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  • Article
    Luo YD, Liu XY, Fang L, Yu HQ, Zhang YJ, Chen M, Zhang LD, Xie CM.
    Theranostics. 2022;12(18):7903-7919.
    Background & Aims: Abnormal activation of mTOR through loss of tuberous sclerosis complex (Tsc) frequently occurs in hepatocellular carcinoma (HCC). Mutant Kras could induce aggressive HCCs. Here, we aim to identify the predictive or prognostic biomarkers for HCC patients with Kras mutant and mTOR hyperactivation, and to provide potential therapeutic approaches for this subtype of HCCs. Methods: We generated transgenic mice in which hepatocytic mTOR was hyperactivated through Tsc1 insufficiency with or without oncogenic KrasG12D. Bioinformatics and gain- or loss-of-function studies were used to illustrate the mechanisms underlying oncogenic pathway alterations. Transcriptional profiling was used to identify biomarker for the subtype of HCC. The therapeutic efficacy of targeting mTOR was tested in a liver orthotropic homogeneous murine model. Results: Oncogenic KrasG12D facilitated mTOR activation via the Mek/Erk/ROS axis, leading to HCC tumorigenesis and metastasis. Inhibition of Mek/Erk enhanced the anticancer effect of mTOR inhibitor via reduction of mTOR activity. Paternally expressed 3 (PEG3) was responsible for Kras/Erk- and mTOR-driven HCC. Elevated PEG3 protein interacted with STAT3 and promoted its transcriptional activity, resulting in the upregulation of proliferation- and metastasis-related proteins. Targeting mTOR significantly inhibited these actions in vitro and in vivo. Moreover, in clinical samples, PEG3 was identified as a new poor prognostic marker for HCC patients with Kras/Erk and mTOR hyperactivation. Conclusion: These findings reveal the underlying mechanism of hepatocytic Kras/Erk-driven mTOR activation and its downstream targets (PEG3 and STAT3) in HCC, identify PEG3 as a new prognostic biomarker for HCC with Kras/Erk and mTOR hyperactivation, and provide a potential therapeutic strategy for this subset of HCC patients.
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  • Article
    Reig C, Cubells-Beltran MD, Muñoz DR.
    Sensors (Basel). 2009;9(10):7919-42.
    The 2007 Nobel Prize in Physics can be understood as a global recognition to the rapid development of the Giant Magnetoresistance (GMR), from both the physics and engineering points of view. Behind the utilization of GMR structures as read heads for massive storage magnetic hard disks, important applications as solid state magnetic sensors have emerged. Low cost, compatibility with standard CMOS technologies and high sensitivity are common advantages of these sensors. This way, they have been successfully applied in a lot different environments. In this work, we are trying to collect the Spanish contributions to the progress of the research related to the GMR based sensors covering, among other subjects, the applications, the sensor design, the modelling and the electronic interfaces, focusing on electrical current sensing applications.
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  • Article
    Petit A, Sandker M, Müller B, Meyboom R, van Midwoud P, Bruin P, Redout EM, Versluijs-Helder M, van der Lest CH, Buwalda SJ, de Leede LG, Vermonden T, Kok RJ, Weinans H, Hennink WE.
    Biomaterials. 2014 Sep;35(27):7919-28.
    In this study, we investigated the in vitro and in vivo properties and performance of a celecoxib-loaded hydrogel based on a fully acetyl-capped PCLA-PEG-PCLA triblock copolymer. Blends of different compositions of celocoxib, a drug used for pain management in osteoarthritis, and the acetyl-capped PCLA-PEG-PCLA triblock copolymer were mixed with buffer to yield temperature-responsive gelling systems. These systems containing up to 50 mg celecoxib/g gel, were sols at room temperature and converted into immobile gels at 37 °C. In vitro, release of celecoxib started after a ∼10-day lag phase followed by a sustained release of ∼90 days. The release was proven to be mediated by polymer dissolution from the gels. In vivo (subcutaneous injection in rats) experiments showed an initial celecoxib release of ∼30% during the first 3 days followed by a sustained release of celecoxib for 4-8 weeks. The absence of a lag phase and the faster release seen in vivo were likely due to the enhanced celecoxib solubility in biological fluids and active degradation of the gel by macrophages. Finally, intra-articular biocompatibility of the 50 mg/g celecoxib-loaded gel was demonstrated using μCT-scanning and histology, where no cartilage or bone changes were observed following injection into the knee joints of healthy rats. In conclusion, this study shows that celecoxib-loaded acetyl-capped PCLA-PEG-PCLA hydrogels form a safe drug delivery platform for sustained intra-articular release.
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  • Article
    Cao Y, Zhang H, Tang J, Wang R.
    Bioengineered. 2022 03;13(3):7919-7925.
    Long non-coding RNA (lncRNA) FAM230B has been reported to participate in gastric cancer and papillary thyroid cancer, while its role in other cancers has not been reported. We then explored the role of FAM230B in lung adenocarcinoma (LA). This study enrolled a total of 60 LA patients, 60 patients with gastric reflux disease (GRD), 60 cases of chronic obstructive pulmonary disease (COPD), 60 cases of asthma and 60 cases of healthy controls. LA and paired non-tumor tissues were donated by all LA patients. Plasma samples were donated by all participants. Expression of FAM230B in these samples was determined by RT-qPCR. The 60 LA patients were followed up for 5 years to evaluate the prognostic value of plasma FAM230B for LA. Diagnostic value of FAM230B for LA was analyzed with ROC curve analysis. FAM230B was highly expressed in LA tissues compared to that in non-tumor samples. In addition, plasma FAM230B was specifically upregulated in LA patients, but not in GRD, COPD and asthma patients. High expression levels of FAM230B in plasma samples were closely correlated with poor survival. Plasma FAM230B effectively separated LA patients from GRD, COPD, asthma and control groups. Plasma FAM230B was closely correlated with tumor size, but not other clinical factors of LA patients. Therefore, FAM230B is highly upregulated in LA and may serve as a potential diagnostic and prognostic biomarker for LA.
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  • Article
    Sato K, Oaki Y, Imai H.
    Chem Commun (Camb). 2015 May 07;51(37):7919-22.
    The hierarchical porous structures of vinyl polymers, such as polystyrene (PSt) and poly(methyl methacrylate) (PMMA), were derived from morphologies of a biomineral through replication. The resultant PSt hierarchical structures showed enhanced adsorption properties of organic molecules as hydrophobic adsorbents in an aqueous medium.
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  • Article
    Ning B, Guo S, Mei Y.
    Bioengineered. 2021 12;12(1):7907-7919.
    Long non-coding RNA (lncRNA) CASC9 is reported to be a tumor promoter in oral cancer, but its mechanism in oral squamous cell carcinoma (OSCC) has not been fully explored. Our study aimed to identify the interaction between lncRNA CASC9, microRNA-545-3p (miR-545-3p), and laminin subunit gamma 2 (LAMC2) in OSCC cells. Our study confirmed that lncRNA CASC9 and LAMC2 were upregulated in OSCC, whereas miR-545-3p expression was reduced. After performing a series of cell functional experiments, it was found that knockdown of lncRNA CASC9 or LAMC2 resulted in the inhibition of proliferation, colony formation, and migration of OSCC cells, but their negative effects could be partly impaired by the miR-545-3p inhibitor. In addition, we proved for the first time that lncRNA CASC9 can sponge miR-545-3p to upregulate LAMC2. In conclusion, our study revealed that lncRNA CASC9 promotes the malignancy of OSCC cells by sponging miR-545-3p to enhance LAMC2 expression, implying that lncRNA CASC9/miR-545-3p/LAMC2 may be an intervention approach in OSCC therapy.
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  • Article
    Omara T, Karungi S, Kalukusu R, Nakabuye B, Kagoya S, Musau B.
    PeerJ. 2019;7:e7919.
    The mercury content and the contamination characteristics of water, sediments, edible muscles of a non-piscivorous fish (Oreochromis nilotica Linnaeus 1758 [Cichlidae]) and yams (Dioscorea alata) from Namukombe stream in Busia gold district of Uganda were evaluated. Human health risk assessment from consumption of contaminated fish and yams as well as contact with contaminated sediments from the stream were performed. Forty-eight (48) samples of water (n = 12), sediments (n = 12), fish (n = 12) and yams (n = 12) were taken at intervals of 10 m from three gold recovery sites located at up, middle and down sluices of the stream and analyzed for total mercury (THg) using US EPA method 1631. Results (presented as means  ±  standard deviations) showed that water in the stream is polluted with mercury in the range of < detection limit to 1.21  ±  0.040 mg/L while sediments contain mean THg from < detection limit to 0.14  ±  0.040 ugg-1. Mean THg content of the edible muscles of O. nilotica ranged from < detection limit to 0.11 ± 0.014 ugg-1while D. alata contained from < detection limit to 0.30  ±  0.173 ugg-1mean THg. The estimated daily intake ranged from 0.0049 ugg-1day-1 to 0.0183 ugg-1day-1 and 0.0200 ugg-1day-1 to 0.0730 ugg-1day-1 for fish consumed by adults and children respectively. The corresponding health risk indices ranged from 0.0123 to 0.0458 and 0.0500 to 0.1830. Estimated daily intake was from 0.0042 ugg-1day-1 to 0.1279 ugg-1day-1 and 0.0130 ugg-1day-1 to 0.3940 ugg-1day-1 for D. alata consumed by adults and children respectively. The health risk indices recorded were from 0.011 to 0.320 and 0.033 to 0.985 for adults and children respectively. The mean THg content of the sediments, edible muscles of O. nilotica and D. alata were within acceptable WHO/US EPA limits. About 91.7% of the water samples had mean THg above US EPA maximum permissible limit for mercury in drinking water. Consumption of D. alata grown within 5 m radius up sluice of Namukombe stream may pose deleterious health risks as reflected by the health risk index of 0.985 being very close to one. From the pollution and risk assessments, mercury use should be delimited in Syanyonja artisanal gold mining areas. A solution to abolish mercury-based gold mining in the area needs to be sought as soon as possible to avert the accentuating health, economic and ecological disaster arising from the continuous discharge of mercury into the surrounding areas. Other mercury-free gold recovering methods such as use of borax, sluice boxes and direct panning should be encouraged. Waste management system for contaminated wastewater, used mercury bottles and tailings should be centralized.
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  • Article
    Motta S, Siani P, Donadoni E, Frigerio G, Bonati L, Di Valentin C.
    Nanoscale. 2023 May 04;15(17):7909-7919.
    Inorganic nanoparticles show promising properties that allow them to be efficiently used as drug carriers. The main limitation in this type of application is currently the drug loading capacity, which can be overcome with a proper functionalization of the nanoparticle surface. In this study, we present, for the first time, a computational approach based on metadynamics to estimate the binding free energy of the doxorubicin drug (DOX) to a functionalized TiO2 nanoparticle under different pH conditions. On a thermodynamic basis, we demonstrate the robustness of our approach to capture the overall mechanism behind the pH-triggered release of DOX due to environmental pH changes. Notably, binding free energy estimations align well with what is expected for a pH-sensitive drug delivery system. Based on our results, we envision the use of metadynamics as a promising computational tool for the rational design and in silico optimization of organic ligands with improved drug carrier properties.
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  • Article
    Foresti S, Di Bella S, Rovelli A, Sala A, Verna M, Bisi L, Nisii C, Gori A.
    Antimicrob Agents Chemother. 2015 Dec;59(12):7919-20.
    Catheter-related bacteremias carry high mortality rates in hematological patients. When a multidrug-resistant microorganism is involved, the catheter should ideally be removed; however, this approach is not always possible. Tigecycline lock therapy was used in two pediatric oncohematological patients with intravascular catheter-related infection due to KPC-producing Klebsiella pneumoniae. The catheter was salvaged in both cases, and the patients were later discharged. Our experience suggests the usefulness of this approach in treating this type of infection.
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  • Article
    Solsi A, Pho K, Shojaie S, Findakly D, Noori T.
    Cureus. 2020 May 01;12(5):e7919.
    Solitary fibrous tumors (SFT) represent a unique subset of mostly benign heterogeneous tumors with mesenchymal cell origins. These tumors have been reported in the past as being mostly indolent, with a slowly evolving clinical course and low potential for malignancy. Although found systemically, the incidence of SFT arising intrathoracically, from the pleura of the lung, is relatively poorly documented in the medical literature. SFT is a rare phenomenon, but in even rarer circumstances, these tumors are associated with distinctive paraneoplastic syndromes, such as Pierre-Marie-Bamberger syndrome (PMBS) and Doege-Potter syndrome (DPS). PMBS presents as digital clubbing and hypertrophic pulmonary osteoarthropathy. DPS has been characterized as a non-islet cell tumor hypoglycemia due to the ectopic secretion of insulin-like growth factor 2 (IGF-2), a pattern seen in fewer than 5% of cases of SFT. Treatment is typically through surgical resection. In our research of the medical literature, we found only very few cases in which the association with SFT and both paraneoplastic syndromes were described. Here, we report an uncommon case of a 68-year-old male patient found to have an incidental right hemithoracic tumor with digital clubbing and intermittent severe episodes of fasting hypoglycemia after initially presenting with a syncopal episode.
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  • Article
    Int J Nanomedicine. 2019;14:7919.
    [This corrects the article DOI: 10.2147/IJN.S210731.].
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  • Article
    Purnomo A, Hayashibe M.
    Sci Rep. 2023 May 16;13(1):7919.
    The autonomous distillation of physical laws only from data is of great interest in many scientific fields. Data-driven modeling frameworks that adopt sparse regression techniques, such as sparse identification of nonlinear dynamics (SINDy) and its modifications, are developed to resolve difficulties in extracting underlying dynamics from experimental data. However, SINDy faces certain difficulties when the dynamics contain rational functions. The Lagrangian is substantially more concise than the actual equations of motion, especially for complex systems, and it does not usually contain rational functions for mechanical systems. Few proposed methods proposed to date, such as Lagrangian-SINDy we have proposed recently, can extract the true form of the Lagrangian of dynamical systems from data; however, these methods are easily affected by noise as a fact. In this study, we developed an extended version of Lagrangian-SINDy (xL-SINDy) to obtain the Lagrangian of dynamical systems from noisy measurement data. We incorporated the concept of SINDy and used the proximal gradient method to obtain sparse Lagrangian expressions. Further, we demonstrated the effectiveness of xL-SINDy against different noise levels using four mechanical systems. In addition, we compared its performance with SINDy-PI (parallel, implicit) which is a latest robust variant of SINDy that can handle implicit dynamics and rational nonlinearities. The experimental results reveal that xL-SINDy is much more robust than the existing methods for extracting the governing equations of nonlinear mechanical systems from data with noise. We believe this contribution is significant toward noise-tolerant computational method for explicit dynamics law extraction from data.
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  • Article
    Zhang P, Xu X, Zhang M, Wang J, Bai G, Yan H.
    Langmuir. 2015 Jul 28;31(29):7919-25.
    The self-aggregation of amphiphilic dendrimers G1QPAMCm based on poly(amidoamine) PAMAM possessing the same hydrophilic group but differing in alkyl chain length in aqueous solution was investigated. Differences in the chemical structures lead to significant specificities in the aggregate building process. A variety of physicochemical parameters presented monotonous regularity with the increase in alkyl chain length in multibranched structure, as traditional amphiphilic molecules. A significant difference, however, existed in the morphology and the microenvironment of the microdomain of the aggregates, with G1QPAMCm with an alkyl chain length of 16 intending to form vesicles. To obtain supporting information about the aggregation mechanism, the thermodynamic parameters of micellization, the free Gibbs energy ΔGmic, and the entropy ΔSmic were derived subsequently, of which the relationship between the hydrophobic chain length and the thermodynamic properties indicated that the self-assembly process was jointly driven by enthalpy and entropy. Other than traditional surfactants, the contribution of enthalpy has not increased identically to the increase in hydrophobic interactions, which depends on the ratio of the alkyl chain length to the radius in the headgroup. Continuous increases in the hydrophobic chain length from 12 to 16 lead to the intracohesion of the alkyl chain involved in the process of self-assembly, weakening the hydrophobic interactions, and the increase in -ΔHmic, which offers an explanation of the formation of vesicular structures.
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  • Article
    Chiu TC.
    Anal Bioanal Chem. 2013 Oct;405(25):7919-30.
    This article highlights recent methodological developments in the on-line concentration and separation of amino acids and their enantiomers using capillary electrophoresis. Sections are dedicated to recent contributions to on-line concentration strategies such as field-amplified sample stacking, large-volume sample stacking, dynamic pH junction, transient isotachophoresis, sweeping, and the combination of two methods. The main applications, advantages, and limitations of these procedures in the biological, food, and pharmaceutical fields are addressed. Comprehensive tables listing on-line techniques for the concentration and separation of amino acids and their enantiomers, categorized by the stacking strategies used, background electrolytes, sample matrix, limit of detection, and enhancement factor, are provided.
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  • Article
    Sun M, Hao B, Yang S, Wang X, Majidi C, Zhang L.
    Nat Commun. 2022 12 23;13(1):7919.
    Miniature magnetic soft machines could significantly impact minimally invasive robotics and biomedical applications. However, most soft machines are limited to solid magnetic materials, whereas further progress also relies on fluidic constructs obtained by reconfiguring liquid magnetic materials, such as ferrofluid. Here we show how harnessing the wettability of ferrofluids allows for controlled reconfigurability and the ability to create versatile soft machines. The ferrofluid droplet exhibits multimodal motions, and a single droplet can be controlled to split into multiple sub-droplets and then re-fuse back on demand. The soft droplet machine can negotiate changing terrains in unstructured environments. In addition, the ferrofluid droplets can be configured as a liquid capsule, enabling cargo delivery; a wireless omnidirectional liquid cilia matrix capable of pumping biofluids; and a wireless liquid skin, allowing multiple types of miniature soft machine construction. This work improves small magnetic soft machines' achievable complexity and boosts their future biomedical applications capabilities.
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  • Article
    Chen D, Bryden NA, Bryden WA, McLoughlin M, Smith D, Devin AP, Caton ER, Haddaway CR, Tameris M, Scriba TJ, Hatherill M, Gessner S, Warner DF, Wood R.
    Sci Rep. 2022 05 13;12(1):7919.
    Human breath contains trace amounts of non-volatile organic compounds (NOCs) which might provide non-invasive methods for evaluating individual health. In previous work, we demonstrated that lipids detected in exhaled breath aerosol (EBA) could be used as markers of active tuberculosis (TB). Here, we advanced our analytical platform for characterizing small metabolites and lipids in EBA samples collected from participants enrolled in clinical trials designed to identify molecular signatures of active TB. EBA samples from 26 participants with active TB and 73 healthy participants were processed using a dual-phase extraction method, and metabolites and lipids were identified via mass spectrometry database matching. In total, 13 metabolite and 9 lipid markers were identified with statistically different optimized relative standard deviation values between individuals diagnosed with active TB and the healthy controls. Importantly, EBA lipid profiles can be used to separate the two sample types, indicating the diagnostic potential of the identified molecules. A feature ranking algorithm reduced this number to 10 molecules, with the membrane glycerophospholipid, phosphatidylinositol 24:4, emerging as the top driver of segregation between the two groups. These results support the use of this approach to identify consistent NOC signatures from EBA samples in active TB cases. This suggests the potential to apply this method to other human diseases which alter respiratory NOC release.
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  • Article
    Zohar N, Haran G.
    Langmuir. 2014 Jul 08;30(26):7919-27.
    Dimers of metallic nanoparticles can serve as antennas to locally enhance optical fields through plasmonic excitations. Such dimeric structures can be particularly useful for sensing applications using surface-enhanced Raman scattering (SERS). It has been challenging to devise a synthetic scheme that facilitates creating dimer antennas from different types of particles, at the same time allowing control over the size of the gap between the particles and enabling the introduction of any molecule into the gap. We describe here a method that answers to this challenge. We first introduce a recipe for the creation of a silica shell as thin as 1 nm on silver particles. Analyte molecules are attached to the silica shell, and finally, the silica-shell silver-core particles, whose surface is negatively charged, are mixed with positively charged bare silver particles to create dimers. A demonstration of SERS from individual dimers with gaps of 1.4 and 3.7 nm paves the way to systematic studies of the effect of gap size and composition on plasmonic enhancement.
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  • Article
    Sato H, Matsuda R, Mir MH, Kitagawa S.
    Chem Commun (Camb). 2012 Aug 18;48(64):7919-21.
    Photochemical [2+2] cycloaddition reactions in a two-dimensional interdigitated porous crystalline framework proceed in a single-crystal-to-single-crystal manner, and one-dimensional channels show structural changes that have a significant impact on the CO(2) sorption.
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  • Article
    Hashimoto K, Inada M, Yamamoto Y, Ochiya T.
    Heliyon. 2021 Sep;7(9):e07919.
    Early detection and treatment are crucial for increasing the five-year survival rates of various cancers. Low-cost and convenient cancer screening tests are also critically important. Circulating microRNAs are reported as potential biomarkers for various cancers. Recently, miR-1307-3p was found to be a cancer-related microRNA. We evaluated the expression levels of miR-1307-3p in sera obtained from 254 patients with thirteen types of cancer (colon cancer, lung cancer, gastric cancer, liver cancer, bladder cancer esophageal cancer, breast cancer, ovarian cancer, prostate cancer, pancreatic cancer, biliary tract cancer, brain cancer, sarcoma) and 27 non-cancer samples using isothermal amplification and microRNA chip. The expression levels of miR-1307-3p in sera obtained from cancer patients were clearly different from those obtained from non-cancer samples and differentiated the validation cohort into cancer patients and non-cancer control with high accuracy (AUC: 0.98; sensitivity: 0.98; specificity: 0.85). These results showed the potential relevance of miR-1307-3p in serum for the development of new diagnostic examination tools for cancer patients.
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  • Article
    Thomas N, Baltezar P, Lagomasino D, Stovall A, Iqbal Z, Fatoyinbo L.
    Sci Rep. 2021 04 12;11(1):7919.
    Trees outside forests (TOF) are an underrepresented resource in forest poor nations. As a result of their frequent omission from national forest resource assessments and a lack of readily available very-high-resolution remotely sensed imagery, TOF status and characterization has until now, been unknown. Here, we assess the capacity of openly available 10 m ESA Sentinel constellation satellite imagery for mapping TOF extent at the national level in Bangladesh. In addition, we estimate canopy height for TOF using a TanDEM-X DEM. We map 2,233,578 ha of TOF in Bangladesh with a mean canopy height of 7.3 m. We map 31 and 53% more TOF than existing estimates of TOF and forest, respectively. We find TOF in Bangladesh is nationally fragmented as a consequence of agricultural activity, yet is capable of maintaining connectedness between remaining stands. Now, TOF accounting is feasible at the national scale using readily available datasets, enabling the mainstream inclusion of TOF in national forest resource assessments for other countries.
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