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2021 ◽  
Author(s):  
Mehdi Azizi ◽  
Asrin Pakravan ◽  
Hadi Valizadeh ◽  
Reza Rahbarghazi ◽  
Hassan Dianat-Moghadam ◽  
...  

Abstract To improve the efficacy of cancer therapeutics, highly sensitive imaging with precise accuracy is mandatory for timely diagnosis and selection of strategic approaches. Despite recent advances in technologies associated with tumor imaging, the application of conventional single-mode imaging is the subject of debate. Herein, two types of pH-responsive gold-polymer nanostructures, GNSts and GNRs, containing CD and MTX, [email protected] and [email protected] were designed. Dual-imaging modalities (fluorescence and CT imaging) and synergistic chemo-photothermal therapy were examined in human breast cancer MDA-MB 231 cells. MTT assay showed NIR irradiation of cells pre-treated with synthesized nanoparticles promoted tumoricidal synergy via the reduction of survival rate after 48 hours in comparison with the control group (p<0.05), indicating a high absorption coefficient in the NIR area and efficient heat production rate. Flow cytometry, real-time PCR and western blot, analyses indicated an apoptotic cell death induced by the up-regulation of Caspases 3, 6, 7, 8, and 9, Bax, and Annexin-V, confirming the activation of intrinsic and extrinsic apoptosis pathways inside the host cells. The elevation of p27 and p53 in line with the increase of cell percent at the subG1 phase showed apoptotic changes and inhibition of dynamic cell growth compared to the non-treated cells (p<0.05). Evident fluorescence intensity at lower pH values (6.3) showed pH-dependent activity of nanoparticles internalized by surface folate receptor. Of note, we showed strong capability for CT imaging in cells incubated with [email protected] and [email protected] Taken together, all data show that gold-polymer nanostructures have considerable capability in theranostic applications like simultaneous diagnostic imaging and therapy.


2021 ◽  
Vol 929 ◽  
Author(s):  
Saman Ebrahimi ◽  
Prosenjit Bagchi

A computational study is presented on cross-stream migration and focusing of deformable capsules in curved microchannels of square and rectangular sections under inertial and non-inertial regimes. The numerical methodology is based on immersed boundary methods for fluid–structure coupling, a finite-volume-based flow solver and finite-element method for capsule deformation. Different focusing behaviours in the two regimes are predicted that arise due to the interplay of inertia, deformation, altered shear gradient, streamline curvature effect and secondary flow. In the non-inertial regime, a single-point focusing occurs on the central plane, and at a radial location between the interior face (i.e. face with highest curvature) of the channel and the location of zero shear. The focusing position is nearly independent of capsule deformability (represented by the capillary number, $Ca$ ). A two-step migration is observed that is comprised of a faster radial migration, followed by a slower migration toward the centre plane. The focusing location progressively moves further toward the interior face with increasing curvature and width, but decreasing height. In the inertial regime, single-point focusing is observed near the interior face for channel Reynolds number $Re_{C}\sim {O}(1)$ , that is also highly sensitive to $Re_{C}$ and $Ca$ , and moves progressively toward the exterior face with increasing $Re_{C}$ but decreasing $Ca$ . As $Re_{C}$ increases by an order, secondary flow becomes stronger, and two focusing locations appear close to the centres of the Dean vortices. This location becomes practically independent of $Ca$ at even higher inertia. The inertial focusing positions move progressively toward the exterior face with increasing channel width and decreasing height. For wider channels, the equilibrium location is further toward the exterior face than the vortex centre.


Biosensors ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 420
Author(s):  
Gyu Seong Yeom ◽  
In-ho Song ◽  
Shrikant Dashrath Warkad ◽  
Pramod B. Shinde ◽  
Taewoon Kim ◽  
...  

The measurement of cysteine in human urine and live cells is crucial for evaluating biological metabolism, monitoring and maintaining the immune system, preventing tissue/DNA damage caused by free radicals, preventing autoimmune diseases, and diagnosing disorders such as cystinuria and cancer. A method that uses a fluorescence turn-on probe and a portable fluorescence spectrometer device are crucial for highly sensitive, simple, rapid, and inexpensive cysteine detection. Herein, we present the synthesis and application of a benzimidazole-based fluorescent probe (ABIA) along with the design and development of a portable fluorescence spectrometer device (CysDDev) for detecting cysteine in simulated human urine. ABIA showed excellent selectivity and sensitivity in detecting cysteine over homocysteine, glutathione, and other amino acids with the response time of 1 min and demonstrated a detection limit of 16.3 nM using the developed CysDDev. Further, ABIA also demonstrated its utility in detecting intracellular cysteine, making it an excellent probe for bio-imaging assay.


2021 ◽  
Author(s):  
Diana R Withrow ◽  
Brian Shine ◽  
Jason Oke ◽  
Andres Tamm ◽  
Tim James ◽  
...  

Objective: Faecal immunochemical tests (FITs) are used to triage primary care patients with low risk colorectal cancer symptoms for referral to colonoscopy. The aim of this study was to determine whether combining FIT with routine blood test results could improve the performance of FIT in the primary care setting. Design: Results of all consecutive FITs requested by primary care providers between March 2017 and December 2020 were retrieved from the Oxford University Hospital Trust. Demographic factors (age, sex), reason for referral, and results of blood tests within 90 days were also retrieved. Patients were followed up for incident colorectal cancer in linked hospital records. The sensitivity, specificity, positive and negative predictive values of FIT alone, FIT paired with blood test results, and several multivariable FIT models, were compared. Results: Among 16,604 eligible patients, 139 colorectal cancers were diagnosed (0.8%). Sensitivity and specificity of FIT alone at a threshold of 10 μg Hb/g were 92.1% and 91.5% respectively. Compared to FIT alone, blood test results did not improve the performance of FIT. Pairing blood test abnormalities with FIT reduced the number of abnormal results needed to detect one cancer but increased the number of cancers missed. Multivariable models retaining FIT, sex, and mean cell volume performed similarly to FIT alone. Conclusion: FIT is a highly sensitive tool for identifying higher risk individuals presenting to primary care with lower risk symptoms. Combining blood test results with FIT does not appear to lead to better discrimination for colorectal cancer than using FIT alone.


2021 ◽  
Vol 18 (20) ◽  
pp. 5767-5787
Author(s):  
Alexandra Pongracz ◽  
David Wårlind ◽  
Paul A. Miller ◽  
Frans-Jan W. Parmentier

Abstract. The Arctic is warming rapidly, especially in winter, which is causing large-scale reductions in snow cover. Snow is one of the main controls on soil thermodynamics, and changes in its thickness and extent affect both permafrost thaw and soil biogeochemistry. Since soil respiration during the cold season potentially offsets carbon uptake during the growing season, it is essential to achieve a realistic simulation of the effect of snow cover on soil conditions to more accurately project the direction of arctic carbon–climate feedbacks under continued winter warming. The Lund–Potsdam–Jena General Ecosystem Simulator (LPJ-GUESS) dynamic vegetation model has used – up until now – a single layer snow scheme, which underestimated the insulation effect of snow, leading to a cold bias in soil temperature. To address this shortcoming, we developed and integrated a dynamic, multi-layer snow scheme in LPJ-GUESS. The new snow scheme performs well in simulating the insulation of snow at hundreds of locations across Russia compared to observations. We show that improving this single physical factor enhanced simulations of permafrost extent compared to an advanced permafrost product, where the overestimation of permafrost cover decreased from 10 % to 5 % using the new snow scheme. Besides soil thermodynamics, the new snow scheme resulted in a doubled winter respiration and an overall higher vegetation carbon content. This study highlights the importance of a correct representation of snow in ecosystem models to project biogeochemical processes that govern climate feedbacks. The new dynamic snow scheme is an essential improvement in the simulation of cold season processes, which reduces the uncertainty of model projections. These developments contribute to a more realistic simulation of arctic carbon–climate feedbacks.


2021 ◽  
Vol 28 ◽  
pp. 32-38
Author(s):  
T. P. Gizatulina ◽  
L. U. Martyanova ◽  
T. I. Petelina ◽  
E. V. Zueva ◽  
N. E. Shirokov

Aim. To study the relationship between growth differentiation factor 15 (GDF-15) level in blood serum and patient clinical and functional status parameters, and to determine predictors of GDF-15 level in pts with non-valvular atrial fibrillation (AF).Material and methods. Eighty-seven pts (with the mean age of 56.9±9.2 years) with non-valvular AF were studied. A general clinical examination, as well as echocardiography and laboratory tests were performed. These included fasting serum glucose (mmol/l), highly sensitive C-reactive protein (h/s CRP) (mg/l), creatinine level (μmol/l) and subsequent calculation of glomerular filtration rate (ml/min/1.73m2), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (pg/ml). The level of GDF-15 (pg/ml) in blood serum was determined using an enzyme immunoassay with a human ELISA analytical kit.Results. An increase in GDF-15 level was associated with age, ischemic heart disease, severity of hypertension, and heart failure, resulting in a higher risk of stroke, according to the CHA2DS2 -VASc score, carbohydrate metabolism disorders and obesity, increased h/s CRP and NT-proBNP levels, enlargement of the right and left atria, signs of diastolic left ventricular dysfunction and structural remodeling in the form of eccentric hypertrophy. Multiple linear regression analysis revealed 2 independent predictors of GDF-15 levels: age and fasting glucose.Conclusion. GDF-15 is an integral biomarker of age-related metabolic disorders and structural and functional changes in the heart, which opens up prospects for further study of its prognostic significance in pts with non-valvular AF.


Nano Letters ◽  
2021 ◽  
Author(s):  
Zuocai Zhang ◽  
Tianyun Lu ◽  
Dan Yang ◽  
Shaorong Lu ◽  
Ren Cai ◽  
...  

2021 ◽  
Vol 28 (5) ◽  
pp. 64-71
Author(s):  
Wan Nur Aimi Wan Mohd Zamri ◽  
◽  
Noorazliyana Shafii ◽  
Tuan Salwani Tuan Ismail ◽  
Adlin Zafrulan Zakaria ◽  
...  

Background: In end-stage renal disease (ESRD), troponin T concentrations can be elevated even without cardiac ischaemia, which hampers the diagnosis of acute myocardial infarction (AMI). The objectives of our study were to determine the proportion of dialysisdependent ESRD patients without acute coronary syndrome (ACS) but with highly sensitive cardiac troponin T (hs-cTnT) levels above the 99th percentile upper reference limit and to evaluate the range of hs-cTnT among this population. Methods: A cross-sectional study was conducted at the haemodialysis (HD) unit of a tertiary hospital in Malaysia from January 2018 to February 2019. Dialysis-dependent ESRD patients were included and those with a recent history of ACS (within 30 days) were excluded. Pre-dialysed serum hs-cTnT levels were measured using Cobas e411. The upper limit of the 99th percentile value for troponin T was 14 ng/L. Results: A total of 150 patients were recruited as study participants. The majority were female (62%) and of Malay ethnicity (94%), and the mean (SD) age was 45.19 (16.36) years old. The hs-cTnT range (min, max) was 11.39–738.30 ng/L and the median (interquartile range [IQR]) of hs-cTnT was 59.20 (83.41) ng/L. Elevated hs-cTnT levels were observed in 149/150 (99%) of the study participants (54/55 [98.2%] of the patients were on HD, and 95/95 [100.0%] of the patients were on continuous ambulatory peritoneal dialysis). Conclusion: This study supports prior research showing that even without ACS, most ESRD patients have elevated concentrations of cardiac troponin. Furthermore, our study illustrates the need to revisit the use of absolute troponin values when making a diagnosis of ACS in ESRD patients.


2021 ◽  
Vol 118 (44) ◽  
pp. e2107306118
Author(s):  
Florie Giacona ◽  
Nicolas Eckert ◽  
Christophe Corona ◽  
Robin Mainieri ◽  
Samuel Morin ◽  
...  

Snow is highly sensitive to atmospheric warming. However, because of the lack of sufficiently long snow avalanche time series and statistical techniques capable of accounting for the numerous biases inherent to sparse and incomplete avalanche records, the evolution of process activity in a warming climate remains little known. Filling this gap requires innovative approaches that put avalanche activity into a long-term context. Here, we combine extensive historical records and Bayesian techniques to construct a 240-y chronicle of snow avalanching in the Vosges Mountains (France). We show evidence that the transition from the late Little Ice Age to the early twentieth century (i.e., 1850 to 1920 CE) was not only characterized by local winter warming in the order of +1.35 °C but that this warming also resulted in a more than sevenfold reduction in yearly avalanche numbers, a severe shrinkage of avalanche size, and shorter avalanche seasons as well as in a reduction of the extent of avalanche-prone terrain. Using a substantial corpus of snow and climate proxy sources, we explain this abrupt shift with increasingly scarcer snow conditions with the low-to-medium elevations of the Vosges Mountains (600 to 1,200 m above sea level [a.s.l.]). As a result, avalanches migrated upslope, with only a relict activity persisting at the highest elevations (release areas >1,200 m a.s.l.). This abrupt, unambiguous response of snow avalanche activity to warming provides valuable information to anticipate likely changes in avalanche behavior in higher mountain environments under ongoing and future warming.


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