The N-acylhydrazone function has been reported as a pharmacophore group of molecules with diverse pharmacological activities, including anti-inflammatory effects. Thus, this study evaluated the anti-inflammatory potential of the compound N'-(3-(1H-indol-3-yl)benzylidene)-2-cyanoacetohydrazide (JR19) in vivo. The study started with the carrageenan-induced peritonitis model, followed by an investigation of leukocyte migration using the subcutaneous air pouch test and an assessment of the antinociceptive profile using formalin-induced pain. To find out the likely mechanism of action, a preliminary molecular docking study was performed focusing on the crystallographic structures of NFκB, iNOS, and sGCs. The computational study revealed satisfactory interaction energies with the selected targets, and the same peritonitis model was used to validate the involvement of the nitric oxide pathway and cytokine expression in the peritoneal exudate of mice pretreated with L-NAME or methylene blue. In the peritonitis assay, JR19 (10 and 20 mg/kg) reduced leukocyte migration by 59% and 52%, respectively, compared to the control group, with the 10 mg/kg dose used in subsequent assays. In the subcutaneous air pouch assay, the reduction in cell migration was 66%, and the response to intraplantar formalin was reduced by 39%, particularly during the inflammatory phase, suggesting that the compound lacks central analgesic activity. In addition, a reversal of the anti-inflammatory effect was observed in mice pretreated with L-NAME or methylene blue, indicating the involvement of iNOS and sGC in the anti-inflammatory response of JR19. The compound effectively and significantly decreased the levels of IL-6, TNF-α, IL-17, and IFN-γ, and this effect was reversed in animals pretreated with L-NAME, supporting a NO-dependent anti-inflammatory effect. In contrast, pretreatment with methylene blue only reversed the reduction in TNF-α levels. Therefore, these results demonstrate the pharmacological potential of the novel N-acylhydrazone derivative, which acts through the nitric oxide pathway and cytokine signaling, making it a strong candidate as an anti-inflammatory and immunomodulatory agent.

TNF-related apoptosis-inducing ligand (TRAIL or Apo2 or TNFSF10) belongs to the TNF superfamily. When bound to its agonistic receptors, TRAIL can induce apoptosis in tumour cells, while sparing healthy cells. This tumour selectivity prompted, over the last three decades, many studies aiming at evaluating the anti-tumoral potential of TRAIL or its derivatives. Although most of these attempts have failed, so far, novel formulations are still being evaluated. Yet, emerging evidence indicates that TRAIL can also trigger, on the other hand, a non-canonical signal transduction pathway that is likely to be detrimental for its use in oncology. Likewise, increasing studies suggest that TRAIL can induce, through Death receptor 5 (DR5) in some circumstances, tumour cell motility, potentially leading to and contributing to tumour metastasis. While the pro-apoptotic signal transduction machinery of TRAIL is well known from a mechanistic point of view, that of the non-canonical pathway is less understood. We are reviewing here the current state of knowledge of TRAIL non-canonical signalling.

(1) Background: P-cadherin (CDH3) is a transmembrane protein that plays a crucial role in maintaining the structural integrity of epithelial tissue and homeostasis. Its role in carcinogenesis remains a subject of debate, as its behavior can vary depending on the molecular context and the specific tumor cell model under study. In this study, we explored the role of P-cadherin in head and neck squamous cell carcinoma (HNSCC) and the mechanism underlying its function. (2) Methods: We analyzed P-cadherin expression in HNSCC patients using The Cancer Genome Atlas (TCGA) database. For in vitro functional analysis, we conducted proliferation, migration, invasion, and western blot assays after either suppressing or overexpressing P-cadherin. For in vivo functional analysis, we utilized mouse xenograft models. (3) Results: P-cadherin was significantly overex-pressed in tumor samples compared to normal samples in the TCGA-HNSCC cohort. P-cadherin knockdown resulted in decreased proliferation, migration, and invasion compared to control cells, while P-cadherin overexpression increased cell proliferation and migration in HNSCC cells. We discovered that c-Met functioned as an upstream regulator of P-cadherin. Surprisingly, we found that P-cadherin knockdown increased the phosphorylation of c-Met and STAT3. Combining P-cadherin siRNA with the c-Met inhibitor SU11274 resulted in a more effective reduction in HNSCC cell growth, both in vitro and in vivo, compared to either treatment alone. (4) Conclusions: Our study uncovered a previously unknown aspect of P-cadherin-mediated c-Met regulation. The enhanced activation of c-Met/STAT3 following P-cadherin inhibition could be responsible for the survival of resistant tumor cells. Therefore, dual inhibition of P-cadherin and c-Met may be a potentially effective approach for treating HNSCC.

A large number of studies have concluded that since housing pressure will affect the mobility of highly skilled young migrants (HSYM) in Chinese cities and regions, it is necessary to apply corresponding housing policies to adjust housing unaffordability for HYSM. This study uses a survey data conducted in China's Zhejiang Province of China, where specific policies have been implemented to attract talent and found that housing does crowds out the HSYM from a city, but the HSYM who have a master's degree or above or who work in government organizations or state-owned enterprises are more tolerant of housing unaffordability. The unmarried or those staying in the city for a long period are less tolerant of housing unaffordability. Meanwhile, there are the heterogeneous impacts of factors on the HSYM's tolerance for housing unaffordability across cities of different levels. Therefore, housing policies should highlight urban differences and intra-group differences.

Dual specificity phosphatase 2 (DUSP2) regulates the activation of members in the mitogen-activated protein kinase (MAPK) family, which is involved in a variety of cellular processes like cell proliferation, differentiation, apoptosis and migration. DUSP2 also regulates the expression of inflammatory mediators in macrophages, however, it remains unknown whether DUSP2 participates in macrophage migration. Here, using the tail fin injury model in zebrafish larvae, we found that deletion of DUSP2 inhibited expression of pro-inflammatory cytokines and macrophage chemokines. Moreover, live imaging results showed that migration of macrophages to the injury site was inhibited after DUSP2 deletion. This inhibitory effect was mediated through reduced activation of extracellular regulated protein kinases (ERK) in DUSP2 knockout zebrafish.

Pregnancy entails bidirectional interactions between the developing fetus, the maternal tissues, and the organ systems. To this end, the phenomenon of migration of fetal cells (FCs) into the maternal circulation is poorly understood. Here, we review literature underlying the migration of FCs from the placenta to the maternal circulation, which is likely a dynamic process, including trophoblast invasion, placental angiogenesis, modulation of maternal immune responses, and enlargement of maternal organs. As placental neovascularization fosters direct connections between fetal and maternal circulatory systems, the trophoblast, a pivotal to placental development, adeptly deploys an array of invasive strategies to breach maternal tissue barriers, facilitating FC escapade into the maternal circulation. The intricate balance struck by the maternal immune system, which both acts as a guardian against potential foreign cell threats and orchestrates a niche conducive to FC survival and differentiation, is facilitated by finely tuned interactions among regulatory T cells, cytokines, and inhibitory receptors. FC presence in mothers’ circulation may be clinically relevant and unveil novel molecular participants like lncRNA, exosomes, and intricate signaling pathways that drive innovative clinical approaches for diagnostics and therapeutics. Ongoing research should reshape our knowledge of pregnancy and maternal-fetal health by improving our understanding of fetal-maternal interactions.

Lung cancer is a prevalent and aggressive neoplasm worldwide, contributing to significant mortality rates. Dehydroepiandrosterone (DHEA) constitutes the bulk of the steroid hormone in human plasma, has a robust antiproliferative effect, and induces cell death in various tumor cells. However, its role in lung cancer cells remains unexplored. This study aimed to investigate the influence of DHEA on the proliferation, viability, autophagy, and migration of several lung cancer cell lines, including A549, HCC827, and NCI-H2347. Cell proliferation was assessed through crystal violet staining; cell number and viability were evaluated using trypan blue staining; viability was confirmed by MTT reduction, a method that is also an indicator of metabolic activity; migration was assessed via a wound healing assay. Autophagy was evaluated using a specific kit, while cell death was determined by annexin-V-FITC/propidium iodide staining and caspase-3/7 activity assay. The results indicate that DHEA significantly reduced proliferation, cell number, metabolic activity, and migration in all examined lung tumor cells. These effects correlate with an increased autophagy induced by DHEA. No signs of apoptosis or necrosis were observed across the range of DHEA concentrations used. Although these findings are preliminary, they suggest that DHEA could hold promise as an alternative treatment option for various subtypes of lung cancer.

This study was conducted to identify soil cadmium (Cd) removal pathways and their contribution rates during phytoremediation by Pennisetum hybridum, as well as to comprehensively assess its phytoremediation potential. Multilayered soil column tests and farmland simulating lysimeter tests were conducted to investigate the Cd phytoextraction and migration patterns in topsoil and subsoil simultaneously. The aboveground annual yield of P. hybridum grown in the lysimeter was 206 ton·ha–1. The total amount of Cd extracted in P. hybridum shoots was 234 g·ha–1, which was similar to that of other typical phytoremediation plants. After the test, the topsoil Cd removal rate was 21.50%–35.81%, whereas the extraction efficiency in P. hybridum shoots was only 4.17%–8.53%. These findings indicate that extraction by plant shoots was not the most important contributor to the decrease of Cd in the topsoil. The proportions of Cd retained by root cell wall was approximately 50% of the total Cd in root. Based on column test results, P. hybridum treatment led to a significant decrease in soil pH and considerably enhanced Cd migration to subsoil and groundwater. P. hybridum decreases Cd in the topsoil through multiple pathways and provides a relatively ideal material for phytoremediation of Cd-contaminated soils.

Global climate change, dominated by climate warming, is seriously affecting the balance of global ecosystems, but the risk of species extinction is particularly high in low-altitude mountain areas. To clarify the response of the endemic and critically endangered species Ilex nanchuanensis to climate change, this study used the MaxEnt model to simulate and predict the potential habitat of I. nanchuanensis during the Last Interglacial, Last Glacial Maximum, the current period, and two future periods (the 2050s and 2070s). The results showed that the hottest monthly minimum temperature is the most important climatic factor affecting the geographical distribution of I. nanchuanensis. Furthermore, I. nanchuanensis will be at risk of population shrinkage and extinction in the future, with the center of mass moving further northwest as concentrations of greenhouse gases increase, especially in the 2070s, when its geographical distribution shrinks the most under the RCP6 scenario. Global warming is causing habitat degradation for many species and will continue to migrate to higher altitudes and latitudes in the future, seriously affecting the global ecosystem balance. Therefore, to actively respond to the impacts of climate change, protected areas should be established around the geographical distribution centers of species, and core, buffer, and experimental areas should be scientifically and rationally delineated for the conservation and cultivation of germplasm resources.

Pore fluid pressure is very important to the generation, migration and accumulation of petroleum. The previous studies indicate that the Chezhen sag region is typically characterized by pore fluid overpressure (the difference between pore fluid pressure and hydrostatic pressure). To date, the formation mechanism of pore overpressure and the accumulation regularity of “upper source-lower reservoir” type in this region remains unknown. In order to investigate these problems, a 2-D finite element model is established with regards to the fluid-solid coupling in Chegu 25 block of Chezhen depression, fully considering the existing seismic, logging data and regional tectonic stress environment. Meanwhile, we calculate the abnormal overpressure generated at the source rock during hydrocarbon generation and the process of hydrocarbon migration and accumulation along the faults, analyzing the dynamic conditions of hydrocarbon downward accumulation. The results show that overpressure can accelerate migration of hydrocarbon and improve the efficiency of hydrocarbon accumulation. However, when the overpressure is too large, tensile fractures and shear fractures may occur, resulting in hydrocarbon dissipation, and changing the results of oil and gas accumulation. The overpressure at the source rock is mainly caused by hydrocarbon generation, while the overpressure at the reservoir is primarily created by unbalanced compaction. As the dominant channel of hydrocarbon migration, overpressure will change the direction and path of hydrocarbon migration in the fault. Therefore, the “upper source-lower reservoir” hydrocarbon accumulation model is strongly explained by the high permeability of faults and the presence overpressure. In summary, the simulated overpressure results are in good agreement with the mud weight equivalent overpressure and the drill stem tests (DSTs).

Among Crustacea, Decapoda Brachyura represent a good candidate for studies on the dispersal capability of coastal benthos by means of larvae. One oceanographic cruise allowed us to describe larvae dispersal routes in the South Adriatic Sea thanks to a multidisciplinary approach. In May 2013 a swarm of zoeae (11 Brachyura taxa, mostly at first instar, with Xantho granulicarpus at 87%) was recorded in the neuston of the Italian side of the basin. Complementary collections of zooplankton, in the same cruise, demonstrated that Decapoda larvae were not abundant below the neuston and concentrated in the first 20-30 m surface layer, with which probably they drift together. The availability of four satellite-tracked surface drifters in the same area and period of the larvae presence, represented a possibility to discuss the geographic dispersal of larvae on the basis of the surface circulation in successive days. During the studied period, only one drifter crossed the south Adriatic passing from the Italian to the Balkan neritic area, employing about 40 days. The daily vertical migration of larvae suggest that they can only employ more time to cross the basin, subtracting and re-entering the surface moving waters. The actual genetic homogeneity of populations of many Brachyura coastal species on the opposite sides of the Adriatic Sea suggests the existence of a genetic connection which, however, should not rely exclusively upon larvae circulation and needs to be fueled by additional strategies of biological communication.

The growing worldwide cancer incidence, coupled to the increasing occurrence of multidrug cancer resistance, requires a continuous effort towards the identification of new leads for cancer management. In this work, two C-scorpionate complexes, [FeCl2(κ3-Tpm)] (1) and [Co(κ3-TpmOH)2] (2), (Tpm = hydrotris(pyrazol-1-yl)methane and TpmOH = 2,2,2-tris(pyrazol-1-yl)ethanol), are studied as potential scaffolds for future anti-cancer drug development. Their cytotoxicity and cell migration inhibitory activity are analyzed, and an untargeted metabolomics approach is em-ployed to elucidate the biological processes significantly affected by these two complexes, using two tumoral cell lines (B16 and HCT116) and a non-tumoral cell line (HaCaT). While [FeCl2(κ3-Tpm)] did not display a significant cytotoxicity, [Co(κ3-TpmOH)2] was particularly cy-totoxic against the B16 cell line. While [Co(κ3-TpmOH)2] significantly inhibited cell migration in all tested cell lines, [FeCl2(κ3-Tpm)] displayed a mixed activity. From a metabolomics perspective, exposure to [FeCl2(κ3-Tpm)] is associated with changes in various metabolic pathways involving tyrosine, where iron-dependent enzymes are particularly relevant. On the other hand, [Co(κ3-TpmOH)2] is associated with dysregulation of cell adhesion and membrane structural pathways, suggesting its antiproliferative and anti-migration properties can be due to changes in the overall cellular adhesion mechanisms.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease due to early metastatic spread, late diagnosis and the lack of efficient therapies. A major driver of cancer progression and hurdle to successful treatment is the desmoplastic reaction of the tumor stroma, the formation of which is orchestrated by transforming growth factor (TGF)-β. Recent data from pancreatic cancer mouse models have shown that the TGF-β pathway is controlled by transcriptionally active p73 (TAp73) through secretion of biglycan (Bgn) via intermittent expression of the TGF-β signaling intermediates, Smad3 and Smad4. Genetic knockout of TP73, and, as a consequence, deficient induction of Smad3/Dpc4 and secretion of Bgn led to activation of TGF-β signaling through a (Smad-independent) ERK pathway, favoring epithelial-mesenchymal transition (EMT) and cell motility. Except for BGN, these functions of TAp73 have recently been shown to also operate in human PDAC cells and are reminiscent of what we previously observed for the small GTPase, RAC1b. This prompted us to hypothesize that TAp73 and RAC1b are part of the same tumor-suppressive pathway in human PDAC cells. The two objectives of this study, therefore, were to reveal i) if the regulatory interactions between TAp73 and Bgn previously discovered in murine PDAC-derived cells also operate in their human counterparts, and ii) if RAC1b collaborates with TAp73 in these tumor-suppressive activities in human PDAC cells. Using a variety of experimental approaches, including mutual rescue experiments, we were able to show that the previously proposed tumor-suppressive TAp73-Smad4-Bgn signaling also operates in human cells and that RAC1b is as an upstream activator of this pathway. Our findings highlight the complex role of TGF-β in pancreatic tumorigenesis and might have implications for therapeutic approaches targeting this growth factor for inhibition.

This research uses a gravity model method to investigate the factors determining the number of tourists visiting Australia. Understanding the variables that draw visitors to specific locations is essential for policymakers and other stakeholders in the tourism sector since tourism continues to play a significant role in the economy of many countries worldwide. Despite the widespread use of gravity models in the analysis of international tourism flows, only a tiny amount of attention has been paid to particularly researching the flow of tourists to Australia. This research addresses this knowledge gap by analyzing the variables influencing travel patterns to Australia. The gravity model framework is used, and it considers factors like gross domestic product, gross domestic product per capita, migratory stocks, distance, population size, cost of living, and cultural similarities. The purpose of this research is to aid in developing focused marketing strategies by providing insights into the factors that influence the flow of tourists to Australia via the analysis of these variables. The results are anticipated to add to the current literature on gravity modeling in tourist research and give practical implications for industry stakeholders and policymakers. The discussion of the findings, their ramifications, and possible directions for further study serves as the conclusion of the work.

Macrophages play a pivotal role in the process of healing burns. One of the major risks in the course of burns healing, in the absence of regenerating epidermis, is infections which greatly contribute to morbidity and mortality in such patients. Therefore, it is widely agreed that accelerating recruitment of macrophages into burns may contribute to faster regeneration of the epidermis and thus, decreasing the risk of infections. This review describes a unique method for rapid recruitment of macrophages into burns and activation of these macrophages to mediate accelerated regrowth of the epidermis and healing of burns. The method is based on application of bio-degradable “alpha-gal” nanoparticles to burns. These nanoparticles present multiple alpha-gal epitopes (Gal alpha1-3Gal beta1-4GlcNAc-R) which bind the abundant natural anti-Gal antibody that constitutes ~1% of immunoglobulins in humans. Anti-Gal/alpha-gal nanoparticles interaction activates the complement system, resulting in localized production of the complement cleavage-peptides C5a and C3a that are highly effective chemotactic factors for monocytes derived macrophages. The macrophages recruited into the alpha-gal nanoparticles treated burns are activated following interaction between the Fc portion of anti-Gal coating the nanoparticles and the multiple Fc receptors on macrophages cell membranes. The activated macrophages secrete a variety of cytokines/growth factors that accelerate the regrowth of the epidermis and regeneration of the injured skin, thereby cutting the healing time by half. Studies on healing of thermal injuries in the skin of anti-Gal producing mice, demonstrated a much faster recruitment of macrophages into burns treated with alpha-gal nanoparticles than in control burns treated with saline and healing of the burns within 6 days, whereas healing of control burns takes ~12 days. alpha-Gal nanoparticles are non-toxic, and do not cause chronic granulomas or keloids. These findings suggest that alpha-gal nanoparticles treatment may harness anti-Gal for inducing similar accelerated burn healing effects also in humans.

During deep-sea mining, the heavy metals pollutants can cause contamination in the marine environment. In this paper, the multiphasic coupling model is established to describe the heavy metal migration process during deep-sea mining, which takes the effects of convection-diffusion, adsorption-desorption and sedimentation-resuspension of heavy metals in the aquatic environment into full consideration. Due to the advantages of Lattice Boltzmann method, it is adopted to numerically solve the multiphasic coupling model and achieve the simulation for heavy metal migration process during deep-sea mining. In addition, taking Cadmium as an example, the concentration variations are discussed and analyzed in detail. Based on the established model and Lattice Boltzmann method, the concentration distribution of heavy metals can be accurately described to provide the reasonable bases for the evaluation of marine environmental protection.

Colony-stimulating factor 1 receptor (CFS-1R) is a myeloid receptor with a crucial role in monocyte survival and differentiation. Its overexpression is associated with aggressive tumor characterized by an immunosuppressive microenvironment and poor prognosis. CSF-1R ligands, IL-34 and M-CSF, are produced by many cells in the tumor microenvironment (TME), suggesting a key role for the receptor in the crosstalk between tumor, immune and stromal cells in the TME. Recently, CSF-1R expression was reported at the cell membrane of cancer cell from different solid tumors, capturing the interest of various research group interested in investigating the role of this receptor in non-myeloid cells. This review summarizes current data available on the expression and activity of CSF-1R in different tumor types. Notably, CSF-1R+ cancer cells have been shown to produce CSF-1R ligands, indicating that CSF-1R signaling is positively regulated in autocrine manner in cancer cells. Recent research demonstrated that CSF-1R signaling enhances cell transformation by supporting tumor cell proliferation, invasion, stemness and drug resistance. In addition, this review covers recent therapeutic strategies, including monoclonal antibodies and small molecule inhibitors, targeting the CSF-1R and designed to block the pro-oncogenic role of CSF-1R in cancer cell.

SETD7 is a member of the SET domain-containing lysine methyltransferase family and is a crucial component in the development and spread of a number of human cancers. However, the specific function of the SETD7 gene in ovarian cancer (OC) is still unclear. The purpose of this research was to elucidate the expression and role of SETD7 in OC. In comparison to normal controls, OC tissues (83%, 73/88) and cell lines exhibited higher protein levels of SETD7 (p < 0.001). High SETD7 protein levels were substantially correlated with M category (p = 0.019) and FIGO stage (p = 0.021). Furthermore, the high mRNA levels of SETD7 were correlated to poor progression-free survival (PFS) in all patients and serous patients with OC (p < 0.05). Importantly, the biological function experiments showed that SETD7 behaved as an oncogene in OC by dramatically facilitating the proliferation and migration of A2780 and SKOV3 cells. Additionally, SETD7 might promote cell migration via accelerating the EMT process in A2780 and SKOV3 cells. Our findings reveal that SETD7 may be a valuable molecular marker for identifying and anticipating the development of OC.

In order to formulate a reasonable water input model for cotton fields in southern Xinjiang, scientific and rational fertilization, reduce soil carbon leaching, and improve soil carbon sequestration capacity, the undisturbed soil column leaching test was used to simulate the current field management method in the study area. Two methods of drip irrigation and flood irrigation were set up, and three irrigation and three nitrogen fertilizer levels were used to carry out the undisturbed soil column leaching test. The results showed that the amount and mode of water and nitrogen input affected the distribution and leaching loss of organic carbon and inorganic carbon in soil. When the nitrogen application rate increased from 270 kg·hm-2 to 450 kg·hm-2, the leaching loss of soluble organic carbon and soluble inorganic carbon increased significantly. When the water input increased from 6000 m3·hm-2 to 9000 m3·hm-2, the leaching loss of DOC and DIC increased significantly. The carbon leaching loss under drip irrigation was higher than that under flood irrigation. The leaching rates of DOC and DIC were the fastest under the conditions of high water ( 9000 m3·hm-2 ) and high fertilizer ( 450 kg·hm-2 ). It shows that water and nitrogen input and irrigation methods are important factors affecting soil carbon leaching. In the case of excessive water input, long-term high-frequency irrigation is the main factor affecting carbon leaching.

Cardiac development is a complex developmental process that results in the formation of the four-chambered organ from a single linear heart tube. In the early stages of development, the linear heart tube is composed of only two tissue layers, an external myocardium that is internally lined by the endocardium. Subsequently, the proepicardium emerges at the septum transversum and soon thereafter proepicardial cells will migrate into the naked myocardium, leading to the formation of the embryonic epicardium. As cardiac development proceeds, epicardial-derived cells migrate into the subepicardial space and subsequently invade the developing ventricular chambers leading to the contribution of distinct cardiovascular cell types such as the cardiac fibroskeleton and different components of coronary vasculature. At present, the molecular mechanisms that regulate the transitional process from the proepicardium to the embryonic myocardium are largely unexplored. In this study we have implemented an ex vivo proepicardium/septum transversum (PE/ST)-embryonic myocardium explant model and we demonstrated that miR-223, but not miR-195, is capable of modulating PE/ST migration, a process that seems to be mediated by Slug expression. Thus, our study demonstrates for the first time the implication of distinct microRNAs in the PE/ST to embryonic myocardium transition in chicken embryonic hearts.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease due to early metastatic spread, late diagnosis and the lack of efficient therapies. A major driver of cancer progression and hurdle to successful treatment is transforming growth factor (TGF)-β. Recent data from pancreatic cancer mouse models have shown that transcriptionally active p73 (TAp73), a p53 family member, inhibits tumor progression through promoting tumor suppressive canonical TGF-β/Smad signaling, while preventing non-canonical TGF-β signaling through extracellular signal-regulated kinases (ERK)1/2. Here, we have studied whether this mechanism also operates in human PDAC. Using the PDAC-derived tumor cell lines PANC-1 and HPAFII, we show that TAp73 induces the expression of the epithelial marker and invasion suppressor E-cadherin and the common-mediator Smad, SMAD4, while at the same time suppressing expression of the EMT master regulator SNAIL and basal and TGF-β1-induced activation of ERK1 and ERK2. Using dominant-negative and RNA interference-based inhibition of SMAD4 function we went on to show that inhibition of ERK activation by TAp73 is mediated through SMAD4. Intriguingly, both SMAD4 and the α isoform of TAp73 - but not the isoform - interfered with cell migration as shown by xCELLigence technology. Our findings highlight the role of TAp73-SMAD4 signaling in tumor suppression of human PDAC and identify direct inhibition of basal and TGF-β-stimulated pro-invasive ERK activation as an underlying mechanism.

In preserving genetic diversity among domestic animal breeds, the strategies emphasizing be-tween-breed diversity may be not optimal by neglecting within-breed variation. The present study aimed to assess the extent of the population subdivision of Mangalica pigs and the contri-bution of migration intensity to their substructure. Genealogy analysis was performed for breeding animals born between 1981 and 2023 examining three colour variations (Blonde, Swal-low-Belly, and Red). The fixation index (FST) was calculated and evaluated by Multidimensional Scaling and Clustering to expose the population substructure. The average FST is 0.04 for the Blonde and 0.05 for the Swallow-Belly and the Red while in the active herds, these parameters are smaller being 0.03 and 0.04, respectively. The migration of individuals affected 61.63% of the Blonde, 75.53% of the Swallow-Belly, and 63.64% of the Red breed herds. No population sub-structure was found in any Mangalica breed which can be explained by the extensive within breed migration among the herds.

For deep-penetrating geochemistry, there is a frontier issue as to how to explore ore-bearing information deep in covered areas, while it is, too, important to investigate the geochemical migration of ore-forming elements for the development of exploration geochemistry. In this study, a 380-day migration column experiment was conducted with surface soil and pure Cu powder collected from the Yujiashan study area in Wuhan City, Hubei Province taken as the object of research to simulate the migration process of ore-forming elements under natural conditions. The results showed obvious vertical migration of the ore-forming elements and conversion of mobile metal forms in the process; further, according to 6 groups of simulation experiments that took 45 days to conduct on migration column samples and the surface oil and Cu powder collected from the Pulang mining area in Yunnan Province, the vertical migration of the ore-forming element was still visible, and the exogenous substance (pure Cu powder) could enhance the anomaly without changing the basic migration mechanism. This indicates that Cu might migrate in a stable manner in soil cover in the Pulang mining area, and its migration was mostly driven by the transformation of Fe-Mn oxide bound state and organic bound state; finally, a multifractal analysis was conducted, revealing that the ore-forming elements presented a nonlinear and complex structure during their upward migration, which caused anomalies in the covered area, and multiple parameters exerted a certain indicative effect on different source intensities and properties of soil. In this study, laboratory simulations were performed to summarize the active-state evolution pattern and migration mechanism of ore-forming elements with a view to providing technical support and theoretical guidance for geochemical prospecting in the covered region.

The prevailing challenge in our current era is climate change, a crisis recognized by the global community that has prompted immediate actions to confront and mitigate its consequences. There is a consensus among scientists that human activities, driven by developmental ambitions, are the driving force behind the ongoing climate crisis. “The well-documented aftermath, including the rise in sea levels, coastal erosion, reduced agricultural yields, compromised access to clean water, and health implications, emphasizes the intricate and wide-ranging effects of climate change.” Furthermore, there is an increasing recognition that climate change gives rise to distinct social, economic, and divergent consequences. “Although all countries worldwide will undergo the impacts of climate change, the distribution of these effects will differ among regions, generations, age groups, income levels, occupations, and genders.” Notably, the adverse consequences will disproportionately impact the impoverished, predominantly situated in developing nations. “This paper explores the effects of climate change on displacement and the ensuing refugee dilemma.” It aims to scrutinize the inclusion of climate-induced displacement in the present international framework, encompassing both climate change and refugee regimes. The paper promotes a human rights-centred approach to tackling displacement stemming from climate change.

With the intensification of population aging in rural areas, it becomes increasingly important to analyze the post-retirement migration intention of rural residents and the variables influencing these intentions. In this study, we focus on rural residents aged 45 to 60 and investigate the main variables that influence the post-retirement migration intention of rural residents, using survey data collected from 164 households in three different rural areas and the logistic regression model. From the result of this study, we found that gender, part-time employment, savings level, children's residence and occupation stability, and interest in urban living positively affect migration intention. In contrast, the number of rural companions, relationships with others in rural areas, and evaluation of rural living have a negative effect. In addition, we employ age and the proportion of mobile income as control variables to examine the variables that influence the post-retirement migration intention in different age groups and mobile income groups. The analysis reveals that, the variables influencing post-retirement migration intention varied across age groups and mobile income groups, and this variation can be attributed to the differences between groups' characteristics.

The migration paths and distribution driving factors of heavy metals in dry and windy area polluted by their production in the North China need a further research. To address this research gap, we collected 675 soil samples, 72 atmospheric deposition samples and 20 water samples around a production area and measured its heavy metal concentrations. Results showed that the Cu, Zn, As and Pb in 0-10 cm soil layer showed a fan-shaped distribution, which was consistent with their atmospheric deposition fluxes. It indicated the distribution patterns of these heavy metals were driven by strong winds in studied area. Although Cr concentrated to the production area in the 0-10 cm soil layer, principal component analysis showed that this migration was through wind as well. The concentration of Cd in the river increased from 0.257 mg/L to 0.460 mg/L along water flowing, and caused the same distribution trend in soil near the river from upstream to downstream. Unlike the above, surface runoff should drive the Cd migration. The concentration of Pb in the river was over threshold of pollution, and also led to an accumulation in the 5-10 cm soil layer. It suggested that the migration of Pb was through both wind and surface runoff. Six studied heavy metals showed different migration behaviors, and specific control strategies for individual heavy metal should be concerned.

Disulfiram (DSF), an anti-alcoholism medicine, exerts treatment effects in patients suffering from persistent Borreliosis and also exhibits anti-cancer effects by its copper chelating derivatives. Since chronic/persistent borreliosis is characterized by increased amounts of proinflammatory macrophages, this study investigated opsonin-independent phagocytosis, migration and surface marker expression of in vivo activated human monocyte-derived macrophages and dendritic cells with and without DSF treatment. Phagocytosis of non-opsonized Dynabeads® M-450 and migration of macrophages and dendritic cells were monitored using live cell analyzer Juli™ Br for 24h by imaging every 3.5 min. Results were analyzed by a newly developed software based on the differential phase contrast images of cells before and after ingestion of Dynabeads bearing an electron dense iron core. As a control, phagocytosis was also monitored by visual counting of ingested beads. DSF decreased the phagocytic capacities exhibited by global macrophages and dendritic cells. DSF also impaired the migration of human monocyte-derived macrophages and dendritic cells (hMDMD) and significantly reduced the expression densities of surface antigens CD45 and CD14. In cells consisting of anti-inflammatory M2 macrophages, DSF led to a remarkable cell death and also increased oxidative stress as determined by MitoSox staining. Mitochondrial oxidative stress was a prominent feature in M2 macrophages which were more sensitive to DSF-induced cytotoxicity.

The Doppler band compensated by the keystone transform (KT) is limited. Therefore, it needs to be used in conjunction with the Doppler ambiguity compensation function to correct the range migration (RM) caused by maneuvering targets with Doppler ambiguity. However, the KT implemented by sinc interpolation suffers from significant performance loss at boundaries of compensation Doppler bands. Additionally, in a multi-target scenario, KT implementation methods occupy high complexity when the Doppler range of targets spans over two compensation Doppler bands. To address aforementioned issues, this study presents a variable Doppler starting point keystone transform (VDSPKT) method, where a new form of ambiguity compensation function is constructed, turning the Doppler starting point of the compensation band in KT variable. Firstly, the position of the compensation Doppler band is changed from fixed to adjustable as needed, enhancing the flexibility of KT. Crucially, the connection points of the compensation Doppler bands in sinc interpolation are reset, avoiding the performance loss at their boundaries. Also, the compensation band is adjusted to cover the narrow Doppler frequency range caused by targets, significantly improving the computational efficiency. Finally, the simulation results demonstrate that the proposed approach effectively addresses the performance degradation and high computational complexity of KT in the aforementioned scenarios, resulting in a computational load reduced by approximately 50% compared to traditional methods.

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodelling of glioblastoma (GBM) cells and invasion of the surrounding parenchyma through activation of a RhoA-ROCK pathway. We also described that GBM cells can control the expression of ODZ1 through transcriptional mechanisms triggered by binding of IL-6 to its receptor and a hypoxic environment. Epidermal growth factor (EGF) plays a key role in the invasive capacity of GBM. However, the molecular mechanisms that enable tumor cells to acquire the morphological changes to migrate out from the tumor core have not been fully characterized. Here we show that EGF is able to induce the expression of ODZ1 in primary GBM cells. We analysed the levels of EGF receptor (EGFR) in 20 GBM primary cell lines and found expression in 19 of them by flow cytometry. We selected two cell lines that do or do not express EGFR and found that EGFR-expressing cells responded to EGF ligand by increasing ODZ1 at the mRNA and protein level. Moreover, blockade of EGF-EGFR binding by Cetuximab, inhibition of the p38 MAPK pathway or siRNA-mediated knockdown of MAPK11 (p38 MAPK) reduced the induction of ODZ1 in response to EGF. Overall, we show that EGF may activate an EGFR-mediated signalling pathway through p38 MAPK, to upregulate the invasion factor ODZ1, which may initiate morphological changes for tumor cells to invade the surrounding parenchyma. These data identify a new candidate of the EGF-EGFR pathway for novel therapeutic approaches.

Mass transfer and phase transition have important effect on the velocity of bubble migration in deepwater wellbore, and accurate prediction of bubble migration velocity is crucial for calculating the safe shut-in period of deepwater oil and gas well. Therefore, the effect of bubble dissolution mass transfer and hydrate phase transition on bubble migration behavior in deepwater environment have attracted extensive attention from researchers in the fields of energy, marine chemistry, and marine engineering safety. In this work, a new model of bubble migration velocity in deepwater is developed, which considers the effect of hydrate phase transition and gas-water bidirectional cross-shell mass transfer during bubble migration. Based on the observation data of bubble migration in deepwater, the reliability of the model in predicting bubble migration velocity is verified. Then, the model is used to calculate and analyze the bubble migration velocity and bubble migration cycle under different initial bubble size, different annular fluid viscosity and density. The results show that the initial size of bubble and the viscosity of annulus fluid are the main factors affecting the migration velocity of bubble, but the density of annulus fluid has little effect on the migration velocity of hydrated bubble and clean bubble. In addition, the migration velocity of clean bubble gradually increases during the migration process from the bottom to the wellhead, while the migration velocity of hydrated bubble is divided into gradually decreasing stage and slowly increasing stage. The gas consumption and the thickening of hydrate shell in the gradually decreasing stage play a dominant role, and the increase of bubble volume caused by the decrease of pressure in the slowly increasing stage is the most important factor. The formation of hydrated bubble can significantly reduce the migration velocity of bubble and effectively prolong the safe shut-in period. This study provides a reference for quantitative description and characterization of complex bubble migration behavior with phase change and mass transfer in deepwater environment.

The development of mineral deposits causes changes that are comparable to natural exogenous geological processes, and in local areas of intensive mining activity prevail over them. In this article, a diamond deposit is selected, developed by quarries of great depth, and a forecast is made of the impact of drainage water discharge on changes in the composition of surface water and bottom sediments during the entire period of development of the deposit. Modeling was per-formed according to various scenarios, taking into account changes in the total dissolved solids of groundwater from 0.5 to 21.7 g/kg H2O. Thermodynamic calculations were carried out using the HCh software package. The role of dissolved organic carbon in the migration of chemical elements and the effect of DOC on the precipitation of chemical elements from mixing solutions is given. It has been established that fulvic acid completely binds to Fe in the Fe(OH)2FA– complex in all types of natural waters and under all mixing scenarios. With humic acid, such a sharp competitive complex formation does not occur. It is distributed among the various elements more evenly. It was determined that the mass of precipitating iron in the presence of DOC decreases by 18-27%, and its precipitation in winter is more intense. In contrast to Fe, precipitation of Ca, Mg, and C from solution with DOC is higher in summer, and there are more of them in solution in winter. This study contributed to a better understanding of the behavior of heavy metals in surface waters and sediments under anthropogenic pressures in order to improve the sustainable management of water resources in the face of anthropogenic activities.

ERK1/2 phosphorylation is frequently downregulated in the early phase of colon tumorigenesis with subsequent activation of ERK5. In the current work, we studied the advantage of ERK1/2 downregulation for tumor growth by dissecting the individual functions of ERK1 and ERK2. The patient sample data demonstrated decreased ERK1/2 phosphorylation in the early phase of tumorigenesis followed by upregulation of the phosphorylation in late-stage colon adenocarcinomas with intratumoral invasion or metastasis. In vitro results indicated SOD3-mediated coordination of small GTPase RAS regulatory genes in the inhibition of RAS-ERK1/2 signaling. In vitro and in vivo studies suggested that ERK2 has a more prominent role in chemotactic invasion, collective migration, and cell proliferation than ERK1. Noteworthily, simultaneous ERK1 and ERK2 expression inhibited collective cell migration and proliferation but tended to promote invasion, therefore suggesting that ERK1 controls ERK2 function. According to the present data, phosphorylated ERK1/2 at the early phase of colon adenocarcinoma limits tumor mass expansion, whereas reactivation of the kinases at the later phase of colon carcinogenesis is associated with the initiation of metastasis. Additionally, our results suggest that ERK1 is a regulatory kinase, which coordinates ERK2-promoted chemotactic invasion, collective migration, and cell proliferation. Our findings indicate that ROS, especially H2O2, are associated with the regulation of ERK1/2 phosphorylation in colon cancer either increasing or decreasing the kinase activity. The data suggesting a growth-promoting role for ERK2 and a regulatory role for ERK1 could result in new avenues in the developmental strategies for cancer therapy.

Members of the SOX (SRY-related HMG-box) family of transcription factors are crucial for embryonic development and cell fate determination. This review investigates the role of SOX3 in cancer, as aberrations in SOX3 expression have been implicated in several cancers, including osteosarcoma, breast, esophageal, endometrial, ovarian, gastric, hepatocellular carcinomas, glioblastoma, and leukemia. These dysregulations modulate key cancer outcomes such as apoptosis, epithelial-mesenchymal transition (EMT), invasion, migration, cell cycle, and proliferation, contributing to cancer development. SOX3 exhibits varied expression patterns correlated with clinicopathological parameters in diverse tumor types. This review aims to elucidate the nuanced role of SOX3 in tumorigenesis, correlating its expression with clinical and pathological characteristics in cancer patients and cellular models. By providing a comprehensive exploration of SOX3 involvement in cancer, this review underscores the multifaceted role of SOX3 across distinct tumor types. The complexity uncovered in SOX3 function emphasizes the need for further research to unravel its full potential in cancer therapeutics.

Abstract: The migration and transformation of pesticides in the environment will have an impact on the ecosystem. This study collected greenhouse soil from Shouguang, Shandong Province, and studied the photodegradation and leaching of 17 common pesticides in the soil. The results of photodegradation experiments showed that the degradation rate of certain pesticides was increased in the light environment, compared with that in the dark controls. The light half-lives of emamectin benzoate, pyraclostrobin, and metalaxyl were all shorter than their respective dark half-lives, indicating that their residues in soil were greatly affected by light. The leaching experiment showed that the leaching potential of the leachable pesticides was: nitenpyram ≫ metalaxyl &gt; acetamiprid &gt; carbendazim &gt; diethofencarb ≈ chlorantraniliprole &gt; isoprothiolane &gt; oxadixyl &gt; boscalid ≈ tebuconazole &gt; hexaconazole. Pesticides that are easy to leach but not easy to degrade, such as chlorantraniliprole and metalaxyl, have a high potential risk of groundwater pollution, and more degradation technologies should be used to reduce their pollution risk. The study on photodegradation and vertical migration behavior of various pesticides in this study was conducive to providing references for the agricultural use and pollution control of pesticides.

Cell-to-cell distant mechanical communication has been demonstrated by using in-vitro and in-vivo models. However, the molecular mechanisms underlying long-range cell mechanoresponsive interactions remain to be more elucidated. This study further examined the roles of α-Catenin and Piezo in traction force-induced rapid branch assembly of airway smooth muscle (ASM) cells on Matrigel hydrogel containing type I collagen. Our findings demonstrate that siRNA-mediated downregulation of α-Catenin or chemical inhibition of Piezo activity significantly reduced both cell directional movement and branching assembly. In regarding the role of N-cadherin in regulating branch assembly but not directional migration, our results further confirmed that siRNA downregulation of α-Catenin caused a remarked reduction of focal adhesion formation, as assessed by focal Paxillin and Integrin α5 localization. These observations implied that mechanosensitive α-Catenin was involved in both cell-cell and cell-matrix adhesions. Additionally, Piezo showed partial localization with Paxillin in focal adhesions, which was inhibited by α-Catenin downregulation with siRNA. This provides a plausible clue for Piezo mechanosensing traction force in the hydrogel. Collectively, our findings highlight the significance of α-Catenin in regulating cell-matrix interactions along with possible interpretation for Piezo mechanosensation at focal adhesions during cell-cell distant mechanical communication.

Soil organic matter (SOM) is important for the global carbon cycle, and hyperspectral remote sensing has proven a promising method for fast SOM content estimation. However, soil physical properties significantly affect the sensitivity of satellite hyperspectral imaging to SOM, leading to poor generalization ability of the estimation model. This study aims to improve the spatiotemporal transferability of the SOM prediction model by alleviating the coupling effect of soil physical properties on the spectra. Based on satellite hyperspectral images and soil physical variables, including soil moisture (SM), soil surface roughness (root mean squared height, RMSH), and soil bulk weight (SBW), a soil spectral correction strategy was established based on the information unmixing method. Two important grain-producing areas in Northeast China were selected as study areas to verify the performance and transferability of the spectral correction model and SOM content prediction model. The results showed that soil spectral corrections based on fourth-order polynomials and the XG-Boost algorithm had excellent accuracy and generalization ability, with residual predictive deviations (RPD) exceeding 1.4 in almost all bands. In addition, when the soil spectral correction strategy was adopted, the accuracy of the SOM prediction model and the generalization ability after model migration were significantly improved. The SOM prediction accuracy based on the XG-Boost corrected spectrum was the highest, with a coefficient of determination (R2) of 0.76, root mean square error (RMSE) of 5.74 g/kg, and RPD of 1.68. The prediction accuracy, R2, RMSE, and RPD of the model after migration were 0.72, 6.71 g/kg, and 1.53, respectively. Compared with the direct migration prediction of the model, adopting the soil spectral correction strategy based on fourth-order polynomials and XG-Boost reduced the RMSE of the SOM prediction results by 57.90% and 60.27%, respectively. The performance comparison highlighted the advantages of considering soil physical properties in regional-scale SOM prediction.

Parental labour migration, either one or both parents, has been associated with various challenges among left-behind children (LBC). However, there is a limited understanding of the LBC’s own views and experiences of social and mental wellbeing and how the new daily life circumstances they encounter following their parents’ migration impact them. This study aimed to understand the influence of parental migration and its aftermath on the social and mental wellbeing of children and adolescents (referred to as LBC) in two rural districts in Indonesia. Employing a qualitative design, data were collected through individual in-depth interviews with LBC (n=24) aged 14 to 18 years, recruited using the snowball sampling technique. Data were thematically analysed, guided by a qualitative data analysis framework. The findings showed that parental migration negatively impacted the social wellbeing of LBC. This impact was reflected in negative labelling from friends and changes in familial roles which influenced their social interactions and activities with peers. Parental migration also caused challenges to the mental wellbeing of LBC. These manifested in the LBC experiencing fractured emotional bonds, leading to negative emotions, including stress, anxiety, sadness, depression, frustration, loss of motivation, and self-imposed isolation, which were associated with their parents’ migration and abrupt disruptions in parent-child communication. The transition to new life situations with caregivers after parental migration and the dynamics within the caregivers’ households were additional factors that detrimentally affected their mental well-being. Unmet basic needs and educational needs due to financial hardships faced by mothers and caregivers, further exacerbated mental health challenges for the children. The findings indicate the importance and improvement of policies and interventions in Indonesia (e.g., counselling services, non-cash food assistance, family hope program, direct cash assistance) that cover and address the diverse needs of mothers or caregivers and the LBC.