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The appearance of senescent cells in age-related diseases has spurred the search for compounds that can target senescent cells in tissues, termed senolytics. However, a major caveat with current senolytic screens is the use of cell lines as targets where senescence is induced in vitro, which does not necessarily reflect the identity and function of pathogenic senescent cells in vivo. Here, we developed a new pipeline leveraging a fluorescent murine reporter that allows for isolation and quantification of p16Ink4a+ cells in diseased tissues. By high-throughput screening in vitro, precision-cut lung slice (PCLS) screening ex vivo, and phenotypic screening in vivo, we identified a HSP90 inhibitor, XL888, as a potent senolytic in tissue fibrosis. XL888 treatment eliminated pathogenic p16Ink4a+ fibroblasts in a murine model of lung fibrosis and reduced fibrotic burden. Finally, XL888 preferentially targeted p16INK4a-hi human lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis (IPF), and reduced p16INK4a+ fibroblasts from IPF PCLS ex vivo. This study provides proof of concept for a platform where p16INK4a+ cells are directly isolated from diseased tissues to identify compounds with in vivo and ex vivo efficacy in mice and humans, respectively, and provides a senolytic screening platform for other age-related diseases.

Abstract The Chinese Mars rover Zhurong successfully landed in southern Utopia Planitia on Mars in May 2021. Previous research suggested a Hesperian ocean may have existed in the northern lowland on Mars. Recent research observed water-related features at the Zhurong landing site from in situ data. In this study, we conducted a comprehensive geomorphological analysis of the landing area using remote sensing data, supplemented by in situ observations, and unveiled features consistent with the existence of a nearshore zone in southern Utopia. Different types of water-related geomorphological features were separated by specific topographic contours, suggesting different types of marine environments. The area was subdivided into a foreshore highland-lowland transition unit, a shallow marine unit and a deep marine unit. In situ observations including sedimentary deposit rocks, water-related lamination features, and subsurface sedimentary layers, also indicate past water activities. Results suggested an evolution scenario of the nearshore zone in southern Utopia: (1) Flooding of the Utopia Planitia in Late Noachian around 3.65–3.68 Ga reached the foreshore unit; (2) formation of the shallow and deep marine units after the flooding was completed by about 3.5 Ga and 3.42 Ga in Early Hesperian, respectively; (3) gradual loss of subsurface volatiles during the Amazonian epoch.

RELEVANCE of the study is determined by the fact that vertical conical diffusers are used as auxiliary devices in many technical applications in various industries (chemical industry, power engineering, technological devices, etc.).THE PURPOSE. The influence of the method (design) of air supply, the cross-sectional shape of the supply channels and nozzle tubes on the gas-dynamic structure of the flow in a vertical diffuser for different flow characteristics was assessed.METHODS. The structure (distribution) of the flow inside a vertical diffuser for supplying air using different designs of supply channels was studied on an experimental bench. Based on the thermal imaging method, the flow structure in a vertical diffuser was studied. In this study, two methods of supplying air to a vertical diffuser were studied: supplying air through one straight channel from the bottom and nozzle supplying air through four tubes. The channels and nozzles had cross sections in the shape of a circle, square and triangle. Accordingly, the influence of six air supply designs into a vertical diffuser and their influence on the gas-dynamic flow structure were studied.RESULTS. The experiments were carried out under stationary air flow conditions in the diffuser for air flow rates from 0.015 to 0.06 m3/s. The Reynolds number for the air flow at the outlet of the supply channel was in the range from 42500 to 150000. Thermograms of the flow structure in a vertical diffuser were obtained for different methods of air supply for different flow characteristics.CONCLUSION. Features of the flow structure in a vertical diffuser with traditional air supply from below through one channel consist in the formation of a pronounced central air flow along the vertical axis of the diffuser when using all channel configurations. In this case, the cross-sectional shape of the supply channel has a significant impact on the flow structure in the conical diffuser. Features of the flow structure in a vertical diffuser with nozzle air supply through four tubes are the absence of stagnant zones and a central air flow along the axis. At the same time, the use of square and triangular nozzle tubes leads to a more uniform distribution of air flow throughout the entire volume of the vertical diffuser.

Objective: to summarize the available data on the features of vascularization of endometrioid adenocarcinoma (EAC). Material and Methods. The search for relevant sources was performed in the “PubMed” database using the keywords “endometrium + cancer + angiogenesis”, “endometrium + cancer + angiogenesis + lymph”. Of the selected sources, 78 were included in this review. Results. Angiogenesis is an important and necessary stage in the pathogenesis of the appearance, progression and metastasis of EAC and, thus, the study of tumor vascularization provides an opportunity to improve diagnosis and personalized approach to treatment. Vascular density correlates with advanced stage of EAC, high grade of malignancy, myometrial invasion, cervical and adnexal lesions, vascular invasion, metastases to lymph nodes (LN), the presence of cancer cells in the peritoneal fluid, low overall survival and survival without tumor progression. There are publications that deny the connection of vascularization with the histological type of tumor, its grade, lymphovascular invasion, lymph node metastases, the depth of myometrial invasion, and these publications even prove that microvessel density is not an independent prognostic factor. So, there is still no consensus and final opinion, as evidenced by low or high vascularization of EAC. Recently, there are many drugs that affect both the processes of angiogenesis directly and the inducers and factors that control vascular growth. Unfortunately, all such drugs have a fairly high toxicity, and resistance to them very quickly develops. Conclusion. Despite numerous results of studies devoted to the study of the formation of blood vessels and isolated data on lymphangiogenesis in EAC, there is no data in the literature on studying changes in the vascularization of LN in gynecological cancer. However, proangiogenic and antiangiogenic factors are disseminated throughout the body and must exert their effects in distant organs and tissues. Based on changes in the vascularization of LN, it will apparently become possible to predict the activity of angiogenesis in the primary tumor, assess the prognosis of the disease, and the effectiveness of the treatment. In addition, significant expression of the vascular network in an enlarged lymph node biopsied for diagnosis may be a symptom of the development of a malignant tumor in the lymph collection region, even in the absence of metastases.

The aim of the work is to study the legislative support for the development of creative industries in the Russian Arctic using the example of the Murmansk Oblast. The following tasks have been solved: the legislative framework of the federal level, providing the development of creative industries in Russia as a whole, has been studied; the regional legislative framework has been studied on the example of the Murmansk Oblast; the measures of support for the development of Arctic creative industries at different levels of government have been analyzed. It was revealed that until 2021 the creative sector of the economy was reflected in legal acts of all levels through the concepts of “small and medium-sized businesses”, “self-employed citizens” and “individual entrepreneurs”. The concept of “creative industries” received legislative recognition with the adoption at the federal level of the “Concept for the development of creative industries and mechanisms for the implementation of their state support in large and major urban agglomerations until 2030” in 2021. The Concept and the Action Plan for its implementation, adopted in 2030, laid the regulatory and legal basis for the development of this sector of the economy, but the legislative framework for the development of creative industries in the Russian Federation has not yet been fully formed. The study showed that in the Arctic zone of the Russian Federation the situation with regulatory support for the development of creative industries is similar. Using the example of the Murmansk Oblast, it was revealed that the regional legislative framework for this promising area is currently in the nascent stage, and the first normative-legal acts directly related to the development of the Arctic creative industries began to appear only in 2023. It was concluded that it is necessary to develop a concept for the development of Arctic creative industries in the Russian Arctic in order to ensure uniform approaches, consistency of actions and coordination of measures for the development of this sector of the economy in the Russian Arctic. The need to use the term “creative industries” in various legal acts in order to avoid discrepancies and to ensure the uniformity of legal support for this sector of the economy is substantiated.

Abstract This study presents a global database of pitted cones on Mars. This database was created using an active deep-learning approach based on a global mosaic of Mars Context Camera (CTX) images, followed by extensive manual verification. The global database contains 250,547 pitted cones along with their central coordinates and diameters. 94.2% of the pitted cones have diameters ranging from 100 m to 1 km. Most of them are in the northern lowlands, while some are scattered in the southern highlands. Systematic evaluation of the extracted pitted cones is performed in Isidis Planitia, Acidalia Planitia, and Cerberus Palus on Mars. The results reveal that the precision ranges from 79.2% to 85.6%, and the recall rate ranges from 62.4% to 87.7%, indicating a varying among regions but satisfactory performance. Manual digitizing evaluation indicates that over 94.1% of manual labels by different annotators have a differentiation rate of 10%, showing promising precision and consistency. This global database can facilitate further research on the origin and evolution of pitted cones on Mars.

High-resolution digital elevation models (DEMs) of the lunar surface are crucial for lunar exploration missions and scientific research. The emergence of advanced technologies, such as Shape-from-Shading (SfS), has enabled the generation of pixel-wise high-resolution DEMs from monocular images of the lunar surface. However, SfS encounters significant challenges in locations with limited illumination, such as the lunar south pole, where the surface is largely covered by shadows. Therefore, this paper presents a novel shadow-constrained SfS approach for pixel-wise 3D surface reconstruction at the lunar south pole. The proposed approach uses multiple high-resolution images captured under different illumination conditions and an existing low-resolution DEM as the inputs and generates a high-resolution DEM with the same resolution as that of the input image through hierarchical SfS processing incorporating shadow constraints. Experiments were conducted using actual images collected by the Lunar Reconnaissance Orbiter (LRO) Narrow Angle Camera (NAC) at the lunar south pole. Comparisons with respect to photogrammetric DEMs generated from stereo NAC images show that the DEMs generated using the proposed approach exhibit the smallest root mean square error (RMSE). Moreover, shaded relief images rendered from the DEMs generated using the proposed approach demonstrate the highest similarity to the actual NAC images. Detailed profile comparisons further validate the effectiveness of the shadow constraint in optimizing 3D reconstruction in regions in proximity to shadows and within shadowed regions. The proposed shadow-constrained SfS approach can be used to generate high-resolution DEMs to support future missions to explore the lunar south pole, with applications including landing site evaluation and route planning for lunar probes or astronauts.

Exogenous geological processes (EGP) on the territory of Perm Krai have a wide development. Karst occupies a special position in this list, as this process is widespread, and, in addition, can serve as a catalyst for associated hazardous geological processes. Therefore, under the guidance of the Ministry of Natural Resources of Perm Krai, the work on assessment of manifestations of dangerous geological processes within the urbanized karst territories of the region has been carried out. The aim of the study is a set of field and office works allowing assessing the consequences of hazardous geological processes in the karst territories of Perm Krai to make appropriate management decisions to minimize the negative impact on infrastructure and facilities, and ensure the safety of the population in the future. The results of this study for 2023 are presented in the article.

Science education and research have the potential to drive profound change in low- and middle-income countries (LMICs) through encouraging innovation, attracting industry, and creating job opportunities. However, in LMICs, research capacity is often limited, and acquisition of funding and access to state-of-the-art technologies is challenging. The Alliance for Global Health and Science (the Alliance) was founded as a partnership between the University of California, Berkeley (USA) and Makerere University (Uganda), with the goal of strengthening Makerere University's capacity for bioscience research. The flagship program of the Alliance partnership is the MU/UCB Biosciences Training Program, an in-country, hands-on workshop model that trains a large number of students from Makerere University in infectious disease and molecular biology research. This approach nucleates training of larger and more diverse groups of students, development of mentoring and bi-directional research partnerships, and support of the local economy. Here, we describe the project, its conception, implementation, challenges, and outcomes of bioscience research workshops. We aim to provide a blueprint for workshop implementation, and create a valuable resource for bioscience research capacity strengthening in LMICs.

We engineered an ultrasensitive reporter of p16INK4a, a biomarker of cellular senescence. Our reporter detected p16INK4a-expressing fibroblasts with certain senescent characteristics that appeared shortly after birth in the basement membrane adjacent to epithelial stem cells in the lung. Furthermore, these p16INK4a+ fibroblasts had enhanced capacity to sense tissue inflammation and respond through their increased secretory capacity to promote epithelial regeneration. In addition, p16INK4a expression was required in fibroblasts to enhance epithelial regeneration. This study highlights a role for p16INK4a+ fibroblasts as tissue-resident sentinels in the stem cell niche that monitor barrier integrity and rapidly respond to inflammation to promote tissue regeneration.

This article considers the theoretical grounds for advancing the existing aquatic research techniques, including a complex of thermometry and resistivimetry methods. The transient processes that influence the temperature change in the “water–air” system were explored. The need to take into account the thermal characteristics of all elements involved was highlighted. Using the theory of heat exchange and the idea that the water source can be distinguished from the general temperature field, a formula for measuring the general temperature field was derived. It was found that the areas of subaqueous discharge of near-surface water can be localized by the temperature difference between the watercourses and the water source. The multivariate analysis based on the absolute value and sign of the difference temperature parameter was used to determine the salinity value and the changes of the salinity type with depth. The criteria obtained during the theoretical studies were successfully tested and verified on a watercourse located within the industrial agglomeration of the Perm region, which indicates their high potential for solving practical hydrogeological problems.

Introduction. The changes in the economic situation, which happened after certain events of February 2022, required signifi cant investment in the development of small and medium-sized businesses. Parallel imports, new market niches to be fulfi lled after foreign producers had left, the desire to preserve and increase capital while experiencing ruble devaluation– these and other reasons formed the basis of crowdlending studying in this paper. Theoretical analysis. The growth rates of the crowdlending market in Russia are analyzed and the dynamics of crowdlending and bank loans to small and medium-sized businesses are compared. Empirical analysis. Based on the example of the company “JetLend” LLC, an analysis of the requirements for borrowers and investors, the stages of potential borrowers’ business checking were carried out. A comparative characteristic of the JetLend, IFX Cbond, Cbonds-CBI RU High Yield indices is presented, which suggests that during 3 years, an average investor of the JetLend platform had a higher yield than if he owned a portfolio of high-yield bonds or bonds of the most liquid companies in Russia. Results. Positive and negative aspects of using crowdlending for both investors and borrowers are summed up. It is concluded that crowdlending is a promising tool for small and medium-sized businesses, especially for those economic entities which do not have collateral, credit history or other factors necessary for a bank loan.

SARS-CoV-2, the causal agent of the COVID-19 pandemic, is characterized by rapid evolution, which poses a significant public health challenge. Effective vaccines that provide robust protection, elicit strong immune responses, exhibit favorable safety profiles, and enable cost-effective large-scale production are crucial. The RBD-Fc-based Betuvax-CoV-2 vaccine has previously demonstrated a favorable safety profile and induced a significant anti-SARS-CoV-2 humoral immune response in clinical trials. Due to the rapid evolution and emergence of new SARS-CoV-2 strains, the relevance of bivalent vaccine formulations has increased. Methods: This study compared the neutralizing capacity of monovalent and bivalent vaccine formulations against different SARS-CoV-2 strains detected with a SARS-CoV-2 microneutralization assay (MNT). Findings: The monovalent Wuhan-based vaccine generated neutralizing antibodies against the Wuhan and Omicron BA.2 variants but not the distinct Omicron BQ.1 strain. Conversely, the monovalent BA.2-based vaccine induced neutralizing antibodies against both Omicron strains but not Wuhan. While the bivalent Wuhan and BA.2-based vaccine was effective against strains containing the same antigens, it was insufficient to neutralize the distinctive BQ.1 strain at a small dosage. Interpretation: These findings suggest that the vaccine composition should closely match the circulating SARS-CoV-2 strain to elicit the optimal neutralizing antibody response and include the appropriate dosage. Moreover, this study did not find additional advantages of using the bivalent form over the monovalent form for the vaccination against a single prevailing SARS-CoV-2 strain.

RNA-based enzyme RNase P is a ribonucleoprotein complex responsible primarily for 5’-maturation of tRNAs. S. cerevisiae RNase P comprises a catalytic RNA component and nine proteins. The assembly and maturation of S. cerevisiae RNase P involves an abundant and catalytically active precursor form, which includes all components except for proteins Rpr2 and Pop3. Rpr2 and Pop3 are essential proteins, but their roles in RNase P were not clear. Here we use a step-wise in vitro assembly of yeast RNase P to show that the addition of proteins Rpr2 and Pop3 increases the activity and thermal stability of the RNase P complex, similar to the effects previously observed for archaeal RNases P.

The results of the study of non-isothermal mass-exchange processes occurring during liquid corrosion of iron-concrete are presented. The degree of development of this direction of research is shown: the classification of liquid corrosion of concrete is given, the effect of “free calcium hydroxide” on the stability of cement stone minerals is described, the relative change in the strength of concrete depending on the dimensionless concentration of calcium hydroxide is shown. For concrete and reinforced concrete structures subjected to liquid corrosion, the boundary value problem of non-isothermal mass transfer in the “cement concrete - liquid” system is formulated on the basis of a nonlinear differential equation of mass conductivity of a parabolic type with an arbitrary form of the initial concentration distribution function and combined boundary conditions of the first, second and third kind. A combined approach to solving the problem of non-isothermal unsteady mass transfer is proposed, based on the division of the life cycle of a building structure into “micro-processes”, followed by the separation of the thickness of the structure within the considered small time interval into concentration zones. Analytical solutions to the problem of unsteady mass transfer in the processes of liquid corrosion of concrete for each selected concentration zone have been obtained, allowing to calculate the concentrations of the target component in the solid phase, thereby predicting the dynamics and kinetics of destructive processes of cement concretes. Extensive numerical experiments have been carried out showing the effect of process parameters on the dynamics and kinetics of liquid corrosion of reinforced concrete.

Breast cancer (BC) occupies the second place in terms of incidence and the first ranking place in terms of mortality among oncopathology in women. The article presents the current state of the problem of the combination of BC and pregnancy, the impact of pregnancy on the course and outcome of breast oncopathology, as well as modern hypotheses for the development of breast cancer during pregnancy. It is shown that the current studies are quite contradictory and in many ways not accurate enough in methodology and materials. We present a clinical case of BC associated with pregnancy. The case is interesting from 2 positions: on the one hand, the patient’s tumor process is associated with pregnancy, on the other hand, there is a very rare combination of HER2/neu- and BRCA1-positive status.According to the presented literature data and our own data, it was concluded that the treatment of patients with BC during pregnancy is a difficult task and is often accompanied by tumor progression, despite the standard treatment regimens. Undoubtedly, this group of patients needs to develop new methodological approaches to antitumor treatment based on a deep analysis of the molecular genetic characteristics of the tumor, the hormonal background in general, and its effect on the tumor process during pregnancy. Such a personalized approach will improve the results of treatment of young patients with BC during pregnancy.

Background: Transarterial chemoembolization (TACE) is coming into use in the treatment of liver tumors, with drug-eluting microspheres as one of the technique variations. However, at the moment there are no systematic studies that would answer the questions: what is the role of the method in the treatment regimen for patients with primary and metastatic liver tumor and at what stage should it be used? Aim: to evaluate the effectiveness of transarterial chemoembolization with drug-eluting microspheres for the treatment of metastatic and primary malignant liver tumors at different stages of the disease. Methods: We performed а retrospective observational uncontrolled study of 65 patients with liver metastases (Group 1), and 10 patients with primary malignant liver tumors (Group 2), who underwent 102 operations of transarterial chemoembolization with drug-eluting microspheres. To plan transarterial chemoembolization and evaluate its effectiveness, computed tomography and magnetic resonance imaging were used every 89 weeks during the treatment. Results: After two transarterial chemoembolization controls, Group 1 included 51 responders (79%) and 14 non-responders (21%). Among the responders by the 16th week there was a decrease in the volume of the tumor mass in the liver from 12.4 [4.7; 24.6] to 5.2 cm3 [2; 15.5] for colorectal cancer, from 26 [18; 35] to 19 cm3 [13; 25] for neuroendocrine cancer, from 12 [4; 20] to 4 cm3 [0.6; 9] for adenocarcinomas of different localizations. There was no progression in Group 2, while, by week 16, there was a decrease in the tumor volume from 142 [51; 206] to 68 cm3 [23; 185] for hepatocellular carcinoma, from 465 [330; 600] to 187 cm3 [137;237] for intrahepatic cholangiocarcinoma. With repeated transarterial chemoembolization, a decrease in the volume of the tumor mass was also noted, while the time without progression decreased from 303 [170; 369] to 180 [105; 225] days in Group 1, from 266 [200; 367] to 120 [62; 215] days in Group 2. Conclusions: Transarterial chemoembolization with drug-eluting microspheres is an effective treatment for primary and metastatic liver tumors. It should be considered as a palliative therapy, which allows achieving a good antitumor response at different stages of cancer.

Objectives: This study aimed to determine the safety, tolerability and immunogenicity of TetraFluBet, an inactivated subunit influenza vaccine that contains a corpuscular immuno-adjuvant derived from natural betulin. Methods: We conducted a prospective, randomized, open-labeled, single-center, phase I trial. The study was conducted in two stages: 5 volunteers in stage I and 25 volunteers in stage II. Eligible participants received one single dose (20 μg/0.5 mL) of TetraFluBet intramuscularly. Participants were followed for adverse events and reactogenicity. Seroconversion rate, seroprotection level, geometric mean titers (GMTs) of virus-neutralizing antibodies, IFN-γ induction and cell-mediated immunity were assessed. Results: A total of 30 participants were enrolled. No vaccine-related serious adverse events were observed. The proportions of study participants with 4-fold seroconversions assessed by the HI assay (with 95% CIs) were 80.0% (62.7; 90.5), 70.0% (52.1; 83.3), 63.3% (45.5; 78.1) and 73.3% (55.6; 85.8) for influenza virus subtypes A (H1N1), A (H3N2), B1 and B2, respectively. Seroprotection levels (with 95% CIs) were 83.3% (66.4; 92.7), 83.3% (66.4; 92.7), 73.3% (55.6; 85.8) and 66.7% (48.8; 80.8), respectively. The fold increases in the GMTs of virus-neutralizing antibodies for subtype H1N1 was 6.50, for subtype H3N2 was 3.03, for subtype B1 was 3.56 and for subtype B2 was 6.07. The population of cytotoxic T-cells increased significantly in the post-vaccination period, indicating a strong CD3+CD8+ response. Conclusions: TetraFluBet tetravalent inactivated subunit vaccine with adjuvant demonstrated pronounced immunogenic properties, leading to the formation of both specific humoral and cellular immunity at a 20 μg dose.

Acute shortage of water resources and high unproductive water losses are the key problems of irrigated agriculture in arid regions. One of the possible solutions is to optimize soil water retention using natural and synthetic polymer water absorbers. Our approach uses the HYDRUS-1D design to optimize the placement of organic water absorbents such as peat and composite hydrogels in the soil profile in the form of water-storing capillary barriers. Field testing of the approach used a water balance greenhouse experiment with the cultivation of butternut squash (butternut squash (Cucurbita moschata (Duchesne, 1786)) under sprinkler irrigation with measurement of the soil moisture profile and unproductive water losses in the form of lysimetric water outflow. In addition, the biodegradation rate of organic water absorbents was studied at the soil surface and at a depth of 20 cm. Organic capillary barriers reduced unproductive water losses by 40–70%, retaining water in the topsoil and increasing evapotranspiration by 70–130% with a corresponding increase in plant biomass and fruit yield. The deepening of organic soil modifiers to the calculated depth not only allowed capillary barriers to form, but also prevented their biodegradation. The best results in soil water retention, plant growth and yield according to the “dose-effect” criterion were obtained for a composite superabsorbent with peat filling of an acrylic polymer matrix. The study showed good compliance between the HYDRUS design and the actual efficiency of capillary barriers as an innovative technology for irrigated agriculture using natural and synthetic water absorbents.