Integration of observations of the coastal ocean continuum from regional oceans to shelf seas and estuaries/deltas with models can substantially increase the value of observations and enable a wealth ...of applications. In particular, models can play a critical role at connecting sparse observations, synthesizing them, and assisting the design of observational networks; in turn, whenever available, observations can guide coastal model development. Coastal observations should sample the two-way interactions between nearshore, estuarine and shelf processes and open ocean processes, while accounting for the different pace of circulation drivers, such as the fast atmospheric, hydrological and tidal processes and the slower general ocean circulation and climate scales. Because of these challenges, high-resolution models can serve as connectors and integrators of coastal continuum observations. Data assimilation approaches can provide quantitative, validated estimates of Essential Ocean Variables in the coastal continuum, adding scientific and socioeconomic value to observations through applications (e.g. sea-level rise monitoring, coastal management under a sustainable ecosystem approach, aquaculture, dredging, transport and fate of pollutants, maritime safety, hazards under natural variability or climate change). We strongly recommend an internationally coordinated approach in support of proper integration of global and coastal continuum scales, as well as for critical tasks such as community-agreed bathymetry and coastline products.
Intravascular ultrasound (IVUS)-guided drug-eluting stent (DES) implantation is associated with fewer major adverse cardiovascular events compared with angiography guidance for patients with ...individual lesion subset. However, the beneficial effect on major adverse cardiovascular event outcome of IVUS guidance over angiography guidance in all-comers who undergo DES implantation still remains understudied.
This study aimed to determine the benefits of IVUS guidance over angiography guidance during DES implantation in all-comer patients.
A total of 1,448 all-comer patients who required DES implantation were randomly assigned (1:1 ratio) to either an IVUS guidance or angiography guidance group. The primary endpoint was target-vessel failure (TVF) at 12 months, including cardiac death, target-vessel myocardial infarction, and clinically driven target-vessel revascularization (TVR). The procedure was defined as a success if all IVUS-defined optimal criteria were met.
At 12 months follow-up, 60 TVFs (4.2%) occurred, with 21 (2.9%) in the IVUS group and 39 (5.4%) in the angiography group (hazard ratio HR: 0.530; 95% confidence interval CI: 0.312 to 0.901; p = 0.019). In the IVUS group, TVF was recorded in 1.6% of patients with successful procedures, compared with 4.4% in patients who failed to achieve all optimal criteria (HR: 0.349; 95% CI: 0.135 to 0.898; p = 0.029). The significant reduction of clinically driven target-lesion revascularization or definite stent thrombosis (HR: 0.407; 95% CI: 0.188 to 0.880; p = 0.018) based on lesion-level analysis by IVUS guidance was not achieved when the patient-level analysis was performed.
The present study demonstrates that IVUS-guided DES implantation significantly improved clinical outcome in all-comers, particularly for patients who had an IVUS-defined optimal procedure, compared with angiography guidance. (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in “All-Comers” Coronary Lesions ULTIMATE; NCT02215915)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A novel method for facile fabrication of glycopolymer-based iron oxide nanoparticles (GIONs) is developed.
Via
perfluorophenylazide photochemically induced C-H insertion, alkynyl groups were ...introduced onto the polymer which was precoated on the iron oxide nanoparticle surface. GIONs were then prepared by conjugating the azide-functionalized carbohydrate to the introduced alkynyl groups
via
click chemistry. Polyvinyl alcohol-coated and dextran-coated iron oxide NPs were chosen as scaffolds to attach two different carbohydrates, α-
d
-mannose and β-
d
-glucose, to fabricate multivalent GIONs, respectively. The multivalent GIONs demonstrated high binding affinities towards the corresponding lectins in both protein and cell chips. As a proof of concept, fluorescent GIONs (Gal-RhB-IONPs) were fabricated, which showed selective and efficient internalization by ASGP-R overexpressing HepG2 cells targeted.
A novel method for facile fabrication of glycopolymer-based iron oxide nanoparticles (GIONs) is developed.
Background Chemotherapy is the only therapy option for the majority of AML patients, however, there are several limitations for this treatment. Our aim was to find a new chemotherapy strategy that is ...more effective and less toxic. Methods MTT assays and a xenograft mouse model were employed to evaluate the synergistic activity of all-trans retinoic acid (ATRA) combined with topotecan (TPT). Drug-induced DNA damage and apoptosis were determined by flow cytometry analysis with PI and DAPI staining, the comet assay and Western blots. Short hairpin RNA (shRNA) and a RARalpha plasmid were used to determine whether RARalpha expression influenced DNA damage and apoptosis. Results We found that ATRA exhibited synergistic activity in combination with Topotecan in AML cells, and the enhanced apoptosis induced by Topotecan plus ATRA resulted from caspase pathway activation. Mechanistically, ATRA dramatically down regulated RARalpha protein levels and led to more DNA damage and ultimately resulted in the synergism of these two agents. In addition, the increased antitumor efficacy of Topotecan combined with ATRA was further validated in the HL60 xenograft mouse model. Conclusions Our data demonstrated, for the first time, that the combination of TPT and ATRA showed potential benefits in AML, providing a novel insight into clinical treatment strategies. Keywords: AML, Topotecan, All-trans retinoic acid, Apoptosis, DNA damage, RARalpha
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BackgroundQinxiang Qingjie (QXQJ), an oral solution containing various Chinese herbs, is indicated for pediatric upper respiratory tract infections. The treatment of influenza also shows potential ...advantages in shortening the duration of illness and improving symptoms. However, there is still a lack of high-quality clinical evidence to support this. The trial was to explore the efficacy and safety of QXQJ for treating pediatric influenza and provide an evidence-based basis for expanding its applicability. MethodsA randomized, double-blind, double-dummy, positive-controlled, multicenter clinical trial was conducted in 14 hospitals in China. Children aged 1-13 years with influenza and "exterior and interior heat syndromes" as defined by traditional Chinese medicine (TCM) were randomly assigned to two groups with 1:1 radio. Children in the test group received QXQJ oral solution and oseltamivir simulant, while the control group received oseltamivir phosphate granules and QXQJ simulant. The duration of treatment was five days, followed by a two-day follow-up period. The primary endpoint was the clinical recovery time. Secondary endpoints included the time to defervescence, incidences of complications and severe or critical influenza, negative conversion rate, improvement of TCM syndromes, and safety profiles of the therapeutics, which mainly contained the adverse clinical events and adverse drug reactions. ResultsA total of 231 children were randomized to either the QXQJ (n=117) or oseltamivir (n=114) group. The FAS and PPS results showed that both groups experienced a median clinical recovery time of three days (P>0.05). The median time to defervescence of both groups were 36 hours in FAS and PPS (P>0.05), and two groups did not differ in terms of the other secondary endpoints (P>0.05). 14 patients (12.39%) in the QXQJ group and 14 patients (12.50%) in the oseltamivir group reported at least one adverse event, respectively. One serious adverse event occurred in the QXQJ group. There was no significant difference in the incidence of adverse events or adverse drug reactions between the groups. ConclusionsThe efficacy of QXQJ oral solution was comparable to that of oseltamivir for treating influenza in children, with an acceptable safety profile. Trial RegistrationChinese Clinical Trial Registry ChiCTR1900021060.
This paper introduced a monitoring system of rice production, which can monitor the ambient temperature, humidity, the temperature of rice water and soil and Terrace surface runoff water in the ...process of rice production. All the testing data are firstly aggregated to a cluster node, and then transmitted to network datacenter through the GSM, so that users can access the datacenter server for the data related to the production environment. The monitoring system has been installed in the experimental field at the village of Qingkou, Yuanyang County, Yunnan Province. It has been running normally for one year. The system can monitor the real-time meteorological factors affecting the growth of rice, which provides the supporting data for exerting comprehensive control of insect pests and studying in-depth the problems of water terraces and nutrient balance before increasing the yield of rice and improving the quality of rice.
Previous animal studies by us and others have indicated that catheter-administered plasmin or its des-kringle derivatives may be more appropriate alternatives to plasminogen activators for treating ...thrombolytic diseases, since it has a very short serum half-life and therefore does not result in hemorrhaging. We have previously produced recombinant miniPlasmin (mPlasmin) that was proven suitable for treating peripheral arterial occlusion in animal models. However, our previous results showed that non-specific cleavage at position K698 of mPlasmin during activation hindered the further development of this promising therapeutic candidate. In order to minimize or eliminate the non-specific cleavage problem, we performed saturation mutagenesis at the K698 position to develop a mutant form of mPlasmin for thrombolytic therapy.
We changed K698 to 16 other amino acids, with preferred E. coli codons. Each of these mutants were expressed in E. coli as inclusion bodies and then refolded, purified, and subsequently characterized by detailed kinetic assays/experiments/studies which identified highly active mutants devoid of non-specific cleavage.
Activation studies indicated that at those conditions in which the wild type enzyme is cut at the non-specific position K698, the active mutants can be activated without being cleaved at this position.
From the above results, we selected two mutants, K698Q and K698N, as our lead candidates for further thrombolytic drug developments. The selected mutants are potentially better therapeutic candidates for thrombolytic therapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Chemotherapy is the only choice for most of the advanced hepatocellular carcinoma (HCC) patients, while few agents were available, making it an urgent need to develop new chemotherapy strategies. A ...phase II clinical trial suggested that the efficacy of irinotecan in HCC was limited due to dose-dependent toxicities. Here, we found that gefitinib exhibited synergistic activity in combination with SN-38, an active metabolite of irinotecan, in HCC cell lines. And the enhanced apoptosis induced by gefitinib plus SN-38 was a result from caspase pathway activation. Mechanistically, gefitinib dramatically promoted the ubiquitin-proteasome-dependent degradation of Rad51 protein, suppressed the DNA repair, gave rise to more DNA damages, and ultimately resulted in the synergism of these two agents. In addition, the increased antitumor efficacy of gefitinib combined with irinotecan was further validated in a HepG2 xenograft mice model. Taken together, our data demonstrated for the first time that the combination of irinotecan and gefitinib showed potential benefit in HCC, which suggests that Rad51 is a promising target and provides a rationale for clinical trials investigating the efficacy of the combination of topoisomerase I inhibitors and gefitinib in HCC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite significant progress made in past decades, it is still challenging to elucidate dynamics mechanisms for polyatomic reactions, in particular, involving complex formation. The reaction of ...O((1)D) with methane has long been regarded as a prototypical polyatomic system of direct insertion reaction in which the O((1)D) atom can insert into the C-H bond of methane to form a "hot" methanol intermediate before decomposition. Here, we report a combined theoretical and experimental study on the O((1)D) + CHD3 reaction, on which good agreement between theory and experiment is achieved. Our study revealed that this complex-forming reaction actually proceeds via a trapped abstraction mechanism, rather than an insertion mechanism as has long been thought. We anticipate that this reaction mechanism should also be responsible for the reaction of O((1)D) with ethane and propane, as well as many other chemical reactions with deep wells in the interaction region.
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