High Migratory Potential Research Articles

IL-1β-activated PI3K/AKT and MEK/ERK pathways coordinately promote induction of partial epithelial–mesenchymal transition

Epithelial–mesenchymal transition (EMT) is a cellular process in embryonic development, wound healing, organ fibrosis, and cancer metastasis. Previously, we and others have reported that proinflammatory cytokine interleukin-1β (IL-1β) induces EMT. However, the exact mechanisms, especially the signal transduction pathways, underlying IL-1β-mediated EMT are not yet completely understood. Here, we found that IL-1β stimulation leads to the partial EMT-like phenotype in human lung epithelial A549 cells, including the gain of mesenchymal marker (vimentin) and high migratory potential, without the complete loss of epithelial marker (E-cadherin). IL-1β-mediated partial EMT induction was repressed by PI3K inhibitor LY294002, indicating that the PI3K/AKT pathway plays a significant role in the induction. In addition, ERK1/2 inhibitor FR180204 markedly inhibited the IL-1β-mediated partial EMT induction, demonstrating that the MEK/ERK pathway was also involved in the induction. Furthermore, we found that the activation of the PI3K/AKT and MEK/ERK pathways occurred downstream of the epidermal growth factor receptor (EGFR) pathway and the IL-1 receptor (IL-1R) pathway, respectively. Our findings suggest that the PI3K/AKT and MEK/ERK pathways coordinately promote the IL-1β-mediated partial EMT induction. The inhibition of not one but both pathways is expected yield clinical benefits by preventing partial EMT-related disorders such as organ fibrosis and cancer metastasis.

Dendritic cell force-migration coupling on aligned fiber networks

Dendritic cells (DCs) are antigen-presenting cells that reside in peripheral tissues and are responsible for initiating adaptive immune responses. As gatekeepers of the immune system, DCs need to continuously explore their surroundings, for which they can rapidly move through various types of connective tissue and basement membranes. DC motility has been extensively studied on flat 2D surfaces, yet the influences of a contextual 3D fibrous environment still need to be described. Using ECM-mimicking suspended fiber networks, we show how immature DCs (iDCs) engage in migratory cycles that allow them to transition from persistent migration to slow migratory states. For a subset of iDCs with high migratory potential, we report the organization of protrusions at the front of the cell body, which reverses upon treatment with inflammation agent PGE2. We identify an unusual migratory response to aligned fiber networks, whereby iDCs use filamentous protrusions to attach laterally and exert forces on fibers to migrate independent of fiber alignment. Increasing the fiber diameter from 200 to 500 nm does not significantly affect the migratory response; however, iDCs respond by forming denser actin bundles around larger diameters. Overall, the correlation between force-coupling and random migration of iDCs in aligned fibrous topography offers new insights into how iDCs might move in fibrous environments in vivo.

Human Umbilical Cord Mesenchymal Stem Cells Alleviate Rat Knee Osteoarthritis via Activating Wnt/ β-catenin Signaling Pathway.

Osteoarthritis (OA) is a chronic disease characterized by joint cartilage degeneration, destruction, and osteogenic hyperplasia. Human umbilical cord mesenchymal stem cells (hUCMSCs) have attracted increasing research interest due to their high clonogenic, proliferative, and migratory potential, as well as their improved secretion of relevant chondrogenic factors. This study evaluated the therapeutic potential and underlying mechanism of hUC-MSCs in alleviating pathological symptoms of OA. For the in vivo study, OA rats were established by the Hulth method to observe the therapeutic effect of intra-articular injection of hUC-MSCs. X-ray tests, gross observations, and histological and immunohistochemical assessments were conducted in rats. Levels of interleukin-1 beta (IL-1β), IL-6, matrix metalloproteinase-13 (MMP-13), and tissue inhibitor matrix metalloproteinase-1 in rats' synovial fluid were measured using enzyme-linked immunosorbent assay kits. For the in vitro study, hUC-MSCs and chondrocytes were cultured to explore the effect and underlying mechanisms of hUC-MSCs on OA. Apoptosis, proliferation, and glycosaminoglycan (GAG) were measured in the chondrocytes. The relative expression of aggrecan, COL-2, and SOX-9 mRNA was quantified by real-time polymerase chain reaction. Expressions of Wnt/β-catenin signaling molecules were measured by Western blot. We found that intra-articular injection of hUC-MSCs reduced the combined score, increased the expression of collagen II, and decreased the expression of MMP-13, IL-1β, and IL-6 in rat knee joints. Additionally, hUC-MSCs increased the content of GAGs, inhibited chondrocyte apoptosis, and promoted chondrocyte proliferation. The expression of aggrecan, COL-2, and SOX-9 mRNA in chondrocytes was promoted by hUC-MSCs via activation of the Wnt/β-catenin signaling pathway. Overall, this study demonstrated that hUC-MSCs induce the secretion of some cytokines via the paracrine function to activate the Wnt/β-catenin signaling pathway to reduce the pathological condition of OA and maintain the proper expression of cytokines and extracellular matrix proteins.

Studies on the Migration of Sulphur and Chlorine in the Pyrolysis Products of Floor and Furniture Joinery

This article discusses research on the low-temperature pyrolysis of waste floor and furniture joinery as an example of chemical recycling. Pyrolysis was carried out at 425 °C to obtain solid, liquid, and gaseous products. In line with the circular economy concept, the waste was transformed into economical and environmentally friendly raw materials suitable for application. Research results related to the chemical composition and properties of pyrolysis products are shown, with particular emphasis on the migration process of acidic impurities, i.e., sulphur and chlorine. In some processes, the presence of such substances can be a problem. Research has shown the high potential for sulphur and chlorine migration in pyrolysis products. It was shown that for woodwork, the most sulphur was discharged with the pyrolysis gas and the least was immobilised in the oil fraction. For vinyl panels, more than 50% of the sulphur was immobilised in the char. Chlorine was immobilised mainly in the char and pyrolysis gas. A high chlorine content of 12.55% was found in the vinyl panel. At the same time, a high chlorine content was also found in the pyrolysis products of these panels. This value is several times higher than in wood-based waste.

GDNF triggers proliferation of rat C6 glioma cells via the NF-κB/CXCL1 signaling pathway.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor that is characterized by its high proliferative and migratory potential, leading to a high invasiveness of this tumor type. However, the underlying mechanism of GBM proliferation and migration has not been fully elucidated. In this study, at first, we used RNA-seq together with bioinformatics technology to screen for C-X-C motif ligand 1 (CXCL1) as a proliferation-related gene. And exogenous glial cell line-derived neurotrophic factor (GDNF) induced proliferation and up-regulated the level of CXCL1 in rat C6 glioma cells determined by sqPCR and ELISA. Then, we manipulated the CXCL1 expression by using a lentiviral vector (CXCL1-RNAi) approach. By this, the proliferation of C6 cells was decreased, suggesting that CXCL1 plays a key role in proliferation in these cells. We hypothesized that exogenous GDNF promoted NF-κB nuclear translocation and therefore, analyzed the interaction of CXCL1 with NF-κB by Western Blot and immunofluorescence. Additionally, we used BAY 11-7082, a phosphorylation inhibitor of NF-κB, to elucidate NF-κB mediated the effect of GDNF on CXCL1. These results demonstrated that GDNF enhanced the proliferation of rat C6 glioma cells through activating the NF-κB/CXCL1 signaling pathway. In summary, these studies not only revealed the mechanism of action of exogenous GDNF in promoting the proliferation of C6 glioma cells but may also provide a new biological target for the treatment of malignant glioma.

Persistent thallium enrichment and its high ecological risks developed from historical carbonaceous Hg-Tl mining waste

Thallium (Tl) is a priority pollutant with high biotoxicity and has been of great concern worldwide in recent years. The former Lanmuchang Hg-Tl mining site in southwest China is a hotspot of multiple metal(loid)s pollution that previously caused large-scale chronic Tl poisoning, mainly resulting from carbonaceous Tl-bearing mining waste. However, arable land destroyed by historical mining wastes persists at high ecological risks decades after reclamation, but little is known about the solid phase partitioning and species of Tl during soil formation of underlying mining wastes as potential Tl sources. In this study, a representative reclaimed soil profile (100 cm depth) was selected in the lowlands to explore the geochemical cycling and environmental fate of Tl in mining waste-derived subsoil. The Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) analysis revealed an unexpected enrichment of Mn (2920–7250 mg/kg) and Tl (205–769 mg/kg) in the mining waste-derived subsoil. Results from BCR sequential extraction, X-ray Photoelectron Spectroscopy (XPS), and Electron Probe Microanalyses (EPMA) indicate that high Tl loading Mn oxide particulates (up to 15,712 ppm Tl) dominate the sequestration of Tl in the subsoil via oxidation-complexation and have a high potential for migration to both topsoil and groundwater. In addition, insights from microbial fossils and Fe-metabolizing bacteria closely related to Tl indicated that Fe (hydr)oxide particulates showing high Tl levels (up to 3865 mg/kg) point to biomineralization. Detailed mineralogical investigations revealed that hematite-siderite syngenetic particulates could serve as a promising mineralogical proxy for redox oscillations under periodic flooding and recorded the frequent groundwater level fluctuations experienced in the probed profile. Despite the potential for long-term preservation of high Tl loading Fe/Mn (hydr)oxides under HCO3-rich groundwater conditions in karst areas, the reductive release of Tl will be inevitable during flooding, implying that underlying carbonaceous mining waste will pose persistent and severe hazards to the ecosystem.

Altered expression of anti-apoptotic protein Api5 affects breast tumorigenesis

BackgroundApoptosis or programmed cell death plays a vital role in maintaining homeostasis and, therefore, is a tightly regulated process. Deregulation of apoptosis signalling can favour carcinogenesis. Apoptosis inhibitor 5 (Api5), an inhibitor of apoptosis, is upregulated in cancers. Interestingly, Api5 is shown to regulate both apoptosis and cell proliferation. To address the precise functional significance of Api5 in carcinogenesis here we investigate the role of Api5 in breast carcinogenesis.MethodsInitially, we carried out in silico analyses using TCGA and GENT2 datasets to understand expression pattern of API5 in breast cancer patients followed by investigating the protein expression in Indian breast cancer patient samples. To investigate the functional importance of Api5 in breast carcinogenesis, we utilised MCF10A 3D breast acinar cultures and spheroid cultures of malignant breast cells with altered Api5 expression. Various phenotypic and molecular changes induced by altered Api5 expression were studied using these 3D culture models. Furthermore, in vivo tumorigenicity studies were used to confirm the importance of Api5 in breast carcinogenesis.ResultsIn-silico analysis revealed elevated levels of Api5 transcript in breast cancer patients which correlated with poor prognosis. Overexpression of Api5 in non-tumorigenic breast acinar cultures resulted in increased proliferation and cells exhibited a partial EMT-like phenotype with higher migratory potential and disruption in cell polarity. Furthermore, during acini development, the influence of Api5 is mediated via the combined action of FGF2 activated PDK1-Akt/cMYC signalling and Ras-ERK pathways. Conversely, Api5 knock-down downregulated FGF2 signalling leading to reduced proliferation and diminished in vivo tumorigenic potential of the breast cancer cells.ConclusionTaken together, our study identifies Api5 as a central player involved in regulating multiple events during breast carcinogenesis including proliferation, and apoptosis through deregulation of FGF2 signalling pathway.

Immunophenotypic and Functional Characterization of Eosinophil and Migratory Dendritic Cell Subsets during Filarial Manifestation of Tropical Pulmonary Eosinophilia.

The role of eosinophil and migratory dendritic cell (migDC) subsets during tropical pulmonary eosinophilia (TPE), a potentially fatal complication of lymphatic filariasis, has not been explored. We show that the onset of TPE is characterized by the accumulation of ROS and anaphylatoxins and a rapid influx of morphologically distinct Siglec-Fint resident eosinophils (rEos) and Siglec-Fhi inflammatory eosinophils (iEos) in the lungs, BAL fluid, and blood of TPE mice. While rEos display regulatory behavior, iEos are highly inflammatory cells, as evident in upregulated expression of activation markers CD69 and CD101, anaphylatoxin receptor C5AR1, alarmins s100a8 and s100a9, components of NADPH oxidase, and copious secretion of TNF-α, IFN-γ, IL-6, IL-1β, IL-4, IL-10, IL-12, and TGF-β. Importantly, iEos exhibited heightened ROS generation, higher phagocytic and increased antigen presentation capacity, elevated Ca2+ influx, and increased F-actin polymerization but downregulated negative regulators of the immune response, i.e., Cd300a, Anaxa1, Runx3, Lilrb3, and Serpinb1a, underlining their essential role in promoting lung damage during TPE. Interestingly, TPE mice also showed significant expansion of CD24+CD11b+ migDCs, which showed upregulated expression of maturation and costimulatory markers CD40, CD80, CD83, CD86, and MHCII, increased antigen presentation capacity, and higher migratory potential as evidenced by increased expression of cytokine receptors CCR4, CCR5, CXCR4, and CXCR5. CD24+CD11b+ migDCs also upregulated the expression of immunoregulators PD-L1 and PD-L2 and secreted proinflammatory cytokines, suggesting their significant involvement during TPE. Taken together, we document important morphological, immunophenotypic, and functional characteristics of eosinophil and migDC subsets in the lungs of TPE mice and suggest that they contribute to worsening lung histopathological conditions during TPE.

Tumor-suppressor p53 specifically binds to miR-29c-3p and reduces ADAM12 expression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an extremely aggressive malignant tumor associated with high migratory and invasive potential. The present study intends to explore regulatory mechanism of p53/microRNA (miR)-29c-3p/A disintegrin and metalloproteinase 12 (ADAM12) axis in HCC based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology. Putative miR-29c-3p binding sites on ADAM12 3'UTR were verified by a luciferase assay. The binding affinity of p53 to miR-29c-3p was assessed based on CRISPR/Cas9 technology to construct a p53 knockout (p53-/-) HCCLM3 cell line. Furthermore, the effect of p53/miR-29c-3p/ADAM12 was assessed on maligant phenotypes in vitro and tumor formation and metastasis in nude mice. ADAM12 was highly expressed but miR-29c-3p was poorly expressed in HCC. miR-29c-3p inhibited migratory and invasive abilities of HCC cells by targeting ADAM12 expression. p53 was found to target and upregulate miR-29c-3p, thus downregulating ADAM12 and conferring inhibitory effect on HCC cell activities. Moreover, ADAM12 knockout or p53 overexpression reduced HCC tumor formation and metastasis, which were reversed by further silencing of miR-29c-3p. The identification of the p53/miR-29c-3p/ADAM12 axis in migration and invasion of HCC may potentially further our understanding of mechanisms underpinning HCC, and also bear translational value as novel molecular targets.

PIM1-Induced Cytoplasmic Expression of RBMY Mediates Hepatocellular Carcinoma Metastasis

Metastasis indicates a grave prognosis in patients with hepatocellular carcinoma (HCC). Our previous studies showed that RNA binding motif protein Y-linked (RBMY) is potentially a biomarker for poor survival in HCC patients, but its role in metastasis is largely unclear. A total of 308 male patients with primary HCC were enrolled. RBMY expression was traced longitudinally by immunostaining from the manifestation of a primary HCC tumor to the formation of a distant metastasis, and its upstream regulators were screened with a protein microarray. Aseries of metastasis assays in mouse models and HCC cell lines were performed to explore new functional insights into RBMY. Cytoplasmic expression of RBMY was associated with rapid distant metastasis (approximately 1 year after resection) and had a predictive power of 82.4% for HCC metastasis. RBMY conferred high migratory and invasive potential upon phosphorylation by the provirus integration in Moloney 1 (PIM1) kinase. Binding of PIM1 to RBMY caused mutual stabilization and massive translocation of RBMY from nuclei to mitochondria, thereby preventing mitochondrial apoptosis and augmenting mitochondrial generation of adenosine triphosphate/reactive oxygen species to enhance cell motility. Depletion of RBMY suppressed Snail1/zinc finger E-box binding homeobox transcription factor 1-mediated epithelial-mesenchymal transition and dynamin-related protein 1-dependent mitochondrial fission. Inactivation and knockout of PIM1 down-regulated the expression of RBMY. In nude mice, cytoplasmic RBMY promoted liver-to-lung metastasis by increasing epithelial-mesenchymal transition, mitochondrial proliferation, and mitochondrial fission, whereas nuclear-restricted RBMY impeded the mitochondrial switch and failed to induce lung metastasis. This study showed the regulation of HCC metastasis by PIM1-driven cytoplasmic expression of RBMY and suggested a novel therapeutic target for attenuating metastasis.

Profiling of Tregs across tissues reveals plasticity in ST2 expression and hierarchies in tissue-specific phenotypes

SummaryFoxp3+ regulatory T cells (Tregs) are critical mediators of peripheral tolerance and immune homeostasis and exert tissue-specific functions. In many nonlymphoid tissues, Tregs show enriched expression of the IL-33 receptor ST2. Through comprehensive profiling of murine ST2+ and ST2- Tregs, we found that Treg transcriptomes and phenotypes formed a hierarchical relationship across tissues. Only a small core signature distinguished ST2+ Tregs from ST2- Tregs across all tissues, and differences in transcriptional profiles were predominantly tissue-specific. We also identified unique, highly proliferative, circulating ST2+ Tregs with high migratory potential. In adoptive transfers, both ST2+ and ST2- Tregs seeded various host tissues and demonstrated plasticity in ST2 expression. Furthermore, Tregs from donor lungs were differentially recovered from host nonlymphoid tissues in an IL-33-dependent manner. In summary, our work identified tissue residency rather than ST2 expression as a primary driver of tissue Treg identity and highlights the unique, tissue-specific adaption of ST2+ Tregs.

Effects of substrate stiffness on the viscoelasticity and migration of prostate cancer cells examined by atomic force microscopy.

The stiffness of the extracellular matrix of tumour cells plays a key role in tumour cell metastasis. However, it is unclear how mechanical properties regulate the cellular response to the environmental matrix. In this study, atomic force microscopy (AFM) and laser confocal imaging were used to qualitatively evaluate the relationship between substrate stiffness and migration of prostate cancer (PCa) cells. Cells cultured on stiff substrates (35 kPa) undergone several interesting phenomena compared to those on soft substrates (3 kPa). Here, the stimulation generated by the stiff substrates triggered the F-actin skeleton to bundle its filaments, increasing the polarity index of the external contour of PCa cells. Analysis of AFM force–distance curves indicated that the elasticity of the cells cultured on 35 kPa substrates increased while the viscosity decreased. Wound-healing experiments showed that PCa cells cultured on 35 kPa substrates have higher migration potential. These phenomena suggested that the mechanical properties may be correlated with the migration of PCa cells. After actin depolymerisation, the elasticity of the PCa cells decreased while the viscosity increased, and the migration ability was correspondingly decreased. In conclusion, this study clearly demonstrated the relationship between substrate stiffness and the mechanical properties of cells in prostate tumour metastasis, providing a basis for understanding the changes in the biomechanical properties at a single-cell level.

Особенности территориальной мобильности населения Якутии в условиях пандемии COVID-19

The article discusses the special characteristics of the territorial mobility of the population of the Republic of Sakha (Yakutia). Changes in the migration situation, structure of migration and migration activity of the population in different social and economic zones of the region in the context of the coronavirus pandemic are analyzed. The analysis shows that the peculiarities of distribution of productive forces and human resources in the labor market retain a fairly high potential for labor migration to the Republic of Sakha (Yakutia) from the CIS countries and far abroad in the context of a pandemic, the share of arriving migrants indicating work among the reasons for migration continues to grow. The influence of socio-economic characteristics and urgent problems of the republic on the formation of migration activity and migration intentions of the population is considered. The article is based on the results of a mass survey in Yakutia (n=200). Analysis of the survey results shows that the features of territorial mobility, migration intentions of the population and absence of migration plans depend on the socio-economic conditions of residence, various factors of individual social status and position, and mobility resources. With mostly satisfactory assessments of the socio-economic situation in the republic and most factors of social life in the region, the respondents’ migration intentions are conditioned by low incomes and territorial specifics — remoteness from the central regions of the country, the high cost of air fares and harsh climatic conditions. In the pandemic conditions, the spatial mobility of the population, as one of the most important social resources of society, is most characteristic of the part of young people who have financial resources, unmarried, seeking better socio-economic and climatic conditions, to regions with better infrastructure, where they can get a decent job, quality education, medical services, recreation and leisure.

Abstract 2690: Loss of E-cadherin induces IGF1R activation revealing a targetable pathway in invasive lobular breast carcinoma

Abstract Invasive Ductal Carcinoma (IDC) and Invasive Lobular Carcinoma (ILC) are two major subtypes of breast cancer with significant differences in their histological and molecular underpinnings. ILC has a unique loss of E-cadherin (CDH1) which we have previously demonstrated as a negative regulator of the Insulin-like Growth Factor 1 receptor (IGF1R) through a comprehensive analysis of cell line models and tumor samples. We propose that loss of E-cadherin in ILC sensitizes cells to growth factor signaling and thus alters their sensitivity to growth factor signaling inhibitors. To investigate this, we used CRISPR to generate CDH1 knockout (KO) IDC cell lines (MCF7, T47D, ZR75.1) to uncover the mechanism by which E-cadherin loss activates the IGF pathway while also assessing its targetability. CDH1 KO cells exhibited anchorage independent growth in suspension culture and altered p120 catenin localization as observed in ILC tumors. Through in vitro studies, we show increased signaling sensitivity to IGF/insulin ligands and enhanced signaling duration in CDH1 KO cells. In addition, we observed a higher migratory potential of CDH1 KO cells compared to wild type (WT) cells, which was further enhanced as a chemotactic response to IGF1 or serum. Further, this phenotype could be reversed with an IGF1R inhibitor, BMS-754807. We additionally identified an increase in Collagen I haptotaxis in the CDH1 KO cells, which was also translated into a novel invasive phenotype towards serum in the T47D CDH1 KO cells. Despite no significant differences in membranous IGF1R levels between WT and CDH1 KO cells, higher ligand-receptor interaction was observed with CDH1 KO cells, demonstrating an increased ligand-receptor complex formation upon stimulation. Our results suggest that loss of CDH1 results in an increase in IGF1 receptor availability for ligand binding which in turn allows for an enhanced downstream signaling activation. Interestingly, a physical repression of E-cadherin on IGF1R could not be demonstrated, suggesting spatial changes on the membrane following E-cadherin loss may control ligand binding. Critically, increased sensitivity to IGF1R, PI3K, AKT and MEK inhibitors was observed in CDH1 KO cells suggesting that these targets should be further explored in ILC and that CDH1 loss may be exploited as a biomarker of response, or for patient stratification to inhibitors targeting these pathways. Citation Format: Ashuvinee Elangovan, Laura Savariau, Megan E. Yates, Jagmohan Hooda, Alison M. Nagle, Steffi Oesterreich, Jennifer M. Atkinson, Adrian V. Lee. Loss of E-cadherin induces IGF1R activation revealing a targetable pathway in invasive lobular breast carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2690.

A DFT study of two-dimensional P2Si monolayer modified by single transition metal (Sc-Cu) atoms for efficient electrocatalytic CO2 reduction

In the present work, a stable two-dimensional (2D) P2Si monolayer was predicted. The monolayer is semimetallic/metallic under the PBE/HSE06 functional and is mechanically isotropic. The stability of the P2Si monolayer has been proved via cohesive energy, mechanical criteria, molecular dynamics simulation, and phonon dispersion respectively, and the monolayer possesses high carrier mobility which is three times that of MoS2. On the other hand, the catalytic performance of the P2Si monolayer modified with a single transition metals (M = Sc-Cu) atom for the electrochemical reduction of CO2 was investigated, and the monolayer can catalyze CO2 with three constraints: stable molecular dynamics, high migration potential of metal atoms, and suitable band gap for electrocatalyst after metal doping exhibiting excellent catalytic stabilization activity and CRR selectivity. In addition, the reduction product of V@P2Si is HCOOH with an overpotential as low as 0.75 V, and the most suitable reaction path is *CO2 → *CHOO → O*CHOH → * + HCOOH with the final reduction product HCOOH obtained. As a whole, the above results endow the P2Si monolayer to be a good 2D material holding great promises for applications in nanoelectronics and CO2 reduction catalysts.

Insights Into Energy Accumulation and Allocation Strategy of Reproductive Migration of Black Amur Bream (Megalobrama terminalis) in the Pearl River Basin, China

Energy allocation is an important component of the reproductive cycle, and as such, it will affect survival, migration, and reproductive success. To reduce the risk of reproductive migration failure and to optimally allocate a limited amount of energy, it is vital to first understand the trade-off between reproduction and somatic growth in migrating fish. In this study, we chose Megalobrama terminalis, an endemic species residing in the Pearl River basin with relatively high migratory potential, as a candidate to investigate energy accumulation and allocation strategy during reproductive migration. The analysis used a quantitative assessment of biochemical composition and energy density in somatic and visceral tissues of M. terminalis females during the reproductive cycle. The results indicated that stage III to stage IV of M. terminalis was the vital migration-launching period. The asynchrony of development was confirmed in energetic relationships in muscle and ovary. Specifically, there was a regulatory mechanism for allocating lipids to each tissue reasonably during the breeding migratory preparation period (stage III). The significant change in lipid content of the ovary is considered as a crucial physiological index, which reflects the readiness for breeding migration of M. terminalis. In addition, the negative energy density relationship between somatic and reproductive tissues indicated a trade-off between maximum metabolic ability and energy efficiency before migration launching in M. terminalis. The present findings provide effective information for initiating further research on the ecological adaptation of migrating fish species.

Sorption properties and mechanisms of erythromycin and ampicillin in loess soil: Roles of pH, ionic strength, and temperature

The concern over veterinary antibiotic (VA) pollution has significantly increased. To understand the sorption properties and mechanisms of macrolides and β-lactam antibiotics in loess soil, batch equilibrium experiment was adopted to explore the sorption kinetics, sorption thermodynamics, and factors that influence erythromycin (ERY) and ampicillin (AMP) in loess soil. The equilibrium time of ERY and AMP sorption by loess soil was about 9 h and 2 h, respectively, and the sorption process was in line with a pseudo-second-order model. A linear sorption model can well describe the sorption of ERY in loess soil, while AMP was more consistent with the Freundlich model. The sorption affinity (Kd) of AMP on loess soil was 95.3–276.6L/kg and the Kd of ERY was only 8.3–9.7L/kg. The sorption capacity (Cs) of ERY first increased and then decreased, whereas the Cs of AMP gradually decreased with an increase in temperatures. A weak acid condition was favorable for the sorption of ERY, whereas an alkaline condition was favorable for the sorption of AMP. With the enhance of ionic concentration, the Cs of target pollutants was more effective, but ionic strengths too high inhibited the sorption of ERY. The Cs of the two pollutants increased with an increase in initial concentration. The results indicated that ERY is mainly adsorbed to loess soil by electrostatic sorption and cation exchange, whereas AMP depended on complexation, cationic bridging, and hydrogen bonding. Overall, AMP indicated the higher sorption expected in loess, whereas ERY displayed a high migration potential. Data presented in this study reveal aspects of the transport of macrolide and β-lactam antibiotics in soil–aqueous systems.

Региональная идентичность молодежи Хабаровского края и ее «социальные якоря»

The article presents the main results of sociological research conducted by the authors over the past ten years, devoted to the problems of self-identification of the youth of the Khabarovsk territory and their life strategies. We have noticed that the state authorities of the country and the region are working to create favorable conditions for the life and development of young people, but this does not have a significant positive impact on changing their migration moods, which over the past three decades have been directed towards changing their place of residence to more favorable regions of Russia or more favorable countries. The conducted sociological studies revealed nine types of self-identification of the youth of the Khabarovsk territory, three of which turned out to be the most interesting from the point of view of migration strategies - this is the Far Eastern (regional) self-identification with a characteristic reduced migration potential and a predominant desire to live in the territory of the region; Russian (state) self-identification with an average migration potential and a desire to change their place of residence within the country to a more comfortable region and global (planetary) self-identification with a high migration potential and a craving for living abroad of our Homeland. Thus, we confirmed the main hypothesis of the study that the determination of the youth's migration strategy is largely determined by its identification with the territory of residence. In the course of sociological measurements, we also found five «social anchors» that have a greater impact on the regional self-determination of young people and their desire to develop here without resorting to changing their place of residence - these are social activity and participation in public activities, entrepreneurship, long-term residence by family clans on the territory of the Khabarovsk territory, the presence of a reproductive family and geographical knowledge of the region. The conclusions we have obtained in the research can be used to substantiate, make changes and evaluate the effectiveness of the implementation of state programs aimed at implementing youth policy in the region, the purpose of which is to preserve (increase) the number of young generation in the region, as well as to create favorable living conditions and self-realization for them.

Прогнозирование миграционных процессов методами цифровой демографии

The nature and intensity of migration processes are constantly changing. Demographic statistics are not suitable for obtaining up-to-date information and making timely decisions in the field of demographic and social policy. Thus, digital demography is becoming increasingly important, as this area of population research uses new methods and data sources resulting from the Internet expansion and the digitalisation of society. Using digital demography methods and emerging data sources, the study aims to identify current migration trends in Russia at the municipal level. The duality of the object (real and virtual population) and methods (demographic and data science methods) of digital demography is demonstrated. Digital data sources for studying migration and relevant processing methods were considered. Further, it was proposed to assess migration flows by examining social network information and graphs of migration routes. The analysis of data obtained from the “Virtual population of Russia” project for 2356 urban and municipal regions revealed the features of intermunicipal migration and the centres of migration attraction in the country. An indicator for assessing the potential of future migrations based on the graphs of migration routes was presented. The analysis results show that balanced spatial development of Russia requires the stimulation of human capital development in local centres characterised by high migration potential. These include regional capitals, “second” cities in terms of population, and some research and industrial centres. The study findings can be used to consider demographic processes at the municipal level and elaborate strategic documents in the field of regional spatial development. Further digitalisation and the implementation of digital economy projects will lead to the accumulation of population data at the national level. Therefore, future research should focus on improving digital demography methods for studying and forecasting demographic processes.

CYT387 Inhibits the Hyperproliferative Potential of Fibroblast-like Synoviocytes via Modulation of IL-6/JAK1/STAT3 Signaling in Rheumatoid Arthritis

ABSTRACT Fibroblast-like synoviocytes (FLS) are the critical effector cells primarily involved in rheumatoid arthritis (RA) disease pathogenesis. Interleukin (IL)-6, a proinflammatory cytokine most abundantly expressed in the rheumatoid synovium, promotes Janus kinase (JAK)/signal transducer and transcriptional activator (STAT) signaling cascade activation in RA-FLS, thus leading to its aggressive phenotype, invasiveness, and joint destruction. Momelotinib (CYT387) is a selective small-molecule inhibitor of JAK1/2 and is clinically approved to treat myelofibrosis. However, the therapeutic efficacy of CYT387 in FLS mediated RA pathogenesis is less known. In the present study, we investigated the modulatory effect of CYT387 on IL6/JAK/STAT signaling cascade in FLS induced RA pathogenesis. CYT387 treatment inhibited IL-6 induced high proliferative and migratory potential of FLS cells isolated from adjuvant-induced arthritic (AA) rats. CYT387 reduced the expression of PRMT5, survivin, and HIF-1α mediated by IL-6/sIL-6R in AA-FLS in a dose-dependent manner. The IL-6/sIL-6R induced expression of angiogenic factors such as VEGF and PIGF in AA-FLS cells was found downregulated by CYT387 treatment. Importantly, CYT387 significantly reduced IL-6/sIL-6R dependent activation of JAK1 and STAT3 and increased SOCS3 expression in AA-FLS cells. Next, the S3I-201 mediated blockade of STAT3 activation supported the inhibitory effect of CYT387 on IL-6/JAK1/STAT3 signaling cascade in AA-FLS. Overall, this study proves that CYT387 inhibits proliferation, migration, and pathogenic disease potential of FLS isolated from adjuvant-induced arthritic (AA) rats via targeting IL-6/JAK1/STAT3 signaling cascade.