, intensive care unit (ICU) length of stay (LOS), and in-hospital mortality. Setting Tertiary Zhongshan Hospital (Fudan University, China). Patients Consecutive adult patients admitted to the cardiac surgical ICU (CSICU) after heart surgery. Interventions Phase I patients treated by cardiac surgeons, and phase II patients treated by intensivists. Main variables of interest Successful extubation, ICU LOS and in-hospital mortality. Results A total of 1792 (phase I) and 3007 patients (phase II) were enrolled. Most variables did not differ significantly between the two phases. However, patients in phase II had a higher successful extubation rate (99.17% vs. 98.55%; p = 0.043) and a shorter median duration of mechanical ventilation (MV) (18 vs. 19 h; p 48 h, those in phase II had a comparatively higher successful extubation rate (p = 0.033), shorter ICU LOS (p = 0.038) and a significant decrease in in-hospital mortality (p = 0.039). Conclusions The intensivist-directed care model showed improved rates of successful extubation and shorter MV durations after cardiac surgery.

In solving Bayesian inverse problems, it is often desirable to use a common density parameterization to characterize the prior and posterior. Typically, we seek an optimal approximation of the true posterior from the same distribution family as the prior. As one of the most important classes of distributions in statistics, the exponential family is considered as the parameterization. The optimal parameter values for representing the approximated posterior are achieved by minimizing the deviation between the parameterized density and a homotopy that deforms the prior density into the posterior density. Instead of the usual moment parameters, we introduce a new parameter system in the process, by which we reduce the dimension of the parameter and therefore the computational cost. The parameters are ruled by a system of explicit first-order differential equations. Solving this system over finite “time” interval yields the desired optimal density parameters. This method is proven to be effective using some numerical examples.

We prepared a series of highly porous Polyrotaxane/sodium alginate, and Polyrotaxane/Chitosan foam alloys according to a sustainable pathway by using water as the only solvent. The foam alloys were further used as supporter materials for poly (ethylene glycol) (PEG) encapsulation, to fabricate shape-stable bio-based phase change materials (PCMs). The pore morphology and the internal interface between PEG and foam alloys were characterized by scanning electron microscope (SEM). Due to the good compatibility between foam alloys and PEG, the PCM performed perfect anti-leakage properties. The introduction of sodium alginate or Chitosan ensures the shape stability of the PCMs during the phase transition. The PCMs performed good cycle stability and showed ultra-high latent heat (171.6 J g−1–189.5 J g−1). Finally, we compared the typical indicators of this work with those reported in the literature, and the comparison highlighted that the present PCMs have the significant advantages: high melting enthalpy, convenient preparation and outstanding sustainability. Notably, the work provided a sustainable idea for the design of anti-leakage and shape-stable PEG-based PCMs. pre-print 1327 KB

With the improvement of people's living level, smart home and comfortable life put forward novel and highly scientific requirements for building materials and home environment. Environmental protection, renewability, processing convenience and use safety (non-toxic/fire safety) are all core indicators that need to be considered in an all-round way in the process of material design. In this work, we used a simple and efficient green process by blending ammonium polyphosphate (APP) and poly (glycerol-itaconic acid) loaded polyethylene glycol (PEG) to prepare fire safe phase change materials (PCMs). The flame retardancy, phase change performance and thermal response behavior (including form stability, thermal conductivity, cycle stability, and latent heat etc.) were systematically characterized. The results showed that limiting oxygen index (LOI) increased significantly with the increase of APP content. Typically, when the filling amount of APP reached 15 wt%, the LOI value increased from 21.6% to 28.7%, vertical testing reached UL-94 V0 rating and the pHRR decreased by 36.15%. The as-prepared PCMs show excellent form stability, and the enthalpy of phase change keeps higher than 70 J g−1, which is at the high level as that of same kinds of PCMs. Notably, due to its high preparation efficiency for PCM fabrication and the profiles of all bio-based supporting matrix, solvent-free pathway, mild curing temperature, and fire safety, it is expected to be effectively applied in building for the thermal regulation. pre-print 1269 KB

Background: Melanin concentrating hormone (MCH), an orexigenic neuropeptide, is primarily secreted by the hypothalamus and acts at its receptor, the melanin-concentrating hormone receptor 1 (MCHR1), to regulate energy homeostasis and body weight. The Melanocortin Receptor Accessory Protein 2 (MRAP2), a small single transmembrane protein broadly expressed in multiple tissues, has been defined as a vital endocrine pivot of five melanocortin receptors (MC1R-MC5R) and several other GPCRs in the regulation of central neuronal appetite and peripheral energy homeostasis. However, the regulatory and relationship between MCHR1 and MRAP2 is unknown.Results: In this study, we show that MRAP2 interacts with MCHR1 and suppresses MCHR1 signaling in vitro. We also identified the C-terminal domains of MRAP2 protein required for pharmacological modulation of intracellular Ca2+ cascades and membrane transport. Conclusions: These findings elucidated the broad regulatory profile of MRAP2 protein in the central nervous system and may provide implications for the modulation of central MCHR1 function in vivo.

As a member of the seven-transmembrane rhodopsin-like G protein-coupled receptor superfamily, the melanocortin-3 receptor (MC3R) is vital for the regulation of energy homeostasis and rhythms synchronizing in mammals, and its pharmacological effect could be directly influenced by the presence of melanocortin receptor accessory proteins (MRAPs), MRAP1 and MRAP2. The tetrapod amphibian Xenopus laevis (xl) retains higher duplicated genome than extant teleosts and serves as an ideal model system for embryonic development and physiological studies. However, the melanocortin system of the Xenopus laevis has not yet been thoroughly evaluated. In this work, we performed sequence alignment, phylogenetic tree, and synteny analysis of two xlMC3Rs. Co-immunoprecipitation and immunofluorescence assay further confirmed the co-localization and in vitro interaction of xlMC3Rs with xlMRAPs on the plasma membrane. Our results demonstrated that xlMRAP2.L/S could improve α-MSH-stimulated xlMC3Rs signaling and suppress their surface expression. Moreover, xlMC3R.L showed a similar profile on the ligands and surface expression in the presence of xlMRAP1.L. Overall, the distinct pharmacological modulation of xlMC3R.L and xlMC3R.S by dual MRAP2 proteins elucidated the functional consistency of melanocortin system during genomic duplication of tetrapod vertebrates.

Objectives. The present study aimed to evaluate prognostic value of inflammatory markers for in-hospital mortality and renal complication in patients undergoing surgery for acute type A aortic diss...

Cancer cells reprogram their energy metabolic system from the mitochondrial oxidative phosphorylation (OXPHOS) pathway to a glucose-dependent aerobic glycolysis pathway. This metabolic reprogramming phenomenon is known as the Warburg effect, a significant hallmark of cancer. However, the detailed mechanisms underlying this event or triggering this reprogramming remain largely unclear. Here, we found that histone H2B monoubiquitination (H2Bub1) negatively regulates the Warburg effect and tumorigenesis in human lung cancer cells (H1299 and A549 cell lines) likely through controlling the expression of multiple mitochondrial respiratory genes, which are essential for OXPHOS. Moreover, our work also suggested that pyruvate kinase M2 (PKM2), the rate-limiting enzyme of glycolysis, can directly interact with H2B in vivo and in vitro and negatively regulate the level of H2Bub1. The inhibition of cell proliferation and nude mice xenograft of human lung cancer cells induced by PKM2 knockdown can be partially rescued through lowering H2Bub1 levels, which indicates that the oncogenic function of PKM2 is achieved, at least partially, through the control of H2Bub1. Furthermore, PKM2 and H2Bub1 levels are negatively correlated in cancer specimens. Therefore, these findings not only provide a novel mechanism triggering the Warburg effect that is mediated through an epigenetic pathway (H2Bub1) but also reveal a novel metabolic regulator (PKM2) for the epigenetic mark H2Bub1. Thus, the PKM2-H2Bub1 axis may become a promising cancer therapeutic target.

Increasing water content in fixed beds is a prospective way to improve the gas storage density by means of hydrate formation. However, the high water content strongly hinders the hydrate formation. In this study, diesel oil was mixed into highly water-saturated activated carbon beds to establish gas channels so that to improve methane hydrate formation. Hydrate formation experiments in four activated carbons with different particle sizes were conducted at 274.15 K and 6.0 MPa. For wet carbon beds without diesel oil, both of the storage capacity of hydrate (Sw) and the storage density of bed (Sb) increased with an decrease in particle size. When the mass ratio of water to activated carbon was set to 2.0, the highest Sw of 67.98 V/Vw and corresponding Sb of 51.92 V/Vbed among the beds were obtained in the bed with particle size of 100–400 mesh. Sodium dodecyl sulfate (SDS) was found to suppress hydrate formation in fine-particle beds. By adding diesel oil, both the formation kinetics and Sw in highly water-saturated beds especially in small-particle ones were significantly improved. The Sw and Sb in the bed with particle size of 100–400 mesh were increased to 180.41 V/Vw and 111.75 V/Vbed, respectively. Furthermore, by adjusting the proportions of water, oil and activated carbon in the bed, the Sw was further improved. The successive gas storage tests suggested that the oil-contained bed can be simply renewed by manual stirring. Gas recovery experiments showed that the hydrate dissociated faster in the oil-contained bed than that in SDS solution, suggesting more efforts should be made to control the hydrate dissociation to drive this method into practical application.

Acetyl-CoA synthetase 2 (ACSS2) generates acetyl-CoA from acetate is important for histone acetylation and gene expression. ACSS2 fulfills distinct functions depending on its cellular location in tumor cells. The role and cellular localization of ACSS2 in hepatocellular carcinoma (HCC) remains to be studied. Herein, we identified that the alternative transcription start site selection of ACSS2 was significantly different between HCC and corresponding adjacent tissues. Alternative transcription start site selection produced two different ACSS2 transcripts, ACSS2-S1 and ACSS2-S2. The two isoforms of ACSS2 had different subcellular localization and different functions. Overexpression of ACSS2-S2 promoted cell proliferation and invasion, but ACSS2-S1 did not. The ACSS2-S1 was mainly present in cytoplasm, and ACSS2-S2 was distributed in both nucleus and cytoplasm. Finally, we demonstrated that alternative transcription start site selection of ACSS2 correlates ribosome biogenesis in HCC. Our findings reveal an oncogenic role of ACSS2-S2 in HCC progression via increase of ribosome biogenesis, and suggest ACSS2-S2 might be a potential therapeutic target against the HCC.

Background and aimsPancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death worldwide. Neurotransmitter-initiated signalling pathway is profoundly implicated in tumour initiation and progression. Here, we investigated whether dysregulated neurotransmitter receptors play a role during pancreatic tumourigenesis.MethodsThe Cancer Genome Atlas and Gene Expression Omnibus datasets were used to identify differentially expressed neurotransmitter receptors. The expression pattern of gamma-aminobutyric acid type A receptor pi subunit (GABRP) in human and mouse PDAC tissues and cells was studied by immunohistochemistry and western blot analysis. The in vivo implications of GABRP in PDAC were tested by subcutaneous xenograft model and lung metastasis model. Bioinformatics analysis, transwell experiment and orthotopic xenograft model were used to identify the in vitro and in vivo effects of GABRP on macrophages in PDAC. ELISA, co-immunoprecipitation, proximity ligation assay, electrophysiology, promoter luciferase activity and quantitative real-time PCR analyses were used to identify molecular mechanism.ResultsGABRP expression was remarkably increased in PDAC tissues and associated with poor prognosis, contributed to tumour growth and metastasis. GABRP was correlated with macrophage infiltration in PDAC and pharmacological deletion of macrophages largely abrogated the oncogenic functions of GABRP in PDAC. Mechanistically, GABRP interacted with KCNN4 to induce Ca2+ entry, which leads to activation of nuclear factor κB signalling and ultimately facilitates macrophage infiltration by inducing CXCL5 and CCL20 expression.ConclusionsOverexpressed GABRP exhibits an immunomodulatory role in PDAC in a neurotransmitter-independent manner. Targeting GABRP or its interaction partner KCNN4 may be an effective therapeutic strategy for PDAC.

This study investigated the water resource potential for bioenergy production from sweet sorghum (Sorghum bicolor (L.)) in Northern China according to the distribution of water resources, climate conditions and the total water consumption of bioenergy based on sweet sorghum, which consisted of blue water, green water and grey water. At a case study site in Inner Mongolia, simulation with a plant phenological model was used to determine whether sweet sorghum could reach the harvestable stage for sugar juice production. The blue water in the agricultural phase was estimated according to the potential crop evapotranspiration (ETc), the drought sensitivity of sweet sorghum in different stages and the precipitation during the growing season. The results showed that the irrigation water was significantly different among the districts, ranging from 730 to 5500 m3/ha and 2060 to 6680 m3/ha for early-maturing and late-maturing varieties, respectively. To avoid the water pressure level to be exacerbated and the severe reallocation of water resources resulting in negative effects on other sectors, the maximal annual water withdrawal was set to not surpass the upper threshold of water stress level of 40%. That makes the maximum area for the production of sweet sorghum cannot exceed 1.95 × 104 ha, representing only 0.24% of the total marginal land area in Inner Mongolia. However, the economic benefits of bioenergy production from sweet sorghum would be negative due to the high labour input. Therefore, not only the availability of marginal land, the climate conditions and local water resources but also the improvement of mechanisation and agricultural production techniques should be considered to attain the sustainable development of bioenergy production and address global energy and environmental crises.

Background Hepatic fibrosis is caused by chronic liver injury and may progress toward liver cirrhosis, and even hepatocellular carcinoma. However, current treatment is not satisfactory. Therefore, there is a mandate to find novel therapeutic targets to improve therapy, and biomarkers to monitor therapeutic response. Methods Liver fibrosis was induced by carbon tetrachloride (CCl4) or thioacetamide (TAA) in wild type (WT) or CTHRC1−/− mice, followed by immunofluorescence and immunohistochemical analyses. CTHRC1 monoclonal antibody (mAb) was used to abrogate the effect of CTHRC1 in vitro and in vivo. Results Here, we reported that collagen triple helix repeat containing 1 (CTHRC1), a secreted protein derived from hepatic stellate cells (HSCs), was significantly up-regulated in fibrotic liver tissues. CTHRC1 promoted HSCs transformation from a quiescent to an activated state, and enhanced migratory or contractile capacities of HSCs by activating TGF-β signaling. Meanwhile, CTHRC1 competitively bound to Wnt noncononical receptor and promoted the contractility but not activation of HSCs. CCl4 or TAA-induced liver fibrosis was attenuated in CTHRC−/− mice compared with littermate control, while a monoclonal antibody of CTHRC1 suppressed liver fibrosis in WT mice treated with CCl4 or TAA. Interpretation We demonstrated that CTHRC1 is a new regulator of liver fibrosis by modulating TGF-β signaling. Targeting CTHRC1 could be a promising therapeutic approach, which can suppress TGF-β signaling and avoid the side effects caused by directly targeting TGF-β. CTHRC1 could also be a potential biomarker for monitoring response to anti-fibrotic therapy. Fund This study was supported by the National Natural Science Foundation of China (ID 81672358, 81871923, 81872242, 81802890), the Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (ID 20181708), the Natural Science Foundation of Shanghai (ID 17ZR1428300, 18ZR1436900), and Shanghai Municipal Health Bureau (ID 2018BR32). The funders did not play a role in manuscript design, data collection, data analysis, interpretation nor writing of the manuscript.

Background Endometrial cancer is one of the most common gynecological malignancies and has exhibited an increasing incidence rate in recent years. Cancer stem cells (CSCs), which are responsible for tumor growth and chemoresistance, have been confirmed in endometrial cancer. However, it is still challenging to identify endometrial cancer stem cells to then target for therapy. Methods Flow cytometry was used to identify the endometrial cancer stem cells. Sphere formation assay, western blotting, qRT-PCR assay, cell viability assay, xenograft assay and immunohistochemistry staining analysis were utilized to evaluate the effect of SPARC-related modular calcium binding 2 (SMOC-2) on the cells proliferation and drug resistance. Cell viability assay, qRT-PCR assay, immunofluorescence staining, Co-IP assay and luciferase reporter gene assay were performed to explore the possible molecular mechanism by which SMOC-2 activates WNT/β-catenin pathway. Findings We found the expression of SPARC-related modular calcium binding 2 (SMOC-2), a member of SPARC family, was higher in endometrial CSCs than that in non-CSCs. SMOC-2 was also more highly expressed in spheres than in monolayer cultures. The silencing of SMOC-2 suppressed cell sphere ability; reduced the expression of the stemness-associated genes SOX2, OCT4 and NANOG; and enhanced chemosensitivity in endometrial cancer cells. By co-culture IP assay, we demonstrated that SMOC-2 directly interacted with WNT receptors (Fzd6 and LRP6), enhanced ligand-receptor interaction with canonical WNT ligands (Wnt3a and Wnt10b), and finally, activated the WNT/β-catenin pathway in endometrial cancer. SMOC-2 expression was closely correlated with CSC markers CD133 and CD44 expression in endometrial cancer tissue. Interpretation Taken together, we conclude that SMOC-2 might be a novel endometrial cancer stem cell signature gene and therapeutic target for endometrial cancer. Fund National Natural Science Foundation of China, Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission, Scientific and Technological Innovation Act Program of Fengxian Science and Technology Commission, Natural Science Foundation of Shanghai.

Background Lysyl oxidase-like 4 (LOXL4) has been found to be dysregulated in several human malignancies, including hepatocellular carcinoma (HCC). However, the role of LOXL4 in HCC progression remains largely unclear. In this study, we investigated the clinical significance and biological involvement of LOXL4 in the progression of HCC. Methods LOXL4 expression was measured in HCC tissues and cell lines. Overexpression, shRNA-mediated knockdown, recombinant human LOXL4 (rhLOXL4), and deletion mutants were applied to study the function of LOXL4 in HCC. Exosomes derived from HCC cell lines were assessed for the ability to promote cancer progression in standard assays. The effects of LOXL4 on the FAK/Src pathway were examined by western blotting. Results LOXL4 was commonly upregulated in HCC tissues and predicted a poor prognosis. Elevated LOXL4 was associated with tumor differentiation, vascular invasion, and tumor-node-metastasis (TNM) stage. Overexpression of LOXL4 promoted, whereas knockdown of LOXL4 inhibited cell migration and invasion of HCC in vitro, and overexpressed LOXL4 promoted intrahepatic and pulmonary metastases of HCC in vivo. Most interestingly, we found that HCC-derived exosomes transferred LOXL4 between HCC cells, and intracellular but not extracellular LOXL4 promoted cell migration by activating the FAK/Src pathway dependent on its amine oxidase activity through a hydrogen peroxide-mediated mechanism. In addition, HCC-derived exosomes transferred LOXL4 to human umbilical vein endothelial cells (HUVECs) though a paracrine mechanism to promote angiogenesis. Conclusions Taken together, our data demonstrate a novel function of LOXL4 in tumor metastasis mediated by exosomes through regulation of the FAK/Src pathway and angiogenesis in HCC. Electronic supplementary material The online version of this article (10.1186/s12943-019-0948-8) contains supplementary material, which is available to authorized users.

In this work, a series of advanced phase change materials (PCMs) were fabricated by using polyrotaxane (PLR) as supports for encapsulating poly (ethylene glycol) (PEG). Phase-change enthalpy is mainly regulated by the PEG contents, whereas phase change temperature is controlled by PEG molecular weight. All PCMs have good form stabilities due to the good compatibility between PLR and PEG, and supporting ability of PLR. Given that the PLR support itself has phase-transition properties, the resulting composites have high phase change enthalpies (116.1–162.2 J g -1) and very high enthalpy efficiency (>100%). It is a green and efficient preparation method because the whole preparation process did not involve organic solvents, and the material was prepared at room temperature. In addition, the obtained PCMs can be easily extruded and re-molded, which provides technical premise and convenience for the large-scale applications. As a typical application example, the PCMs showed its significant advantages in simulated solid-state disk model temperature regulation, which fully demonstrates the practical and superior application value of the PCMs in the field of thermal management for electronic devices. post-print 9729 KB

Monopolar spindle 1 (MPS1), which plays a critical role in somatic mitosis, has also been revealed to be essential for meiosis I in oocytes. Spermatogenesis is an important process involving successive mitosis and meiosis, but the function of MPS1 in spermatogenesis remains unclear. Here, we generated Mps1 conditional knockout mice and found that Ddx4-cre-driven loss of Mps1 in male mice resulted in depletion of undifferentiated spermatogonial cells and subsequently of differentiated spermatogonia and spermatocytes. In addition, Stra8-cre-driven ablation of Mps1 in male mice led to germ cell loss and fertility reduction. Spermatocytes lacking Mps1 have blocked at the zygotene-to-pachytene transition in the prophase of meiosis I, which may be due to decreased H2B ubiquitination level mediated by MDM2. And the expression of many meiotic genes was decreased, while that of apoptotic genes was increased. Moreover, we also detected increased apoptosis in spermatocytes with Mps1 knockout, which may have been the reason why germ cells were lost. Taken together, our findings indicate that MPS1 is required for mitosis of gonocytes and spermatogonia, differentiation of undifferentiated spermatogonia, and progression of meiosis I in spermatocytes.

Autosomal recessive microcephaly and chorioretinopathy (MCCRP) is a neurodevelopmental disorder characterized by delayed psychomotor development, growth retardation with dwarfism, and ocular abnormalities, and its occurrence has been found to be closely related to variants of the gene encoding centrosomes. However, the association between centrosomal duplication defects and the etiology of microcephaly syndromes is poorly understood. It is well known that polo-like kinase 4 (PLK4) is a key regulator of centriole duplication, and the abnormalities of centrosomal function caused by its protein variation need to be further explored in the pathogenesis of microcephaly. In our study, we found that a patient with microcephaly and chorioretinopathy harbored compound heterozygous missense variants NM_014264.4: c.2221C T (p.Gln741*) and NM_014264.4: c.2062 T C (p.Tyr688His) in the PLK4 gene. Overexpression experiments of the variant PLK4 proteins then showed that the G741 variant rather than the T688H variant had lost centrosomal amplification ability, and the G741 variant but not the T688H variant induced centrosomal replication disorder, which further inhibited cell proliferation, cycle division and cytoskeleton morphology in HeLa cells. Moreover, the overexpression of the two variant proteins had inconsistent effects on the target protein PLK4 by western blot analysis, also indicating that T688H variant overexpression is not functionally equivalent to WT-PLK4 overexpression. Therefore, all data support the idea that the PLK4 mutation induces centriolar duplication disorder and reduces the efficiency of mitosis inducing cell death or cell proliferation in the etiology of microcephaly disorder.

Pancreatic ductal adenocarcinoma (PDAC), cancer with a high mortality rate and the highest rate of KRAS mutation, reportedly internalizes proteins via macropinocytosis to adapt to low amino acid levels in the tumor microenvironment. Here, we aimed to identify a key regulator of macropinocytosis for the survival of tumor cells in a low amino acid environment in PDAC. FYVE, RhoGEF, and PH domain-containing protein 6 (FGD6) were identified as key regulators of macropinocytosis. FGD6 promoted PDAC cell proliferation, macropinocytosis, and tumor growth both in vitro and in vivo. The macropinocytosis level was decreased with FGD6 knockdown in PDAC cell lines. Moreover, FGD6 promoted macropinocytosis by participating in the trans-Golgi network and enhancing the membrane localization of growth factor receptors, especially the TGF-beta receptor. TGF-beta enhanced macropinocytosis in PDAC cells. Additionally, YAP nuclear translocation induced by a low amino acid tumor environment initiated FGD6 expression by coactivation with YY1. Clinical data analysis based on TCGA and GEO datasets showed that FGD6 expression was upregulated in PDAC tissue, and high FGD6 expression was correlated with poor prognosis in patients with PDAC. In tumor tissue from Kras

Purpose: Understanding the soil nitrogen (N) mineralization potential (N0) and crop N availability during the growing season is essential for improving nitrogen use efficiency (NUE) and preventing over-fertilization, which lead to negative environmental impacts. Methods: Five black soils with different levels of fertility were selected in Northeast China. The N0 and kinetics of these soils were estimated through laboratory experiments at different incubation temperatures (15, 25, and 35 °C). N mineralization dynamics were simulated using field soil temperature according to the incubation results. Moreover, the N uptake dynamics of maize were simulated according to the literature. Results: Compared with the very low-fertility soils, the cumulative mineralized nitrogen increased under all incubation temperatures (15, 25, and 35 °C), by 48–136%, 8–61%, and 24–59%, respectively, in the medium- and high-fertility soils. The highest N0 values (96.90, 115.31, and 121.33 mg/kg at the three different temperatures) were recorded in the very high-fertility soils. The soil N mineralization dynamics and N uptake of maize in the growing season were highly consistent over time, although the soil N supply could not meet the maize growth requirements. The higher the soil fertility, the lower the N fertilizer requirement. Conclusions: Different fertilizer strategies were developed based on the cumulative mineralized N, N uptake by maize, and NUE in soils with different fertility levels. We suggested a reduction of 50–65 kg N/ha in N fertilizer in the two highest fertility soils. This study provided basic data to reduce chemical N fertilizer to improve NUE and reduce negative environmental impacts.

The aim of the study was to investigate the intelligent recognition of radiomics based on the convolutional neural network (CNN) in predicting endometrial cancer (EC). In this study, 158 patients with EC in hospital were selected as the research objects and divided into a training group and a test group. All the patients underwent magnetic resonance imaging (MRI) before surgery. Based on the CNN, the imaging model of EC prediction was constructed according to the characteristics. Besides, the comprehensive prediction model was established through the clinical information and imaging parameters. The results showed that the area under the working characteristic curve (AUC) of the radiomics model and comprehensive prediction model was 0.897 and 0.913 in the training group, respectively. In addition, the AUC of the radiomics model was 0.889 in the test group and that of the comprehensive prediction model was 0.897. The comprehensive prediction model was established through specific imaging parameters and clinical pathological information, and its prediction performance was good, indicating that radiomics parameters could be applied as noninvasive markers to predict EC.

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Metastasis is a major cause of cancer-related deaths. Tumor-intrinsic properties can determine whether tumor metastasis occurs or not. Here, by comparing the gene expression patterns in primary colorectal cancer (CRC) patients with or without metastasis, we found that Collagen Triple Helix Repeat Containing 1 (CTHRC1) in primary CRC served as a metastasis-associated gene. Animal experiments verified that CTHRC1 secreted by CRC cells promoted hepatic metastasis, which was closely correlated with macrophage infiltration. Depletion of macrophages by liposomal clodronate largely abolished the promoting effect of CTHRC1 on CRC liver metastasis. Furthermore, we demonstrated that CTHRC1 modulated macrophage polarization to M2 phenotypes through TGF-β signaling. A mechanistic study revealed that CTHRC1 bound directly to TGF-β receptor II and TGF-β receptor III, stabilized the TGF-β receptor complex, and activated TGF-β signaling. The combination treatment of CTHRC1 monoclonal antibody and anti-PD-1 blocking antibody effectively suppressed CRC hepatic metastasis. Taken together, our data demonstrated that CTHRC1 is an intrinsic marker of CRC metastasis and further revealed that CTHRC1 promoted CRC liver metastasis by reshaping infiltrated macrophages through TGF-β signaling, suggesting that CTHRC1 could be a potential biomarker for the early prediction of and a therapeutic target of CRC hepatic metastasis.

Gene mutations play important roles in tumour development. In this study, we identified a functional histone H2B mutation H2BL-T11C, causing an amino acid variation from Leu to Pro (L3P, H2BL-L3P). Cells overexpressing H2BL-L3P showed stronger proliferation, colony formation, tumourigenic abilities, and a different cell cycle distribution. Meanwhile, the c-Myc expression was elevated as evident by RNA-seq. We further revealed that an H2BK5ac-H2BK120ubi crosstalk which regulates gene transcription. Moreover, EdU staining demonstrated an important role of c-Myc in accelerating cell cycle progression through the G1/S checkpoint, while treatment with 10058-F4, an inhibitor of the c-Myc/MAX interaction, alleviated the abnormal cell proliferation and cell cycle distribution in vitro and partially inhibited tumour growth in vivo. The mutation of amino acid L3P is associated with tumour progression, suggesting patients carrying this SNP may have higher risk of tumour development.

SUMMARYEnvironmental stress-induced epigenetic changes are inherited by germlines and profoundly affect the behavior and physiology of subsequent generations. However, the mechanisms by which acquired transgenerational epigenetic imprints are established in the parental germline remain poorly understood. In this study, we used Caenorhabditis elegans as a model system and demonstrated that a key node of metabolism-Pod-2, an acetyl-CoA carboxylase, together with vitellogenins (Vits), cholesterol-binding/transport proteins, guide establishment of the acquired transgenerational epigenetic modifications H3K27me3 in the parental germline. The loss of function of a Vit; its transporter or receptor; or its binding partner, pod-2, resulted in the loss of acquired epigenetic memory in the germline. Our findings indicate that lipid metabolism is a critical mediator for establishing transgenerational epigenetic imprints in the germline.

Background Osteoporosis (OP) is an age-related systemic bone disease. MicroRNAs (miRNAs) are involved in the regulation of osteogenic differentiation. The purpose of this study was to explore the role and mechanism of miR-1249-5p for promoting osteogenic differentiation of adipose-derived stem cells (ADSCs). Methods GSE74209 dataset was retrieved from NCBI Gene Expression Omnibus (GEO) database and performed bioinformatic analyses. OP tissue and healthy control tissues were obtained and used for RT-PCR analyses. ADSCs were incubated with miR-1249-5p mimic, inhibitor and corresponding negative control (NC), alkaline phosphatase (ALP) staining, and Alizarin Red Staining (ARS) were then performed to assess the role of miR-1249-5p for osteogenesis of ADSCs. Targetscan online website and dual-luciferase reporter assay were performed to verify that the 3′-UTR of PDX1 mRNA is a direct target of miR-1249-5p. RT-PCR and western blot were also performed to identify the mechanism of miR-1249-5p for osteogenesis of ADSCs. Results A total of 170 differentially expressed miRNAs were selected, among which, 75 miRNAs were downregulated and 95 miRNAs were upregulated. Moreover, miR-1249-5p was decreased in OP patients, while showed a gradual increase with the extension of induction time. miR-1249-5p mimic significantly increased osteogenic differentiation capacity and p-PI3K and p-Akt protein levels. Luciferase activity in ADSCs co-transfected of miR-1249-5p mimic with PDX1-WT reporter plasmids was remarkably decreased, but there was no obvious change in miR-1249-5p mimic with PDX1-MUT reporter plasmids co-transfection group. Overexpression PDX1 could partially reverse the promotion effects of miR-1249-5p on osteogenesis of ADSCs. Conclusion In conclusion, miR-1249-5p promotes osteogenic differentiation of ADSCs by targeting PDX1 through the PI3K/Akt signaling pathway.

Recently, the outbreak of coronavirus disease 2019 (COVID-19) is threatening human health globally. There is a dire need to find potential therapeutic agents. Angiotensin converting enzyme 2 (ACE2), as an entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is considered as potential therapeutic target in COVID-19 pandemic. Here, our bioinformatics analysis revealed that the biological function of ACE2 was correlated with regulation of blood pressure and mediation of SARS-CoV-2 entry into host cells. Ten ACE2 cooperative proteins were identified by using STRING with a high score. ACE2 expressed highly in the small intestine, testis, and kidney. The level of ACE2 expression in tumor tissues varies in different types of cancers compared with that in normal tissues. It was worth noting that the expression level of ACE2 in the tumor has no effect on patient survival. MiRNA hsa-miR-942-5p, and three transcription factors (TFs) including Signal transducer and activator of transcription 4 (STAT4), Estrogen related receptor α (ESRRA), and Signal transducer and activator of transcription 3 (STAT3) were selected as novel ACE2 regulators. Moreover, nine potential therapeutic drugs were predicted by two online databases. Thus, our research may expand the overall view of ACE2 in COVID-19 treatment.

To further investigate fresh‐keeping effect of fucoidan from Laminaria japonica (FL) on postharvest strawberry, this study assessed the degradation kinetics of antioxidant capacity and antioxidants in cold‐stored strawberry coated with FL by layer‐by‐layer method. Fruit coated with FL were subjected to determine antioxidant capacity and endogenous antioxidants contents during the scheduled cold‐storage period. Results showed that FL obviously suppressed degradation rates of both antioxidant capacity and contents of phenolic compounds and ascorbic acid, which were demonstrated by reduced rate constant and increased half‐time periods of antioxidant activity and antioxidants in FL‐coated strawberry during cold storage. High Pearson correlation coefficients and significant differences among antioxidant‐associated indicators indicated that there was a close relationship between antioxidant activity degradation and antioxidants degradation in strawberry fruit during cold‐storage period. FL treatment inhibited degradation of total polyphenol and ascorbic acid which ultimately controlled degradation of antioxidant capacity in cold‐storage strawberry. PRACTICAL APPLICATIONS: Laminaria japonica rich in brown seaweed may be developed to be a natural and nontoxic preservative for postharvest strawberry or other fruit and vegetables.

Nowadays, vigorously researching and developing biodegradable materials is an effective way to solve the problem of white pollution. As far as we know, systematic research in environmental compatibility of biodegradable polymers has not been reported. Furthermore, there are few tangible products in the relevant frontier fields that really benefit consumers. The research and development of biodegradable materials still has a long way to go, which is mainly manifested in its low consumption nowadays and the series of degradation effects all may adding burden to the current environment. Combined with the current background, this work reviewed the general classification and the application of typical biodegradable polymers, providing readers an intuitive and systematic understanding of biodegradable polymers. Moreover, we analyzed some shortcomings of the recent research, and briefly proposed some development directions and solutions to the main existed problems, namely, cost control, in-depth development of functions and applications, materials source extension, enhancement of environmental protection awareness and regulations, and systematical assessment of environmental compatibility of the biodegradable polymers.

The regulation of histone deposits mediated by multi-chaperone complexes under physiological conditions remains to be further investigated. Here, we studied the function of nuclear autoantigenic sperm protein (NASP) in the regulation of liver cancer. We found that NASP levels in liver tumors were generally higher than in normal liver tissues and NASP down-regulation inhibited liver cancer cells from forming tumors. We further analyzed cellular responses and epigenetic mechanisms of the histone H3-H4 shortage induced by NASP knockdown in liver cancer cells. The results showed that the major effects of NASP knockdown were globally enhanced chromatin accessibility, which facilitates transcription release, and failure of replication initiation. Furthermore, we demonstrated that NASP depletion led to a global decrease of histone H3K9me1 modification associated with newly H3 processing, which occurred directly at the promoters of up-regulated anti-tumor genes BACH2 and RunX1T1. This also resulted in a synergistic effect on enhanced apoptosis with Myc and p53 decreases. Overall, our work provides new insights into the roles of NASP in tumorigenesis and cancer prevention.

A new method to improve the methane hydrate formation rate and gas uptake was developed through continuous impact on hydrate block with high interstitial water cut. Experimental investigations were conducted at temperature and pressure ranges of 273.3–279.2 K and 3.4–6.0 MPa, respectively, for different water loads and impact frequencies. Hydrate formation in quiescent sodium dodecyl sulfate (SDS) solution and pure water with rotational stirring was investigated for comparison. The reciprocating impact intensification method significantly improved the formation rate in both slurry and hydrate block stages as well as the final gas uptake. The fastest formation was observed at 274.7 K and 6.0 MPa, where 90% of hydrate formation was completed within 4 h. The largest gas uptake (150.3 V/V) in the hydrate was observed at 279.2 K and 6.0 MPa, which was slightly higher than that obtained from SDS. The advantage of the proposed method is that the final hydrate block is compacted in a significantly smaller bulk volume than that of the fluffy hydrate formed from SDS. Multi-growth was observed in hydrate formation when the reciprocating impact method was adopted. Temperature and pressure affected the formation kinetics but not methane uptake. The optimal conditions for hydrate formation in bulk water included a water/inner reactor space volume ratio of 0.18 and an impact frequency of 30 times/min. Additionally, the lowest power consumption for reciprocating impact was calculated as 3.77 × 10−3 kW h/mol. These results indicate that it is feasible to store methane using clathrate hydrates without additives.

Background To evaluate the efficacy of using internal jugular vein variability (IJVV) as an index of fluid responsiveness in mechanically ventilated patients after cardiac surgery. Methods Seventy patients were assessed after cardiac surgery. Hemodynamic data coupled with ultrasound evaluation of IJVV and inferior vena cava variability (IVCV) were collected and calculated at baseline, after a passive leg raising (PLR) test and after a 500-ml fluid challenge. Patients were divided into volume responders (increase in stroke volume ≥ 15%) and non-responders (increase in stroke volume

Background: Gastric cancer (GC) is one of the leading causes of lethal malignancies worldwide, especially in Eastern Asia. Clinical responses to antitumor therapies are often limited to a subset of patients. Methods: To uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we performed ultra-deep targeted sequencing in a cohort with 72 patients (41 with chemotherapy sensitivity and 31 with chemotherapy resistance). Results: We found that sixteen mutated cancer genes were associated with widely used agent in chemotherapy of gastric cancer. Genes identified in these study are mainly involved in activation and inactivation of cancer chemotherapeutic agents, changes of apoptosis and proliferation, drug efflux, DNA damage repair, and the tumor microenvironment. Discussion: A novel group of chemo-sensitivity related genes provided new therapeutic strategies to overcome the development and evolution of resistance to cancer chemotherapy.

Fully bio-sourced oligoesters based on poly(glycerol-succinate) (PGS) with controllable sizes and topologies were prepared by melt phase polycondensation. The oligoesters were further used to modify poly(e-caprolactone) (PCL) by the blending method under mild processing conditions. As can be observed, the PGS modifier was well dispersed in the PCL matrix. The PGS could influence the crystallization and significantly accelerate the degradation of the PCL matrix. There was no significant decrease of mechanical properties after blending modification. Notably, the method used here is quite convenient and solvent-free, by which we can achieve PCL modification under very mild conditions. Therefore, the work proposed here is an effective, sustainable and environmentally friendly modifying method for PCL to accelerate the degradation rate.

Background To investigate the impact of timing the initiation of renal replacement therapy (RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI), focusing on the randomized controlled trials (RCTs) in this field. Methods The PubMed, EMBASE and Cochrane databases were searched between January 1, 1985, and June 30, 2016, to identify randomized trials that assessed the timing of initiation of RRT in patients with AKI. Results Nine RCTs, with a total of 1636 patients, were enrolled in this meta-analysis. A pooled analysis of the studies indicated no mortality benefit with “early” RRT, with an RR of 0.98 (95% CI 0.78 to 1.23, P = 0.84). There was no significant difference in intensive care unit (ICU) length of stay (LOS) or hospital LOS between the early and late RRT groups for survivors or nonsurvivors. Pooled analysis also demonstrated no significant change in renal function recovery (RR 1.02, 95% CI 0.88 to 1.19, I2 = 59%), RRT dependence (RR 0.76, 95% CI 0.42 to 1.37, I2 = 0%), duration of RRT (Mean difference 1.43, 95% CI -1.75 to 4.61, I2 = 78%), renal recovery time (Mean difference 0.73, 95% CI -2.09 to 3.56, I2 = 70%) or mechanical ventilation time (Mean difference − 0.95, 95% CI -3.54 to 1.64, I2 = 64%) between the early and late RRT groups. We found no significant differences in complications between the groups. Conclusions Our meta-analysis revealed that the “early” initiation of RRT in critically ill patients did not result in reduced mortality. Pooled analysis of secondary outcomes also showed no significant difference between the early and late RRT groups. More well-designed and large-scale trials are expected to confirm the result of this meta-analysis. Electronic supplementary material The online version of this article (doi:10.1186/s12882-017-0667-6) contains supplementary material, which is available to authorized users.

The mechanisms of secondary brain injury after traumatic brain injury (TBI) are complex and are the result of multiple factors. Protecting the blood-brain barrier (BBB) and ameliorating cerebral edema are two key factors for improving the prognosis of TBI patients. The BBB is regulated by the hedgehog pathway through Scube2 and Shh protein. Matrix metalloproteinase-9 (MMP-9) influences the transport system and enzyme system of vascular endothelial cells, possibly via the hedgehog pathway. The present study aimed to investigate the role and mechanism of MMP-9 in TBI via the hedgehog pathway. Eighty male Sprague-Dawley rats were used to establish a murine model of TBI. Subsequently, the effect of SB-3CT—a specific inhibitor of MMP-9—was assessed via Western blotting, real-time PCR, immunofluorescence, apoptotic assays, and neurological scoring. The results showed that, compared with those of the sham-operation group, the mRNA and protein levels of MMP-9 were significantly increased after TBI, while the expressions of Scube2 and Shh were decreased. Application of SB-3CT at 24 h after TBI significantly reduced neuronal apoptosis and BBB permeability, while increasing expressions of Scube2 and Shh. In conclusion, these findings demonstrate an influence of TBI-induced MMP-9 upregulation in the induction of post-traumatic nerve and BBB injury, which may be partially mediated by Scube2 and Shh via the hedgehog pathway.

To establish and validate the design space of the Digeda-4 flavored decoction( DGD-4D) extraction process by using the quality by design( Qb D) concept. With DGD-4D decoction pieces as a model drug,with the transfer rate of aesculin,picroside I,picroside Ⅱ,geniposide and the yield of extract as critical quality attributes( CQAs),the single factor experiment design was used to determine the level of each factor; the Plackett-Burman experiment design was used to select the critical process parameters( CPPs);and the Box-Behnken experiment design was used to optimize the extraction process. The design space of the DGD-4D extraction process was established,and finally,four experimental points were selected to verify the established model. The single factor experiment determined the levels of each factor,including soaking time 60 min and 30 min,water adding volume 12 times and 8 times,extraction time 90 min and 30 min,number of extraction times 3 times and 1 time,as well as extraction temperature 100 ℃ and 90 ℃.By Plackett-Burman experimental design,the DGD-4D water addition,extraction time and number of extraction times were determined to be CPPs. The Box-Behnken experimental variance analysis showed that P of the regression model was less than 0. 01 and the misstated value was more than 0. 01,indicating that the model had good predictive ability,and the operation space of CPPs in the DGD-4D extraction process was determined as follows: the amount of water addition was 10-12 times; extraction time 50-80 min; and number of extraction times was 3 times. The design space of DGD-4D extraction process based on the concept of Qb D is conducive to improving the stability of product quality and laying a foundation for the future development of DGD-4D.

The present study aimed to evaluate the effect of the CX3CR1 inhibitor AZD8797 in early recovery after acute SCI and elucidate its potential mechanism in blocking inflammation and apoptosis. Adult rats were sacrificed after 3, 7, 10, or 14 days of SCI. The injured spinal tissues were collected for assessing C‑X3‑C motif chemokine ligand 1(CX3CL1)/C‑X3‑C motif chemokine receptor 1 (CX3CR1) expression at each time point via western blotting (WB) and quantitative PCR. The cellular localization of the proteins was detected by immunofluorescence. Another batch of rats (subdivided into sham, injury model, AZD8797 and methylprednisolone groups) were used to evaluate locomotive recovery with a Basso Beattie Bresnahan score. Based on the expression level of CX3CR1, these rats were sacrificed at the most prominent stage of CX3CR1 expression (10 days after SCI), for assessing the serum levels of tumor necrosis factor‑α/interleukin (IL)‑6/IL‑1β and the expression of CX3CL1/CX3CR1/caspase 3/Bcl‑2/Bax in the spinal cord tissues through WB and ELISA. Additionally, apoptosis and necrosis in the injured spinal cord were evaluated by terminal deoxynucleotidyl transferase‑-mediated dUTP nick‑end labeling staining/fluoro‑jade B staining. Expression levels of both CX3CR1 and CX3CL1 reached their peak 10 days after the injury, followed by a dramatic downward trend at 14 days. The enhanced expression of CX3CR1 was detected in astrocytes and microglia of the injured spinal cord. AZD8797 improved locomotive recovery after 10 days of SCI and was as effective as methylprednisolone. The effect of AZD8797 was mediated by suppressing apoptosis, necrosis and inflammatory responses, as assessed by WB/ELISA and morphological examinations. The current study has demonstrated that AZD8797 can effectively block overwhelming inflammation, apoptosis and necrosis after SCI and facilitate early recovery of locomotive function.

Background Gastric cancer is one of the deadliest malignant tumours, with a high incidence in China, and is regulated by aberrantly overexpressed oncogenes. However, existing therapies are insufficient to meet patients’ needs; thus, the identification of additional therapeutic targets and exploration of the underlying mechanism are urgently needed. GPAA1 is the subunit of the GPI transamidase that transfers the GPI anchor to proteins within the ER. The functional impacts of increased expression levels of GPAA1 in human cancers are not well understood. Methods Data mining was performed to determine the pattern of GPAA1 expression and the reason for its overexpression in tumour and adjacent normal tissues. In vitro and in vivo experiments evaluating proliferation and metastasis were performed using cells with stable deletion or overexpression of GPAA1. A tissue microarray established by the Ren Ji Hospital was utilized to analyse the expression profile of GPAA1 and its correlation with prognosis. Western blotting, an in situ proximity ligation assay, and co-immunoprecipitation (co-IP) were performed to reveal the mechanism of GPAA1 in gastric cancer. Results GPAA1 was a markedly upregulated oncogene in gastric cancer due to chromosomal amplification. GPAA1 overexpression was confirmed in specimens from the Ren Ji cohort and was associated with ERBB2 expression, predicting unsatisfactory patient outcomes. Aberrantly upregulated GPAA1 dramatically contributed to cancer growth and metastasis in in vitro and in vivo studies. Mechanistically, GPAA1 enhanced the levels of metastasis-associated GPI-anchored proteins to increase tumour metastasis and intensified lipid raft formation, which consequently promoted the interaction between EGFR and ERBB2 as well as downstream pro-proliferative signalling. Conclusions GPAA1 facilitates the expression of cancer-related GPI-anchored proteins and supplies a more robust platform—the lipid raft—to promote EGFR-ERBB2 dimerization, which further contributes to tumour growth and metastasis and to cancer progression. GPAA1 could be a promising diagnostic biomarker and therapeutic target for gastric cancer. Electronic supplementary material The online version of this article (10.1186/s13046-019-1218-8) contains supplementary material, which is available to authorized users.

Background: To evaluate the effect of inhaled nitric oxide (iNO) therapy on oxygenation and clinical outcomes in patients with refractory hypoxemia after surgical reconstruction for acute type A aortic dissection (TAAD). Methods: A before-and-after interventional study was conducted in patients with refractory hypoxemia after surgical reconstruction for TAAD. Postoperative refractory hypoxemia was defined as a persistent PaO 2 /FiO 2 ratio ≤100 mmHg despite conventional therapy. From January to November 2016, conventional treatment was carried out for refractory hypoxemia. From December 2016 to October 2017, on the basis of conventional therapy, we explored the use of iNO to treat refractory hypoxemia. Results: Fifty-three TAAD patients with refractory hypoxemia were enrolled in this study. Twenty-seven patients received conventional treatment (conventional group), while the remaining 26 patients received iNO therapy. The PaO 2 /FiO 2 ratio was significantly higher in the iNO group after treatment than in the conventional group when analyzed over the entire 72 hours. The duration of invasive mechanical ventilation was significantly reduced in the iNO group (69.19 vs . 104.56 hours; P=0.003). Other outcomes, such as mortality (3.85% vs . 7.41%, P=1.000), intensive care unit (ICU) duration (9.88 vs . 12.36 days, P=0.059) and hospital stay (16.88 vs . 20.76 days, P=0.060), were not significantly different between the two groups. Conclusions: iNO therapy might play an ameliorative role in patients with refractory hypoxemia after surgical reconstruction for TAAD. This therapy may lead to sustained improvement in oxygenation and reduce the duration of invasive mechanical ventilation.

A rapid detection method of pesticide residues in milk by enzyme inhibition was researched. Construction of a quickly reaction system of enzyme inhibition for determination of organophosphorus and carbamate pesticide residues was achieved. The analysis of color reactions of milk showed a good correlation between color intensity and content of tolclofos-methyl, methamidophos and isoprocarb 1-naphthalenyl methyl carbamate. The detection limits of the four pesticide were 0.5~1.0 mg/kg, which were below the level of detection required to satisfy legislation in china. This method is simple and inexpensive and suitable for rapid detection of pesticide residues in milk.