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  • Article
    Shi Y, van der Meel R, Chen X, Lammers T.
    Theranostics. 2020;10(17):7921-7924.
    Following its discovery more than 30 years ago, the enhanced permeability and retention (EPR) effect has become the guiding principle for cancer nanomedicine development. Over the years, the tumor-targeted drug delivery field has made significant progress, as evidenced by the approval of several nanomedicinal anticancer drugs. Recently, however, the existence and the extent of the EPR effect - particularly in patients - have become the focus of intense debate. This is partially due to the disbalance between the huge number of preclinical cancer nanomedicine papers and relatively small number of cancer nanomedicine drug products reaching the market. To move the field forward, we have to improve our understanding of the EPR effect, of its cancer type-specific pathophysiology, of nanomedicine interactions with the heterogeneous tumor microenvironment, of nanomedicine behavior in the body, and of translational aspects that specifically complicate nanomedicinal drug development. In this virtual special issue, 24 research articles and reviews discussing different aspects of the EPR effect and cancer nanomedicine are collected, together providing a comprehensive and complete overview of the current state-of-the-art and future directions in tumor-targeted drug delivery.
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  • Article
    Del Carratore F, Lussu M, Kowalik MA, Perra A, Griffin JL, Atzori L, Grosso M.
    Anal Chem. 2016 08 16;88(16):7921-9.
    In a typical metabolomics experiment, two or more conditions (e.g., treated versus untreated) are compared, in order to investigate the potential differences in the metabolic profiles. When dealing with complex biological systems, a two-class classification is often unsuitable, since it does not consider the unpredictable differences between samples (e.g., nonresponder to treatment). An approach based on statistical process control (SPC), which is able to monitor the response to a treatment or the development of a pathological condition, is proposed here. Such an approach has been applied to an experimental hepatocarcinogenesis model to discover early individual metabolic variations associated with a different response to the treatment. Liver study was performed by nuclear magnetic resonance (NMR) spectroscopy, followed by multivariate statistical analysis. By this approach, we were able to (1) identify which treated samples have a significantly different metabolic profile, compared to the control (in fact, as confirmed by immunohistochemistry, the method correctly classified 7 responders and 3 nonresponders among the 10 treated animals); (2) recognize, for each individual sample, the metabolites that are out of control (e.g., glutathione, acetate, betaine, and phosphocholine). The first point could be used for classification purposes, and the second point could be used for a better understanding of the mechanisms underlying the early phase of carcinogenesis. The statistical control approach can be used for diagnosis (e.g., healthy versus pathological, responder versus nonresponder) and for generation of an individual metabolic profile, leading to a better understanding of the individual pathological processes and to a personalized diagnosis and therapy.
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  • Article
    Bull JJ, Remien CH, Gomulkiewicz R, Krone SM.
    PeerJ. 2019;7:e7921.
    Gene drives may be used in two ways to curtail vectored diseases. Both involve engineering the drive to spread in the vector population. One approach uses the drive to directly depress vector numbers, possibly to extinction. The other approach leaves intact the vector population but suppresses the disease agent during its interaction with the vector. This second application may use a drive engineered to carry a genetic cargo that blocks the disease agent. An advantage of the second application is that it is far less likely to select vector resistance to block the drive, but the disease agent may instead evolve resistance to the inhibitory cargo. However, some gene drives are expected to spread so fast and attain such high coverage in the vector population that, if the disease agent can evolve resistance only gradually, disease eradication may be feasible. Here we use simple models to show that spatial structure in the vector population can greatly facilitate persistence and evolution of resistance by the disease agent. We suggest simple approaches to avoid some types of spatial structure, but others may be intrinsic to the populations being challenged and difficult to overcome.
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  • Article
    Khaderi SN, den Toonder JM, Onck PR.
    Langmuir. 2012 May 22;28(20):7921-37.
    Natural cilia are hairlike microtubule-based structures that are able to move fluid on the micrometer scale using asymmetric motion. In this article, we follow a biomimetic approach to design artificial cilia lining the inner surfaces of microfluidic channels with the goal of propelling fluid. The artificial cilia consist of polymer films filled with superparamagnetic nanoparticles, which can mimic the motion of natural cilia when subjected to a rotating magnetic field. To obtain the magnetic field and associated magnetization local to the cilia, we solve the Maxwell equations, from which the magnetic body moments and forces can be deduced. To obtain the ciliary motion, we solve the dynamic equations of motion, which are then fully coupled to the Navier-Stokes equations that describe the fluid flow around the cilia, thus taking full account of fluid inertial forces. The dimensionless parameters that govern the deformation behavior of the cilia and the associated fluid flow are arrived at using the principle of virtual work. The physical response of the cilia and the fluid flow for different combinations of elastic, fluid viscous, and inertia forces are identified.
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  • Article
    Xia J, Sun J, Li L, Fang LX, Deng H, Yang RS, Li XP, Liao XP, Liu YH.
    Antimicrob Agents Chemother. 2015 Dec;59(12):7921-2.
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  • Article
    Chacha R, Miry A, Serji B, Brahmi SA, Afqir S.
    Cureus. 2020 May 01;12(5):e7921.
    Ovarian granulosa cell tumors are rare gynecological cancers with favorable clinical evolution and survival outcomes. We report a new case of this presentation in a patient that was initially diagnosed as a bilateral primary melanoma of the ovary. The patient is a 51-year-old woman with a history of abdominal swelling and deterioration of her general conditions. Physical examination revealed abdominal distension and diffuse dullness with initially highly elevated cancer antigen 125. Contrast-enhanced thoracoabdominal-pelvic computed tomography showed a left-sided ovarian mass and abundant ascites and pleurisy. Ex-lap surgery found two large bilateral ovarian masses associated with peritoneal carcinomatosis and highly abundant ascites. The histopathological examination of the omental biopsy revealed an undifferentiated tumor proliferation of cells with highly positive Human Melanoma Black 45 marker in favor of an achromic malignant melanoma according to the pathologist. Because of her advanced disease, the patient received a combination of six cycles of neoadjuvant dacarbazine, cisplatin, and paclitaxel and showed partial response based on the response evaluation criteria in solid tumors, followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy with cytoreductive surgery. Unexpectedly, the histopathological analysis of the surgical specimens was in favor of an advanced adult granulosa cell tumor with positive inhibin B. Our patient is alive at her 13th month of survival and is being followed by the oncology team. The challenges of the pathological diagnosis of this case are discussed. The diagnosis of primary ovarian melanoma should not be based on one immunohistochemical marker only. A single biopsy of omental implants in peritoneal carcinomatosis during ex-lap surgery should be avoided.
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  • Article
    Audran G, Brémond P, Marque SR.
    Chem Commun (Camb). 2014 Jul 28;50(59):7921-8.
    Alkoxyamines--per-alkylated derivatives of hydroxylamine R(1)R(2)NO-R(3)--can undergo C-ON bond homolysis to release a persistent nitroxyl radical R(1)R(2)NO˙ and a transient alkyl radical R(3)˙. Although they were considered as an oddity when discovered in 1974, their properties have been extensively studied since the seminal work of Solomon, Rizzardo and Cacioli (Chem. Abstr., 102, 221335q), who patented the key role of alkoxyamines in nitroxide-mediated polymerization (NMP) in 1985. This feature article surveys and assesses the various applications of alkoxyamines: in tin-free radical chemistry, e.g., for the elaboration of carbo- or hetero-cycles, for the development of new reactions, for total synthesis of natural products; in polymerization under thermal conditions (NMP) or photochemical conditions (nitroxide-mediated photo-polymerization, NMP2); and in the design of smart materials. In this feature article, we also describe our recent findings concerning the chemical triggering of the C-ON bond homolysis in alkoxyamines, affording the controlled generation of alkyl radicals at room temperature. Based on these results, we describe herein some new opportunities for applications in the field of smart materials, and of course, some possible developments as new initiators for NMP as well as an entirely new field of application: the use of alkoxyamines as theranostic agents. Indeed, each of the radicals released after homolysis can play an appealing role: the nitroxide, through dynamic nuclear polarization (DNP), can be used for imagery purposes (diagnostic properties), while the alkyl radical can be used to induce cellular disorders in abnormal cells (therapeutic activity).
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  • Article
    Rehman HU, Ullah K, Rasool A, Manzoor R, Yuan Y, Tareen AM, Kaleem I, Riaz N, Hameed S, Bashir S.
    Sci Rep. 2023 05 16;13(1):7921.
    Diabetes mellitus is a syndrome and an endocrine disorder, primarily considered as a loss of glucose homeostasis because of the insulin action and/or secretion or both. Currently there are more than 150 million people in the world affected by diabetes mellitus with a higher share of Asian and European countries. The current study aimed to investigate the comparative altering properties of streptozotocin (STZ), based on up-turn and down-turn configuration of biochemical, toxicological and hematological parameters in comparison with normoglycemic male albino rats. This comparative study was conducted among normoglycemic and STZ based induced-type 2 diabetic male albino rats groups. The male albino rats were intra-peritoneally injected with STZ with the dose rate of 65 mg/kg body weight for one time to developed type 2 diabetic model. Biochemical (blood glucose, uric acid, urea and creatinine), toxicological (AST, ALT and ALP) and hematological parameters (red and white blood cells) and their functional indices were evaluated in type 2 diabetic induced group along with normoglycemic rats. The STZ based induced- type 2 diabetic rats showed statistically significance (p < 0.001) higher level in the blood glucose, alongwith the change in the levels of biochemical parameters including urea, uric acid, and creatinine. Toxicological parameters comprising AST, ALT and ALP were also shown significance (p < 0.001) as sufficient after experimental evaluation of biologically important parameter in STZ based induced-type 2 diabetic rats. Likewise, the red blood cells, white blood cells and their efficient components were exposed significantly insufficient after the injecting of STZ to induce the rats as type 2 diabetic. The results of the current study indicates the comparatively higher levels of variation among biochemical, toxicological and hematological parameters in STZ based Induced-type 2 diabetic model as compared to normoglycemic group.
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  • Article
    Gruber M, Ibrahim F, Boukari S, Joly L, Da Costa V, Studniarek M, Peter M, Isshiki H, Jabbar H, Davesne V, Arabski J, Otero E, Choueikani F, Chen K, Ohresser P, Wulfhekel W, Scheurer F, Beaurepaire E, Alouani M, Weber W, Bowen M.
    Nano Lett. 2015 Dec 09;15(12):7921-6.
    We experimentally and theoretically show that the magnetic coupling at room temperature between paramagnetic Mn within manganese phthalocyanine molecules and a Co layer persists when separated by a Cu spacer. The molecule's magnetization amplitude and direction can be tuned by varying the Cu-spacer thickness and evolves according to an interlayer exchange coupling mechanism. Ab initio calculations predict a highly spin-polarized density of states at the Fermi level of this metal-molecule interface, thereby strengthening prospective spintronics applications.
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  • Article
    Yao QM, Li PP, Liang SM, Lu K, Zhu XJ, Liu YX, Zhang F, Yuan T, Wang X.
    Int J Clin Exp Pathol. 2015;8(7):7921-8.
    High dose methylprednisolone (HDMP) has been an effective salvage therapy for patients with relapsed chronic lymphocytic leukemia (CLL), while little is known about the exact mechanisms implicated in glucocorticoid-induced cell death. To explore the mechanism of glucocorticoid-induced cell death, we investigated the effect of HDMP on canonical Wnt signaling which emerged as a key pathway implicated in the pathogenesis of CLL. In this study, the human CLL cell line MEC-1 was incubated with various concentrations of methylprednisolone. Cell proliferation activity was detected by CCK8 assay, the apoptotic effect was evaluated by TUNEL assay. Western blot was used to detect active-caspase 3, and the key proteins in Wnt signaling pathway (LEF-1, β-catenin). RT-PCR was performed to assess the mRNA levels of β-catenin, LEF-1, c-myc and cyclin D1. We observed that high concentration of methylprednisolone could suppress the proliferation activity of MEC-1 cells, promote the relative expression of active-caspase 3, and induce apoptotic cell death. Furthermore, methylprednisolone could inhibit LEF-1 protein expression, consequently down-regulate mRNA levels of c-myc and cyclin D1, but could not affect the transcription level of β-catenin and LEF-1 mRNA. The results of this study indicate that methylprednisolone can suppress Wnt signaling pathway by down-regulating LEF-1 protein expression, indicating a novel mechanism for HDMP therapy in CLL.
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  • Article
    Suzuki E, Imoto I, Pimkhaokham A, Nakagawa T, Kamata N, Kozaki KI, Amagasa T, Inazawa J.
    Oncogene. 2007 Dec 13;26(57):7921-32.
    Array-based comparative genomic hybridization (array-CGH) has good potential for the high-throughput identification of genetic aberrations in cell genomes. In the course of a program to screen a panel of oral squamous-cell carcinoma (OSCC), cell lines for genomic copy-number aberrations by array-CGH using our in-house arrays, we identified a 3-Mb homozygous deletion at 10p12 in 1 of 18 cell lines (5.6%). Among seven genes located within this region, expression of PRTFDC1 mRNA was not detected in 50% (9/18) or decreased in 5.6% (1/18) of OSCC cell lines, but detected in normal oral epithelia and restored in gene-silenced OSCC cells without its homozygous loss after treatment with 5-aza-2'-deoxycytidine. Among 17 cell lines without a homozygous deletion, the hypermethylation of the PRTFDC1 CpG island, which showed promoter activity, was observed in all nine cell lines with no or reduced PRTFDC1 expression (52.9%). Methylation of this CpG island was also observed in primary OSCC tissues (8/47, 17.0%). In addition, restoration of PRTFDC1 in OSCC cells lacking its expression inhibited cell growth in colony-formation assays, whereas knockdown of PRTFDC1 expression in OSCC cells expressing the gene promoted cell growth. These results suggest that epigenetic silencing of PRTFDC1 by hypermethylation of the CpG island leads to a loss of PRTFDC1 function, which might be involved in squamous cell oral carcinogenesis.
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  • Article
    Helman D, Bonfil DJ.
    Sci Rep. 2022 05 13;12(1):7921.
    Future atmospheric carbon-dioxide concentration ([CO2]) rise is expected to increase the grain yield of C3 crops like wheat even higher under drought. This expectation is based on small-scale experiments and model simulations based on such observations. However, this combined effect has never been confirmed through actual observations at the nationwide or regional scale. We present the first evidence that warming and drought in the world's leading wheat-producing countries offset the benefits of increasing [CO2] to wheat yield in the last six decades. Using country-level wheat yield census observations, [CO2] records, and gridded climate data in a statistical model based on a well-established methodology, we show that a [CO2] rise of ~ 98 μmol mol-1 increased the yield by 7% in the area of the top-twelve wheat-producing countries, while warming of 1.2 °C and water depletion of ~ 29 mm m-2 reduced the wheat grain yield by ~ 3% and ~ 1%, respectively, in the last six decades (1961-2019). Our statistical model corroborated the beneficial effect of [CO2] but contrasted the expected increase of grain yield under drought. Moreover, the increase in [CO2] barely offsets the adverse impacts of warming and drought in countries like Germany and France, with a net yield loss of 3.1% and no gain, respectively, at the end of the sampling period relative to the 1961-1965 baseline. In China and the wheat-growing areas of the former Soviet Union-two of the three largest wheat-producing regions-yields were ~ 5.5% less than expected from current [CO2] levels. Our results suggest shifting our efforts towards more experimental studies set in currently warm and dry areas and combining these with statistical and numerical modeling to improve our understanding of future impacts of a warmer and drier world with higher [CO2].
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  • Article
    El Moll H, Zhu W, Oldfield E, Rodriguez-Albelo LM, Mialane P, Marrot J, Vila N, Mbomekallé IM, Rivière E, Duboc C, Dolbecq A.
    Inorg Chem. 2012 Jul 16;51(14):7921-31.
    We report the synthesis and characterization of eight new Mo, W, or V-containing polyoxometalate (POM) bisphosphonate complexes with metal nuclearities ranging from 1 to 6. The compounds were synthesized in water by treating Mo(VI), W(VI), V(IV), or V(V) precursors with biologically active bisphosphonates H(2)O(3)PC(R)(OH)PO(3)H(2) (R = C(3)H(6)NH(2), Ale; R = CH(2)S(CH(3))(2), Sul and R = C(4)H(5)N(2), Zol, where Ale = alendronate, Sul = (2-Hydroxy-2,2-bis-phosphono-ethyl)-dimethyl-sulfonium and Zol = zoledronate). Mo(6)(Sul)(2) and Mo(6)(Zol)(2) contain two trinuclear Mo(VI) cores which can rotate around a central oxo group while Mo(Ale)(2) and W(Ale)(2) are mononuclear species. In V(5)(Ale)(2) and V(5)(Zol)(2) a central V(IV) ion is surrounded by two V(V) dimers bound to bisphosphonate ligands. V(6)(Ale)(4) can be viewed as the condensation of one V(5)(Ale)(2) with one additional V(IV) ion and two Ale ligands, while V(3)(Zol)(3) is a triangular V(IV) POM. These new POM bisphosphonates complexes were all characterized by single-crystal X-ray diffraction. The stability of the Mo and W POMs was studied by (31)P NMR spectroscopy and showed that all compounds except the mononuclear Mo(Ale)(2) and W(Ale)(2) were stable in solution. EPR measurements performed on the vanadium derivatives confirmed the oxidation state of the V ions and evidenced their stability in aqueous solution. Electrochemical studies on V(5)(Ale)(2) and V(5)(Zol)(2) showed reduction of V(V) to V(IV), and magnetic susceptibility investigations on V(3)(Zol)(3) enabled a detailed analysis of the magnetic interactions. The presence of zoledronate or vanadium correlated with the most potent activity (IC(50)~1-5 μM) against three human tumor cell lines.
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  • Article
    Hong J, Rui W, Fei X, Chen X, Shen K.
    Cancer Med. 2021 11;10(22):7921-7933.
    PURPOSE: To evaluate the predictive and prognostic value of tumor-infiltrating lymphocytes (TILs) before and after neoadjuvant chemotherapy (NAC) in patients with breast cancer.
    PATIENTS AND METHODS: Consecutive breast cancer patients treated with NAC between August 2008 and November 2019 were retrospectively analyzed. TIL levels were evaluated of invasive tumor samples, and high expression was defined as TILs >10%. Total pathological complete response (pCR) was defined as no invasive tumor in the breast or lymph nodes. Univariate and multivariate analyses were used to assess factors associated with pCR rate, disease-free survival (DFS), and overall survival.
    RESULTS: A total of 461 patients were included. The mean pre-NAC TIL level was higher among patients with pCR than among patients without pCR (24.28% ± 2.34% vs. 11.34% ± 0.60%, respectively, p < 0.0001). The multivariate analysis demonstrated that a high pre-NAC TIL level was an independent risk factor for a higher pCR (odds ratio = 3.92, 95% CI = 2.23-6.90, p < 0.001). Patients with high pre-NAC TIL levels had a better 5-year DFS than those with low pre-NAC TIL levels (84.5% vs. 68.9%, HR = 0.50, 95% CI = 0.31-0.81, p = 0.005). The multivariate analysis showed that pre-NAC TIL (HR = 0.48; 95% CI = 0.29-0.81, p = 0.006) but not post-NAC TIL (HR = 0.89, 95% CI = 0.50-1.59, p = 0.699) was significantly associated with DFS among patients without pCR. Furthermore, patients with low pre- and post-NAC TIL levels had a worse 5-year DFS than those with high pre-NAC TIL levels (HR = 2.09, 95% CI = 1.23-3.56, p = 0.007).
    CONCLUSIONS: Pre-NAC TIL level can predict pCR and DFS in patients with breast cancer receiving NAC. For patients without pCR, pre-NAC TIL, and TIL category change, but not post-NAC TIL, were significantly associated with DFS.
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  • Article
    Filippi I, Lucero P, Bonansea RI, Lerda D, Butinof M, Fernandez RA, Wunderlin DA, Amé MV, Muñoz SE.
    Heliyon. 2021 Sep;7(9):e07921.
    The characterization of the population exposed to pesticides and the use of effective biomarkers to evaluate potential health effects are determinant to identify vulnerable groups, understanding the causality of diverse pathologies and propose prevention policies. This is particularly important in countries where intensive agricultural practices had an explosive expansion in last decades. The aim of this study was assessing the usefulness of two exposure indexes questionnaire-based: Intensity Level of the pesticide Exposure (ILE) and Cumulative Exposure Index (CEI) and their scales, in terrestrial applicators of pesticide from the Province of Córdoba (Argentina). The analysis was performed contrasting ILE and CEI results with perceived symptomatology, in addition to effect and exposure biomarkers. A cross-sectional study was designed to compare pesticides body burdens and effect biomarkers between subjects occupationally (OE) and non-occupationally exposed (NOE) to pesticides. Prevalence of perceived symptomatology and genotoxicity damage was higher in the OE group. The exposure condition was the only variable explaining these differences. Significant associations were found between CEI and neurologic symptomatology (p < 0.05) and between ILE and plasmatic cholinesterase (p < 0.1). However, residues of HCB, β-HCH, α-endosulfan, pp'DDE, endrin, β-endosulfan, pp'DDT, endosulfan sulfate and mirex were found in blood samples from both groups. To our knowledge, this is the first report on pesticides body burdens in occupational exposure settings in Argentina. So far, our current results indicate that the occupational condition affects the health of the workers. Significant associations found between symptomatology and biomarkers with scales of CEI and ILE suggest their usefulness to verify different levels of exposure. Further research is necessary to propose these indexes as an affordable tool for occupational health surveillance in areas with difficult access to health care centres.
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  • Article
    Ramia E, Zeenny RM, Hallit S, Salameh P.
    Sci Rep. 2021 04 12;11(1):7921.
    There is a limited number of studies assessing the epidemiology of Adverse Drug Events (ADEs) in the outpatient setting, especially those that do not result in healthcare use. The primary objective of this study was to assess the prevalence and determinants of self-reported ADEs among Lebanese outpatients. It was a cross-sectional observational study performed among Lebanese outpatients visiting community pharmacies across Lebanon. A questionnaire was designed to elicit patients' relevant information. The association between categorical variables were evaluated using Pearson χ2 test or Fisher's exact test. Binary logistic regression was performed to identify factors that affect the experience of self-reported ADEs. The study comprised 3148 patients. Around 37% of patients reported experiencing an ADE in the previous year. When ADEs occur, 70.5% of the respondents reported informing their physicians. Increasing number of medications per patient, use of injectable medication, and inquiring about potential drug-drug interactions were associated with higher experience of ADEs (p = 0.049; p = 0.003; and p = 0.009 respectively). Patients who received hospital discharge counseling reported experiencing less ADEs (p = 0.002). Our study showed prevalence of ADEs among Lebanese outpatients especially patients with polypharmacy, and highlighted the need to educate patients about the importance of reporting ADEs to their physicians.
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  • Article
    Paulik LB, Donald CE, Smith BW, Tidwell LG, Hobbie KA, Kincl L, Haynes EN, Anderson KA.
    Environ Sci Technol. 2016 07 19;50(14):7921-9.
    Natural gas extraction, often referred to as "fracking", has increased rapidly in the United States in recent years. To address potential health impacts, passive air samplers were deployed in a rural community heavily affected by the natural gas boom. Samplers were analyzed for 62 polycyclic aromatic hydrocarbons (PAHs). Results were grouped based on distance from each sampler to the nearest active well. Levels of benzo[a]pyrene, phenanthrene, and carcinogenic potency of PAH mixtures were highest when samplers were closest to active wells. PAH levels closest to natural gas activity were comparable to levels previously reported in rural areas in winter. Sourcing ratios indicated that PAHs were predominantly petrogenic, suggesting that PAH levels were influenced by direct releases from the earth. Quantitative human health risk assessment estimated the excess lifetime cancer risks associated with exposure to the measured PAHs. At sites closest to active wells, the risk estimated for maximum residential exposure was 0.04 in a million, which is below the U.S. Environmental Protection Agency's acceptable risk level. Overall, risk estimates decreased 30% when comparing results from samplers closest to active wells to those farthest from them. This work suggests that natural gas extraction is contributing PAHs to the air, at levels that would not be expected to increase cancer risk.
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  • Article
    Syme CD, Sirimuthu NM, Faley SL, Cooper JM.
    Chem Commun (Camb). 2010 Nov 14;46(42):7921-3.
    We report for the first time the time-resolved mapping of intracellular nanoparticle labels from within living cells retained in a microstructured trap using Raman spectroscopy. The methods employed here also demonstrate the ability to rapidly discriminate between cell populations containing different SERS labels.
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  • Article
    Song X, Gou R, Wen A.
    Sci Rep. 2020 May 13;10(1):7921.
    As an important subtopic of classical cryptography, secure multiparty quantum computation allows multiple parties to jointly compute their private inputs without revealing them. Most existing secure multiparty computation protocols have the shortcomings of low computational efficiency and high resource consumption. To remedy these shortcomings, we propose a secure multiparty quantum computation protocol by using the Lagrange unitary operator and the Shamir (t, n) threshold secret sharing, in which the server generates all secret shares and distributes each secret share to the corresponding participant, in addition, he prepares a particle and sends it to the first participant. The first participant performs the Lagrange unitary operation on the received particle, and then sends the transformed particle to the next participant. Until the last participant's computation task is completed, the transformed particle is sent back to the server. The server performs Lagrange unitary operation on the received particle by using a secret message, and then measures the transformed particle to obtain the sum of the calculations of multiple participants. Security analysis shows that the proposed protocol can resist intercept-measurement attack, intercept-resend attack, entanglement-swapping attack, entanglement-measurement attack and collusion attack. Performance comparison shows that it has higher computation efficiency and lower resource consumption than other similar protocols.
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  • Article
    Alsagaby SA, Vijayakumar R, Premanathan M, Mickymaray S, Alturaiki W, Al-Baradie RS, AlGhamdi S, Aziz MA, Alhumaydhi FA, Alzahrani FA, Alwashmi AS, Al Abdulmonem W, Alharbi NK, Pepper C.
    Int J Nanomedicine. 2020;15:7901-7921.
    INTRODUCTION: Zinc oxide nanoparticles (ZnO NPs) have recently attracted attention as potential anti-cancer agents. To the best of our knowledge, the toxicity of ZnO NPs against human chronic myeloid leukemia cells (K562 cell line) has not been studied using transcriptomics approach.
    OBJECTIVE: The goals of this study were to evaluate the capability of ZnO NPs to induce apoptosis in human chronic myeloid leukemia cells (K562 cells) and to investigate the putative mechanisms of action.
    METHODS: We used viability assay and flowcytometry coupled with Annexin V-FITC and propidium iodide to investigate the toxicity of ZnO NPs on K562 cells and normal peripheral blood mononuclear cells. Next we utilized a DNA microarray-based transcriptomics approach to characterize the ZnO NPs-induced changes in the transcriptome of K562 cells.
    RESULTS: ZnO NPs exerted a selective toxicity (mainly by apoptosis) on the leukemic cells (p≤0.005) and altered their transcriptome; 429 differentially expressed genes (DEGs) with fold change (FC)≥4 and p≤0.008 with corrected p≤0.05 were identified in K562 cells post treatment with ZnO NPs. The over-expressed genes were implicated in "response to zinc", "response to toxic substance" and "negative regulation of growth" (corrected p≤0.05). In contrast, the repressed genes positively regulated "cell proliferation", "cell migration", "cell adhesion", "receptor signaling pathway via JAK-STAT" and "phosphatidylinositol 3-kinase signaling" (corrected p≤0.05). Lowering the FC to ≥1.5 with p≤0.05 and corrected p≤0.1 showed that ZnO NPs over-expressed the anti-oxidant defense system, drove K562 cells to undergo mitochondrial-dependent apoptosis, and targeted NF-κB pathway.
    CONCLUSION: Taken together, our findings support the earlier studies that reported anti-cancer activity of ZnO NPs and revealed possible molecular mechanisms employed by ZnO NPs to induce apoptosis in K562 cells.
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