Tribology of particle suspensions in rolling-sliding soft contacts

We investigate the lubrication of microsphere suspensions between compliant substrates, and probe the influence of matrix viscosity, particle phase volume, surface roughness and wetting, and slide-to-roll ratio (SRR). In general, the suspensions behave as a continuum in the elastohydrodynamic regime provided the film thickness, which is predicted from the product of speed and viscosity, is greater than the particle diameter. Below this, the frictional response is characteristic of the mixed and boundary regimes. In the boundary regime, friction is independent of phase volume above 5% and it is governed by the rolling friction associated with particles being entrained into the contact that is independent of SRR, which is made possible by substrate deformation. This study provides a benchmark for soft-tribology and biotribology studies involving more complex particle suspensions and particle-containing soft materials

Probing the effect of aroma compounds on the hydrodynamic properties of mucin glycoproteins

© 2020, The Author(s). Aroma compounds are diverse low molecular weight organic molecules responsible for the flavour of food, medicines or cosmetics. Natural and artificial aroma compounds are manufactured and used by the industry to enhance the flavour and fragrance of products. While the low concentrations of aroma compounds present in food may leave no effect on the structural integrity of the mucosa, the effect of concentrated aroma volatiles is not well understood. At high concentrations, like those found in some flavoured products such as e-cigarettes, some aroma compounds are suggested to elicit a certain degree of change in the mucin glycoprotein network, depending on their functional group. These effects are particularly associated with carbonyl compounds such as aldehydes and ketones, but also phenols which may interact with mucin and other glycoproteins through other interaction mechanisms. This study demonstrates the formation of such interactions in vitro through the use of molecular hydrodynamics. Sedimentation velocity studies reveal that the strength of the carbonyl compound interaction is influenced by compound hydrophobicity, in which the more reactive short chain compounds show the largest increase in mucin-aroma sedimentation coefficients. By contrast, the presence of groups that increases the steric hindrance of the carbonyl group, such as ketones, produced a milder effect. The interaction effects were further demonstrated for hexanal using size exclusion chromatography light scattering (SEC-MALS) and intrinsic viscosity. In addition, phenolic aroma compounds were identified to reduce the sedimentation coefficient of mucin, which is consistent with interactions in the non-glycosylated mucin region

Преобразование кардиологических палат интенсивной терапии в кардиологическую реанимацию. Пятилетняя эволюция

The article highlights the key elements and results of the restructuring of emergency care for patients with acute myocardial infarction, the core of which is the teamwork of surgeons, anesthesiologist-intensivists and cardiologists of the department. The restructuring included a change in ideology, personnel changes, updating and expanding the range of equipment, development of inner protocols and their implementation. It took two years to transform the intensive care unit for patients with acute myocardial infarction into the cardiac intensive care unit, where patients with acute cardiac pathologies of various etiologies are treated and preoperative preparation and postoperative nursing are carried out.В статье освещаются ключевые элементы и результаты реструктуризации неотложной помощи пациентам с острым инфрактом миокарда, ядром которой является командная работа хирургов, анестезиологов-реаниматологов и кардиологов в отделении. Реструктуризация включала в себя изменение идеологии, кадровые перестановки, обновление и увеличение номенклатуры оборудования. Трансформация отделения интенсивной терапии для пациентов с острым инфарктом миокарда в отделение кардиореанимации, где проходят лечение пациенты с острой кардиальной патологией разной этиологии и проводится предоперационная подготовка и послеоперационное выхаживание, заняла два года

DEFECTIVE KERNEL1 regulates cellulose synthesis and affects primary cell wall mechanics

The cell wall is one of the defining features of plants, controlling cell shape, regulating growth dynamics and hydraulic conductivity, as well as mediating plants interactions with both the external and internal environments. Here we report that a putative mechanosensitive Cys-protease DEFECTIVE KERNEL1 (DEK1) influences the mechanical properties of primary cell walls and regulation of cellulose synthesis. Our results indicate that DEK1 is an important regulator of cellulose synthesis in epidermal tissue of Arabidopsis thaliana cotyledons during early post-embryonic development. DEK1 is involved in regulation of cellulose synthase complexes (CSCs) by modifying their biosynthetic properties, possibly through interactions with various cellulose synthase regulatory proteins. Mechanical properties of the primary cell wall are altered in DEK1 modulated lines with DEK1 affecting both cell wall stiffness and the thickness of the cellulose microfibril bundles in epidermal cell walls of cotyledons

Small Molecules Target the Interaction between Tissue Transglutaminase and Fibronectin

Tissue transglutaminase (TG2) is a multi-functional protein, with enzymatic, GTP-ase and scaffold properties. TG2 interacts with fibronectin (FN) through its N-terminus domain, stabilizing integrin complexes, which regulate cell adhesion to the matrix. Through this mechanism, TG2 participates in key steps involved in metastasis in ovarian and other cancers. High throughput screening identified several small molecule inhibitors (SMIs) for the TG2/FN complex. Rational medicinal chemistry optimization of the hit compound (TG53) led to second generation analogues (MT1–6). ELISA demonstrated that these analogues blocked TG2/FN interaction and bio-layer interferometry (BLI) showed that the SMIs bound to TG2. The compounds also potently inhibited cancer cell adhesion to FN and decreased outside-in signaling mediated through the focal adhesion kinase (FAK). Blockade of TG2/FN interaction by the small molecules caused membrane ruffling, delaying the formation of stable focal contacts and mature adhesions points and disrupted organization of the actin cytoskeleton. In an in vivo model measuring intraperitoneal (ip) dissemination, MT4 and MT6 inhibited the adhesion of ovarian cancer (OC) cells to the peritoneum. Pre-treatment with MT4 also sensitized OC cells to paclitaxel. The data support continued optimization of the new class of SMIs that block the TG2/FN complex at the interface between cancer cells and the tumor niche

Эндоскопически ретроградно контролируемое перкутанное лечение мочевых свищей после парциальной нефрэктомии

Background. Urinary fistulas (UFs) are one of the most significant complications after partial nephrectomy. Placement of an ureteral stent eliminates urine extravasation in the majority of patients. However, some of them have persistent UFs despite upper urinary tract drainage. Such cases require retrograde injection of fibrin glue into the renal cavity through a ureteroscope or via the percutaneous approach. Some authors reported cases of simultaneous use of 2 stents and percutaneous cryoablation of the fistula, but these techniques are rare and, therefore, it is problematic to evaluate their efficacy.Objective: to evaluate the results of the new treatment method for the elimination of persistent UFs using the retrograde endoscopic percutaneous approach.Materials and methods. This study included 5 patients (3 males and 3 females) with UFs developed after kidney resection. Mean age of the patients was 55.8 years. The tumor size was 2.5 to 4.8 cm; mean R.E.N.A.L. score was 7.8. All patients had earlier undergone minimally invasive partial nephrectomy; the time between surgery and UF development varied between 3 and 10 days. Four out of 5 patients had a large amount of discharge from their paranephral drainage system, examination of which confirmed high creatinine level. Patients underwent flexible ureteropyelography in the lithotomy position. During this procedure, we identified the damaged calyx and then performed percutaneous puncture targeting the distal end of the endoscope at this calyx, ensuring that the tip of the needle appeared in the paranephral cavity in front of the injured calyx. Using the flexible ureteroscope, we inserted the needle into the pelvis, dilated the puncture opening along the string, and installed a nephrostomy drainage system (12 Fr). Then the endoscope was removed and the ureter was additionally drained with a stent. The stent was removed after 8-10 days with subsequent antegrade pyelography. If there was no extravasation, the nephrostomy tube was removed and the patient was discharged from hospital to continue treatment in outpatient settings.Results. All patients with UFs resulting from partial nephrectomy was successfully operated on. No complications were registered. The mean surgery time was 45.0 ± 20.5 min (range: 40-65 min). Only two patients had some discharge from the fistula within 1 day after nephrostomy tube removal and it stopped without any additional interventions. Three patients had their fistula healed immediately. The treatment efficacy during the whole follow-up period of 18 ± 4 months (range: 6-26 months) was 100 %.Conclusion. Ureteral stenting ensures elimination of UFs in the majority of patients after partial nephrectomy. In individuals with persistent UFs, retrograde endoscopic percutaneous drainage of the pelvicalyceal system is the method of choice, because it allows rapid and effective treatment of UFs.Введение. Мочевые свищи (МС) являются одними из значимых осложнений парциальной нефрэктомии. У большинства пациентов установка мочеточникового стента приводит к ликвидации подтекания мочи. Однако у некоторых из них, несмотря на дренирование верхних мочевых путей, наблюдаются стойкие МС, при которых ретроградно через уретероскоп или перкутанным доступом в полостную систему почки вводится фибриновый клей. Описаны случаи одновременного использования 2 стентов, перкутанная криоаблация свищевого хода. Однако эти операции выполнялись только в единичных случаях, поэтому сложно оценить их окончательную эффективность. Цель исследования - изучение результатов предложенной нами методики ликвидации стойких МС путем ретроградно эндоскопически контролируемого перкутанного лечения. Материалы и методы. В исследование были включены 5 пациентов (2 мужчин, 3 женщины) с МС, развившимися после резекции почки. Средний возраст больных составил 55,8 года. Размер опухоли колебался от 2,5 до 4,8 см, среднее число баллов по нефрометрической системе R.E.N.A.L. составляло 7,8. Всем больным ранее выполнялась малоинвазивная парциальная нефрэктомия, сроки развития МС после нее колебались в пределах 3-10 дней. У 4 из 5 больных наблюдалось большое количество отделяемого по паранефральному дренажу, результат биохимического анализа которого подтвердил высокий уровень креатинина. В литотомическом положении выполняли гибкую уретеропиелоскопию, обнаруживали поврежденную чашку. Далее перкутанно прицельно на нее и дистальный конец эндоскопа проводили пункцию таким образом, чтобы кончик иглы появлялся в паранефральной полости напротив травмированной чашки. Под контролем гибкого уретероскопа иглу проводили в лоханку, по струне пункционный ход бужировали и устанавливали нефростомический дренаж 12 Шр. Эндоскоп извлекали и дополнительно проводили дренирование мочеточника стентом. Спустя 8-10 дней стент извлекали, выполняли антеградную пиелографию. При отсутствии затека из зоны МС нефростому извлекали и больного выписывали на амбулаторное лечение.Результаты. Все больные с МС после парциальной нефрэктомии были успешно прооперированы. Осложнений не зарегистрировано. Время операции составило в среднем 45,0 ± 20,5 (40-65) мин. После удаления нефростомического дренажа только у 2 больных в течение 1 дня наблюдалось отделяемое по свищу, которое самостоятельно прекратилось. У 3 пациентов свищ зажил сразу. Эффективность лечения за период наблюдения 18 ± 4 (6-26) мес составила 100 %. Заключение. Стентирование мочеточника позволяет ликвидировать МС у большинства больных после парциальной нефрэктомии. При стойких МС методом выбора может быть ретроградно эндоскопически контролируемое перкутанное дренирование чашечно-лоханочной системы почки, что позволяет в короткие сроки и с высокой эффективностью избавить больного от МС.

Phosphorothioate oligonucleotides, suramin and heparin inhibit DNA-dependent protein kinase activity

Phosphorothioate oligonucleotides and suramin bind to heparin binding proteins including DNA polymerases, and inhibit their functions. In the present study, we report inhibition of DNA-dependent protein kinase activity by phosphorothioate oligonucleotides, suramin and heparin. Inhibitory effect of phosphorothioate oligonucleotides on DNA-dependent protein kinase activity was increased with length and reached a plateau at 36-mer. The base composition of phosphorothioate oligonucleotides did not affect the inhibitory effect. The inhibitory effect by phosphorothioate oligodeoxycytidine 36-mer can be about 200-fold greater than that by the phosphodiester oligodeoxycytidine 36-mer. The inhibitory effect was also observed with purified DNA-dependent protein kinase, which suggests direct interaction between DNA-dependent protein kinase and phosphorothioate oligonucleotides. DNA-dependent protein kinase will have different binding positions for double-stranded DNA and phosphorothioate oligodeoxycytidine 36-mer because they were not competitive in DNA-dependent protein kinase activation. Suramin and heparin inhibited DNA-dependent protein kinase activity with IC50 of 1.7 μM and 0.27 μg ml−1 respectively. DNA-dependent protein kinase activities and DNA double-stranded breaks repair in cultured cells were significantly suppressed by the treatment with suramin in vivo. Our present observations suggest that suramin may possibly result in sensitisation of cells to ionising radiation by inactivation of DNA-dependent protein kinase and the impairment of double-stranded breaks repair

Functionalized Positive Nanoparticles Reduce Mucin Swelling and Dispersion

Multi-functionalized nanoparticles (NPs) have been extensively investigated for their potential in household and commercial products, and biomedical applications. Previous reports have confirmed the cellular nanotoxicity and adverse inflammatory effects on pulmonary systems induced by NPs. However, possible health hazards resulting from mucus rheological disturbances induced by NPs are underexplored. Accumulation of viscous, poorly dispersed, and less transportable mucus leading to improper mucus rheology and dysfunctional mucociliary clearance are typically found to associate with many respiratory diseases such as asthma, cystic fibrosis (CF), and COPD (Chronic Obstructive Pulmonary Disease). Whether functionalized NPs can alter mucus rheology and its operational mechanisms have not been resolved. Herein, we report that positively charged functionalized NPs can hinder mucin gel hydration and effectively induce mucin aggregation. The positively charged NPs can significantly reduce the rate of mucin matrix swelling by a maximum of 7.5 folds. These NPs significantly increase the size of aggregated mucin by approximately 30 times within 24 hrs. EGTA chelation of indigenous mucin crosslinkers (Ca2+ ions) was unable to effectively disperse NP-induced aggregated mucins. Our results have demonstrated that positively charged functionalized NPs can impede mucin gel swelling by crosslinking the matrix. This report also highlights the unexpected health risk of NP-induced change in mucus rheological properties resulting in possible mucociliary transport impairment on epithelial mucosa and related health problems. In addition, our data can serve as a prospective guideline for designing nanocarriers for airway drug delivery applications