Essentials
Tissue factor (TF) isoforms are expressed in pancreatic neuroendocrine tumors (pNET).
TF knockdown inhibits proliferation of human pNET cells in vitro.
mTOR kinase inhibitor ...sapanisertib/MLN0128 suppresses TF expression in human pNET cells.
Sapanisertib suppresses TF expression and activity and reduces the growth of pNET tumors in vivo.
Summary
Background
Full‐length tissue factor (flTF) and alternatively spliced TF (asTF) contribute to growth and spread of pancreatic ductal adenocarcinoma. It is unknown, however, if flTF and/or asTF contribute to the pathobiology of pancreatic neuroendocrine tumors (pNETs).
Objective
To assess TF expression in pNETs and the effects of mTOR complex 1/2 (mTORC1/2) inhibition on pNET growth.
Methods
Human pNET specimens were immunostained for TF. Human pNET cell lines QGP1 and BON were evaluated for TF expression and responsiveness to mTOR inhibition. shRNA were used to knock down TF in BON. TF cofactor activity was assessed using a two‐step FXa generation assay. TF promoter activity was assessed using transient transfection of human TF promoter‐driven reporter constructs into cells. Mice bearing orthotopic BON tumors were treated with the mTORC1/2 ATP site competitive inhibitor sapanisertib/MLN0128 (3 mg kg−1, oral gavage) for 34 days.
Results
Immunostaining of pNET tissue revealed flTF and asTF expression. BON and QGP1 expressed both TF isoforms, with BON exhibiting higher levels. shRNA directed against TF suppressed BON proliferation in vitro. Treatment of BON with sapanisertib inhibited mTOR signaling and suppressed TF levels. BON tumors grown in mice treated with sapanisertib had significantly less TF protein and cofactor activity, and were smaller compared with tumors grown in control mice.
Conclusions
TF isoforms are expressed in pNETs. Sapanisertib suppresses TF mRNA and protein expression as well as TF cofactor activity in vitro and in vivo. Thus, further studies are warranted to evaluate the clinical utility of TF‐suppressing mTORC1/2 inhibitor sapanisertib in pNET management.
Abstract
The study is aimed at assessing the suitability of plum varieties cultivated in Tambov region for the production of dried fruits (prunes). Large-fruited (average weight of more than 31 g) ...varieties were identified. Renklod by Kharitonovoy, Etude, Vengerka by Kursakov and Nochka are characterized by intense violet and dark purple integumentary colors. A combination of high skin strength, pulp hardness and good stone separation was found in Renklod by Kharitonov, Renklod Tambov, Etude, Vengerka by Kursakov and 23-135 Elite. A high accumulation of soluble solids, sugars, a low content of organic acids, as well as a high sugar-acid index were found in Renklod by Kharitonov, Renklod Tambov and Elite 23-135. Prunes produced from Renklod by Kharitonov, Renklod Tambov and 23-135 Elite were characterized by high commercial and consumer qualities, which makes it possible to recommend these varieties for the production of dried fruits.
The article presents the results of application of Implicit Large Eddy Simulation method to numerical simulation of under-ice radiatively driven convection, developing in ice-covered water bodies in ...the moderate zone at the end of freeze-up period. Studies of the radiatively driven convection are of importance because of the role it plays in the temperature regime of lakes and the functioning of lake ecosystems at the end of freeze-up period. The simulation was carried out with the use of the finite-volume software code SINF/Flag-S, developed in SPbPU. The SIMPLEC algorithm with second-order accuracy was used for advancing in time. The discretization of the convective terms was made with the use of QUICK scheme. The results of calculations were used to study variations in the temperature and pulsation velocity components with periodically varying intensity of external energy pumping during the daily cycle. The dissipation of the kinetic energy, background potential energy, and buoyancy flux were evaluated, and changes in these variables during a daily cycle of radiation impact were calculated. The efficiency mixing of water column was evaluated for the period of development of radiatively driven convection in a model domain simulating a small lake covered by ice.
A method to assess the gas resistance of woody plants was developed based on the level of inhibition of the photosynthetic activity of leaves exposed to toxic gases in the laboratory and could be ...used to identify plants resistant to environmental pollution for further practical and breeding use. The effective quantum yield of photosystem II was used as an indicator of genotype tolerance. The sensitivity of the indicator was sufficient to differentiate control and experimental variants. The objects under study were ranked according to the degree of gas resistance. Recommendations were given for the practical application of the new method.
The regime of lake mixing has a considerable effect on many aspects of the functioning of aquatic ecosystems, which increases the importance of identifying changes in water mass stability under the ...effect of climatic factors. This study is focused on the stability of the water mass of a small Vendyurskoe Lake (southern Karelia) in the open-water season in years with various weather conditions. Water temperature measurements in 2008–2013 and 2015–2022 at an autonomous station (thermistor chain) in the central vertical of the lake were used to assess the duration of stratification and the stability of water mass according to various criteria, including the temperature difference over water column of 1 and 2°C, and by threshold values of Schmidt stability, Wedderburn number, and Lake Number. To study the role of radiation mixing in weakening the stability of the lake water mass, the seasonal and interannual variability of the temperature difference between the upper layer of the lake and the air was analyzed using ERA-5 reanalysis data. For detail analysis of this parameter, an appropriate density function was constructed for each year, and its major characteristics were calculated. It was shown that, despite the continuing regional warming and an increase in the temperature of air and the top water layer in Vendyurskoe Lake, no increase in stability was recorded in 2008–2022. Limiting factors can be an increase in convective mixing due to radiative cooling, as well as increased wind load on the water body.
The fruits of
Prunus domestica
L. are a valuable source of phenolic compounds, in particular hydroxycinnamic acids and their esters. Hybrid origin of
Prunus domestica
hexaploid species, the ample ...number of the varieties, and expanded geograph y of the cultivation preclude scientists from arriving at a definitive conclusion on the content levels and composition of phenolic compounds in plum fruits. The goal of our study is to determine and identify the phenolic composition of fruits of
Prunus
domestica
L. grown in Tambov oblast of the Russian Federation. The research focused on eight fresh-eating and all-purpose varieties. Experimental plantations were established in 2014 in the 6 × 3-m setup. The plum–cherry hybrid (
SVG
) 11–19 was used as a rootstock. The phenolic components of plum fruits were determined by reverse phase high performance liquid chromatography (RP HPLC) using a Thermo Ultimate 3000 liquid chromatography system equipped with a DAD‑3000 detector. A chromatography run of the plum fruit methanol extracts was performed through a mobile phase binary gradient represented by acetonitrile and aqueous potassium dihydrogen phosphate acidified with orthophosphoric acid to pH 2.5. The hydroxycinnamic acids in the plum fruits were determined to be as follows: 5.33–181.54 mg/100 g of 4-Caffeoylquinic acid, 1.69‒31.73 mg/100 g of 5-Caffeoylquinic acid, 0.54–5.77 mg/100 g of 3-p-Coumaroylquinic acid, and 0.04–0.63 mg/100 g of 3-Caffeoylquinic acid. Quercitin-3-rutinoside at 0.77–9.17 mg/100 g was dominant among flavonols. Three anthocyanins, namely, cyanidin-3-glucoside, cyanidin-3-rutinoside, and peonidin-3-glucoside, were identified in the studied plum fruits. The structural composition of plum fruit anthocyanins was dominated by cyaniding-3-glucoside, accounting for 60 to 90% of the total anthocyanin content. The obtained data on the content of phenolic components in fruits of specified plum varieties (
Prunus domestica
L.) point toward the potential of the use of the specified plum varieties as a source of hydroxycinnamic acids, anthocyanins, and flavonols in the population diet.
The research was aimed at evaluating sweet cherry forms on a complex of economically valuable traits and the allocation of promising genotypes for further use in breeding and production. The forms of ...sweet cherries grow in Michurinsk city of Tambov region. The study of frost resistance was carried out in laboratory conditions. Annual branches were frosted for 12 hours at -32°C and -35°C. Reproductive buds in all studied forms were characterized by reversible damage (less than 3 points) at temperature regime -32°C and complete death at -35°C. 10-117 form was characterized by -35°C frost resistance in the middle of winter, in which the freezing degree of annual branches tissues and vegetative buds did not exceed 2 points. Over the years of research, elites 4/8-24, 10-115, 7-38, 10-117, 6-87, 4/9-15, 7-5 possessed resistance to moniliosis and coccomycosis (the damage degree not more than 2 points). The highest yield (9.75-9.84 t/ha) on average over three years was shown by forms 4/8-24, 7-38, 7-5. Yield at the control level was noted in forms 6-87, 4/9-15, 10-115. Elite forms 4/9-15, 7-38 were characterized by the largest mass of fruits, significantly exceeding the control variety. The average weight amounted to 7.3 and 7.2 g, and the maximum was 9.4 and 8.4 g respectively. Forms 4/8-24, 4/9-15, 7-38 combined the dessert taste of fruits (tasting assessment of 4.6-4.8 points), very juicy and dense pulp.
Two basic alternative atomistic simulation methods (molecular dynamics and Monte-Carlo) have been used to reproduce the dealloying phenomenon in Cu-Pt nanoalloys. Using the Gupta (tight-binding) ...potential, we simulated nanoparticles consisting initially of 1500 Cu and 1500 Pt atoms. The involved programs propose search and following removing Cu atoms with the lowest specific binding energies. We have found that as a result of dealloying the particle surface layer is really enriched with Pt atoms. However the particle core keeps in general the structure of the initial nanoalloy. This effect is especially noticeable in molecular dynamics simulation. We have also established that dealloying results in formation of a defected particle structure (vacancies, first of all). Presumably, just such an effect yields the porous structure of bigger Cu-Pt particles in laboratory experiments on dealloying.
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The solvatochromic behavior of a model compound mimicking the chromophore of cyan fluorescent protein (CFP) in the spectral and time domains has been studied. Analysis of the time-resolved ...fluorescence signal, carried out in 40 solvents belonging to different classes, showed that the lipophilic environment promotes an increase, while aromatic solvents and tertiary amines, a decrease in the fluorescence lifetime of the chromophore. Based on this study, the possible rational design of CFP-like proteins was proposed.
Aim
. To optimize the surgical technique for left atrial appendage (LAA) occlusion in patients with atrial fibrillation (AF) during coronary artery bypass grafting.
Material and methods
. The study ...included 60 patients with atrial fibrillation (AF). The patients were randomly divided into 2 groups. In the first group of patients, LAA was closed using the developed two-suture technique. In patients of the second group, a purse string suture was applied to the LAA. All patients underwent transesophageal echocardiography (TEE) before surgery to rule out the presence of intracardiac blood clots. To assess the effectiveness of the method in the postoperative period, TEE was performed.
Results
. According to postoperative TEE, one case of LAA recanalization in each group was revealed (p>0,05). In the second group, the residual LAA cavity after applying a purse string suture was revealed. During the follow-up period, there were no neurological complications and deaths.
Conclusion
. According to the study results, it was found that the proposed two-suture technique for LAA occlusion is not less effective than the purse-string suture. The developed technique of two-suture epicardial occlusion of LAA showed actual technical advantages, allowing to optimize this surgery in different categories of patients.
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