Turing miRNA into infinite coordination supermolecule: a general and enabling nanoengineering strategy for resurrecting nuclear acid therapeutics

Background Clinical translation of therapeutic nuclear acid, particularly those targeting tumor progression, has been hampered by the intrinsic weaknesses of nuclear acid therapeutic including poor systemic stability, rapid clearance, low membrane permeability and lack of targeting ability. Small nuclear acid engineered into carrier-free nanodrugs with structural stability and disease targeting may be viable to overcome pharmaceutical obstacles of nuclear acid. Methods A general method through a mild and simple chemistry was established to convert therapeutic miRNA into an infinite Auric-sulfhydryl coordination supramolecular miRNA termed IacsRNA with near-spherical nanostructure, high colloid as well as anti-hydrolysis stability and low macrophage uptakes. Results IacsRNA presented the increased half-life period in circulation and accumulation at tumor sites in comparison to normal miRNA. Moreover, Iacs-miR-30c showed no toxicity of viscera and sanguis system in the 5-time injection dosage of the treatment. More importantly, Iacs-miR-30c potently suppressed the Wnt signaling pathway in vitro and in vivo, and effectively sensitized both potency of 5-Fu in PDX model of colon cancer and Anti-PD1 in B16F10 homograft model of melanoma. Conclusion Collectively, this work amply confirmed the design of IacsRNA as a general and viable strategy of nano-pharmaceutic to concert flimsy therapeutic miRNA into potential drugs. Considering from a broader perspective, the miRNA-initiated infinite coordination self-assembly strategy has distinct advantages in resurrecting nuclear acid therapeutics, probably bringing new inspiration to RNA-derived therapeutics of a great variety of human diseases including cancer. Graphical Abstract

Real-Time Water Injection Monitoring with Distributed Fiber Optics Using Physics-Informed Machine Learning

This paper introduces a novel technique that allows real-time injection monitoring with distributed fiber optics using physics-informed machine learning methods and presents results from Clair Ridge asset where a cloud-based, real-time application is deployed. Clair Ridge is a structural high comprising of naturally fractured Devonian to Carboniferous continental sandstones, with a significantly naturally fractured ridge area. The fractured nature of the reservoir lends itself to permanent deployment of Distributed Fiber Optic Sensing (DFOS) to enable real-time injection monitoring to maximise recovery from the field. In addition to their default limitations, such as providing a snapshot measurement and disturbing the natural well flow with up and down flowing passes, wireline-conveyed production logs (PL) are also unable to provide a high-resolution profile of the water injection along the reservoir due to the completion type. DFOS offers unique surveillance capability when permanently installed along the reservoir interface and continuously providing injection profiles with full visibility along the reservoir section without the need for an intervention. The real-time injection monitoring application uses both distributed acoustic and temperature sensing (DAS & DTS) and is based on physics-informed machine learning models. It is now running and available to all asset users on the cloud. So far, the application has generated high-resolution injection profiles over a dozen multi-rate injection periods automatically and the results are cross-checked against the profiles from the warmback analyses that were also generated automatically as part of the same application. The real-time monitoring insights have been effectively applied to provide significant business value using the capability for start-up optimization to manage and improve injection conformance, monitor fractured formations and caprock monitoring.

The effect of the microelement preparation on the morphobiochemical composition of the blood of calves

The paper presents an assessment of the effect of the Sedimine microelement product on the morphobiochemical composition of the blood of calves during the milk feeding period. For the experiment, 2 groups of heifers of HolsteinKholmogory breed at the age of 2-3 weeks were formed. The calves of the experimental group were injected intramuscularly with Sedimine at a dose of 5 ml three times with an interval of 7 days, and the control animals were given a saline solution in the same way. Blood for hematological and biochemical studies was obtained at the beginning of the experiment and a week after the first and last injection. According to the research it has been established, that after a single injection of Sedimine, there were no evident changes in the biochemical profile of the blood, with the exception of a decrease in the level of urea by 30.6% (from 4.9 to 3.4 mmol/l; P<0.001). After three-time administration of the drug, there was an increase in total protein by 9.6 % (from 54.2 to 59.4 g / l; P<0.05) and an increase in AlAT activity by 1.2 times (P<0.001), while in comparison with the control, the activity of AsAT was greater (P<0.01) by 43.4 % (57.5 U/l). The de Ritis coefficient in the experimental group decreased by 43.1 % (to 6.2; P<0.01), while in the control group, on the contrary, the indicator increased by 32.1 % (to 11.1). The ratio of calcium to phosphorus in all animals decreased by 28.8...32.1 % (P<0.001), but in young animals treated with Sedimine, the ratio was 16.7 % (0.84) higher compared to the intact group of calves (P<0.05). The concentration of thyroglobulin in the experimental group significantly decreased by 29.4 % (from 0.34 to 0.24; P<0.01), with stable values in calves that were treated with saline. Injections of the preparation contributed to the stable maintenance of iron in the blood of animals of the experimental group, the concentration of which was 3 times higher (P<0.01) in relation to the control, where the indicator was 5.9 micromol/l. Also, the control animals showed a decrease in the number of red blood cells by 31.9% (from 4.7 * 10 12 to 3.2*10 12) and hemoglobin by 19.5% (from 87.2 to 70.2 g / l; P<0.05), with stable values in the experimental group, which were higher by 56.3 % (5.0*1012) and 22.2 % (90.2 g/l) compared to the control (P<0.05). Changes in white blood were characterized by a higher level of white blood cells in calves of the experimental group (by 27.7 %), primarily due to a 36.7 % (4.1*109 ; Р<0.01) higher number of lymphocytic cells. Thus, a three-time injection of the test drug was quite effective in preventing iron deficiency in calves during milk feeding and had a positive effect on metabolic processes.

Effect of 6-Gingerol on Growth Factors and Apoptosis Indices in Rats Exposed to Gold Nanoparticles

Introduction: Research has shown that gold nanoparticles (AuNPs) can damage brain tissue physiological processes. Given the antioxidant properties of gingerol (GING), the aim of this study was to determine the protective effect of 6-gingerol on hippocampal levels of brain-derived neurotrophic factor, nerve growth factor, DNA oxidative damage, and the amount of Bax and Bcl-2 Apoptosis indices of rats exposed to AuNPs. Methods: Forty two male Wistar rats were divided into four groups: control (30 days 0.5 ml saline), AuNPs (one time injection of 0.5 ml AuNPs, 200 ppm and 60 Nm + 30 days 0.5 ml saline), AuNPs+GING 50 (one time injection of 0.5 ml AuNPs, 200 ppm and 60 Nm + 30 days 0.5 ml density of gingerol 50 mg / kg), AuNPs+GING100 (one time injection of 0.5 ml AuNPs, 200 ppm and 60 Nm + 30 days 0.5 ml density of gingerol 100 mg / kg). At the end of the treatment period, the hippocampal levels of NGF, BDNF, 8-HodG and Apoptotic indices of Bax and Bcl-2 were assessed through ELISA method. Results: Compared with the AuNPs group, hippocampal levels of BDNF, NGF, and Bcl-2 in rats from AuNPs+GING 50 and AuNPs+GING 100 groups significantly increased depending on the dose of injection. The hippocampal levels of Bax and HOdG-8 significantly decreased in a dose-dependent manner (P < 0.05). Conclusion: According to obtained results, it may be suggested that gingerol improves hippocampal BDNF and NGF levels in rats exposed to AuNPs maybe by reducing apoptosis and oxidative DNA damage.

Revisiting the Polyol Synthesis and Plasmonic Properties of Silver Nanocubes

Background: Noble-metal nanocrystals have been extensively studied over the past decades because of their unique optical properties. The polyol process is considered an effective method for silver (Ag) nanocrystals’ synthesis in solution even though the reproducibility of its shape controlling is still a challenge. Here, Ag nanowires and nanocubes were synthesized by the polyol process, in which the Ag+ ions are directly reduced by ethylene glycol with a certain amount of Cl− ions added. We present the relationship between the final morphology of the Ag nanostructures with the parameters of reaction, including temperature, growth time, injection rate, and the amount of sodium chloride. The as-synthesized nanowires and nanocubes were characterized by scanning electron microscopy, transmission electron microscopy and X-ray diffraction. The uniformly distributed nanocubes with a mean edge length of 140 nm were obtained. The localized surface plasmon resonance of Ag nanocubes was characterized by laser scanning fluorescence confocal microscopy. The photoluminescence enhancement was observed on the perovskite film coupled with Ag nanocubes. Objective: We aimed to synthesize uniform and controllable silver nanocubes and nanowires through the polyol process and explore the interaction between CsPbBr3 perovskite film and Ag nanocubes antennas. Methods: We synthesized silver nanocubes and nanowires through the polyol process where the silver nitrate (AgNO3) was reduced by Ethylene Glycol (EG) in the presence of a blocking agent polyvinylpyrrolidone (PVP). Results: We successfully synthesized Ag nanocubes with an average edge length of 140 nm and Ag nanowires with a uniform distribution in terms of both shape and size through a polyol process with sodium chloride (NaCl) as the additive. In addition, the local photoluminescence (PL) enhancement was observed in a perovskite film by combining Ag nanocubes, which is attributed to the antennas plasmonic effect of the Ag nanocubes. Conclusion: In summary we studied the parameters in the polyol process such as reaction temperature, growth time, injection rate, kind of halide ion and NaCl amount for the synthesis of Ag nanowires and nanocubes. Our results suggest that the concentration of Cl- and the growth time have the main influence on Ag nanowires and nanocubes formation. The optimum growth time was found to be 60 min and 120 min for the formation of Ag nanowires and nanocubes, respectively. In addition, we revealed that the opportune reaction temperature of Ag nanowires was 140 °C. The injection rate of precursors was also found to play an important role in the final morphology of Ag nanowires and nanocubes. In addition, for the generation of Ag nanocubes, the presence of Cl− ion in the reaction is critical, which can eliminate most of the byproducts. We obtained the Ag nanowires with a uniform distribution in terms of both shape and size, and nanocubes with average lengths of 140 nm by the polyol process with the optimal parameters. Plasmon-coupled emission induced by noble-metal nanocrystals has attracted more attention in recent years. In this work, the PL of a perovskite film was enhanced by the coupling of Ag nanocubes due to the surface plasmonic effect.

Aspects of prophylaxis of the latent endometritis of cows in dairy farms of the Khabarovsky Krai

На молочных фермах Хабаровского края обследовано 2334 коровы в период охоты. Выявлено 31,6 % особей, больных скрытой формой эндометрита. Оплодотворяемость коров с данной патологией на 42,2 % ниже, чем здоровых особей. Опытным путем разработаны более эффективные по сравнению с существующими способы диагностики скрытого эндометрита у коров перед осеменением. Однократная инъекция селенита натрия глубокостельным коровам снижает количество больных эндометритом на 21,7 %. In dairy farms of the region 2.334 cows were inspected during the wish period. 31.6 % of sick cows with latent endometritis were revealed. The impregnation of animals with this pathology is 42.2 % lower in comparison with healthy individuals. The more effective methods of diagnostics of cow latent endometritis before the insemination are developed empirically. The one-time injection of sodium selenite to the down-calving cows lowers the quantity of sick cow endometritis on 21.7 %.