Abstract The expression patterns of microRNAs (small non-coding RNAs) are altered in many biological processes such as myogenesis. In this study, we aimed to investigate the impact of predicted miR-202, its target genes Akt2 and Rock-1 as a potential regulator of myoblast in the myocyte differentiation process using the C2C12 cell line. After confirmation of the differentiation process induced by 3% horse serum, the expression level of miRNA and its targets were evaluated. In the following, a luciferase assay was conducted to approve the effect of miRNA on its target. Our results indicated that miR-202 and Akt2 were significantly up-regulated during differentiation, while Rock-1 was downregulated. Co-transfection of miRNA with psiCHECK2-Rock-1 significantly presented that Rock-1 was directly targeted by miR-202. On the contrary, miR-202 has failed to enforce its inhibitory effect on Akt2 expression. In particular, miR-202 seems to be a regulator of muscle differentiation pathway thought targeting Rock-1.

Manual measurement of rock discontinuities is time-consuming and subjective according to the experience of the surveyor. This work proposes a three-dimensional laser scanning-based method for the semi-automatic identification of rock discontinuities. Multisite cloud scanning is performed with real-time kinematic (RTK)-assisted orientation to estimate the rock fracturing degree; then, discontinuity orientations are extracted with the man–machine interactive method or automatic method. The proposed method was applied to actual examples to illustrate its accuracy at identifying rock discontinuities. The sensitivity of the identification accuracy to different parameters was investigated.

Over the years, various models have been developed in the stages of the mining process that have allowed predicting and enhancing results, but it is the breakage the variable that connects all the activities of the mining process from the point of view of costs (drilling, blasting, loading, hauling, crushing and grinding). To improve this process, we come up with an idea to develop a breakage prediction model; on the basis of the main variables involved in the drilling and blasting process. For this purpose, we design a computer model based on an Artificial Neuronal Networks (ANN), built by using the most representative variables that come into play with drilling and blasting, such as: the properties of the explosives, the geomechanical parameters of the rock mass, and the design parameters of drilling-blasting. For its experimentation and validation, we have taken the data from a copper mine as reference located in the north of Chile, because of we have the dataset of that ore deposit, which is valid and reliable to evaluate prediction problems based on ANN applied to copper mines. The ANN architecture was of the supervised type, feedforward, with 3 layers and 13 neurons in the only hidden layer, trained with the input data using a dataset with the previously mentioned variables, which then were compared with the breakage results. The model was feed backed in its learning process until it becomes perfected, and is a prediction option that can be used in future blasting of ore deposits with similar characteristics using the same representative variables. Therefore, this is a valid alternative for predicting rock breakage, given that it has been experimentally validated, and has achieved moderately reliable results, providing higher correlation coefficients than traditional models, and with the additional advantage that an ANN model provides, due to its ability to learn and recognize compiled dataset patterns. In this way, using this computer model we can obtain satisfactory results that allow us to predict breakage, providing an alternative for evaluating the costs that this entails.

Karakoram highway (K.K.H.) the only road link between two countries China and Pakistan. This road network is essential for two countries due to its strategic location and socioeconomic. The highway is more vulnerable due to landslide disasters, especially in rain and snow melting seasons, and different kinds of mass movement activities have occurred along K.K.H., such as rockfall, debris flow, and snow avalanche. The slope stability problems are widespread along with Karakorum (K.K.H.) between Besham city and the Dasu area because of the high seismic zone, rainfall, snow melting, and complex geology slope geometry, week, and adverse discontinuities sets. The detailed fieldwork was done along the Karakorum highway to minimize the risk of slope stability and for planning purposes in Besham to Dasu area and selected nine road-cut slopes. However, in these nine selected roadcut slopes, three slopes were already failed, four slopes are partially stable, and two slopes were stable. Both kinematic and empirical approaches are applied on all these nine road cut slopes and their discontinuities. The kinematic result has shown that all kinds of mode failure such as Toppling, Planar, and Wedge failure mode occurred in these slopes. The RMRb result has shown that all discounters lie in between fair to good rock. Both discrete and continuous (S.M.R.) results show that all discontinuity sets lie between the unstable, partially stable, and stable conditions.

We evaluated the transcriptional response of interferon (IFN)-related genes in rock bream iridovirus (RBIV)-infected rock bream under high-, low-, or no-mortality conditions induced by different stocking water temperatures. Under the high susceptibility condition (group A, water temperature 26 °C, 100% mortality), only the Mx gene was expressed early, with prolonged expression, and with heavy viral loads of approximately 106–107 major capsid protein gene copies/μL from 4 to 10 days post infection (dpi). However, IRF1, IRF3, IRF8, STAT1, ISG15, PKR, Viperin, GVIN1, IFI44, and ISG56 were activated at later time points (8 dpi) and then quickly decreased (10 dpi). For the low susceptibility condition, the water temperature was set at 23 °C for 7 days (group B) and then reduced to 17 °C. Group B exhibited a 28% mortality rate, in which persistent and effective antiviral responses were observed for long periods of time. In particular, at 20 and 22 dpi, when virus replication was peaked at approximately 107/μL, the expressions of most of the IFN-related genes (IRF1, IRF3, IRF8, Mx, STAT1, ISG15, PKR, Viperin, GVIN1, IFI44, and ISG56) were significantly higher in group B than in the control group. Moreover, prolonged and higher levels of IRF3 (at least 30 dpi), IRF8 (at least 30 dpi), ISG15 (at least 30 dpi), PKR (at least 28 dpi), Viperin (at least 30 dpi), and IFI44 (at least 30 dpi) were also observed in the recovery stage of infection. Under the no-susceptibility condition at 17 °C (0% mortality), significantly elevated levels of IRF3, Mx, ISG15, and PKR were observed mostly until 20 dpi. The findings indicate that RBIV infection can induce an efficient IFN-mediated antiviral immune response in low- and no-susceptibility conditions. The findings could be valuable for effective control of viral pathogens in fish.

The study of mechanical properties of rock mass can be effectively carried out through rock-like material model test. The similarity of mechanical properties between rock-like material and protolith is dependent on the appropriate selection of composition and content of rock-like materials. In this research, X-Ray diffraction test was conducted to analyze the composition of deep rock, which confirmed silica, quartz, and dolomite as the primary components of deep sandstone. An orthogonal design test was used to execute the ratio test of rock-like material. River sand was used as an aggregate, cement as a binder, gypsum powder as a regulator, and polystyrene foam (EPS) as rock damage simulation material. The influencing factors considered in the orthogonal mechanical tests were the proportion of aggregate and binder, ratio of binder and regulator, quantity of damage simulation material, and size of damage simulation material. Three levels were set for each factor, and mechanical parameters such as compressive strength, tensile strength, elastic modulus, axial strain, and Poisson's ratio were tested for each group of samples. The changes of those parameters with the levels of the above four factors were studied. The study revealed that adjusting the size of polystyrene foam (EPS) can adjust the values of elastic modulus, tensile strength, and Poisson's ratio of rock-like material. Similarly, changing the ratio of binder and regulator can adjust the values of axial strain and compressive strength of rock-like material. The rock-like material developed in the study can simulate the mechanical properties of different rock masses such as granite, sandstone, shale, and limestone.

In rock blasting for mining production, stress waves play a major role in rock fracturing along with explosion gases. Better energy distribution improves fragmentation and safety, lowers production costs, increases productivity, and controls ore losses and dilution. Blast outcomes vary significantly with the choice of the explosive and the properties of the rock mass encountered. This study analyzes the effects of rock mass and explosives properties on the blast outcomes through numerical simulation using data from the case study and later validates the simulation results from the field blast fragmentation. The outcomes suggest that, for a given set of rock properties, the choice of explosive has a major influence on the resulting fragmentation. Strong explosives favor large fracture extents in hard rocks, while less strong explosives offer a better distribution of explosive energy and fractures. The presence of rock structures such as rock con-tacts and joints influences the propagation of stress waves and fractures depending on the structures' material properties, intensity and orientations, and the direction and strength of the stress wave. To achieve effective fragmentation, the blast design should mitigate the effect of variability in the rock mass by ensuring adequate energy distribution within the limits of geo-metrical design.

This paper aims to investigate the coal thickness change area of the combined rock strata energy accumulation law. The method of connecting a uniaxial compression experiment with a theoret-ical analysis is used in this work. We employ a combination of coal and rock to carry out our studies. We investigate how different lithologies and ratios of coal-rock height affect the me-chanical properties of the mixture and the law governing energy accumulation. We have deter-mined the following facts: (1) The combination's peak strength and elastic modulus exceed that of coal and are inferior to that of rock but are nearer to that of coal. (2) When the coal-rock height ratios are dissimilar, the peak strength and modulus of elasticity of the combination show a negative correlation with the coal-thickness share, and the pre-peak energy accumulation and impact energy index of the combination shows a positive correlation with the coal-thickness share. (3) For the combination with the same coal-rock height ratio, the peak strength, elastic modulus, pre-peak energy accumulation, and impact energy index all increase with greater rock strength and elastic modulus. The presence of a hard rock layer affects the accumulation of pre-peak energy. ( 4 ) The stress in the surrounding rock gradually decreases as the coal thick-ness increases. In the area where coal thickness declines, the stress in surrounding rock is higher than that in the region where it thickens. The energy stored in the surrounding rock is directly proportional to the coal in the zone. Conversely, areas with thinner coal deposits exhibit a lower energy storage capacity in the surrounding rock than those with thicker coal deposits. The stress distribution of surrounding rock in coal thickness change is abnormal; substantial energy accu-mulation can swiftly initiate dynamic disasters, such as rock bursts. This study has important reference significance for preventing and controlling rock burst in coal thickness change areas.

The surrounding rock during the coal mine excavation is prone to significant engineering disasters such as considerable deformation and rockbursts. Pressure release can improve the stress field of a deep rock mass and prevent the occurrence of dangers such as roadway collapse and coal and gas outbursts. This paper uses the ANSYS/LS-DYNA finite element software to simulate the crush area and fracture zone of a detonation charge with different diameters under in-situ stress. The stability of the surrounding rock was analyzed based on the impact stress and velocity, and was verified by field tests. The research results show that the blasting load primarily affects the damaged area near the borehole, while the in-situ stress affects the far-field crack propagation. The crack propagates in the direction of high surrounding rock pressure. When the uncoupling index is 1.5, the impact pressure of the 60 mm diameter cartridge is 8 times that of the 20 mm diameter cartridge. The impact speed can reach 2 times that of the 20 mm diameter cartridge. The high-energy event of the roof is transferred to the front of the working face, the distribution is no longer concentrated, and a better blasting pressure relief effect is achieved. The research results can help guide the prevention and control measures of rock bursts and other mining disasters.

Fractures are present in hydrocarbon reservoirs of different porosity ranges. Seismic anisotropy has been widely used in fracture characterization and shown to be sensitive to background matrix porosities in theoretical studies. An understanding of the effects of background porosity on seismic anisotropy could improve seismic characterization in different fractured reservoirs. Based on synthetic rocks with controlled fractures, we conducted laboratory experiments to investigate the influence background porosity has on P wave anisotropy and shear wave splitting. A set of rocks containing the same fracture density (0.06) with varying porosities of 15.3%, 22.1%, and 30.8% were constructed. P and S wave velocities were measured at 0.5 MHz as rocks were water saturated. Results show that when porosity increased from 15.3% to 22.1%, P wave anisotropy and shear wave splitting exhibit slight fluctuations. However, when porosity continued to increase to 30.8%, P wave anisotropy declined sharply while shear wave splitting stayed nearly constant. The measured results were compared with predictions from equivalent medium theories. Qualitative agreements were found between theoretical predictions and measured results. In Eshelby-Cheng model, the increase of porosity reduces the fracture-induced perturbation in the fracture normal direction, resulting in a lower P wave anisotropy. In Gurevich(2003) model, the increase of porosity can reduce the compressional stiffness in parallel direction to a larger extent than that in perpendicular direction, thus leading to lower P wave anisotropy.

Rock salt is characterized by specific geomechanical and rheological properties. Layers of rock salt on depth over 900 m cause problems with shaft lining deformation. Methods of shaft lining protection used so far (e.g. in Sieroszowice mine) have not been effective enough. The research presents a patented and copyright protected concept of a shaft lining construction that can be used in rock masses with strong rheological properties and susceptible to leaching. In the case of salt layers, especially at significant depths the relative convergence of the heading contour may be about 40 ‰/year. That results in the fact that any other method of securing the shaft lining, e.g. by making it flexible, is not sufficient to ensure the stability of the shaft guidance geometry. In the new shaft lining concept, the excessive rock creep into the outbreak inside the shaft diameter is removed by local and controlled leaching of the shaft cheeks by means of fresh water through a porous medium at the contact layer behind the watertight tubing lining. The article presents the methodology of performing tests on a special device and the test results.

A single paragraph Arbuscular mycorrhizal fungi (AMF) establish symbiotic relationships with many crops. These soil microbiotas improve the soil fertility through the soil physical, chemical and biological properties. extending the root absorbing area. In return, the symbiont receives plant carbohydrates for the completion of its life cycle. AMF also helps plants to cope with biotic and abiotic stresses such as extreme temperature, heavy metal, diseases, and pathogens. For soil physical properties, the mechanisms used by AMF are the production of a glycoprotein, glomalin, which creates a high quality of soil macro-aggregations. These macro-aggregations control soil erosion, nutrients and organic matter losses. For soil chemical properties, AMF produce acids and an enzyme called phosphatase. This enzyme hydrolyzes the inorganic phosphorus and the rock phosphate (RP) hence making P available in the soil for plant uptake. AMF also are involved in soil nitrogen, carbon and trace element cycling. Regarding the biological component of the soil, AMF influence the composition, diversity and activity of microbial communities in the hydrosphere. They also work in synergy with others soil microorganisms to improve soil fertility, plant growth and resistance against some diseases. In this review, we present the contribution of AMF on soil fertility and importance in polluted soils.

Uranium isotopes actively investigated as mechanistic or time scale tracers of natural processes. This paper describes the occurrence and redistribution of U in the Vendian aquifer of the paleo valley at NW Russia. Forty-four rock samples were collected from boreholes, and twenty-five groundwater samples. The U, Fe concentration, and 234U/238U activity ratio were determined in the samples. We estimated the 14C and 234U-238U residence time of groundwater in an aquifer. It has been established that the processes of chemical weathering of Vendian deposits led to the formation of a strong oxidation zone, developed above -250 m.a.s.l. The inverse correlation between the concentrations of uranium and iron is a result of removal of U from paleo valley slopes in oxidizing conditions and accumulation of U at the bottom of the paleo valley in reducing conditions, and accumulation of Fe on the slopes and removal from bottom. Almost all U on the slopes replaced by a newly formed hydrogenic U with a higher 234U/238U activity ratio. After that dissolution and desorption of hydrogenic U was occurred from the slopes during periods without any glaciations and marine transgressions. Elevated concentrations of U preserved in not oxidized lenses at the paleo valley bottom.

High-efficiency rock breaking by hydraulic jetting is the key to radial horizontal drilling technology. In order to improve the drilling efficiency of hydraulic jet rock breaking in radial horizontal wells, based on LS-Dyna display dynamics, a numerical simulation model of single nozzle jet rock breaking is established to analyze the influence of different nozzle parameters on rock breaking effect. Then, the numerical simulation model of the spin multi-nozzle jet bit is established, and the influence of different rotation speeds on the rock breaking effect of the jet bit is analyzed. Finally, the rock breaking drilling characteristics of the spin multi-nozzle jet bit and the conventional multi-nozzle jet bit are compared and analyzed. The results show that when the jet impacts the rock surface, the larger the inclination angle is, the larger the rock breaking width formed by the jet is. The smaller the dip angle, the greater the rock breaking depth. When the inclination angle is greater than 60 °, it is difficult to meet the needs of reaming. The width and depth of the nozzle gradually increase with the increase of the diameter. When the nozzle diameter is greater than 1.3mm, the growth rate of rock breaking depth begins to decrease. The optimum nozzle diameter is 1.3 mm. When v = 50m / s, the damage caused by the jet to the rock surface is very small, because the condition of rock fracture is not reached at this time. This shows that there is a critical value of the water jet impact velocity, and only when the velocity is reached, the rock will break. When the velocity is v = 150m / s, v = 200m / s, v = 250m / s, v = 300m / s, the rock breaks. At the same time, the higher the speed, the higher the degree of rock fracture, the greater the fracture depth, the greater the fracture area, the better the fracture effect. The tangential and radial velocity of the jet increases the shear and tensile failure rate of the sample, and improves the rock breaking efficiency of the jet, which has certain guiding significance for improving the rock breaking drilling efficiency of radial horizontal well drilling.

The formation of rock fractures in nature has a certain relationship with water seepage. In order to analyze the shape of rock fracture, we propose a rock deformation theoretical model in three-dimensional space considering with the condition of seepage water pressure, and establish the mass conservation equation, seepage equation, surrounding rock displacement equation, so as to deduce the rock deformation control equation under seepage pressure action. The numerical analysis of the nonlinear quadratic partial differential equation obtains the fracture deformation distribution in the example, and verifies with the calculated fracture morphology. And we further use this principle to analyze the fracture morphology in nature and prove the rationality of the theory.

This paper concerns the effect of proppant embedment related with hydraulic fracturing treatment. This phenomenon occurs if the strength of the reservoir rock is lower than proppant grains. The aim of the research is laboratory determining the loss of width of the proppant pack built of light ceramic grains. The laboratory simulation of the embedment phenomenon was carried out for a shale rock on a hydraulic press, in a specially prepared for this purpose a heated embedment chamber. Tests were conducted at high temperature and axial compressive stress conditions. The surfaces of the cylindrical core plugs (fracture faces) were imaged under an optical microscope equipped with 3D software. The fracture faces were examined and compared before and after the embedment phenomenon. The analysis of the obtained images of the fracture face were made based on the research method of the embedment phenomenon developed at Oil and Gas Institute-NRI. On the basis of laboratory tests, the parameters characterizing the embedment phenomenon were collected and discussed. In addition, the percentage reduction in the width of the proppant pack was determined.

Cemented rock fill (CRF) is commonly used in cut-and-fill stoping operation in underground mining. This allows for the maximum recovery of ore. Backfilling can improve stope stability in underground workings, and then improve ground stability of the whole mine site. Backfilling step scenarios vary from site to site. This paper presents the investigation of five different backfilling step scenarios and their impacts on the stability of stopes at four different mining levels. A comprehensive comparison of displacements, major principal stress and stress concentration factor (SCF) was conducted. The results show that different backfilling step scenarios have little influence on the final displacement for displacement in the stopes. Among the five backfilling scenarios, the major principal stress and stress concentration factor (SCF) have almost the same final results. The backfilling scenario SCN-1 is the optimum option among these five backfilling scenarios. It can immediately prevent the increase of the displacement and reduce the sidewall stress concentration, thereby preventing possible failures. Using the same strength of CRF can achieve same effects among the four mining levels. Applying backfilling CRF of the same strength at different mining depths is acceptable and feasible to improve the stability of the stopes.

The issue of monitoring and early warning of rock instability has received increasing critical attention in the study of rock engineering. To investigate the damage evolution process of granite under triaxial compression tests, acoustic emission (AE) tests were performed simultaneously. This study firstly introduced two novel parameters, i.e., the coefficient of variation (CoV) of the information entropy and correlation dimension of the amplitude data from the AE tests, to identify the precursor of the failure of granite. Then the relationship between the changes in these parameters and the stress-time curve was compared and analyzed. The results of this study show that: (1) There is a strong correlation between the CoV of the information entropy and the failure process of granite. The granite failed when the CoV curve raised to a plateau. (2) The fluctuation of the correlation dimension indicates the different stages of the loading process, i.e., the initial compaction stage, the linear elastic stage, the yield stage, and the failure stage. Each stage contains a descending and a rising process in the correlation dimension curve, which indicates that this parameter could be used to identify the precursor of the failure as well. (3) The combined analysis of the two can improve the accuracy of rock instability prediction. This study provides new insights into the prediction of rock instability, which has theoretical implications for the stability of subsurface engineering rock masses.

Poor survival of human pluripotent stem cells (hPSCs) following freezing, thawing, or passaging hinders maintenance and differentiation in stem cell research. Rho-associated kinases (ROCKs) play a crucial role in hPSC survival. To date, a typical ROCK inhibitor, Y-27632, has been the primary agent used in hPSC research. Here, we report that another ROCK inhibitor, fasudil, can be used as an alternative. Fasudil increased hPSC growth due to survival rather than proliferation following thawing and passaging, similar to Y-27632. It did not affect pluripotency and genetic integrity including mitochondrial genome (mtDNA). Notably, the genes related to metabolism, mTORC1, and TP53 have mainly displayed a faster recovery pattern with ROCK inhibitors than control. Furthermore, fasudil was confirmed as useful for the single dissociation of hPSCs and for aggregation. It also increased retinal pigment epithelium (RPE) differentiation and the survival of neural crest cells during differentiation. These findings suggest that fasudil can replace Y-27632 for use in stem cell research.

The use of salt rock for underground radioactive waste disposal facilities requires a comprehensive analysis of creep-damage process in salt rock. A computer-controlled creep setup is employed to carry out a creep test of salt rock lasted as long as 359 days under a constant uniaxial stress. The AE space-time evolution and energy releasing characteristics during creep test are studied in the meantime. A new creep-damage model is proposed on the basis of fractional derivative by combining the AE statistical regularity. It indicates that the AE data in non-decay creep process of salt rock can be divided into three stages. Furthermore, the parameters of new creep-damage model are determined by Quasi-Newton method. The fitting analysis suggests that the creep-damage model based on fractional derivative in this paper provides a precise description of full creep regions in salt rock.

HIV-1 transcribes only one kind of transcript – the full length genomic RNA. To make the mRNA transcripts for the accessory proteins Tat and Rev, the genomic RNA must completely splice. The mRNA transcripts for Vif, Vpr, and Env must splice but not completely. Genomic RNA (which also functions as mRNA for the Gag and Gag/Pro/Pol precursor polyproteins) must not splice at all. HIV-1 can tolerate a surprising range in the relative abundance of individual transcript types, and a surprising amount of aberrant and even odd splicing; however, it must not over-splice, which results in the loss of full length genomic RNA and has a dramatic fitness cost. Cells typically do not tolerate unspliced/incompletely spliced transcripts, so HIV-1 has to circumvent this cell policing mechanism to allow some splicing while suppressing most. Splicing is controlled by RNA secondary structure, cis-acting regulatory sequences which bind splicing factors, and the viral protein Rev. There is still much work to be done to clarify the combinatorial effects of these splicing regulators. These control mechanisms represent attractive targets to induce over-splicing as an antiviral strategy. Finally, splicing has been implicated in latency, but to date there is little supporting evidence for such a mechanism. In this review we apply what is known of cellular splicing to understand splicing in HIV-1, and also present data from our newer and more sensitive deep sequencing assays quantifying the different HIV-1 transcript types.

Identification and segmentation of rock particles is very important in geology, mining, engineering construction, and environmental monitoring. Traditional methods for recognizing the rock particle characteristics are time-consuming, labor-intensive, and limited by the geographical scope of the sampling sites, which makes it more difficult to represent the spatial distribution of the rock particles accurately. Recent advancements in deep learning techniques offer promising solutions to automate this process. This study aims at utilizing state-of-the-art (SOTA) Mask R-CNN deep learning algorithm from the Detectron2 framework, to capture global features of rocks that will enable the recognition of rock particles more efficiently, just from having the rock images. These images are subject to image processing techniques such as a Gaussian filter, to denoise and smoothen the image, and an Illumination Adaptive Transformer (IAT) framework, to adjust the lighting exposure; all of which add to improve the quality of the image dataset. Afterward, the Mask R-CNN and Detectron2 models are utilized in training the images using transfer learning. Experimental results from evaluating the performance of the proposed algorithms showcase the effectiveness of the approach, thereby highlighting its potential to revolutionize rock particle segmentation across various domains.

Based on the analysis of hydrochemical data of 18 samples of shallow groundwater around Hancheng mining area in Guanzhong Basin, Gibbs semi-logarithmic diagram and Piper diagram were used to study the hydrogeochemical behavior of shallow groundwater around Hangcheng mining area in Guanzhong Basin. Chemical composition analysis showed that most of the groundwater was SO₄ · Cl-Ca · Mg type, accounting for 61.1 %. Hydrogen and oxygen isotope data show that groundwater in the study area is recharged by modern precipitation. The main chemical components of most groundwater are Ca²⁺, Mg²⁺, HCO₃^-, Cl^-and SO₄^2-. Ca²⁺, Mg²⁺, and HCO₃^- are mainly dolomite, calcite, and gypsum dissolution precipitation results. Na⁺ and Cl^- originate from the dissolution of halite. The main ion chemistry of shallow groundwater in this area is controlled by rock weathering, and pyrite oxidation is an important factor affecting SO₄^2-concentration. The research results will help analyze the formation mechanism of chemical components and provide some basic data for the evolution of mine water in this area in the future.

In order to study the influence of falling rock shape on its rolling characteristics and realize the optimization of falling rock protection design, the following research was carried out. Design model experiments to explore the rolling characteristics of different shapes of rockfalls. Based on the experimental results, it was found that the slenderness ratio, center of gravity, and rotational inertia of the rockfalls can affect their rolling characteristics, leading to swaying and changing the rolling axis during the rolling process, thereby affecting their rolling speed. On this basis, the formation mechanism of rolling resistance is analyzed, and the main cause of energy loss is the rolling resistance arm formed with the rolling surface during rockfall rolling, and a shape parameter to quantify the rolling resistance is proposed. The parameters are substituted into the kinematic formula, in which the influence of the rockfall shape, slope and slope roughness on the rolling speed is considered. Combined with the offset and initial position of the rockfall, the formula can be used to calculate the rolling speed and impact energy in the rolling region and any position in the region. The calculation formula was validated using model experimental data, and the results showed that the error between the experimental and calculated values was small. The error was corrected based on the experimental data. After on-site testing and verification, it can provide reference for the management of rockfall disasters.

The study seeks to unravel the intricate operational sequence involved in preparing prehistoric pigments for rock art within the Puerto Roque rock art shelter. Sixteen pigment samples, identified as Lab Code Puerto_1 to Puerto_16, were meticulously collected from specific figurative representations. Additionally, three ochre samples (Puerto_17, Puerto_18, and Puerto_19) were sourced from the shelter's soil. Employing a comprehensive multi-analytical approach, including Raman microspectroscopy, X-ray microfluorescence (EDxrf), Fourier-transform Infrared spectroscopy (ATR-FTIR), and Scanning Electron Microscopy (SEM), all nineteen samples underwent thorough analysis. The research unveiled a spectrum of distinct red pigments within the rock art depictions. The sampling strategy for the 16 panels in the Puerto region was meticulously designed to capture the diverse array of rock art manifestations, each presenting unique characteristics that warranted detailed scientific investigation. The selection of these panels was guided by the recognition of various artistic techniques employed in the creation of the paintings, the nuanced hues exhibited, prevalent erosion issues, potential effects of sunlight exposure, and the intriguing hypothesis of distinct chronological periods due to several superimpositions detected. Notably, darker pigments in samples Puerto_02, Puerto_10, and Puerto_19 revealed a composition of hematite with the added presence of carbon. Meanwhile, Puerto_08 exhibited an orange hue primarily composed of goethite. Bright red pigments in samples Puerto_01, Puerto_03, Puerto_05, Puerto_07, Puerto_09, and Puerto_11 were predominantly characterised by hematite, as confirmed by Raman analysis. EDxrf analysis demonstrated an elemental composition akin to the three ochre pieces examined. Furthermore, ATR-FTIR spectroscopy suggested the potential influence of a heating process in enhancing red coloration, corroborated by spectral results from specific samples. This finding aligns with prior research, underscoring the technological sophistication embedded in early artistic endeavours. The detailed understanding of pigment types and their preparation methods provides insights into the artistic choices and technological adeptness of prehistoric communities. Beyond the archaeological implications, these findings contribute significantly to the ongoing conservation efforts of rock art sites. The amalgamation of diverse analytical techniques showcased their efficacy in elucidating the intricate world of pigment preparation. Recognizing the unique microclimates at each rock art site that influence pigment preservation, this localised approach aids informed decisions in safeguarding these invaluable cultural resources. In essence, this study not only unravels the artistic past but also advocates for the sustainable conservation of our shared cultural heritage.

The recognition of coal-rock interface is very crucial for the research in the intelligent production of coal mine. This study investigates the application of terahertz time-domain spectroscopy in the recognition of coal-rock interface, including the identification of coal-rock and coal-rock mixtures, as well as the accurate characterization of coal seam thickness. Terahertz detection was used to obtain the optical parameter information of the pressed pellets prepared by mixing two different kinds of coal and two kinds of rock. Based on the experiment results, the database was established for the identification of coal-rock interfaces in coal mining machines. The terahertz detection was performed on 10 different kinds of sheet anthracite with different thickness, and the terahertz spectra of coal seams with different thickness were simulated and calculated by using simulation software, which can accurately obtain the thickness of coal seams and provide effective mining thickness parameters for coal seam mining. Through the experiment and simulation, the terahertz time-domain spectroscopy technology has a promising application prospect in the identification of coal-rock interface.

A single geological carbon dioxide (CO2) storage within salinity aquifer as a paramount stratagem in the context of forthcoming CO2 sequestration initiatives. Within the expansive tapestry of terrestrial salinity aquifers in China, replete with nuances in mineral composition and structural diversity, a paradigm distinct from the marine sedimentary basins of North America, a labyrinthine stratigraphic environment of elevated complexity unfolds. Consequently, conspicuous lacunae and insufficiencies manifest within the existing knowledge reservoir pertaining to CO2-water-rock (mineral) reaction mechanisms. Notably, a conspicuous dearth of insights prevails concerning the dissolution kinetics inherent to individual minerals embroiled in these reactions. The present investigation undertakes a scrupulous exploration into the dissolution and erosive processes manifest within four emblematic terrestrial minerals in conjunction with CO2. Furthermore, the study meticulously scrutinizes the evolution of ionic composition and pH within the formation water throughout the trajectory of the geochemical reactions. To accomplish this, a simulation apparatus is configured to emulate conditions germane to temperature, pressure, and mineralization characteristics characteristic of a prototypical salinity aquifer reminiscent of the Daqing oilfield in China. The findings that emerge from this scrutiny reveal that the erosive action of CO2 fluid begets varying degrees of dissolution within the four minerals under investigation. Moreover, our meticulous inquiry lays bare that, in the terminal phases of the reaction process, feldspar precipitates secondary minerals, characterized primarily by dawsonite, in response to the aquatic milieu typifying the profound salinity stratum of terrestrial sedimentation. This milieu is notably enriched with Na+ ions and NaHCO3. This phenomenon suggests that feldspar, under these specific conditions, assumes the mantle of a mineral amenable to carbon sequestration, thus enriching the reservoir for CO2 mineralization within the salinity stratum of terrestrial sedimentation.

Enhanced oil recovery (EOR) refers to the various techniques used to increase the amount of crude oil that can be extracted from an oil field. These techniques are used after the primary and secondary recovery methods have been depleted. There are three main types of EOR: thermal, gas injection, and chemical. EOR techniques can be expensive and complex, but they can help to recover additional oil that would otherwise be left in the reservoir. EOR can also extend the life of an oil field and increase the overall production from a given field. The parameters affecting oil recovery are a major concern in EOR systems, and these parameters need more consideration with the factors affecting them. In this study, the influence of permeability variations on fluid flow in a sandstone reservoir was explored, as well as an up-to-date description of three states of EOR with thorough explanations of the methods utilized and the mechanisms driving their oil recovery application. The difficulties encountered in the use of the different standard EOR Mechanisms were noted, and solutions to these difficulties were proposed. Furthermore, the contemporary trend of adding nanotechnology and its synergistic effects on the stability and efficiency of traditional chemicals for EOR were examined and analysed. Finally, laboratory findings and field initiatives were discussed. The review went into detail about the transport of nanoparticles across reservoirs, as well as the evaluation of EOR, mobility ratio, and fluid displacement efficiency. This review provides thorough information on the uses of improved oil recovery mechanisms for sustainable energy production.

The rock strata movement deformation generated by the mining process of the mine will inevitably lead to surface subsidence and a series of environmental hazards, so it is particularly important to monitor the rock strata movement deformation and surface subsidence in the goaf area. With the development of surface subsidence monitoring technology, InSAR technology has been widely used in the research of surface subsidence in mining areas with the advantages of high precision and wide monitoring. In this paper, by obtaining the image data of 59 Sentinel-1A scenes in the mining area, the obtained PS points were analyzed and processed by ArcGIS difference analysis by PS-InSAR technology, and the surface deformation cloud map and settlement curve of the mining area in various periods were obtained, and the rock strata movement deformation and surface subsidence law of the goaf before treatment and after different treatment methods were studied by influencing factors such as stope layout and mining depth. The results show that the rock strata movement deformation and surface subsidence degree of the goaf under different treatment methods are different due to different influencing factors, and their positions also change dynamically with time. Applying InSAR technology to study rock strata movement deformation and surface subsidence can provide an important basis for mine safety mining, goaf treatment, rock strata movement deformation and surface subsidence monitoring.

For the Altai mountainous region, especially the arid south-eastern part, the history of glacier fluctuations in Pleistocene and Holocene is still poorly known. The key plots were located in the Kargy valley (2288-2387 m a. s. l.) that is not currently affected by glaciations. The relative dating method was applied to define Pleistocene moraine chronology and configuration in the Kargy valley. Taking into account that relative dating methods are primarily based on weathering pat-terns, the mineralogy, porosity, and specificity of biological colonization as an agent of weath-ering were obtained for the moraine samples. Three moraine groups of different age (presumably MIS 6, MIS 4, and MIS 2) were identifies based on detailed investigation of morphological features. The moraine age was indirectly confirmed by the mesostructure of the moraine samples repre-sented by fine-grained shale: the older sample is characterized by a more developed fractal sur-face than the younger one. The growth of biota (crustose lichen and micromycetes) leads to initial biomass accumulation and subsequent rock disintegration. The accumulation of autochthonous fine earth on the rock surface was considered the initial stage of fine earth formation affected by biota.

The effects of CO₂-water-rock interactions on the mechanical properties of shale are essential for estimating the possibility of sequestrating CO₂ in shale reservoirs. In this study, uniaxial compressive strength (UCS) tests together with an acoustic emission (AE) system and SEM & EDS analysis were performed to investigate the mechanical properties and microstructural changes of black shales with different saturation times (10 days, 20 days and 30 days) in water dissoluted with sub-/super-critical CO₂. According to the experimental results, the values of UCS, Young’s modulus and brittleness index decrease gradually with increasing saturation time in water with sub-/super-critical CO₂. Compared to intact samples, 30-days’ saturation causes reductions of 56.43% in UCS and 54.21% in Young’s modulus for sub-critical saturated samples, and 66.05% in UCS and 56.32% in Young’s modulus for super-critical saturated samples, respectively. The brittleness index also decreases drastically from 84.3% for intact samples to 50.9% for samples saturated in water with sub-critical CO₂, to 47.9% for samples saturated in water with super-critical carbon dioxide (SC-CO₂). SC-CO₂ causes a greater reduction of shale’s mechanical properties. The crack propagation results obtained from the AE system show that longer saturation time produces higher peak cumulative AE energy. SEM images show that many pores occur when shale samples are saturated in water with sub-/super-critical CO₂. The EDS results show that CO₂-water-rock interactions increase the percentages of C and Fe and decrease the percentages of Al and K on the surface of saturated samples when compared to intact samples.

Diagnosis of kidney diseases has recently become more comprehensive and accurate by using new renal markers. Despite the fact that creatinine and cystatin c have been sufficient in determining kidney function, they did not indicate the exact site of the damage and they were often insufficient in predicting the course of the disease. Aim of the study was to evaluate the potential correlations and differences in levels of six factors related to kidney function and injury: kidney injury molecule-1 (KIM-1), ncalbindin (CALB), glutathione S-transferase Pi (GST-Pi), calbindin and monocyte chemoattractant protein-1 (MCP-1), between renal patients with diabetic nephropathy (DM), congenital defects (CD) of the kidney and glomerulonephritis (GN). Study involved 75 patients: 49 with diabetic nephropathy, 12 with congenital defects and 14 with glomerulonephritis. Levels of renalase was measured using immunoenzymatic tests. Levels of other markers: calbindin, glutathione-S-transferase (GST-pi), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1), were analyzed using Kidney Toxicity-1 Panel and BioPlex system, designed for analyses in urine and optimized by us for serum.From all analyzed markers, only levels of KIM-1 differed significantly between any subgroups, and that was for CD and DM. Renalase correlated significantly negatively with creatinine and positively with all other markers, apart from MCP-1. Obtained results indicate, that serum renalase, KIM-1, calbindin and GST-pi are related to kidney function, with KIM-1 being the most exact, while MCP-1 levels are unrelated to creatinine and glucose levels, does not differ between patients with diabetic nephropathy and other subgroups, and therefore seem to be independent of diabetes. Also, serum-optimized Kidney Toxicity Panel 1 kit for determination of selected markers gave results similar to previous ones and therefore the method can be valuable in determination of analyzed factors.

The degree of ore rock fragmentation of mine blasting is an important index for evaluating the effect of engineering blasting. In order to study the effect of millisecond delayed blasting on the internal fragmentation of the ore rock, LS-DYNA numerical simulation software was used to obtain the damage characteristics of the ore rock in the blasting area using the RHT model. The Mohr-Coulomb strength damage criterion was applied to analyze the internal stress state of the ore rock, and the effects of 25ms, 50ms and 75ms delay time conditions on ore rock fragmentation were studied. The results show that, within a certain range of delay time, the degree of rock fragmentation increases with the increase of delay time. The stress state in the ore rock due to blasting is strengthened with the increase of delay time in the direction of the blast hole, which shows that the stress concentration is strengthened from the excavation face to the interior of the ore rock. The damage and the degree of fragmentation show a characteristic relationship of 25ms＜50ms＜75ms, which is verified by carrying out blasting experiments on site.

The rapid retreat of coastal cliffs poses a profound risk to property, transport infrastructure and public safety both in Ireland and globally. This study combines historical data (maps and orthophotos, 1842 to 2000) with contemporary UAV surveys (2019 to 2023) to quantify cliff top and cliff face retreat along a 250 m wide coastal drumlin at Silverstrand in Galway Bay, Ireland. Retreat rates for the cliff top and cliff face were calculated using 2D mapping and 3D modelling, respectively. Critically, the choice of method appears to have a major impact on apparent rates of cliff top retreat, with output from the 2D mapping approach (0.14 +/- 0.02 m yr-1) being double that of the 3D modelling approach (0.08 +/- 0.02 m year-1). The aperiodic development of a talus cone, which offers temporary protection to the cliff from storm waves, also influences the estimation of cliff retreat. The repeat cycles of talus slope formation and removal in this high wave energy climate suggest that the drumlin transitions between a periodically transport-limited system and supply limited system over short- and long-time periods, respectively, on the continuum of cliff types. These results warrant further research to identify and quantify the rates, patterns, drivers (marine and subaerial processes), and timing of cliff retreat rates in response to climate change.

The wettability of the oil-brine-rock systems is very challenging mainly for the carbonate reservoirs and it plays a significant role to enhance the oil recovery (EOR). Carbonate rocks are mad-up of complex lithology, hence these requires careful treatments in controlling their wetting behavior for enhanced oil recovery. Therefore, it is extremely important to modify their wettability from an oil-wet rock behavior to a water-wet so that the residual oil can be produced efficiently. Thus, the present study has examined the effectiveness of alumina nanofluid as well as a new chemical methyl blue to alter the wettability. The methyl blue is released on massive scale from various industries i.e. pharma, textile and food industry which is a key environmental concern which contaminates the water table. Hence the study, explores the effects of MB and alumina nanofluid on the wettability. The effect of nanofluids formulated via dispersing the alumina nanoparticles in aqueous solutions at various concentration (0. 0.05, 0.3, 0.50, 0.75 and 1.0 wt. %) were tested for wettability modification under different physio-thermal conditions. Subsequently, the wettability change was examined for the samples treated with different concentrations of MB (10, 15, 30, 50 and 100 mg/L) for 7-days at two different temperatures of (25 and 50 0C). The results showed that hydrophobicity of the SML carbonate rock has significantly reversed while treating with alumina nanofluids and MB. Thus, the wettability modification/reversal via treatment of MB and alumina nanofluid can be an effective mechanism to hydrogen injection and for EOR processes.

In this work, some micro-samples belonging to the open-air rock art site of Cueva de la Vieja (Alpera, Albacete, Spain) were analysed. These samples were collected after and before a desalination treatment carried out with the aim of removing a whitish layer of concretion that affected the painted panel. The diagnostic study was performed to study the conservation state of the panel and then to confirm the effectiveness of treatment. Micro energy dispersive X-ray fluorescence spectrometry, Raman spectroscopy and X-ray diffraction were employed for the characterization of the degradation product as well as that of mineral substrate and pigments. The micro-samples analysis demonstrated that the painted layer was settled on a dolomitic limestone with silicon aggregates and aluminosilicates as well as iron oxides. The whitish crust was composed by sulfate compounds like gypsum (CaSO4·2H2O) with minor amount of epsomite (MgSO4.7H2O). An extensive phenomenon of biological activity was demonstrated since, in almost all the samples analysed, the presence of calcium oxalates monohydrate (CaC2O4H2O) and dehydrate (CaC2O42H2O) were found. Probably the presence of both calcium oxalates had favoured the conservation of pictographs. In addition, some carotenoids pigments, scytonemin (C36H20N2O4) and astaxanthin (C40H52O4) were characterized both by Raman spectroscopy and by X-ray diffraction. Hematite was found as a pigment voluntarily used for the painting of the panels used in mix with hydroxyapatite and amorphous carbon. The results of the analyses of the samples taken after the cleaning treatment confirmed a substantial decrease in sulphate patina on the panel surface.

With the rapid development of urbanization, the chemical evolution of groundwater is significantly affected by human activities. However, the driving mechanisms of groundwater chemical evolution at different stages of urbanization remain unclear, severely impacting the implementation of groundwater protection. This study investigated the driving mechanisms of groundwater chemical evolution based on the long-term series (from 1985 to 2015) of hydrochemical data from 19 groundwater monitoring sites in rapidly urbanizing areas (Shijiazhuang, Hebei Province, China). The results show that the concentrations of various chemical components in groundwater gradually increase with the acceleration of urbanization process, especially NO3-, which has increased from 13.7 mg/L in the primary stage of urbanization (PSU) to 65.1mg/L in the advanced stage of urbanization (ASU), exceeding the WHO drinking water standard (50mg/L), indicating that the groundwater chemistry has been significantly affected by human activities. It is interesting to find that the main hydrochemical types have changed from HCO3•SO4-Ca•Mg type water in the PSU to SO4•HCO3-Ca•Mg type water in the ASU. It is worth noting that there were obvious differences in driving factors of groundwater chemical evolution at different urbanization stages. In the PSU, the driving factors of groundwater chemical evolution were carbonate and rock salt dissolution, cation exchange, and industrial activities. However, in the intermediate stage and advanced stage, the driving factors of groundwater chemical evolution were changed to carbonate and gypsum dissolution, groundwater over-exploitation, agricultural fertilization, and domestic sewage. Based on the above conclusions, it is suggested that future groundwater management should control the amount of agricultural fertilizers, apply scientific fertilization, and prohibit the discharge of various types of non-compliant sewage, while strengthening the supervision of groundwater extraction to reduce the impact of urbanization development on the groundwater chemical evolution process.

During the last few years, several approaches have been proposed to improve early warning systems for reducing rock-fall risk. In this regard, this paper introduces a Deep learning-and (IoT) based Framework for Rock-fall Early Warning, devoted to reducing the rock-fall risk with high accuracy. In this framework, the prediction accuracy was augmented by eliminating the uncertainties and confusion plaguing the prediction model. In order to achieve augmented prediction accuracy, this framework fused the prediction model-based deep learning with a detection model-based Internet of Things. In order to determine the framework’s performance, this study adopted parameters, namely overall prediction performance measures, based on a confusion matrix and the ability to reduce the risk. The result indicates an increase in prediction model accuracy from 86% to 98.8%. In addition, a framework reduced the risk probability from (1.51 ×10-3) to (8.57 ×10-9). Our results indicate the framework’s high prediction accuracy; it also provides a robust decision-making process for delivering early warning and lowering the rock-fall risk probability.

Rocks are materials with a wide variety of structures and properties. These can be unprocessed conglomerates of conglomerated minerals as well as crystallized outcrop or metamorphic rocks. Their processing, especially shaping, poses many technological difficulties. Therefore, it is very important to answer the question of how these natural materials yield to high-pressure water jet and abrasive water. It is equally important to determine the effect of key process parameters such as pressure, water nozzle diameter and feed rate on cutting efficiency. The first two parameters determine the water output and power of the jet, while the third determines the jet erosion time per unit volume of material. Their interdependence, using appropriate evaluation indicators, allows to determine the energy intensity of processing and directions for its minimization.

In order to understand the impact of lithologic heterogeneity of continental mixed fine-grained sedimentary rocks on reservoir brittleness in western Qaidam basin, the mechanical properties of the rocks and their correlation with mineral composition and petrographic characteristics were studied by measns of mineralogy, petrography and triaxial stress test. The results show that the reservoir rocks can be divided into 5 different types according to the mechanical properties of the reservoir (characteristics of stress-strain curves), among them Type I and III belong to similar elastoplastic failure model, type II shows a special pulse failure mode for plastic material, type IV shows a failure mode of mixed characteristics, and type V exhibits a typical plastic failure model. The correlation between minerals and mechanical properties indicates that quartz and feldspar, which are often considered brittle minerals, do not contribute much to the brittleness of continental fine-grained sedimentary rocks. The main minerals affecting reservoir brittleness are dolomite and clay minerals, and their contributions to reservoir brittleness are positive and negative, respectively. The petrographic analysis results prove that the abnormal correlation between rock mechanical properties and quartz and feldspar is caused by the different rock fabrics. When dolomite forms a rock skeleton, it typically exhibits greater strength, brittleness and physical properties than other minerals. Based on the results, a brittleness evaluation standard for continental fine-grained sedimentary rock reservoir is proposed, and the validity of the standard is verified by the spatial correlation between the lithology probability model and the micro-seismic monitoring data, indicating that the spatial heterogeneity of dolomite-rich rock is the main controlling factor for the development of ‘sweet spot’ in the Cenozoic continental fine-grained sedimentary rock reservoir in the Western Qaidam Basin.

The efficacy of predicting geochemical parameters with a 2-chain workflow using spectral data as the initial input is evaluated. Spectral measurements spanning the approximate 400-25000nm spectral range are used to train a workflow consisting of a non-negative matrix function (NMF) step, for data reduction, and a random forest regression (RFR) to predict 8 geochemical parameters. Approximately 175000 spectra with their corresponding chemical analysis were available for training, testing and validation purposes. The samples and their spectral and chemical parameters represent 9399 drillcore. Of those, approximately 20000 spectra and their accompanying analysis were used for training and 5000 for model validation. The remaining pairwise data (150000 samples) were used for testing of the method. The data are distributed over 2 large spatial extents (980 km2 and 3025 km2 respectively) and allowed the proposed method to be tested against samples that are spatially distant from the initial training points. Global R2 scores and wt.% RMSE on the 150000 validation samples are Fe(0.95/3.01), SiO2(0.96/3.77), Al2O3(0.92/1.27), TiO(0.68/0.13), CaO(0.89/0.41), MgO(0.87/0.35), K2O(0.65/0.21) and LOI(0.90/1.14), given as Parameter(R2/RMSE), and demonstrate that the proposed method is capable of predicting the 8 parameters and is stable enough, in the environment tested, to extend beyond the training sets initial spatial location.

Purpose: This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor, in a porcine ex vivo pigmentary glaucoma model. Methods: Twenty-eight porcine anterior chambers were perfused with medium supplemented with 1.67 × 10⁷ pigment particles/mL for 48 hours before treatment with RKI-1447 (n = 16) or vehicle control (n = 12). Intraocular pressure (IOP) was recorded and outflow facility was calculated. Primary trabecular meshwork cells were exposed to RKI-1447 or vehicle control; effects on the cytoskeleton, motility, and phagocytosis were evaluated. Result: Compared to baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 hours. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 mmHg to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 hours (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 caused no apparent histological changes in the micro- or macroscopic TM appearance. RKI-1447-treated primary TM cells showed significant disruption of the actin cytoskeleton both in the presence and absence of pigment (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI-1447 reversed. Conclusion: RKI-1447 significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it useful for the treatment of secondary glaucomas with an increased phagocytic load.

Astronauts at are risk of losing 1.0 – 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs designed to preserve the musculoskeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth facor-1 and its receptor IGFR1 play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, and sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.

Expression of Krüppel–like factor 15 (KLF15), a stress induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1 immediate early transcription unit 1 (IEtu1), herpes sim-plex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoter. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 ex-pression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection and KLF15 steady state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following in-fection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene and to a lesser extent bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 pro-moter activity. Collectively, these studies revealed HSV-1 and BoHV-1 productive infection in-creased KLF15 steady state protein levels, which correlated with increased virus production.

Tidal notches, long regarded as reliable indicators of mean sea level, have been extensively studied along carbonate coasts in the central Mediterranean Sea. Previous studies revealed a correlation between the genesis of tidal notches and tidal range, lithology, cliff foot depth and wave energy. In the 2020 Geoswim campaign at Lampedusa, the southernmost island of the Pelagie archipelago (Italy), 'anomalous' tidal notches were identified. Unlike normal notches observed elsewhere, those in Lampedusa's southern bays exhibited a particular behavior —constantly deepening in the inner part of the bays, reaching a maximum depth of approximately 30 cm below sea level and narrowing inwards. Similar phenomena were previously observed by [1] near Marseille (France) and in Gozo Island (Malta). Time-lapse images, alongside measurements of morphometric param-eters, were collected during the survey. Despite the rapid morphological changes of the notches within the bay, the tectonic stability of the studied areas was confirmed by literature and data. Our hypothesis indicates that a combination of marine factors, influenced by local meteomarine conditions driven by the local morphology of the small bays exposed to southern quadrants con-tribute to the formation of these unique landforms. The latter manifest higher lowering erosion rates slightly below mean sea level in sheltered areas, challenging conventional notions about tidal notch formation.

Chert rock is a by-product of sand quarrying (about 40% in the geological section). All attempts to use ordinary technologies for aggregate production from chert have been economically unsuccessful, resulting in significant chert "waste" accumulation covering vast quarry areas. This paper presents the study results of the effect of microwave irradiation on the mechanical properties of chert gravel, which is mineralogically relatively homogenous and consists of fine quartz grains. The results show that an increase in irradiation time decreases the strength of chert gravel (by a factor of 4-6 for the 2.5 min of irradiation), while the quenching changes the fractional content of the samples after the crushing test, decreasing the Gravel-to-Sand ratio.

In order to study the acoustic emission characteristics of sandstone under the action of the high temperature-water cooling cycle, the RMT-150B electro-hydraulic servo rock test system and the DS-5 acoustic emission detection and analysis system were used to conduct a single analysis of the sandstone after the high temperature-water cooling cycle. Experimental study on acoustic emission characteristics under axial compression, analyzing the deformation, strength and acoustic emission characteristics of sandstone under different temperatures and cycles. The results of the study show that the high temperature-water cooling action causes changes in the physical properties of the sandstone. The expansion rate of the rock sample decreases first and then increases when the temperature rises, and the strength first increases and then decreases. The number of cycles has little effect on the physical properties of the rock sample; sandstone acoustic emission ringing count increases with the increase of temperature and cycle times, acoustic emission activities become more frequent with the loading process; with the increase of cycle times and temperature, acoustic emission ringing counts and accumulative acoustic emission energy appear earlier The rock sample enters the elastic deformation stage ahead of schedule, the yielding period increases, and the rock sample presents a trend of transition from brittle failure to ductile failure; the ringing count and cumulative energy increase with the increase in temperature and cycle times, and the high-energy ringing count and cumulative energy increase. The simultaneous sharp increase of the rock sample is the harbinger of the failure and instability of the rock sample.

Blasting pattern optimization is an attempt to optimize blast design parameters aiming to achieve optimum fragmentation, reduce mining operating costs as well as environmental side consequences. The present study aims to propose a multi-objective optimization model, employing artificial intelligence and metaheuristics, to simultaneously minimize the mine-to-crusher operating costs and the impact of blasting consequences including fly-rock and back-break. To achieve the purpose of the study, a multi-variable regression model was developed to model total costs from drilling to crushing. In addition to the costs, multilayer perception neural networks were implemented to predict the blast-induced back-break and fly-rock as a function of collected variables such as number of holes, hole length, burden, spacing, hole slope, stemming, blasted rock per hole, powder factor, and charge per delay. High-precise estimations for both back-break and fly-rock were achieved with the average of 99% coefficient of determination for train, test and validation data sets. Then, the developed regression model and the neural networks were used in an optimization framework, employing Grasshopper algorithm, to find the optimum blast design satisfying practical constraints. The proposed model was tested on a lead-zinc open-pit mine, where 1032 blasting patterns were recorded and analyzed. The results of the optimization model provide a Pareto set of solutions, such that any of these solutions can be implemented according to the strategy of the mining operation management team. The blast pattern with the lowest cost, result in a relatively high fly-rock and back-break, while the pattern with low fly-rock and back-break raises the cost by 20.13 % compared the minimum cost blast design.

The study of fractures in the subsurface is very important in unconventional reservoirs since they are the main conduits for hydrocarbon flow. For this reason, a variety of equivalent medium theories have been proposed for the estimation of fracture and fluid properties within reservoir rocks. We experimentally investigated the feasibility of applying the Galvin model in fractured tight stones. For this proposal, three artificial fractured tight sandstone samples with the same background porosity (11.7% ± 1.2%) but different fracture densities of 0.00, 0.0312, and 0.0624 were manufactured. The fracture thickness was 0.06 mm and the fracture diameter was 3 mm in all the fractured samples. Ultrasonic P- and S-wave velocities were measured at 0.5 MHz in a laboratory setting in dry and water-saturated conditions in directions at 0°, 45°, and 90° to the fracture normal. The results were compared with theoretical predictions of the Galvin model. The comparison showed that model predictions significantly underestimated P- and S- wave velocities as well as P-wave anisotropy in water-saturated conditions, but overestimated P-wave anisotropy in dry conditions. By analyzing the differences between the measured results and theoretical predictions, we modified the Galvin model by adding the squirt flow mechanism to it and used the Thomsen model to obtain the elastic moduli in high- and low-frequency limits. The modified model predictions showed good fits with the measured results.

Maize (Zea mays) is one of the most important staple food and primary source of livestock feed in the world. As the consumption of maize grown on the selenium-enriched soils of Naore Valley is one of the apparent causes of selenosis in the area, this work collected and analyzed total Se, Se fractions, and Se species distributions in maize plant samples, including grains, leaves, stalks, roots, rhizosphere soils, and the most representative parent rock materials from Naore Valley, Ziyang County, China. The Se distribution in soils markedly correlated with the weathered Se-enriched bedrocks, but most of the Se in the analyzed soils is enclosed as recalcitrant residual Se and organic-sulfide bound Se. In contrast, Se in rocks had a comparatively higher bioavailability and is bounded mainly to organic matter and sulfides minerals, with very few of the Se enclosed in the residual fraction. Maize plants might take a large amount of Se from the organic-sulfide bound Se fraction in the Se-rich soils, the weathered products from bedrocks or plant litters. Total Se concentrations in the collected samples were observed in descending order soil>leaf>root>grain>stalk. The predominant Se species detected in maize plants was SeMet. Se inorganic forms, mainly Se(VI), decreased from root to grain and were possibly assimilated into organic forms. Se (IV) was barely present. The natural increases in Se concentration affected mainly leaf and root dry-weight biomass as they are the organs that coped with the highest Se accumulation. This paper offers an insight into the uptake, accumulation, and distribution of Se forms in natural Se-rich maize crops and an opportunity for shifting Se-rich soils from menaces to valuable resources for growing Se-rich agricultural products.

Most of the pore-scale imaging and simulations of non-Newtonian fluid are based on the simplifying geometry of network modeling and overlook the fluid rheology and heat transfer. In the present paper, we developed a non-isothermal and non-Newtonian numerical model of the flow properties at pore-scale by direct simulation of the 3D micro-CT images using a Finite Volume Method (FVM). The numerical model is based on the resolution of the momentum and energy conservation equations. Owing to an adaptive meshing technique and appropriate boundary conditions, rock permeability and mobility are accurately computed. A temperature and concentration-dependent power-law viscosity model in line with the experimental measurement of the fluid rheology is adopted. The model is first applied at isothermal condition to 2 benchmark samples, namely Fontainebleau sandstone and Grosmont carbonate, and is found to be in good agreement with the Lattice Boltzmann method (LBM). Finally, at non-isothermal conditions, an effective mobility is introduced that enables to perform a numerical sensitivity study to fluid rheology, heat transfer, and operating conditions. While the mobility seems to evolve linearly with polymer concentration, the effect of the temperature seems negligible by comparison. However, a sharp contrast is found between carbonate and sandstone under the effect of a constant temperature gradient. Besides concerning the flow index and consistency factor, a good master curve is derived when normalizing the mobility for both the carbonate and the sandstone.

In this paper, a semi-empirical model of air waves induced by falling rock is described. The model is composed of a uniform motion phase (velocity close to 0 m·s^-1) and an acceleration movement phase. The uniform motion phase was determined based on experimentally and the acceleration movement phase was derived by theoretical analysis. A series of experiments were performed to verify the semi-empirical model and elucidated the law of the uniform motion phase. The acceleration movement phase accounted for a larger portion with a greater height of the falling rock. Experimental results of different falling heights of the goaf showed close agreement with theoretical analysis values. The semi-empirical model could accurately and conveniently estimate the velocity of air wave induced by falling rock. Thus, the semi-empirical model can provide a reference and basis for estimating the speed of air waves and designing protective measures in mines.

The study aimed to explore the correlation among Angiopoietin-1, (Ang-1) and Angiopoietin-2, (Ang-2) concentrations and the Angiopoietin-2/Angiopoietin-1 ratio, (Ang-2/Ang-1) with clinical outcomes, potentially serving as disease severity and survival biomarkers. A study at AHEPA University Hospital involved 90 COVID-19 adult patients, with 30 hospitalized in intensive care and 30 in ward units and 30 asymptomatic non-hospitalized individuals as controls. Estimated endothelial dysfunction markers related to angiogenesis were measured, and statistical analysis was performed using IBM SPSS Statistics software, version 29. There was a statistically significant difference only between outpatient and hospitalized patients (non-ICU -ICU groups) for the Ang-1 and Ang-2 indexes. The Ang-2/Ang-1 ratio has differed significantly among all individual patient groups. A ROC analysis was conducted to find an optimal threshold for distinguishing (outpatients – non-ICU) and (non-ICU –ICU) groups. It was based on Youden's Index and was 0.1122 and 0.3825, respectively. The Ang-1, Ang-2 levels, and Ang-2/Ang-1 ratio were analysed as indicators for severity in COVID-19 patients. The Ang-2/Ang-1 ratio demonstrated more excellent prognostic and diagnostic utility than individual biomarker levels. Monitoring the Ang-2/Ang-1 ratio can identify COVID-19 patients at risk and assist clinicians in tailoring treatment strategies for improved outcomes.

Incretin effect helps in regulating glucose homeostasis and maintaining glycaemic control within the human body. This effect is achieved by the two naturally occurring incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Such hormones released by specialized entero-endocrine cells of the gastrointestinal tract cause insulin augmentation after food consumption. However, incretin effects are impaired in type 2 diabetic, primarily attributed to the deterioration of GLP-1 function along with decreased GLP-1 receptor expression. Targeting this hormone has, therefore, become an important therapeutic approach to treat this diabetic condition. Native GLP-1’s brief half-life and rapid proteolytic degradation have generated significant enthusiasm in uncovering the long-acting GLP-1 receptor (GLP-1R) agonists to manage type 2 diabetes. These synthetic peptides mimic the natural GLP-1 to activate GLP-1R and effectively exert various physiological benefits in terms of weight management, blood pressure, lipid profile, obesity and major adverse cardiovascular event. This review paper provides insights into the structure, function and expression of GLP-1 and its receptor. It also summarizes existing literature regarding different types of GLP-1 receptor agonists, their effects on blood pressure and how they exert their actions. While animal models have contributed significantly to this area of study, the scarcity of human studies is noted, indicating a need for more investigation in this domain. Expanding research in humans will help in comprehending the impact of GLP-1 receptor agonists on blood pressure regulation and their underlying mechanisms.

The development of potent antiviral agents is of utmost importance to combat the global burden of viral infections. Traditional antiviral drug development involves targeting specific viral proteins, which may lead to the emergence of resistant strains. To explore alternative strategies, we investigated the antiviral potential of antimicrobial peptidomimetic compounds. In this study, we evaluated the antiviral potential of short anthranilamide-based peptidomimetic compounds 1-17 against two viruses: Murine Hepatitis Virus 1 (MHV-1-single stranded RNA virus) which is a surrogate of human coronaviruses and Herpes Simplex Virus 1 (HSV-1-double stranded DNA virus). The half-maximal inhibitory concentration (IC50) values of these compounds were determined in vitro to assess their potency as antiviral agents. Compounds 11 and 14 displayed the most potent inhibitory effect with IC50 values of 2.38μM, and 6.3μM against MHV-1 while compounds 9 and 14 showed IC50 values of 14.8μM and 13μM, against HSV-1. Multiple antiviral assessments and microscopic images obtained through transmission electron microscopy (TEM) collectively demonstrated that these compounds exert a direct influence on the viral envelope. Based on this outcome, it can be concluded that peptidomimetic compounds could offer a new approach for the development of potent antiviral agents.

This study aimed to overcome the difficulty of conducting the horizontal-well cavity leaching test in the field and to investigate the long-term stability of the horizontal-well salt-cavity natural gas storage. The simulation test design is combined with the similarity theory to study the cavity expansion characteristics and the influence law of cavity leaching parameters. Through the design of a rubber hose connection, an integrated closed test system for multi-stage horizontal-well cavity leaching and brine drainage was built. The test system also realises the repeatable backward movement of the injection well during the test. A similarity simulation of the test design was carried out, and the test platform was constructed to carry out multi-stage horizontal-well leaching tests with a nitrogen cushion. In the horizontal-well leaching tests with a nitrogen cushion, the influence laws of the well spacing, flow rate and liquid level position on cavity expansion were investigated. Based on the morphological characteristics of the horizontal-well cavity, a numerical model of the horizontal-well salt cavity was developed, which reflects the real cavity morphology leached in the test. The long-term stability of the horizontal-well salt-cavity natural gas storage under different internal pressures was investigated through numerical simulation.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a human DNA repair protein. It is a member of the phospholipase D family based on the structure similarity. TDP1 is a key enzyme involved in repairing stalled topoisomerase 1 (TOP1)-DNA complexes. Previously we obtained with the CRISPR/Cas9 method HEK293A cells with the homozygous knockout of the Tdp1 gene and used knockout cells as a cellular model for studying the mechanisms of anticancer therapy. In this work we studied for the first time by transcriptomic analysis the effect of Tdp1 gene knockout on genes expression changes in human HEK293A cell line. We received original data that may indicate a role of TDP1 in other process besides repair of DNA-TOP1 complex. The differentially expressed genes (DEGs) analysis revealed that TDP1 could be involved in different processes such as cell adhesion and communication, spermatogenesis, mitochondrial function, neurodegeneration, cytokine response, and MAPK pathway signaling.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases including oral cancer. Cancer cells usually escape from immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα in the tumor microenvironment of oral squamous cell carcinoma (OSCC), and performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating seven immune-related factors and several clinicopathological statuses. However, the immune-checkpoint related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference of the tumor immunity in the originating-epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC might be different in the originating-epithelium, keratinized or non-keratinized.

In recent years the number of available chemical pesticides has been significantly reduced and there have been an urgent need for discovery of alternative to chemical pesticides products, as among others the natural zeolites (zeolitic rocks). We determined the mineralogical and chemical composition of a specific and continuous layers of zeolitic rock sample (ZeotP) from Petrota, Ev-ros, Greece and evaluated its oviposition deterrent effect for the olive fruit fly Bactrocera oleae (Diptera: Terphritidae). The tested natural zeolite contained 70 wt. % Clinoptilolite, 18 wt. % Amorphous material, 7 wt. % Feldspars, 4 wt. % Cristobalite and 1 wt. % Quartz. We tested the oviposition deterrent effect of ZeotP mixed or not with an emulsifier adjuvant NU-FILM-P® in water and applied on the surface of olive fruits. The ZeotP oviposition deterrent effect for the ol-ive fly was very high under a series of tested temperatures (17°C, 20°C, 25°C and 30°C) and RHs (23%, 33%, 55%, 75%, 94%). In addition, the ZeotP residual deterrent effect after equable water spraying was high and similar to the respective effect of a pyrethroid insecticide (Decis®). Our results may contribute to an effective control of the olive fruit fly using an alternative to chemical pesticides natural zeolite (zeolitic rocks) product.

The paper proposes a rock classification method using the vibration signal of the rotary drilling process. This proposed method classifies four rocks with a reliability of 100 %, from the vibration signal record of a lasting 1/4 second. For the design of a suitable classification method, several attributes of the vibration signal were calculated for two different signal recording lengths. Cluster dendrogram, ANOVA test, and boxplot were used to determine useful attributes and proper signal length. The classification rule was found using a decision tree, machine learning tool. The publication gradually describes the process of creating the classification method and the results of the reliability verification of the proposed classification method. Rock disintegration by rotary drilling was carried out under standardized experimental conditions. The disintegration rocks were andesite, granite, limestone, and concrete.

Mine waste rock and drainage pose lasting environmental, social, and economic threats to the mining industry, regulatory agencies, and society as a whole. Mine drainage can be alkaline, neutral, moderately or extremely acidic and contains significant levels of sulfate, dissolved iron, and frequently a variety of heavy metals and metalloids, such as cadmium, lead, arsenic, and selenium. In acid neutralization by carbonate and silicate minerals, a range of secondary minerals can form and possibly scavenge these potentially harmful elements. Apart from the extensively-studied microbial-facilitated sulfide oxidation, the diverse microbial communities present in mine rock and drainage may also participate in the formation, dissolution, and transformation of secondary minerals influencing the mobilization of these metals and metalloids. This article reviews major microbial-mediated geochemical processes occurring in mine rock piles that affect drainage chemistry, with a focus on the role of microorganisms in the formation, dissolution and transformation of secondary minerals. Understanding this is crucial for developing biologically-based measures to deal with contaminant release at the source, i.e., source control.

The construction of random fillings from the excavation of medium hardness rocks, with high particle sizes, presents limitations in compaction control. This research applies new control techniques with revised test procedures in the construction of the random fillings core, which constitutes the main part of the embankment, with the bigger volume and provides the geotechnical stability to the infrastructure. The maximum layer thickness researched was 800mm. As there are many types of rocks, this research is applied to metamorphic slates. Quality control has been carried out by applying new research associated with the revision of wheel impression test, topographic settlements and plate bearing test (PBT). A statistical analysis of the core of 16 slate random fillings has been carried out, with a total of 2250 in situ determination of density and moisture content, 75 wheel impression tests, 75 topographic settlement control and 75 PBT. The strong associations found between different tests have allowed to simplify the quality control.

With global warming and accelerated degradation of permafrost, the engineering problems caused by the formation of weak zones between the shallow and permafrost layers of soil–rock mixture (S-RM) slopes in permafrost regions have become increasingly prominent. To explore the influence of rock content on the shear strength of the S-RM freezing–thawing interface, the variation in the shear strength for different rock content is studied herein using direct shear tests. In addition, a 3D laser scanner is used for obtaining the topography of the shear failure surface. Combined with the analysis results of the shear band-particle calculation model, the influence of the rock content on the shear strength of the interface is explored. It was found that the impact threshold of the rock content on the interface strength and failure mode is approximately 30%, when the rock content (R) is &gt; 30% and that the shear strength increases rapidly with increasing rock content. When R ≤ 30%, the actual shear plane is similar to waves; when R &gt; 30%, the shear plane appears as gnawing failure. The shear strength of S-RM freezing–thawing interface mainly comes from the bite force and friction between particles. The main reason for the increase in shear strength with increasing rock content is the increase in bite force between particles, which makes the ratio of bite force to friction force approximately 1:1.

The use of natural stone has a historical and environmental value that makes it strategically valuable for landscape conservation in Europe. Marble, among others, is widely spread on Earth, and it offers high-performance features in architectural applications. However, the complexity of these formations and the rock variability in different ore bodies require detailed studies of the natural and induced stress state, the fracturing degree, and the influence of external factor (such as temperature and/or chemical agents) on the mechanical properties in order to optimize the exploitation processes by reducing extractive waste. This article shows a series of studies conducted by the authors over the last 20 years aimed at making the exploitation of marble blocks in the Carrara basin safer, more efficient, and, therefore, more sustainable. In particular, studies for increasing the knowledge on the natural and the induced stress state through on-site measurements and numerical modeling, studies to improve the quality of the exploited material through improvements of cutting technologies, studies to improve the knowledge of the mechanical behavior of the material under varying loads and temperature conditions and studies to improve the reuse of water materials and their reduction are reported.

Strata and surface movement induced by mining under open-pit final slope is a huge threat to mine safety. Physical model test is an important method to study mining-induced strata and surface movement laws. Because of rock joints predominantly control rock mass deformation and failure, thus physical model test leaving out of consideration of rock joints is difficult to reflect the influence of rock joints on rock mass deformation. Therefore, this paper presents a three-dimensional physical model test considering simplified dominant rock joints. This test process includes the design of testing equipment, the construction of physical model with dominant rock joint sets, conduction of mining and deformation monitoring. And mining under eastern final slope of Yanqianshan iron mine was selected as a case to study the behavior of mining-induced strata and surface movement.

Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of regulation of efficient virus replication. In this study, we comprehen-sively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182 are reproducibly deregulated dur-ing productive infection. These miRNAs are predicted to regulate a great number of potential tar-gets involved in different cellular processes and have only 33 shared targets. Among these, mem-bers of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.

HIV-1 Tat protein interacts with TAR RNA and recruits CDK9/cyclin T1 and other host factors to induce HIV-1 transcription. Thus Tat-TAR RNA interaction, which is unique for HIV-1, represents an attractive target for anti-HIV-1 therapeutics. To target Tat-TAR RNA interaction, we used a crystal structure of TAR RNA with acetylpromazine bound to the bulge of TAR RNA, to dock compounds from Enamine database containing 1.6 million individual compounds. Docking identified 173 compounds that were analyzed for the inhibition of HIV-1 infection. Top ten inhibitory compounds with IC50 ≤ 6 µM were selected and the three least toxic compounds, T6780107 (IC50=2.97 μM), T0516-4834 (IC50=0.2 μM) and T5628834 (IC50=3.46 μM), were further tested for HIV-1 transcription inhibition. Only T0516-4834 compound showed selective inhibition of Tat-induced HIV-1 transcription, whereas T6780107 compound inhibited equally basal and Tat-induced transcription and T5628834 compound only inhibited basal HIV-1 transcription. The T0516-4834 compound also showed strongest inhibition of HIV-1 gag RNA expression and p24 production in CEM T cells infected with HIV-1 IIIB. Of the three compounds, only the T0516-4834 compound disrupted Tat-TAR RNA interaction indicating that it might target TAR RNA. Also, of the three tested compounds, T5628834 but not T6780107 or T0516-4834 disrupted Tat-CDK9/cyclin T1 interaction. Taken together, our study identified novel compound T0516-4834 that disrupted Tat-TAR RNA interaction and inhibited Tat-induced transcription and HIV-1 infection suggesting that this compound might serve as a new lead for anti-HIV-1 therapeutics.

Brazil, Russia, China, India, and the Republic of South Africa (BRICS) represent developing economies facing different energy and economic development challenges. The current study aims to forecast energy consumption in BRICS at aggregate and disaggregate levels using the annual time series data set from 1992 to 2019 and to compare results obtained from a set of models. The time-series data are from the British Petroleum (BP-2019) Statistical Review of World Energy. The forecasting methodology bases on a novel Fractional-order Grey Model (FGM) with different order parameters. This study contributes to the literature by comparing the forecasting accuracy and the forecasting ability of the FGM(1,1) with traditional ones, like standard GM(1,1) and ARIMA(1,1,1) models. Also, it illustrates the view of BRICS's nexus of energy consumption at aggregate and disaggregates levels using the latest available data set, which will provide a reliable and broader perspective. The Diebold-Mariano test results confirmed the equal predictive ability of FGM(1,1) for a specific range of order parameters and the ARIMA(1,1,1) model and the usefulness of both approaches for energy consumption efficient forecasting.

Tissue resident memory T cells (TRM) were first described in 2009. While initially the major focus was on CD8 TRM, there has been recently an increased interest in defining the phenotype and the role of CD4 TRM in diseases. Circulating CD4 T cells seed tissue CD4 TRM, but there also appears to be an equilibrium between CD4 TRM and blood CD4 T cells. CD4 TRM are more mobile than CD8 TRM, usually localized deeper within the dermis/lamina propria and yet may exhibit synergy with CD8 TRM in disease control. This has been demonstrated in herpes simplex infections in mice. In human recurrent herpes infections, both CD4 and CD8 TRM persisting between lesions may control asymptomatic shedding through interferon gamma secretion, although this has been more clearly shown for CD8 T cells. The exact role of the CD4/CD8 TRM axis in the trigeminal ganglia and/or cornea in controlling recurrent herpetic keratitis is unknown. In HIV, CD4 TRM have now been shown to be a major target for productive and latent infection in cervix. In HSV and HIV co-infections, CD4 TRM persisting in the dermis support HIV replication. Further understanding of the role of CD4 TRM and their induction by vaccines may help control sexual transmission by both viruses.

Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

The results of the most recent investigation of triterpenoid-based antiviral agents effective namely in the HIV-1 and HSV-1 treatment were reviewed and summarized. Several key historical achievements are included to stress consequences and continuity in this research. Most of the agents studied belong into a series of compound derived from betulin or betulinic acid, and their synthetic derivative called bevirimat. A termination of clinical trials of bevirimat in the Phase IIb initiated a search for more successful compounds partly derived from bevirimat or designed independently of bevirimat structure. Surprisingly, a majority of bevirimat mimics are derivatives of betulinic acid, while other plant triterpenoids, such as ursolic acid, oleanolic acid, glycyrrhetinic acid or other miscellaneous triterpenoids, are relatively rarely involved in a search for novel antiviral agent. Therefore, this review article is divided into three parts based on the leading triterpenoid core structure.

Background: Multidrug-resistant bacteria present resistance mechanisms against β-lactam antibiotics, such as Extended-Spectrum Beta-lactamases (ESBL) and Metallo-β-lactamases enzymes (MBLs) operon encoded in Gram-negative species. Likewise, Gram-positive bacteria have evolved other mechanisms through mec genes, which encode modified penicillin-binding proteins (PBP2). This study aimed to determine the presence and spread of β-lactam antibiotic resistance genes and the microbiome circulating in Quito’s Public Transport (QTP). Methods: A total of 29 station turnstiles were swabbed to extract the surface environmental DNA. PCRs were performed to detect the presence of 13 antibiotic resistance genes and to identify 16S rDNA barcoding, followed by clone analysis, Sanger sequencing and BLAST search. Results: ESBL genes blaTEM-1 and blaCTX-M-1 and MBL genes blaOXA-181 and mecA were detected along QPT stations. Two subvariants were found for blaTEM-1, blaCTX-M-1, and blaOXA-181. Almost half of the circulating bacteria found at QPT stations were common human microbiota species including those classified by the WHO as pathogens of critical and high-priority surveillance. Conclusions: β-lactam antibiotic resistance genes are widely spread throughout QPT. This is the first report of blaOXA-181 in environmental samples in Ecuador. Moreover, we detected a new putative variant of this gene. Some commensal coagulase-negative bacteria may have a role as mecA resistance reservoirs

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

Build a special identical equation, use its calculation characters to prove and search for solution of any odd converging to 1 equation through (*3+1)/2^k operation, change the operation to (*3+2^m-1)/2^k, and get a solution for this equation, give a specific example to verify. Thus prove the Collatz Conjecture is true. Furthermore, analysis the sequences produced by iteration calculation during the procedure of searching for solution, build a weight function model, prove it decrease progressively to 0, build a complement weight function model, prove it increase to its convergence state. Build a (*3+2^m-1)/2^k odd tree, prove if odd in (*3+2^m-1)/2^k long huge odd sequence can not converge, the sequence must outstep the boundary of the tree after infinite steps of (*3+2^m-1)/2^k operation.

Background: Hepatic erythrophagocytosis is augmented in NASH and amplifies inflammation and fibrosis. Although various pro-phagocytic signals have been identified on erythrocytes of NASH patients, the role of bound thrombospondin-1 (TSP-1), which acts as an “eat-me” signal, arginase-1, which regulates the levels of nitric oxide in erythrocytes, and phosphatidylethano-lamine (PE) which can amplify erythrophagocytosis and hepatic inflammation have not been explored. Hence, we sought to investigate the levels of arginase-1 and TSP-1 in erythrocyte lysate and PE in erythrocyte membranes of NASH patients. Methods: Twenty-four patients and 14 healthy controls participated in our study. The levels of TSP-1 and arginase were quantified by ELISA in erythrocyte lysates, and the levels of PE in erythrocyte membranes by thin layer chro-matography. Results: Erythrocytes of NAFLD patients exhibit lower levels of arginase-1 and TSP-1 (p<0.01). Erythrocyte-bound TSP-1 levels correlated with the levels of erythrocyte surface CD47. Phosphatidylethanolamine was increased in erythrocytes of NASH patients and was accompanied by increased release, indicating exposure. Conclusion: Our results imply reduced TSP-1 binding by erythrocytes which could allow free TSP-1 molecules to act on macrophages, enhancing erythrophagocytosis. Increased PE which could amplify inflammation after efferocytosis, while downregulation of arginase-1 could lead to defective efferocytosis.

Immune checkpoint blockade (ICB)-based therapy is revolutionizing cancer treatment by fostering successful immune surveillance and effector cell responses against various types of cancers. However, patients with HER2+ cancers are yet to benefit from this therapeutic strategy. Precisely, several questions regarding the right combination of drugs, drug modality, and effective dose recommendations pertaining to the use of ICB-based therapy for HER2+ patients remain unanswered. In this study, we use a mathematical modeling-based approach to quantify the growth inhibition of HER2+ breast cancer (BC) cell colonies (ZR75) when treated with anti-HER2; trastuzumab (TZ) and anti-PD-1/PD-L1 (BMS-202) agents. Our data show that a combination therapy of TZ and BMS-202 can significantly reduce the viability of ZR75 cells and trigger several morphological changes. The combination decreased the cell’s invasiveness along with altering several key pathways, such as Akt/mTor and ErbB2 compared to monotherapy. In addition, BMS-202 causes dose-dependent growth inhibition of HER2+ BC cell colonies alone, while this effect is significantly improved when used in combination with TZ. Based on the in-vitro monoculture experiments conducted, we argue that BMS-202 can cause tumor growth suppression not only by mediating immune response but also by interfering with the growth signaling pathways of HER2+ BC. Nevertheless, further studies are imperative to substantiate this argument and to uncover the potential crosstalk between PD-1/PD-L1 inhibitors and HER2 growth signaling pathways in breast cancer.

The shear factor of ore drawing is one of the important factors affecting the formation of underground debris flow, and it has an important contribution to the formation of underground debris flow. The purpose of this paper is to study the effect of mining shear factor on underground debris flow in natural caving method. Based on the research background of the underground debris flow in Plan copper mine, this paper analyzes the characteristics of the slurry material structure of the underground debris flow, the influence of drawing shear factor on formation mechanism of underground debris flow is analyzed. The results show that the slurry of the underground debris flow in Plan mine is not only a pseudoplastic fluid but also a thixotropic fluid. It is indicated that once there is shearing force in drawing, it will deform, and its viscosity will decrease with the increase of shear rate and time. It is considered that the shear force produced by the flow of ore particles first produces shear action on the paste in the shear boundary region of ore drawing, it is reduced in viscosity and increased in fluidity, so that its “Activation” and then become a flowable paste, along with the bulk ore flow through the mouth. The continuous ore drawing process will continuously shear the new moraine slurry in the ore drawing channel and continuously “Activate” the moraine slurry in the ore drawing channel, finally, a certain scale and destructive down-hole debris flow accident. This paper is the first to study the effect of ore drawing shear factor on the formation mechanism of underground debris flow. It not only broadens the research field of debris flow, but also fills up the deficiency of systematic research on underground debris flow, and provides theoretical guidance for the prevention and control of underground debris flow.

The coastline in the Ca Mau and the Kien Giang provinces of the Vietnamese Mekong Delta has been severely eroded in recent decades. Pile-Rock Breakwaters (PRBW) are one of the most widely adopted structures for controlling shoreline erosion in this region. These structures are effective for wave energy dissipation, stimulating sediment accumulation, and facilitating the restoration of mangrove forests. These breakwaters are generally considered to be best-engineering practice however there is currently insufficient scientific evidence with regard to specific structural design aspects. This can lead to PRBW structures being compromised when deployed in the field. This study uses a physical model of a PRBW in a laboratory to investigate several design parameters, including crest width and working states (i.e. submerged, transition, and emerged), and investigates their relationship with the wave transmission coefficient, wave reflection coefficient, and wave energy dissipation. To investigate these relationships further, empirical formulas were derived for PRBWs under different sea states and crest widths to aid the design process. The results showed that PRBW width had a significant influence on the wave energy coefficients. The findings revealed that the crest width of the breakwater is inversely proportional to the wave transmission coefficient (K_t) under the emerged state. The crest width is also proportional to the wave reduction efficiency and wave energy dissipation in both working states (i.e., submerged and emerged states). The front wave disturbance coefficient (K_f) was found to be proportional to the wave reflection coefficient, and the wave height in front of the structure was found to increase by up to 1.4 times in the emerged state. The wave reflection coefficient requires special consideration to reduce the toe erosion in the structure. Lastly, empirical equations including linear and non-linear formulas were compared with previous studies for different classes of breakwaters. These empirical equations will be useful for understanding the wave transmission efficiency of PRBWs. The findings of this study provide important guidance for PRBW design in the coastal area of the Mekong Delta.

Laboratory experiments were performed to measure the supercritical CO2 (scCO2) storage ratio (%) of the conglomerate and sandstone in Janggi Basin, which are classified as rock in Korea available for CO2 storage. The scCO2 storage capacity was evaluated by direct measurement of the scCO2 amount replacing pore water in a reservoir rock core. The scCO2 sealing capacity of the cap rock (i.e., tuff and mudstone), was also compared by measuring the initial scCO2 seepage pressure (Δp) into the rock core. The measured average scCO2 storage ratio of the conglomerate and the sandstone in Janggi Basin was 30.7 % and 13.1 %, respectively, suggesting that the scCO2 storage capacity is greater than 360,000 metric tons in the Janggi Basin. The initial scCO2 seepage pressure of the tuff in the Janggi Basin was 15 bar and continuous scCO2 injection into the tuff core occurred at Δp higher than 20 bar. For the mudstone, the initial scCO2 seepage pressure was higher than 150 bar (10 times higher than that of the tuff), demonstrating that the mudstone is more suitable than the tuff to shield scCO2 leakage from the reservoir rock in the Janggi Basin.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.

Ulcerative colitis (UC) is a relatively frequent, chronic disease that impacts significantly the patient’s quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental UC. UC was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Some mice received i.v. dose of CT-1 (200 µg/kg) 2 hours before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS. The severity of UC was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before UC induction improves the clinical course, tissue damage and inflammation degree in DSS-induced UC in mice.

Background High Mobility Group Box-1 (HMGB-1) is implicated in the pathogenesis of thrombosis and cancer. In the present study, we aimed to evaluate its potential role as a diagnostic biomarker of portal vein thrombosis (PVT) among patients with hepatocellular carcinoma (HCC). Methods The study population included N=100 prospectively recruited patients with a novel diagnosis of HCC. We compared circulating HMGB-1 levels between 34 healthy controls, HCC patients with PVT (N=22), and HCC patients without PVT (N=78). Results HCC patients without PVT showed significantly higher median HMGB-1 serum levels (8.2 [5.5-13.1] ng/ml) than those observed in the case of HCC with PVT (5.5 [4.4-8.5] ng/ml; p=0.012) and in healthy controls (4.1 [3.1-8.2] ng/ml; p&lt;0.001). Among HCC patients, at univariate analysis, the presence of PVT was associated with higher median age (p=0.036), larger major cancer node diameter (p&lt;0.001), and lower HMGB-1 serum level (p=0.012). At multivariate analysis, the presence of PVT maintained a positive association with major node diameter p=0.001) and an inverse association with serum HMGB-1 levels (p=0.003). Conclusions These findings indicate that serum HMGB-1 bears an inverse association with PVT complicating HCC at the time of diagnosis and suggest that serum HMGB-1 depletion may mark PVT development in cirrhotic patients with HCC.

Since the first description of SARS-CoV-2 in China in 2019, thousands of variants have emerged worldwide. For some of them, the constellation of mutations caused changes in virus biology, pathogenicity, infectivityity and transmissibility resulting in dissemination throughout the world. Gamma variant (P.1) differs from SARS-CoV-2 Wuhan strain (B.1) by 12 amino acids in the Spike (S) protein, and presented mutations related to greater affinity for the receptor angioten-sin-converting enzyme 2 (ACE-2) and/or immune escape. The Gamma variant and subvariants were responsible for the second wave of COVID-19 in the Brazilian city of Manaus, characterized by high mortality and rapid transmission. The ability of variants to induce cytokine production may be closely related to their pathogenicity. Herein we observed that there was no significant difference in the quantity of cytokines among macrophages or neutrophils infected with P.1 and B.1 strains. Also, no significant difference was observed in the absolute number of macrophages and neutrophils infected with these variants. Furthermore, no evidence of SARS-CoV-2 replication was observed in macrophages when infected by the two analyzed variants. Our findings suggest that the difference in the epidemiological outcome observed during the P.1 variant spread when compared to B.1, it is not explained by differences in the quantity of cytokines and absolute number of macrophages or neutrophils. Through bioinformatics analysis of the S protein, we observed that the physicochemical differences between the variants and subvariants of P.1, probably refer to the degree of infectivity, due to the impact caused in the recognition of antibodies and receptor af-finity

A 2-year prospective study carried out on ventilator-associated pneumonia (VAP) patients in the intensive care unit at King Khalid hospital, Hail, Kingdom of Saudi Arabia (KSA), revealed a high prevalence of extremely drug-resistant (XDR) Acinetobacter baumannii. About a 9% increase in the incidence rate of A. baumannii has occurred in the VAP patients between 2019 and 2020 (21.4% to 30.7%). In 2019 the isolates were positive for IMP-1 and VIM-2 (31.1% and 25.7%, respectively) as detected by PCR. In comparison, a higher proportion of isolates produced NDM-1 in 2020. Here, we observed a high resistant proportion of ICU isolates towards the most common antibiotics in use. Colistin sensitivity dropped to 91.4% in the year 2020 as compared to 2019 (100%). Thus, the finding of this study has a highly significant clinical implementation in the clinical management strategies for VAP patients. Furthermore, strict implementation of antibiotic stewardship policies, regular surveillance programs for antimicrobial resistance monitoring, and screening for genes encoding drug resistance phenotypes have become imperative.

Type 2 diabetes mellitus (T2D) is a metabolic disorder characterized by inappropriate insulin function. Despite wide progress in genome studies, defects in gene expression for diabetes prognosis still incompletely identified. Prolonged hyperglycemia activates NF-κB, which is a main player in vascular dysfunctions of diabetes. Activated NF-κB, triggers expression of various genes that promote inflammation and cell adhesion process. Alteration of pro-inflammatory and profibrotic gene expression contribute to the irreversible functional and structural changes in the kidney resulting in diabetic nephropathy (DN). To identify the effect of some important NF-κB related genes on mediation of DN progression, we divided our candidate genes on the basis of their function exerted in bloodstream into three categories (Proinflammatory; NF-κB, IL-1B, IL-6, TNF-α and VEGF); (Profibrotic; FN, ICAM-1, VCAM-1) and (Proliferative; MAPK-1 and EGF). We analyzed their expression profile in leukocytes of patients and explored their correlation to diabetic kidney injury features. Our data revealed the overexpression of both proinflammatory and profibrotic genes in DN group when compared to T2D group and were associated positively with each other in DN group indicating their possible role in DN progression. In DN patients, increased expression of proinflammatory genes correlated positively with glycemic control and inflammatory markers indicating their role in DN progression. Our data revealed that the persistent activation NF-κB and its related genes observed in hyperglycemia might contribute to DN progression and might be a good diagnostic and therapeutic target for DN progression. Large-scale studies are needed to evaluate the potential of these molecules to serve as disease biomarkers.

Stress Granules formation is a pro-survival mechanism helping cells to cope with environmental challenges. Stress Granules have been studied for two decades in fundamental research, and are now being examined in the context of human pathogenesis. Here, we review studies highlighting stress granules’ involvement in cancer development through translational pattern modification.

The effectiveness of immunotherapy for cervical adenocarcinoma (CA) has not been demonstrated yet. It may be possible for us to use programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and CD8 as biomarkers of response to immune therapy in CA patients. In the present study, we aimed to investigate whether the expression levels of PD-1, PD-L1, and CD8 can predict the prognosis of CA patients and their response to ICI therapy. The levels of the PD-1, PD-L1, and CD8 proteins were analyzed by immunohistochemical analysis from formalin-fixed, paraffin-embedded tumor samples. The correlation between the expression levels and patient prognosis was analyzed by the Kaplan–Meier method and univariate and multivariate Cox proportional hazard regression model. We observed a significant inverse-correlation between the PD-1 and CD8 expression (p=0.001, chi square test). We also found a significant inverse-correlation between the PD-L1 and CD8 expression (p=0.027). The overall survival was significantly worse in patients with positive PD-1 expression (p=0.027). Similarly, the progression-free survival was also worse (p=0.087). Our results demonstrate that a high level of PD-1 expression is associated with a poor prognosis in CA patients. Further research is necessary to identify the molecular mechanisms that mediate this association.

(R)-1-(4-Amino-3,5-dichlorophenyl)-2-bromoethan-1-ol has been synthesised in 93% enantiomeric excess (ee) by asymmetric reduction of the corresponding ketone catalysed by a ketoreductase and NADPH as the co-factor in DMSO. (S)-N-(2,6-Dichloro-4-(1-hydroxyethyl)phenyl)acetamide has been synthesised in >98% ee by the same system. Both synthons are potential precursors for clenbuterol enantiomers. Clenbuterol is a β₂-agonist used in veterinary treatment of asthma in several countries. The drug is listed on the World Anti-doping Agency’s Prohibited list due to its effect on increased protein synthesis in the body. However, racemic clenbuterol has recently been shown to reduce the risk of Parkinson’s disease. In order to reveal which one (or both) of the enantiomers that cause this effect, the pure enantiomers need to be studied separately. Our biocatalytic approach in order to obtain enantiopure clenbuterol should be applicable to industrial scale.

Surface–subsurface soil-rock modeling is crucial for infrastructure design and groundwater yield optimization, especially in the complex crystalline basement terrains of Penang Island, Malaysia. This study conducted large-scale characterization of soil-rock profiles using ERT, SRT, rock quality designation, and soil penetration test (SPT N-values) data, optimized through regression modeling. The approach effectively identified soil-rock structures and their suitability to prevent structural failures and enhance groundwater productivity. Correlations between borehole lithologic logs and velocity–resistivity models revealed distinct soil compositions across the study area. The results highlighted thick, saturated, and loose silty to sandy bodies in the eastern to northern sections, contrasting with sandy compositions and penetrative fractures in the southern part. The study also found good correlations between rock mass quality and N-values for different soil types. Depths of intra-bedrock weathered/fractured units varied between 12 and >35 m. This has significant implications for determining optimal foundation depths in the study area. Groundwater productivity was associated with intra-bedrock planes of weakness at depths exceeding 40 m. Overall, this study developed empirical relations between geophysical and geotechnical parameters for wet tropical granitic terrains, filling critical gaps in understanding subsurface characteristics.

In green chemistry, filamentous fungi are regarded as a kind of robust microorganism for the biotransformation of natural products. Nonetheless, the screening of microorganisms is crucial for the effective biotransformation of natural products such as phenazine compounds. The precursor metabolite of most phenazine derivatives in Pseudomonas spp. is phenazine-1-carboxylic acid (PCA), the key constituent of shenqinmycin, widely used to control rice sheath blight in southern China. In this study, a new fungus strain Aspergillus sclerotiorum was isolated, which can efficiently convert PCA into 3-hydroxy-phenazine 1-carboxylic acid (3-OH-PCA). Moreover, an effective whole cells biotransformation system was constructed by screening optimal reaction conditions and carbon sources. Hence, Aspergillus sclerotiorum exhibited desirable adaptation by consumption of different carbon sources and maximum whole cell biomass (10.6 g/L DCW) was obtained as a biocatalyst from glucose. Optimal conditions for whole-cell biocatalysis of PCA were evaluated, including PCA concentration of 1120 mg/L, pH 7.0, temperature of 25°C, rotation rate 200 rpm and dry cell weight 15 g/L for 60 h, thus 1060 mg/L of 3-OH-PCA was obtained and the conversion efficiency of PCA was 94%. Hence, the results of repeated batch mood revealed that the biotransformation efficiency of fungus pellets reduced with each subsequent cycle but remained stable in all five cycles with the provision of glucose supplement. These findings open the prospective of using filamentous fungi for the whole cell biocatalysis of phenazine in enormous amount and efficient production of 3-OH-PCA. Moreover, these results laid the foundation for further research to disclose the genetic based mechanism of the strain responsible for PCA biotransformation.

The incidence of Type 1 Diabetes (T1D) in the Arab world, particularly, oil and gas rich Gulf Cooperative Council (GCC) countries has more than doubled in the last twenty years. Therefore, there is a dire need for careful systematic familial cohort studies, especially in high-risk populations. Several immunogenetic factors affect the pathogenesis of the disease. Genes in the human leukocyte antigen (HLA) account for the major genetic susceptibility to the disease. The triggering agents initiate disease onset by destruction of pancreatic β-cells. The autoantibodies against glutamic acid decarboxylase (GADA), insulinoma antigen-2 (IA-2A), insulin (IAA), and zinc transporter-8 (ZnT-8A) comprise the most reliable biomarkers for T1D in both children and adults. Although three of the GCC countries, namely Kuwait, Saudi Arabia and Qatar are among the top 10 countries with high incidence rate of T1D, no proper diagnostic and prediction tools were applied in the region. Understanding the disease sequelae in a homogenous gene pool with high consanguinity in the GCC could help solve the challenges in understanding pathogenesis, as well as hasten the prevention of T1D. Arab states must incorporate T1D predictive and intervention policies on a war-footing basis to minimize the burden of this serious disease.

The BRAFV600E mutation, found in approximately 50% of melanoma cases, is associated with aggressive tumor behavior and poor prognosis. This study aimed to assess its impact on immunogenic cell death (ICD), a pivotal cytotoxic process triggering anti-tumor immune responses. Through comprehensive in silico analysis of The Cancer Genome Atlas data, we explored the association between the BRAFV600E mutation, immune subtype dynamics, and tumor mutation burden (TMB). Our findings revealed that the mutation correlated with a lower TMB, indicating a reduced generation of immunogenic neoantigens. Investigation into immune subtypes reveals an exacerbation of immunosuppression mechanisms in BRAFV600E-mutated tumors. To assess the response to ICD inducers, including doxorubicin and Me-ALA-based photodynamic therapy (PDT), compared to the non-ICD inducer cisplatin, we used distinct melanoma cell lines with wild-type BRAF (SK-MEL-2) and BRAFV600E mutation (SK-MEL-28, A375). We demonstrated a differential response to PDT between the WT and BRAFV600E cell lines. Further transcriptomic analysis revealed upregulation of IFNAR1, IFNAR2, and CXCL10 genes associated with the BRAFV600E mutation, suggesting their involvement in ICD. Using a gene reporter assay, we showed that PDT robustly activated the IFN-1 pathway through cGAS-STING signaling. Collectively, our results underscore the complex interplay between the BRAFV600E mutation and immune responses, emphasizing a putative correlation between tumors carrying the mutation and their responsiveness to therapies inducing the IFN-1 pathway, such as the ICD inducer PDT, possibly mediated by the elevated expression of IFNAR1/2 receptors.

Background: Over the past years, there has been a rise in the incidence of type 1 diabetes, partic-ularly among younger individuals. This concerning trend has prompted investigations into po-tential contributing factors, with intestinal dysbiosis emerging as a likely culprit for the escalating annual rates of the disease; (2) Methods: We conducted a retrospective ecologic correlational study involving 37 children from the southern region of Romania between 2019-2021. All participants were within the first six months following the onset of the disease; (3) Results: In the microbiota of the patients we observed a dysbiosis marked by an overabundance of bacteria (Clostridium coccoides, Faecalibacterium, Bacterioides, Enterobacteriaceae) and fungi, compared to the healthy control group. The Spearman correlation revealed a positive association between the presence of Bacteroides (p=0.0442), Butyricicoccus (p=0.0164), and Clostridium leptum (p=0.0023) with recent diabetes onset. Furthermore, a significant correlation was observed between younger age at onset and the pres-ence of Butyricicoccus (p=0.019). The use of antibiotics in the month preceding admission was linked to the presence of fungi in the microbiota (Candida, p=0.0442); (4) Conclusions: The dysbiosis of Romanian type 1 diabetes children correlates with inflammation, more severe onset of the disease and other au-toimmune diseases.

Among cross-sectional imaging modalities, computed tomography (CT) is more available and faster; however, magnetic resonance (MR) performs better in terms of sensitivity and specificity, due to its higher contrast resolution. The appearance of peritoneal deposits on CT and MR depends mainly on the primary tumour histology: in case of unknown primary tumour (3-5% of cases), their behaviour at imaging may provide insights on the tumour origin. The time-point of tumour evolution, previous or ongoing treatments and the peritoneal spaces where they occur, also play an important role in determining the appearance of peritoneal deposits. Thus, knowledge of peritoneal anatomy and fluid circulation is mandatory in detection and characterization of peritoneal deposits. Several benign and malignant conditions may show similar imaging features that overlap those of PC, making the differential diagnosis challenging. Clinical history, laboratory findings and previous imaging examinations must be considered to achieve the correct diagnosis.

Collatz conjecture states that an integer $n$ reduces to $1$ when certain simple operations are applied to it. Mathematically, the Collatz function is written as $f^k(n) = \frac{3^kn + C}{2^{z}}$, where $z, k, C \geq 1$. Suppose the integer $n$ violates Collatz conjecture by reappearing as $2^in$, where $i \geq 1$, then the equation modifies to $n \left(1 - \frac{3^k}{2^{z}2^i}\right) = \frac{C}{2^{z}2^i}$. The article takes an elementary approach to this problem by calculating the bounds on the values of $\frac{C}{2^{z}2^i}$ and $1 - \frac{3^k}{2^{z}2^i}$. Correspondingly, an upper limit on the integer $n$ is placed that can re-appear in the sequence. The integer $n$ lies in the $(-\infty, 5)$ range, and the limit on the number of odd steps is $k < 3$. Finally, it is shown that no integer chain exists that does not lead to 1.

We describe an efficient approach to radiometrically flatten geocoded stacks of calibrated synthetic aperture radar (SAR) data for terrain-related effects. We use simulation to demonstrate that, for the Sentinel-1 mission, one static radiometric terrain flattening factor derived from actual SAR imaging metadata per imaging geometry is sufficient for flattening interferometrically compliant stacks of SAR data. We quantify the loss of precision due to application of static flattening factors, and show that these are well below stated requirements of change detection algorithms. Finally, we discuss the implications of applying radiometric terrain flattening to geocoded SAR data instead of the traditional approach of flattening data provided in the original SAR image geometry. The proposed approach allows for efficient and consistent generation of five different Committee of Earth Observation Satellites (CEOS) Analysis Ready Dataset (ARD) families - Geocoded Single Look Complex (GSLC), Interferometric Radar (InSAR), Normalized Radar Backscatter (NRB), Polarimetric Radar (POL) and Ocean Radar Backscatter (ORB) from SAR missions in a common framework.

We describe an efficient and cost effective data access mechanism for Sentinel-1 TOPS 1 mode bursts. Our data access mechanism enables burst-based data access and processing, thereby 2 eliminating ESA’s Sentinel-1 SLC data packaging conventions as a bottleneck to large scale processing. 3 Pipeline throughput is now determined by available compute resources and efficiency of the analysis 4 algorithms. For targeted infrastructure monitoring studies, we are able to generate coregistered, 5 geocoded stacks of SLCs for any AOI in the world in a few minutes. In addition, we describe our 6 global scale radar backscatter and interferometric products and associated pipeline design decisions 7 that ensure geolocation consistency across the suite of derived products from Sentinel-1 data. Finally, 8 we discuss the benefits and limitations of working with geocoded SAR SLC data.

Infection by human immunodeficiency virus type I (HIV-1) requires virus particle binding to host cell-surface receptor CD4 via the viral envelope glycoprotein gp120. HIV-1 therapy and prevention efforts involve development of mimetic or recombinant gp120 vaccines or deployment of antiviral agents that target specific epitopes of gp120. The unliganded conformational state of gp120 is closed, whereas the CD4-bound state is open. However, in between, there exist dynamic conformational states, indicating intrinsically flexible region(s) of structural dynamics, imposing a structural challenge for developing drug or antibody targets. Known conformational states of gp120 were determined by X-ray crystallographic and cryo-electron microscopy, and neither method captures the population of gp120 species arising from conformational plasticity, motions, and transitions. gp120 plasticity brings up several important questions. How will differences in conformation affect receptor binding, antibody recognition, and neutralization? Which regions are crucial for gp120 structural plasticity? How could structural dynamics influence HIV-1 evasiveness against host immunity and drugs or vaccines, and facilitate the viral entry into its host? This review explores the structural constraints presented by conformational states of the glycoprotein to antibodies or drugs and how these conformational states provide structural avenues for the virus to escape neutralizing agents and evade host immunity.

Before the adaptive immune response is established, retroviruses can be targeted by several cellular host factors at different stages of the viral replication cycle. This intrinsic immunity relies on a large diversity of antiviral processes. In the case of HTLV-1 infection, these active innate host defence mechanisms are debated. Among these mechanisms, we focused on a RNA decay pathway called nonsense-mediated mRNA decay (NMD), which can target multiple viral RNAs, including HTLV-1 unspliced RNA, as it has been recently demonstrated. NMD is a cotranslational process that depends on the RNA helicase UPF1 and regulates the expression of multiple types of host mRNAs. RNA sensitivity to NMD depends on mRNA organization and the ribonucleoprotein (mRNP) composition. HTLV-1 has evolved several means to evade the NMD threat, leading to NMD inhibition. In the early steps of infection, NMD inhibition favours the production of HTLV-1 infectious particles, which may contribute to the survival of the most fit clones despite genome instability; however, its direct long-term impact remains to be investigated.

Purinergic receptors are inflammatory mediators activated by extracellular nucleotides released by dying or injured cells. Several studies have described an important role for these receptors in HIV-1 entry, particularly regarding their activity on HIV-1 viral membrane fusion. Several reports identify purinergic receptor antagonists that inhibit HIV-1 membrane fusion; these drugs are suspected to act through antagonizing Env-chemokine receptor interactions. They also appear to abrogate activity of downstream mediators that potentiate activation of the NLRP3 inflammasome pathway. Here we review the literature on purinergic receptors, the drugs that inhibit their function, and the evidence implicating these receptors in HIV-1 entry.