(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.

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.

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).

Remittances are essential to economies in mountainous regions that face massive labour migration due to limited income generation and employment opportunities. In 2021, the share of remittances to GDP in the top 10 mountainous economies in the world was over 20%. Nonetheless, most are characterized by relatively lower GDP per capita and high poverty levels. Drawing a comparison with other mountainous areas, Phuthadjthaba, an emerging mountainous and border city of South Africa with Lesotho, faces similar out-migration and inferior socio-economic parameters. A global systematic literature review on the impact of remittances on livelihoods specifically targeting mountainous areas is missing. We, therefore, interrogate the role remittances can play in Phuthadijthaba. To inform our intended research, we seek to draw lessons from evidence on how migration and remittances affect mountainous communities globally. Accordingly, we carry out a systematic literature review (SLR) based on an updated Preferred Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement supported by Bibliometric (co-word) Analysis (BA) in VOSViewer. We collected data from Scopus and Dimensions websites and drew 165 publications, of which only 88 were included after exclusion and inclusion assessments. PRISMA results show that Mountain Research and Development, King Russell, and Nepal is the most productive and cited journal, the most productive and cited author, and the most researched country, respectively. Bibliometric analysis on keyword co-occurrences reveals women, agriculture, labour migration, land management, forest, and poverty, to be the research hotspots. In light of these findings, we proffer important recommendations to future researchers and policymakers.

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.

Drainage divide is a dynamic feature that migrates in response to tectonic activity. The asymmetric uplift between two adjacent basins causes the divide migration from a slower to faster uplift area. Sado Island, Japan, has been affected by southeastward tilting uplift since ca. 300k years. Despite the faster uplift on the northwest, the main divides have existed on the southeast side of the geometric center of the island, with no other feature suggesting tectonic inversion of the tilting direction. In this study, we conducted a DEM-based investigation that focused on divide migration. A spectrum from very inactive to active divide migration in the northwest. Regardless of their position, actively migrating divides are comprehensible, but inactive divides located in a relatively slow uplift area remain unclear. We concluded that some divides slowed down owing to the local balance of erosion rates across the divides, not implying the balance between uplift and river erosion at the basin scale, reflecting disequilibrium in river longitudinal profiles. The main divides of Sado have presumably continued to slowly migrate toward the faster uplift area; however, they are most likely to have never overcome the moving geometric center owing to land expansion at the seacoast due to asymmetric uplift.

Individual users' payment behaviors have changed. The diffusion of mobile devices makes people suitable for proximity mobile payment (PMP) services without the need for traditional payment. Existing mobile payment literature mainly focuses on users' adoption and continuous usage behavior, nevertheless, switching behavior on payment received little attention, especially focusing on why users switch from traditional payment to PMP. Thus, the objective of the current research is to investigate factors influencing users’ traditional payment - PMP switching to comprehend how these factors shape users’ switching intentions. We developed a traditional payment - PMP transition model based on the push-pull-mooring framework derived from migration theory. This research adopted a structural equation modeling analysis on 311 valid data. The findings indicate that a push factor drives users away from traditional payment in terms of dissatisfaction. The pull factors, including perceived substitutability and perceived usefulness, attract users to PMP. Furthermore, in terms of perceived technical compatibility, a positive mooring factor facilitates users' switching to PMP. The negative mooring factor, in terms of perceived risk, hinder users' switching intention. However, another pull factor - perceived ease of use, failed to influence switching intention significantly. This study found some distinctions between mobile payment switching and mobile payment adoption. These findings provide pivotal insights for mobile payment service providers.

Self-assembling peptide P11-4 is amphiphilic and pH-triggered with demonstrated effectivity repairing early carious lesions in enamel. However, P11-4 effects on dentin biomineralization and repair remain unexplored. Thus, cytocompatibility and effectiveness of P11-4 inducing mineralization and migration of odontoblast-like cells (MDPC-23) were investigated. MDPC-23 were seeded in contact with P11-4(0.5µg/ml and 1µg/ml), Dentin Matrix Protein 1 (DMP1 0.5µg/ml and 1 µg/ml) or Calcium hydroxide (Ca(OH)2 100µg/ml) solutions. Cytotoxicity was verified using MTT (n=6/group). Mineralization was tested using Alizarin Red (n=4/group). Cell migration was assessed by light microscopy (n=2/group). MTT and Alizarin Red data were compared using Krus-kal-Wallis and Mann-Whitney (α=0.05). P11-4 (0.5µg/ml and 1µg/ml) and DMP1 (0.5µg/ml and 1µg/ml) presented the highest cytocompatibility; Ca(OH)2 presented the lowest. DMP1 1µg/ml exhibited the highest mineralization ability, with no difference to P11-4 1µg/ml. Ca(OH)2 presented lower values than DMP1 1µg/ml (p<0.05), but similar to P11-4 1µg/ml. P11-4 and DMP1 at 0.5 µg/ml showed induced less mineralization than P11-4 and DMP1 at 1µg/ml (p<0.05), with no difference to Ca(OH)2. All materials stimulated cell migration, however, lower concentrations of DMP1 and P11-4 provided better results. P11-4 is cytocompatible, induces mineralization and MDPC-23 migration like DMP1. P11-4 could be an alternative for dentin mineralization and tooth repair.

Oral cancer cells (TYS) and the signalling pathways involved in metastasis, in response to cancer-associated fibroblasts (CAFs, COM) and normal oral mucosal fibroblasts (MM1) was studied. Metastatic cell behaviour was observed by cell-scatter, 3D-collagen gel migration and 3D-spheroid invasion assays. Akt, MAPK, EGFR, TGFβRii and CXCR4 inhibitors were used to identify the signalling pathways involved. Signalling pathway protein expression and activation were assessed by SDS-PAGE and Western Blotting. COM-CM (conditioned medium) and MM1-CM stimulated cancer cell scattering, which was blocked only by the Akt inhibitor. COM-CM induced scattered cancer cells showed higher levels of Akt phosphorylation than the negative control and MM1-CM. Migration and invasion of TYS cells into the collagen gels from the spheroids was stimulated by CM from both sources, compared to the negative control. COM cells stimulated TYS, cancer cell invasion into the collagen more than MM1 and the control. Akt and EGFR inhibitors effectively blocked CM and COM cell-induced invasion. Akt-silenced cancer cells were not stimulated to migrate and invade by fibroblast-CM and did not survive addition of the EGFR inhibitor. This suggests that CAFs stimulate oral cancer cell migration and invasion in an Akt- dependent manner. EGFR and Akt are potential therapy targets in metastatic oral cancer.

ADAM10 is a multi-functional proteinase that can cleave approximately 100 different substrates. Previously, we demonstrated that ADAM10 is expressed by ameloblasts responsible for enamel formation. Here we asked if ADAM10 plays a role in enamel development. Deletion of Adam10 in mice is embryonic lethal and deletion of Adam10 from epithelia is perinatal lethal. We therefore deleted Adam10 from ameloblasts. Here, we confirm ameloblast-specific expression of the Tg(Amelx-iCre)872pap construct. We crossed these mice with Adam10 floxed mice to generate Amelx-iCre; Adam10fl/fl mice (Adam10 cKO). We show that Adam10 cKO mice have discolored teeth with softer than normal enamel. Notably, the Adam10 cKO enamel density and volume were significantly reduced in both incisors and molars. Moreover, the incisor enamel rod pattern became progressively more disorganized moving from the DEJ to the outer enamel surface and this disorganized rod structure created large gaps between and among the rods. ADAM10 cleaves proteins essential for cell signaling and for enamel formation such as RELT and COL17A1. ADAM10 also cleaves cell-cell contacts such as E- and N-cadherins that may support ameloblast movement necessary for normal rod patterns. Here, we show for the first time that ADAM10 expressed by ameloblasts is essential for proper enamel formation.

Hirschsprung disease (HSCR, incidence 1/5000 live births) is caused by failure of neural crest-derived precursors to migrate, survive, proliferate or differentiate during the embryonic development of the Enteric Nervous System (ENS), which could be disrupted by many factors, in-cluding inflammatory processes. The NF-κB family controls several biological processes includ-ing inflammation, neurogenesis and cell migration. With the aim of studying the potential role of NF-κB in HSCR, we have analyzed the expression of the NF-κB main subunits and other NF-κB-related genes by RT-qPCR in HSCR tissue samples (sub-divided in ganglionic and agan-glionic segments). We found a decreased gene expression of the NF-κB main subunit RelA/p65, but also of IkBα, TNF-α, TFGBR2 and ERBB3 in the pathologic distal aganglionic segments com-pared to the proximal ganglionic segments. Moreover, we could also confirm the lower protein expression of RelA/p65 in the aganglionic distal segments by immunofluorescence staining. Fur-ther, we show that the expression of RelA/p65 in the proximal segments concurs with lymphocyte infiltration in the bowel tissue, indicating a pro-inflammatory activation of p65 in the proximal ganglionic HSCR tissue in the patients analyzed. In all, our findings suggest that the modulation of NF-κB signaling in the neuro-enteric system does obviously contribute to the pathological ef-fects in HSCR.

To elucidate mesenchymal stromal cells (MSC)-tumor intricate and ambiguous interactions, the reliable cell labeling and tracking techniques are imperative. Traditional methods of cell labelling have limitations mostly relevant to need for genetic modification what demands the exploration for alternative strategies. Here, we propose using fluorescent photoconvertible microcapsules containing Rhodamine B (RhB) to study mMSC migration in brain tumors. These 3 μm sized microcapsules are readily internalised by cells and undergo photoconversion under 561 nm laser exposure with fluorescence blue shift on demand. Optimal photoconversion was achieved with a laser irradiation duration of 0.4 ms, which provide a maximal brightness of photoconverted label without an excessive laser exposure on cells. Capsules modified with polyallylamine hydrochloride demonstrated the best potential for intracellular uptake without significantly affecting cell viability, motility, or proliferation. The optimal ratio of 20 capsules per mMSC was determined for labeling. Moreover, migration of individual mMSCs within 2D and 3D glioblastoma cell (EPNT-5) colonies over 2 days and in vivo tumor settings over 7 days was tracked. Our study unveils a robust platform for investigating MSC-tumor dynamics, offering insights into therapeutic strategies. Photoconvertible microcapsules could also become an indispensable tool for studying complex fundamental processes of cell-cell interactions for a wide range of problems in biology and medicine.

Climate change is one of the widely acknowledged challenges faced by international communities in the 21^st century. It poses challenges to fundamental elements of our understanding of appropriate goals for socioeconomic policies, such as the connection of prosperity, growth, equity and sustainable development. Human activities-induced climatic changes have been widely perceived as threatening criteria for the long-term resilience of societies and communities throughout the world. The United Nations Intergovernmental Panel on Climate Change (UNIPCC) reported that greenhouse gas (GHG) emissions due to human activities, such as the burning of fossil fuels for energy generation, is changing the climate of Earth. Despite contributing less towards the causes, poor citizens of developing countries bear a lot of its impacts. In particular, women and girls face a major impact and finally, they migrate due to the social gender division and scarcity of food. Studies on gender and climate change-induced migration are scarce. This study provides an overview of the induced impact of climate change on the livelihood, health and migration of women and girls. The aim of this study would significantly advance our understanding of the current inter-linkages between migration, displacement patterns and climate change impacts.

In a rapidly evolving global landscape characterized by increased international travel, migration, and ecological shifts, this study sheds light on the emergence of protozoal and helminthic infections targeting the central nervous system (CNS) within Europe. Despite being traditionally associated with tropical regions, these infections are progressively becoming more prevalent in non-endemic areas. By scrutinizing the inherent risks, potential outcomes, and attendant challenges, this study underscores the intricate interplay between diagnostic limitations, susceptibility of specific population subsets, and the profound influence of climate fluctuations. The contemporary interconnectedness of societies serves as a conduit for the introduction and establishment of these infections, warranting comprehensive assessment. This study emphasizes the pivotal role of heightened clinician vigilance, judicious public health interventions, and synergistic research collaborations to mitigate the potential consequences of these infections. Though rare, their profound impact on morbidity and mortality underscores the collective urgency required to safeguard the neurological well-being of the European populace. Through this multifaceted approach, Europe can effectively navigate the complex terrain posed by these emergent infections.

Genetic discoveries related to Alzheimer’s disease and other dementias have been performed using either large cohorts of affected subjects or multiple individuals from the same pedigree, therefore disregarding mutations in the context of healthy groups. Moreover, a large portion of studies so far have been performed on individuals of European ancestry, with a remarkable lack of epidemiological and genomic data from underrepresented populations. The present study aims at scanning 70 single-point mutations on the APP gene in a publicly available genetic dataset including 2.504 healthy individuals from 26 populations, and analyzing their distribution. Moreover, after gametic phase reconstruction, a pairwise comparison of the segments surrounding the mutations was performed to reveal patterns of haplotype sharing that could point to specific cross-population and cross-ancestry admixture events. Eight mutations have been detected in the worldwide dataset, with several of them being specific for a single individual, population or macroarea. Patterns of segment sharing reflect recent historical events of migration and admixture possibly linked to colonization campaigns. These observations reveal the population dynamics of the considered APP mutations in worldwide human groups, and support the development of ancestry-informed screening practices for the improvement of precision and personalized approaches to neurodegeneration and dementias.

Cell migration is essential for physiological, pathological and biomedical processes such as, in embryogenesis, wound healing, immune response, cancer metastasis, tumour invasion and inflammation. In light of this, quantifying mechanical properties during the process of cell migration is of great interest in experimental sciences, yet few theoretical approaches in this direction have been studied. In this work, we propose a theoretical and computational approach based on the optimal control of geometric partial differential equations to estimate cell membrane forces associated with cell polarisation during migration. Specifically, cell membrane forces are inferred or estimated by fitting a mathematical model to a sequence of images, allowing us to capture dynamics of the cell migration. Our approach offers a robust and potentially accurate framework to compute geometric mechanical membrane forces associated with cell polarisation during migration and also yields geometric information of independent interest, we illustrate one such example that involves quantifying cell proliferation levels which are associated with cell division, cell fusion or cell death.

We utilized all Spanish marriage records available at the municipality level from 2005-2007 to model spatial variations in intermarriage. We constructed a spatial regime zero inflated Poisson model and grouped-data probit model, with spatially lagged regressors, to predict the absolute and relative presence of intermarriage between Spaniards and migrants based on structural characteristics of the local marriage markets and their neighboring areas (i.e., relative group size, homogeneity of national origins, and sex ratio indicators). Our models do not assume collapsibility of the marriage market. Instead, they incorporate the local dimension of the marriage market and examine the association between intermarriage and structural variables at the spatial local level. The model also investigates intermarriage variation by size of place. The local characteristics of the marriage markets are robust indicators of both the absolute and relative importance of intermarriage, but their impact varies by size of municipality. The relative size of the migrant community positively impacts intermarriage. The homogeneity of the origins of migrants is negatively related to it. The impact of sex ratios in the migrant and native communities on intermarriage is not uniform across all municipalities and is not always related to more intermarriage.

Epithelial-mesenchymal transition (EMT) is a cellular biological process involved in migration of primary cancer cells to secondary sites facilitating metastasis. Besides, EMT also confers properties such as stemness, drug resistance and immune evasion which can aid a successful colonization at the distant site. EMT is not a binary process; recent evidence suggests that cells in partial EMT or hybrid E/M phenotype(s) can have enhanced stemness and drug resistance as compared to those undergoing a complete EMT. Moreover, partial EMT enables collective migration of cells as clusters of circulating tumor cells or emboli, further endorsing that cells in hybrid E/M phenotypes may be the ‘fittest’ for metastasis. Here, we review mechanisms and implications of hybrid E/M phenotypes, including their reported association with hypoxia. Hypoxia-driven activation of HIF-1α can drive EMT. In addition, cyclic hypoxia, as compared to acute or chronic hypoxia, shows the highest levels of active HIF-1α and can augment cancer aggressiveness to a greater extent, including enriching for a partial EMT phenotype. We also discuss how metastasis is influenced by hypoxia, partial EMT and collective cell migration, and call for a better understanding of interconnections among these mechanisms. We discuss the known regulators of hypoxia, hybrid EMT and collective cell migration and highlight the gaps which needs to be filled for connecting these three axes which will increase our understanding of dynamics of metastasis and help control it more effectively.

The active layer thickness (ALT) is affected by local soil material and surface vegetation coverage in Tibetan plateau permafrost region. The human activities and engineering construction along the Qinghai-Tibet Highway (QTH) destroyed the surface vegetation coverage, which have seriously influenced the ALT and heat exchange balance. Meanwhile, the changes of the detailed internal structure in the active layer will affect the stability of engineering infrastructure. Ground-penetrating radar (GPR) was used to detect the ALT in the permafrost region. However, researches on the detailed structure of the active layer and spatial variation information of ALT are rare, the main reason given for this is that the lack of advanced imaging techniques to enhance the GPR images. In this paper, the researchers focus on solving this problem by applying the reverse time migration (RTM) method to GPR field data acquired in the Beiluhe region. Analyses of the results led to conclusions as follows: a) The RTM algorithm is proved to be accurate for imaging the characteristics of the active layer through the dielectric constant model obtained by common midpoint and GPR data velocity analysis. b) The result of RTM profiles show the loose structure and graben-like fine internal structure. Combining with drill data and soil materials information, the researchers deduce the graben-like structure might be coarse gravel layer, which may be related to subgrade settlements in some local area. c) The 2D contour maps not only show the spatial variation feature of ALT at two sides of the highway, but also can compensate the defect of the research for single 2D survey line. The ALT is about 0.6~0.8 m in most areas, and about 0.8~0.9 m near the highway at west side of the QTH on the 2D contour maps. From the RTM interpretation profile, the closer to the plash, the deeper thawed active layer. The detailed internal structure of the active layer and 2D contour maps of ALT have great significance for the study of fine internal structure and the characteristic of ALT spatial variation in the Tibetan plateau under the background of climatic change.

Colorectal cancer (CRC) remains a major global health issue. Although chemotherapy is the first-line treatment, its effectiveness is limited due to drug resistance developed in CRC. To overcome resistance and improve the prognosis of CRC patients, investigation for new therapeutic approaches is necessary. Using human colorectal adenocarcinoma (HT29) and metastatic CRC (SW620) cell lines, the potential anticancer properties of a newly synthesized compound 1-(Isobutyl)-3-(4-methylbenzyl) benzimidazolium chloride (IMBZC) were evaluated by performing MTT cytotoxicity, cell migration, and colony formation assays, as well as by monitoring apoptosis-related protein and gene expression using Western blot and reverse transcription-quantitative polymerase chain reaction technologies. Tested at various concentrations, the half-maximal inhibitory concentrations (IC50) of IMBZC on HT29 and SW620 cell growth were determined to be 6.97 μg/mL and 4.89 μg/mL, respectively. IMBZC did not alter cell growth of normal cells HEK293. In addition, IMBZC inhibited cell migration and significantly decreased colony formation, suggesting its promising role in suppressing cancer metastasis. Mechanistic analyzes revealed that IMBZC treatment increased the expression of pro-apoptotic proteins p53 and Bax, while decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL, thus indicating the induction of apoptosis in IMBZC-treated CRC cells, compared to untreated cells. Additionally, the addition of IMBZC to conventional chemotherapeutic drugs (i.e., 5-fluorouracil, irinotecan, and oxaliplatin) resulted in an increase in the cytotoxic potential of the drugs. In conclusion, the study suggests that IMBZC has substantial anticancer effects against CRC cells through its ability to induce apoptosis, inhibit cancer cell migration and colony formation, and enhance the cytotoxic effects of conventional chemotherapeutic drugs. These findings indicate that IMBZC could be a promising chemotherapeutic drug for the treatment of CRC. Further research should be conducted using in vivo models to confirm the anti-CRC activities of IMBZC.

Cancers of the brain and nervous system account for 1 in every 100 cancer diagnoses in the United States and about 0.3 million diagnoses globally, every year. Surgery, radiotherapy, and chemo-therapy constitute the standard of care. Despite advancements in diagnosis and treatment delivery, mortality rate for these cancers have remained steady for over three decades. Immunotherapy is an emerging fourth treatment modality which has been effective against several cancers but not brain cancers, such as glioblastoma, GBM. Here, we develop in vitro assays to quantify molecular readouts of cell death, cell migration and clonogenicity, and synopsize these as biophysical markers for the rapid evaluation of immune checkpoint inhibitors (ICI), durvalumab and pembrolizumab, alone and in combination with radiotherapy (radioimmunotherapy). We find different trends in their direct action on two GBM cell lines (T98G and U87), even in the absence of immune cells. Radiation alone, and pembrolizumab with radiation, both reduced (p < 0.05) cell-cell adhesion. This reduction suggests increased potential for local invasion. Our assays offer additional insights regarding ICIs, may enable evaluation of their potential efficacy, and could set the stage for pa-tient-specific radioimmunotherapy against brain cancers, engendering improved treatment out-comes.

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.

This study posits that for appropriately explaining the complex charland (mid-channel island) processes and formulating policy and planning measures, a comprehensive understanding of the dynamic characteristics of the geomorphological, ecological, and human systems holistically is essential. This is also valid for the territorial and maritime areas of Bangladesh. The objectives of this study are: (i) to analyze the salient features and characteristics of the geomorphological and riparian systems of the Bengal Delta; (ii) to analyze the evolutionary discourse of the legal systems concerning eroded (diluvion) and accreted (alluvion) land in Bangladesh; and (iii) to assess characteristics of coping and adaptation strategies of the charland inhabitants. The findings reveal that the delta-building processes, characterized by the dynamic shifts of river channels, and erosion and accretion of charlands have made the land and water systems of the territory very dynamic and unstable – resulting in consistent displacement of settlers and serious deterioration of their socioeconomic status. The historical evolution of land laws and regulations concerning the accreted land favoured vested interests. As no effective institutional framework and structure presently exists in Bangladesh for resettlement planning, formulation of a comprehensive national resettlement policy is therefore urgently needed.

The power of the river does not always work to the benefit of living things; rather, it has the ability to destroy human society and has negative effects on the environment. River Teesta has a prodigious significance on the riverine dweller and its changing precarious behaviour has repercussions on the lives of millions. Utilizing satellite images and 41 years of temporal analysis, the mapping of channel extraction and channel shifting has been demonstrated. Delineating the exact channel boundary is a laborious operation, but MNDWI technique is really valuable in this situation to produce valuable results. Descriptive statistics are used to analyze the Teesta River's active flow line migration trend and channel migration behaviour. A particular river's oscillating character over time has both beneficial and detrimental power, destroying important resources for environmental sustainability and human society while also providing fertile mother earth as a source of wealth. As a result, another goal of the current study was to determine how vulnerable riverine residents were. A livelihood vulnerability index (LVI) based on the riverine inhabitants' exposure, sensitivity, and capacity for adaptation was created. According to the findings, the river's erratic behaviour is putting the people who live beside it in danger. Therefore, it is vitally necessary to implement a capable management strategy to stop bank failure at the Teesta-Dharala confluence in order to save the riverine residents.

Currently, the design and construction of embankments of roads, railroads and hydraulic structures are based on regulatory documents developed 25-30 years ago. For the construction of granite massifs it is necessary to use sandy soils, the distribution of which in the Arctic zone of Siberia in the areas of construction is not more than 1.5%. In this case, the range of transport of sand in the alluvial area is 35 kilometers, in the rest of the area - an average of 60 kilometers. Large volumes of soil massifs require large amounts of transportation units, fuel consumption and are accompanied by large emissions of hydrocarbons into the atmosphere. Over the past 15 years, the authors have developed designs and technologies that significantly reduce the energy consumption during the construction of soil embankments. Combined structures are cages made of geosynthetic materials filled with unsuitable melted and frozen overmoistened clay and peaty soils. This allowed the use of soils within the construction sites and thereby reduce the range of transportation from 0.2 to 2.0 kilometers. As an example, when reducing the range of transportation from 25 km to 1 km, the energy consumption is reduced by a factor of 21. The use of geosynthetics made it possible to set the initial parameters of the water-heat regime control process, which increased the life cycle of the embankment from 2 to 5 times in comparison with traditional soil massifs and reduced the consumption of energy for repair and maintenance of linear transport structures. This article gives a theoretical substantiation of water-heat regime management, based on which new designs and technologies have been proposed and tested in Siberia in 2008-2013. The results of the tests confirm the theoretical research. Thus, the use of combined constructions of geosynthetics and inapplicable soils not only reduces the distance of transportation, but also reduces the volume of earthworks. It reduces the consumption of energy by 1.5-2 times.

We advance binational link-tracing sampling design, an innovative data collection methodology for sampling from transnational social fields, i.e., transnational networks embedding migrants and non-migrants. This paper shows the practical challenges of such a design, the representativeness of the samples and the qualities of the resulted networks. We performed 303 face-to-face structured interviews on sociodemographic variables, migration trajectories and personal networks of people living in a Romanian migration sending community (Dâmbovița) and in a migration receiving Spanish town (Castellón), simultaneously in both sites. Inter-connecting the personal networks, we built a multi-layered complex network structure embedding 4,855 nominated people, 5,477 directed ties (nominations) and 2,540 edges. Results indicate that the participants’ unique identification is a particularly difficult challenge, the representativeness of the data is not optimal (homophily on observed attributes was detected in the nomination patterns), and the relational and attribute data allow to explore the social organization of the Romanian migrant enclave in Castellón, as well as its connectivity to other places. Furthermore, we provide methodological suggestions for improving link-tracing sampling from transnational networks of migration. Our research contributes to the emerging efforts of applying social network analysis to the study of international migration.

Investigation into geological storage of CO2 is underway at the Technology Development Plant (TDP) at Hontomín (Burgos, Spain), the only current onshore injection site in the European Union. The storage reservoir is a deep saline aquifer located within Low Jurassic Formations (Lias and Dogger), formed by fractured carbonates with low matrix permeability. Understanding the processes involved in CO2 migration within this kind of low-primary permeability carbonates influenced by fractures and faults is key to ensure safe operation and reliable plume prediction. During the hydraulic characterization tests, 2300 tons of liquid CO2 and 14000 m3 of synthetic brine were co-injected on site in various sequences to characterize the pressure response of the seal-storage pair [de Dios et al, 2017] The injection tests were analyzed with a compositional dual media model which accounts for both temperature effects (as the CO2 is liquid at the bottom of the wellbore) and multiphase flow hysteresis (to effectively simulate the alternating brine and CO2 injection tests that were performed). The pressure and temperature responses of the storage formation were history-matched mainly through the petrophysical characteristics of the fracture network [Le Gallo et al, 2017]. The dynamic characterization of the fracture network dominates the CO2 migration while the matrix does not appear to significantly contribute to the storage capacity. This initial modeling approach was improved using the characterization workflow developed within the European FP7 CO2ReMove project for sandstone fractured reservoirs [Ringrose et al., 2011; Deflandre et al., 2011]. Fractured reservoirs are challenging to handle because of their high level of heterogeneity that conditions the reservoir behaviour during the injection. In particular, natural fractures have a significant impact on well performance [Ray et al, 2012]. Furthermore, the understanding of the processes involved in CO2 migration within relatively low-permeability storage influenced by fractures and faults is essential for enabling safe storage operation [Iding and Ringrose, 2010]. As part of the European H2020 ENOS project, the site geological model is updated by integration of the recently acquired data such as the image log interpretations from injection and observation wells. The geological model is generated through the analysis and integration of data including borehole images and well test data. Following a methodology developed for naturally fractured hydrocarbon reservoirs [Ray et al., 2012], the image log analysis identified two sets of diffuse fractures. A Discrete Fracture Network [Bourbiaux et al., 2005] was built around both wells which encompass the caprock, storage and underburden formations. The fracture characteristics of the two sets of diffuse fractures, such as orientations, densities and conductivities, are calibrated upon the interpretation of the injection tests [Le Gallo et al, 2017]. For each facies, the DFN characteristics were then upscaled and propagated to the full-field reservoir simulation model as 3D fracture properties (fracture porosity, fracture permeability and equivalent block size).

Background: Our previous study highlighted important healthcare access and utilization concerns among new immigrants. Hence, in this study, we aimed to explore the role of public and patient involvement (PPI) may have in enhancing the accessibility and their contribution to migration health studies. Method: An open and in-depth interactive consecutive virtual discussion was conducted among volunteer asylum seekers and refugees from Eritrea and Syria in Switzerland. The novel PPI establishment had three phases; inception, training phase, and contribution phase. Result: At the beginning, the concept of PPI was apprehensive to grasp, as it was a new approach. After training and consecutive discussions, volunteers were ardent to engage actively. Hence, among the prime findings were the PPI's role and effect in raising awareness, PPI's role in exploring and communicating the healthcare system accessibilities and utilization among their community, the impact of PPI in echoing the healthcare needs of their fellow migrants, and PPI's contribution in enhancing and strengthening migration health researches. Conclusion: The PPI volunteers in the study were keen to raise their community's awareness through their networks, and bridge the research gap between researchers and the public.

The Hippo pathway plays crucial roles in governing various biological processes during tumorigenesis and metastasis. Within this pathway, upstream signaling stimuli activate a core kinase cascade, involving MST1/2 and LATS1/2, which subsequently phosphorylates and inhibits the transcriptional co-activators YAP and its paralog TAZ. This inhibition modulates the transcriptional regulation of downstream target genes, impacting cell proliferation, migration, and death. Despite the acknowledged significance of protein kinases in the Hippo pathway, the regulatory influence of protein phosphatases remains largely unexplored. In this study, we conducted the first gain-of-functional screen for protein tyrosine phosphatases (PTPs) regulating the Hippo pathway. Utilizing a LATS kinase biosensor (LATS-BS), a YAP/TAZ activity reporter (STBS-Luc), and a comprehensive PTP library, we identified numerous novel PTPs that play regulatory roles in the Hippo pathway. Subsequent experiments validated PTPN12, a master regulator of oncogenic receptor tyrosine kinases (RTKs), as a previously unrecognized negative regulator of the Hippo pathway effectors, oncogenic YAP/TAZ, influencing breast cancer cell proliferation and migration. In summary, our findings offer valuable insights into the roles of PTPs in the Hippo signaling pathway, significantly contributing to our understanding of breast cancer bi-ology and potential therapeutic strategies.

Deficient wound healing is frequently observed in patients diagnosed with diabetes, a clinical complication that compromises mobility and leads to limb amputation, decreasing patient autonomy and family lifestyle. Fibroblasts are crucial for secreting the extracellular matrix to pave the wound site for endothelial and keratinocyte regeneration. The biosynthetic pathways for collagen production are one of the main components of the extracellular matrix, as the crosslinking of extracellular collagen fibers is intimately related to fibroblast redox homeostasis. In this study, human dermic fibroblasts were cultured with 1 mM sodium selenite (inorganic) and 1 mM of two selenium amino acids (organic), Se-cysteine and Se-methionine. This concentration was compatible with long-term exposure necessary for extracellular matrix production and allowed us to examine the impact of these three compounds on the state and response of the thiol-based HyPer biosensor expressed in the cytoplasm. In addition, the abundance of extracellular matrix and ultrastructural properties were evaluated by Picrus Sirius red staining and scanning electronic microscopy, respectively. We also evaluated whether these selenium compounds effectively ameliorated the perturbations induced by culturing fibroblasts at high glucose levels (25 mM) regarding cytoplasmic redox, extracellular matrix, and glycation on collagen fibers. Our results indicate that cytoplasm protein oxidation was sensitive to selenium compound supplementation. Selenium amino acids increased the sensitivity to protein oxidation, and only Se-cysteine increased the disulfide bond reduction in fibroblasts maintained in high glucose. Despite the lack of effect of selenium compounds on the glu-cose-induced increase in matrix fiber thickness, we found that endothelial migration improved in the matrix generated by high glucose-cultured fibroblasts.

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.

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.

For tropical forests to survive anthropogenic climate change, the trees that comprise them will need to tolerate the newly emerging conditions through adaptation or acclimation, or they can avoid climate change through range shifts and “species migrations”. In this review, we show that the rapid pace and extreme severity of modern climate change makes it extremely unlikely that tropical tree species can adapt (with some possible exceptions). We also show that while many tropical tree species are shifting their distributions to higher, cooler elevations, the rate of these migrations are mostly insufficient to offset ongoing changes in temperatures, especially in lowland tropical rainforests where thermal gradients are shallow or nonexistent. We argue that the best hope for tropical tree species to avoid becoming “committed to extinction” is acclimation. While several new methods are being developed to test for acclimation, we unfortunately still do not know if tropical tree species can acclimate or what factors may prevent or facilitate acclimation. Until these questions are answered, our ability to predict the fate of tropical species and tropical forests – and the many services that they provide to humanity – remains critically impaired.

Understanding cell migration is a key step to unravel many physiological phenomena and predict several pathologies, like cancer metastasis. In particular, mechanical confinement has been proved to be a key factor in the cellular migration strategy choice. As our insight in the field improves, new tools are needed in order to empower biologists’ analysis capabilities. In this framework, microfluidic devices have been used to engineer the mechanical stimuli and to investigate cellular migration response in a more controlled way. In this work, we will review the existing technologies employed in the realization of microfluidic cellular migration assays, namely soft lithography of PDMS and hydrogels and femtosecond laser micromachining. We will give an overview of the state of the art of these devices, focusing on the different geometrical configurations that have been exploited to study specific aspects of cellular migration. Our scope is to highlight the advantages and possibilities given by each approach and to envisage the future developments in in-vitro migration studies under mechanical confinement in microfluidic devices.

The traditional bored pile technology has some arduous problems, such as the sediment at the pile tip, the mud skin along the pile shaft, and the stress release due to borehole construction. The post-grouted technology at the pile tip of bored pile has emerged because of demand. The grouting migration height (GMH) is of great significance to the strengthen and reinforcement of the pile foundation. This paper derives the calculation formula of the GMH based on the theory of the column hole expansion and Herschel-Bulkley model. The influence of relevant parameters on the GMH is discussed. Aiming at the problem of the grouting migration along the pile shaft in layered soils, the iterative calculation method of the GMH is proposed. The correctness of the GMH is verified by an engineering case, which can guide the engineering practice. The result shows that the GMH increases with the increase of the grouting pressure, the pile diameter and the thickness of the mud skin, and the grouting pressure is positively correlated with the GMH. The GMH decreases with the increase of the buried depth, the consistency coefficient and the rheological index. On this basis, the correctness of the GMH is verified by an engineering case.

Health of migrant is a widely studied topic. It has been argued that migrant health may deteriorate over time. Though migrants are ‘a hard to reach’ population in survey data, this paper builds on a unique dataset provided by Médecins du Monde from five countries. We study self perceived health (SPH) in connection with socio-economic and demographic factors and length of stay. Results show different results for men and women. Asylum seekers compared to other documented migrants have a worse health. Migrants with better living conditions tend to be in better health. Employment and stable accommodation has a positive effect on SPH. Women from poorer countries have a better physical SPH after 3 months of residing in the host country. This paper contributes widely to knowledge of health of migrants. Contrarily to other evidence, health of migrants tends to improve for some migrants.

A comprehensive study (monitoring, thermodynamic modeling) of natural and anthropogenically polluted waters of the Lovozero Massif has been carried out. A thermodynamic study of the weathering of the Lovozero Massif within the “water-rock-atmosphere” system at a temperature of 5°C showed that the elements contained in the rocks of the studied massif influence the formation of the chemical composition of natural waters. It has been established that an increase in the degree of “water-rock” interaction leads to an increase in the concentrations of F, Cl, SО42-, HCO3- in the solution. This affects the mobility of lanthanum, cerium and other elements due to the formation of complex compounds with them. The relatively high content of fluorine, phosphorus, HCO3- (weak and medium acids) in the solution promotes the dissolution of silicates while Si, Al, P are released into the solution. Monitoring of water from a flooded mine in which there is an increase in the degree of interaction of water with rock showed higher pH values for the concentrations of Na, HCO3-, F-, P, Al, Si, V, U, La, Ce. The conclusions are relevant in the context of groundwater extraction for drinking water supply purposes. The obtained information is useful to evaluated the health of the population of the region under study.

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.

Pancreatic ductal adenocarcinoma (PDAC) is mostly diagnosed at advanced or even metastasized stages limiting patient´s prognosis. Metastasis requires high tumor cell plasticity implying phenotypic switching in response to changing environments. Here, Epithelial-Mesenchymal-Transition (EMT), being associated with the gain of cancer stem cell (CSC) properties, and its reversion are important. Since it is poorly understood whether different CSC-phenotypes exist along the EMT-axis and how these impact malignancy-associated properties, we aimed to characterize CSC-populations of epithelial and mesenchymal PDAC cells. Single-cell cloning revealed CSC (Holoclone) and non-CSC (Paraclone) clones from the PDAC cell lines Panc1 and Panc89. Panc1 Holoclone cells showed a mesenchymal phenotype dominated by high expression of the stemness marker Nestin, while Panc89 Holoclone cells exhibited a SOX2-dominated epithelial phenotype. Panc89 Holoclone cells showed enhanced cell growth and self-renewal capacity but slow cluster-like invasion. Contrarily, Panc1 Holoclone cells showed slower cell growth and self-renewal ability but were highly invasive. Moreover, cell variants differentially responded to chemotherapy. In vivo, Panc1 and Panc89 cell variants significantly differed regarding number and size of metastases as well as organ manifestation leading to different survival outcomes. Overall, these data support the existence of different CSC-phenotypes along the EMT-axis in PDAC manifesting in different metastatic propensities.

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.

Calcium-activated potassium channels (KCa) are the important participants in calcium signaling pathways due to their ability to be activated by increase of the intracellular free calcium concentration. KCa channels are involved in the regulation of various processes in the cells under normal, as well as pathophysiological conditions, including oncotransformation. Previously, with the use of patch-clamp method, we registered the KCa activity in the plasma membrane of human myeloid leukemia K562 cell line. Here, we performed the molecular and functional identification of KCa channels and have uncovered their role in proliferation, migration and invasion of K562 cells. Using a combined approach, we identified the functional activity of SK2, SK3 and IK channels in the plasma membrane of the cells. Selective SK and IK channel inhibitors, apamin and TRAM-34, reduced the proliferative, migratory and invasive capabilities of human myeloid leukemia cells. At the same time, the viability of K562 cells was not affected by KCa channel inhibitors. Our data imply that SK/IK channel inhibitors could be used to slow down the proliferation and spreading of leukemia cells that express functionally active KCa channels in the plasma membrane.

This paper contains a concise overview of the deployment of scattered solar power plants in Poland, mainly from the perspective of their communication networks, and how the recent development of the Polish 4G networks has a very positive impact for the performance of the whole monitoring system (production control and video-surveillance), with a special emphasis on video-analytics, due to its higher bandwidth demand. All the information will be shown from the point of view of the solar photovoltaics developer I+D Energías, and therefore it constitutes a real user’s experience.

In the current natural environment, due to the complexity of the background and the high similarity of the color between immature green tomato and plant, the occlusion of the key organs (flower and fruit) by the leaves and stems will lead to low recognition rate and poor generalization of the detection model. Therefore, an improved tomato organ detection method based on convolutional neural network has been proposed in this paper. Based on the original Faster R-CNN algorithm, Resnet-50 with residual blocks was used to replace the traditional vgg16 feature extraction network, and K-means clustering method was used to adjust more appropriate anchor size than manual setting to improve detection accuracy. A variety of data augmentation techniques were used to train the network. The test results showed that compared with the traditional Faster R-CNN model, the mean average precision (mAP) of the optimal model was improved from 85.2% to 90.7%, the memory requirement decreased from 546.9MB to 115.9 MB, and the average detection time was shortened to 0.073S/sheet. As the performance greatly improved, the training model can be transplanted to the embedded system, which lays a theoretical foundation for the development of precise targeting pesticide application system and automatic picking device.

Purpose: To investigate the effect of pigment dispersion on trabecular meshwork (TM) cells. Methods: Porcine TM cells from ab interno trabeculectomy specimens were exposed to pigment dispersion, then analyzed for changes in morphology, immunostaining, and ultrastructure. Their abilities to phagocytose, migrate, and contract were quantified. An expression microarray, using 23,937 probes, and a pathway analysis were performed. Results: TM cells readily phagocytosed pigment granules. Pigment induced stress fiber formation (pigment (P): 60.1 ± 0.3%, n = 10, control (C): 38.4 ± 2.5%, n = 11, P < 0.001) and contraction at 24 hours onward (P < 0.01). Phagocytosis declined (P: 68.7 ± 1.3%, C: 37.0 ± 1.1%, n = 3, P < 0.001) and migration was reduced after 6 hours (P: 28.0.1 ± 2.3, n = 12, C: 40.6 ± 3.3, n = 13, P < 0.01). Microarray analysis revealed that Rho, IGF-1, and TGFβ signaling cascades were central to these responses. Conclusions: TM cell exposure to pigment dispersion resulted in reduced phagocytosis and migration, as well as increased stress fiber formation and cell contraction. The Rho signaling pathway played a central and early role, suggesting that its inhibitors could be used as a specific intervention in treatment of pigmentary glaucoma.

The origin of the man at the Earth is directly associated with the determination of directions of the flow distribution of the ancient man migration to adjacent territories. In such studies traditionally mainly landscape and climatological changes are considered. We suggest that along with the above factors, regional tectonic-geodynamic factors played a dominant role in the character of migration. The considered African-Levantine-Caucasian region is one of the most complex regions of the world, where collisional and spreading processes of geodynamics converge. First is determined an essential influence of the Akchagylian hydrospheric maximum (about 200 m above the mean sea level) limiting the ancient men migration from Africa to Eurasia. We propose that the Levantine Corridor emerged after the end of the Akchagylian transgression and landscape forming in the Eastern Mediterranean. This corridor location was formed by the movements between the Dead Sea Transform and the boundary of the carbonate platform of the Mesozoic Terrane Belt. Further landscape evolution was largely determined by the geodynamic behavior of the deep mantle rotating structure occurring below the central part of the region under study. All the mentioned events around and in the Levantine Corridor have been studied in detail on the basis of the combined geodynamic, paleogeographic, and paleomagnetic analyzes performed in northern Israel (Carmel uplift and Galilee plateau). Careful studies of the Evron quarry geological section indicate that it is a unique one for the dating of the marine and continental archaeological sequences and sheds light on the movement of the ancient man along the Levantine Corridor.

Natural products have a significant role in the development of new drugs, being relevant the pentacyclic triterpenes extracted from Olea europaea. Anticancer effect of uvaol, a natural triterpene, has been scarcely studied. The aim of this study was to understand the anticancer mechanism of uvaol in HepG2 cell line. Cytotoxicity results showed a selectivity effect of uvaol with higher influence in HepG2 than WRL68 cells used as control. Uvaol presented anti-migratory capacity in HepG2, supported by the morphological changes and higher HSP-60 expression. This compound also induced arrest in G0/G1 phase and an increase in apoptosis rate. These results are supported by decreased Bcl-2 expression and down-regulation of AKT/PI3K signaling pathway. A reduction in reactive oxygen species levels in HepG2 cells was observed. Altogether, results showed anti-proliferative and pro-apoptotic effect of uvaol on hepatocellular carcinoma, constituting an interesting challenge in the development of new treatments against this type of cancer.

At the end of 2023 the Whole Mouse Brain Atlas was announced, revealing that there are about 5,300 molecularly defined neuronal types in the mouse brain. We ask whether brain models exist that contemplate how this is possible. The conventional columnar model, implicitly used by the authors of the Atlas, is incapable of doing so with only 20 brain columns (5 brain vesicles with 4 columns each). We argue that definition of some 1,250 distinct progenitor microzones, each producing over time minimally 4-5 neuronal types, may be sufficient. This is nearly achieved presently by the prosomeric model amplified by secondary dorsoventral and anteroposterior microzonation of progenitor areas, plus clonal variation of cell types produced on average by each of them.

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.

Protein O-GlcNAcylation has been associated with neurodegenerative diseases such as Alzheimer´s disease (AD). O-GlcNAcylation of Amyloid Precursor Protein (APP) regulates both the trafficking and the processing of the APP through the amyloidogenic pathway, resulting in the release and aggregation of the Aβ1-42 peptide. Microglia clear Aβ aggregates and dead cells to maintain brain homeostasis. Here, using LC-MS/MS we reveal that the Aβ1-42 peptide modifies the microglia O-GlcNAcome. We have identified 55 proteins, focusing our research on Galectin-1 protein, since it is a very versatile protein from a functional point of view. Combining biochemical with genetic approaches we demonstrate that Aβ1-42 peptide specifically targets Galectin-1S8 O-GlcNAcylation via OGT. In addition, this Gal-1-O-GlcNAcylated form, in turn, controls human microglia migration. Given the importance of microglia migration in the progression of AD, this study reports the relationship between Aβ1-42 peptide and Serine 8- O-GlcNAcylation of Galectin to drive microglial migration

The Epithelial- Mesenchymal Transition (EMT) is a biological phenomenon associated with explicit phenotypic and molecular changes in cellular traits. Unlike the earlier-held popular belief of it being a binary process, EMT is now thought of as a landscape including diverse hybrid E/M phenotypes manifested by varying degrees of the transition. These hybrid cells can co-express both epithelial and mesenchymal markers and/or functional traits, and can possess the property of collective cell migration, enhanced tumor-initiating ability, and immune/targeted therapy-evasive features, all of which are often associated with worse patient outcomes. These characteristics of the hybrid E/M cells have led to a surge in studies that map their biophysical and biochemical hallmarks that can be helpful in exploiting their therapeutic vulnerabilities. This review discusses recent advances made in investigating hybrid E/M phenotype(s) from diverse biophysical and biochemical aspects by integrating live cell-imaging, cellular morphology quantification and mathematical modeling, and highlights a set of questions that remain unanswered about the dynamics of hybrid E/M states.

Historical legacy of Eastern European and Balkans’ health systems was mutually interdependent and shaped by local socioeconomic circumstances. Three distinctive systems of risk sharing and health financing to develop since the late XIX century were the Bismarck, Beveridge, and Semashko systems. Modern day healthcare systems in these countries are challenged by population ageing, accelerated innovation in medical technology, growing purchasing power and rising demand for healthcare services. Supply side changes contribute to demand side efficiency bottlenecks in financing, driving the costs of the already expensive medical care up. All of the nations have a large share of citizens experiencing difficulty with affordability and access to medical care, particularly in rural and remote areas. Network of Health technology assessment agencies have mushroomed over the past three decades. Principles of health economics theory and cost-effective resource allocation are slowly gaining ground in governing authorities’ mindset and decision-making process. For many years to come, pharmaceuticals and medical services will remain dependent on out-of-pocket spending. Currently accelerating and spreading 4.0 Industrial Revolution, together with the Belt and Road Initiative, are likely to substantially impact the further economic development of this vast region. Post-Pandemic ‘Green’ Recovery strategies adopted by many of the Eastern European governments shall also make this transition towards sustainable development more difficult and challenging given the large dependency of all these economies upon traditional carbon fuels.

The neocortex is an exquisitely organized structure achieved through complex cellular processes from the generation of neural cells to their integration into cortical circuits after complex migration processes. During this long journey, neural cells need to stablish and release adhesive interactions through cell surface receptors known as cell adhesion molecules (CAMs). Several types of CAMs have been described regulating different aspects of neurodevelopment. Whereas some of them mediate interactions with the extracellular matrix, others allow contacts with additional cells. In this review, we will focus on the role of two important families of cell-cell adhesion molecules (C-CAMs), classical cadherins and nectins, as well as in their effectors, in the control of fundamental processes related with corticogenesis, with especial attention in the cooperative actions among the two families of C-CAMs.

Climate change-induced events amplify existing social, political, economic, infrastructural and environmental concerns in many Global South cities, and perhaps no city is more vulnerable than Bangladesh’s capital of Dhaka. Climate-induced rural-urban migration is a profound concern, and Dhaka’s political leaders have embraced technology-based innovation as a solution pathway. This article explores the societal impact of Dhaka’s innovation environment strategies for climate change adaptation and mitigation. Employing a case study qualitative methodology, our three findings expand knowledge about innovation-urban climate mitigation as understood by Dhaka-based entrepreneurs: First, the most effective innovations were not the most technologically advanced, but those with the highest degree of participant ownership. Second, gaps between recipient, corporate and governmental understandings of effective mitigation and adaptation harmed projects, and were driven by different definitions of risk and competing understandings of vulnerability. Third, even the most technical climate adaptation measures were inherently political in their application. We discuss how to better position urban climate innovation infrastructures in Bangladesh and beyond, including developing a better recognition of innovation lifecycles for urban climate adaptation and widening our definitions of ‘innovation’ to better incorporate more effective and inclusive climate adaptation solutions.

The development of a highly specific drug delivery system (DDS) for anti-cancer therapeutics is an area of intense research focus. Chemical engineering of a “smart” DDS to specifically target tumor cells has gained interest, designed for safer, more efficient, and effective use of chemotherapeutics for the treatment of cancer. However, the selective targeting and choosing the critical cancer surface biomarker are essential for targeted treatments to work. The folic acid receptor alpha (FRalpha) has gained popularity as a potential target in triple-negative breast cancer (TNBC). We have previously reported on a functionalized folic acid (FA)-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) that has the essential features for efficient “smart” DDS. This biocompatible DDS self-assembles in a pH-dependent manner, providing stimuli-responsive, active targeting, extended-release of hydrophobic chemotherapeutic agents, and can effectively penetrate the inner core of 3-dimensional cancer spheroid models. The empty FA-DABA-SMA decreased spheroid volume, revealing a previously unknown mechanism of action. Upon further investigation, a size- and shape-dependent interaction FA-DABA-SMA with FR reduced the expression of p53, the product of the highly mutated TP53 gene, and additional oncogenic c-Myc and STAT3 proteins. Here, we investigated how this copolymer influences FR behavior and disrupting the receptor’s functions. Results indicate that FA-DABA-SMA increases FR expression levels in breast MDA MB-231 cancer cells and disrupting FR signaling by the reduction in HES1 and NOTCH1 protein expression levels. Also, FA-DABA-SMA induces apoptosis and further causes a change in the morphology of the MDA MB-231 cells, as well as significantly reduces their ability to migrate in a Scratch wound assay. Collectively, these findings provide a novel insight into the functionalized FA-DABA-SMA copolymer. The 350 kDa and 20 kDa copolymers actively target FRα to initialize internationalization. However, only the large size and sheet-shaped 350 kDa copolymers disrupt FRα signaling. The significance of these novel findings reveals the intracellular activity of the copolymer that is critically dependent on the size and structural shape. This report offers novel therapeutic insight into a dual mechanism of FA-DABA-SMA copolymer for its therapeutic potential for the treatment of cancer.

Background/Objectives: Asthma is a chronic inflammatory disorder of the airways affecting over 10% of the global population. It is characterized by airway inflammation, mucus hypersecretion, and bronchial hyperresponsiveness, driven predominantly by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s) in a subset of patients. However, a significant portion of asthmatic individuals present with "type 2-low" asthma, often refractory to standard inhaled corticosteroid (ICS) therapy. Therefore, developing innovative therapeutic strategies has become essential. Recent studies have highlighted cannabidiol (CBD) as a promising anti-inflammatory agent capable of modulating immune responses. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in asthma; Methods: We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils and asthma mouse model; Results: Our findings indicate that CBD-X extract inhibits Th2 differentiation and reduces the secretion of IL-5 and IL-13, which are crucial cytokines in asthma. Additionally, CBD-X significantly reduces pro-inflammatory cytokines IL-8 and IL-6 in neutrophils and impairs their migration, a critical step in airway inflammation. In a murine asthma model, CBD-X administration led to marked downregulation of IgE and pro-asthmatic cytokines, along with reduced leukocyte, eosinophil, and neutrophil infiltration in lung tissues; Conclusions: These results suggest that CBD-X extract could offer a novel, complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune cell behavior.

This is a study of Political Economy on religion and migration management in the United States of America (USA). This paper offers a review of migrants-citizens relations in the USA, with attention to the pendulum effect, moving from integration policies (open doors and melting pot agenda) to official persecution (raids and deportations), with a high social opportunity cost. There has been a split between the State and civil society, causing civil disobedience and sanctuary network across the country. Also, it is paid attention to the American post-modern paradox, as a result of culture wars and identity politics that imply a violation of American constitutional principles (i.e. religious liberty, freedom of movement, to pursuit the happiness). Special attention is paid to the development of the Sanctuary Movement, as an ongoing example of the sociocultural upheaval bringing grassroots society into confrontation with powerful elites by promoting resistance and offering help to the needy, even if this results in sanctions. This movement was revitalized after the values crisis of 2008, but it has also been polarized between those who follow the traditional approach to socio-religious action in the form of peaceful civil disobedience, and those who follow the ideological anti-system and communitarian approach, which causes greater tension for the immigrants themselves

Many cellular functions important for tumor initiation and progression are mediated by members of the integrin family, a diverse family of cell adhesion receptors. With recent studies emphasising on the role of the tumor microenvironment (TME) in tumor initiation and progression, it is not surprising that a lot of attention is being given to integrins. Several integrins are under trial with many demonstrating appealing activity in patients with different cancers. A deeper knowledge of the functions of integrins within the tumor microenvironment is still required, and might lead to better inhibitors being discovered. Integrin expression is commonly dysregulated in many tumors with integrins playing key roles in signaling as well as promotion of tumor cell invasion and migration. This review report new data on the differential expression of integrins within solid tumors using two publicly available resources: The Cancer Genomic Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA). In this analysis, I investigated the expression of integrin alpha 2 (ITGα2), ITGα3, ITGβ4 and ITGβ6 in tumor tissues versus adjacent normal tissues. This analysis showed that integrins were differentially expressed in cervical squamous cell carcinoma (CESC), head and neck squamous cell carcinoma (HNSC), esophageal carcinoma (ESCA) and lung adenocarcinoma (LUAD). This analysis showed that ITGα2 and ITGβ6 expression are upregulated in CESC and ESCA, ITGα3 is upregulated in HNSC and ESCA whilst ITGβ4 is highly expressed in CESC, HNSC, ESCA and LUAD tumor tissues compared to adjacent normal tissues. Integrins also play a major role in adhesion of circulating tumor cells to new sites and the resulting formation of secondary tumors. Furthermore, integrins have demonstrated the ability to promoting stem cell-like properties in tumor cells as well as drug resistance. Anti-integrin therapies rely heavily on the doses or concentrations used as these determine whether the drugs act as antagonists or as integrin agonists. This review offers the latest synthesis in terms of current knowledge of integrins functions within the tumor microenvironment and potential targets for different cancers.

The fluid seepage in local-saturated zone of subgrade promotes the migration of fine particles in the filler, resulting in the change of pore structure and morphology of the filler and the deformation of solid skeleton, which affects the fluid seepage characteristics. Repeatedly, the muddy interlayer, mud pumping and other diseases are finally formed. Based on the theory of two-phase seepage, the theory of porous media seepage, and the principle of effective stress in porous media, a two-phase fluid-solid coupling mathematical model in local-saturated zone of subgrade considering the effect of fine particles migration is established. The mathematical model is numerically calculated with the software COMSOL Multiphysics○R, the two-phase seepage characteristics and the deformation characteristics of the solid skeleton in local-saturated zone of the subgrade are studied. The research results show that due to the continuous erosion and migration of fine particles in local-saturated zone of the subgrade, the volume fraction of fine particles first increases then decreases and finally becomes stable with the increase of time. And the volume fraction of fine particles for the upper part of the subgrade is larger than that for the lower part of the subgrade. The porosity, the velocity of fluid, the velocity of fine particles, and the permeability show a trend of increasing first and then stabilizing with time; the pore water pressure has no significant changes with time. The vertical displacement increase first and then decrease slightly with the increase of time, and finally tend to be stable. For a filler with a larger initial volume fraction of fine particles, the maximum value of the volume fraction of fine particles caused by fluid seepage is larger, and the time required to reach the maximum value is shorter. It can be concluded that in actual engineering, the volume fraction of fine particles in the subgrade filler should be minimized on the premise that the filler gradation meets the requirements of the specification.

Context: The impact of forced migration on mental health is far reaching and compounded by post- migration contexts in which social determinants of health, such as resettlement, employment and gender, play a key role. Research on refugee men has shown that employment and life transitions are key determinants of mental health. However, a gap in knowledge exists on refugee men’s perspectives on the factors that impact their mental health. Methodology: This study used community-based participatory action research and the arts-based method of Photovoice to understand Syrian refugee men’s (n = 11) experiences of forced migration, resettlement, and employment in a Canadian context, as well as the impacts of these experiences on their mental health. Analysis and Results: Drawing on the critical theoretical perspective of intersectionality, we analyzed photographs taken by research participants, which showed that language and literacy barriers, time and stage of life, isolation and loneliness, belonging and identity and gender-based stress intersected to shape their mental health. Conclusion: Meaningful employment was central to the men’s identities; however, they engaged in low wage, precarious work due to both discriminatory policies that favored Canadian experience and credentialing assessment processes that devalued their experience and knowledge. Adopting gender-responsive and caring policies and practices could shift dominant discourses on masculinity and support the mental health of refugee men in resettlement contexts.

This study aimed to evaluate the proliferation and migration of fibroblast cells derived from chronic wounds and investigate the impact of low-level laser therapy (LLLT) on their growth and migration. A total of 60 dermal samples were obtained from three sites of chronic pressure ulcers and diabetic ulcers in 20 patients. Following collection in the operating room, the dermal samples were isolated using the procedure described by Freshney RI. Fibroblasts from the wound base (Site 1) exhibited a slow proliferation rate and a decrease in proliferative capacity. Fibroblasts from wound margins (Site 2) and adjacent healing skin (Site 3) could be successfully isolated and maintained for multiple generations without any morphological changes. Fibroblasts from chronic wounds at Sites 2 and 3 showed slower proliferation rates and reduced migration capabilities compared to normal dermal fibroblasts (control samples). The fibroblast cells were exposed to LLLT at different energy levels (2.5, 3, and 3.5 J/cm2). The laser-treated groups demonstrated a significantly higher increase in cell count compared to the control sample, with the highest increase observed at an energy level of 3 J/cm2. These findings suggest that LLLT at an energy level of 3 J/cm2 could effectively enhance fibroblast migration, indicating its potential as a therapeutic intervention for chronic wounds.

For its enthusiasts, the blockchain is an archivist's dream come true: an immutable historical record that is publicly accessible and immune from censorship. Proposals like Juried Protocol Galleries could enable bots to compute the provenance of digital artworks and their appearance in exhibitions and publications. Distributed file systems like IPFS claim to store creative works in a redundant, networked fashion outside the control of any single cloud provider. Projects designed to work with blockchains like Filecoin and Arweave propose a dedicated cryptocurrency as financial incentive to support the cost of governing and sustaining this "permaweb." As dreamy as this picture sounds, many of these promises depend on technologies that have yet to be sufficiently developed or adopted. Rather than forecast the future, we can separate the hype from the reality in the present day by examining a real-life example, namely the 2021 auction of Andy Warhol's digital art with NFTs. This essay will focus less on blockchain's general promise as a preservation medium and more on the particular case of the digital Warhols, which both in form and spirit would seem a perfect application of NFTs to preserve historically important works of digital art. Which promises of the crypto-dream of permanent access to digital heritage ring true for this case study, and which are overblown?

Climate change-induced Sea level rise, shoreline changes, and coastal erosion are projected to drive massive population displacement and mobility in Africa. This study was conducted to examine the pattern of shoreline changes, coastal erosion, land use/Land cover dynamics their projections, and its implications on internal migration in Senegal, Kenya and Tanzania representing West and East Africa. The digitized shoreline was mapped into both erosion, accretion and trend analysis which further explains the vulnerability and physical processes that could trigger human displacement within the context of environmental/climate migration. Analysis of landuse and land cover dynamics was obtained from Landsat 5 TM of 1986, Landsat 7 ET of 2006, Landsat 8 OLI/TIRS of 2016 and Landsat 9 OLI/TIRS 2022 and computed using ArcGIS 10.7 for Land-use change and percentage change in square kilometers was conducted to examine landuse/landcover dynamics and their contributions to the risk of coastal erosion in the study regions. The outcome of the shoreline analysis reveals that 972.03sqkm of land has been lost to coastal erosion in Senegal from 1986-2022 with 2016-2022 described as the period with the highest in terms of land loss. In Kenya, -463.30sqkm of land has also been lost to coastal erosion and agents of wave processes with 1986-2006 recording the highest share of -87.74% loss of valuable land while In Tanzania, -1033.35sqkm of valuable land has been lost from 1986-2022 to coastal erosion with 2006-2016 alone recording -10.4634% of land loss. The result of the land use/land cover percentage change analysis indicates a massive loss of vegetation cover with a significant increase in settlement representing urbanization. The scenario modeling of the shoreline on 10,20 and 30ms indicates that 567 persons per sq, 25904.5 persons per sqm and 25904.5 persons per sq km for both 20 and 30ms will be displaced in Senegal while in Kenya 577.5 persons per sq km will be displaced at 10m followed by 1210.3 persons per sq km at 20m and 7737.3 sq km at 30m. In, Tanzania, 702001.9 persons per sq km are projected to be displaced at 10m shift in the shoreline. Structured Questionnaires were administered to elicit responses from coastal dwellers on their perception of coastal erosion and environmental migration as part of ground truthing and the result of the survey affirms that coastal erosion and its exposure are the major drivers of environmental migration in the study area.

The rising incidence of prostate cancer necessitates innovative treatment approaches, particularly as diseases like the COVID-19 pandemic can disrupt traditional cancer care. This study aimed to evaluate the impact of hypofractionated versus conventionally fractionated radiotherapy on prostate cancer cell lines in vitro. Prostate cancer cell lines (PC-3 and DU-145) were exposed to varying doses of radiation alongside non-cancerous BPH-1 cells. We assessed radiation effects on cell proliferation, viability, colony formation, DNA repair, migration, invasion, and cytotoxicity. Results demonstrated that the prostate cell lines exhibited varying responses, with hypofractionation favourably impacting aggressive PC-3 cells while preserving non-cancerous cells. In contrast, conventional fractionation led to increased invasion and cytotoxicity in both prostate cancer cell lines. These findings advocate for personalised radiation therapy approaches that enhance treatment efficacy by considering the distinct behaviours of differing prostate cancer subtypes.

Background: The scaffold protein tyrosine kinase substrate 4 (TKS4) undergoes tyrosine phos-phorylation by the epidermal growth factor receptor (EGFR) pathway via Src kinase. The TKS4 deficiency in humans is responsible for the manifestation of a genetic disorder known as Frank-Ter Haar syndrome (FTHS). Based on our earlier investigation, the absence of TKS4 triggers migration, invasion, and epithelial-mesenchymal transition (EMT)-like phenomena while concurrently suppressing cell proliferation in HCT116 colorectal carcinoma cells. This indicates that TKS4 may play a unique role in the progression of cancer. In this study, we demonstrated that the enhancer of zeste homolog 2 (EZH2) and the histone methyltransferase of polycomb repressive complex 2 (PRC2) are involved in the migration, invasion, and EMT-like changes in TKS4-deficient cells (KO). EZH2 is responsible for the maintenance of the trimethylated lysine 27 on histone H3 (H3K27me3). Methods: We performed the transcriptome sequencing, chromatin immunoprecipitation, protein and RNA quantitative studies, cell mobility, invasion, and proliferation studies combined with/without EZH2 activity inhibitor 3-deazanoplanocine (DZNep) Results: We detected an elevation of global H3K27me3 levels in the TKS4 KO cells, which could be reduced with treatment with DZNep, an EZH2 inhibitor. Inhibition of EZH2 activity reversed the phenotypic effects of the knockout of TKS4, reducing the migration speed and wound healing capacity of the cells as well as decreasing the invasion capacity, while the decrease in cell prolif-eration became stronger. In addition, inhibition of EZH2 activity also reversed most epithelial and mesenchymal markers. We investigated the wider impact of TKS4 deletion on the gene expression profile of colorectal cancer cells using transcriptome sequencing of wild-type and TKS4 knockout cells, particularly before and after treatment with DZNep. Additionally, we observed changes in the expression of several protein-coding genes and long non-coding RNAs that showed a recovery in expression levels following EZH2 inhibition. Conclusions: Our results indicate that the removal of TKS4 causes a notable disruption in the gene expression pattern, leading to the disruption of several signal transduction pathways. Inhibiting the activity of EZH2 can restore most of these transcriptomics and phenotypic effects.

Ecklonia cava (E.cava) can alleviate vascular dysfunction in diseases associated with poor circulation. E. cava contains various polyphenols with different functions, but few studies have compared the effects of these polyphenols. Here, we comparatively investigated four major compounds present in an ethanoic extract of E. cava. These four major compounds were isolated and their effects were examined on monocyte-associated vascular inflammation and dysfunctions. Pyrogallol-phloroglucinol-6,6-bieckol (PPB) significantly inhibited monocyte migration in vitro by reducing levels of inflammatory macrophage differentiation and of its related molecular factors. In addition, PPB protected against monocyte-associated endothelial cell death by increasing the phosphorylations of PI3K-AKT and AMPK, decreasing caspase levels, and reducing monocyte-associated vascular smooth muscle cell proliferation and migration by decreasing the phosphorylations of ERK and AKT. The results of this study show that four compounds were effective for reduction of monocyte-associated vascular inflammation and dysfunctions, but PPB might be more useful for the treatment of vascular dysfunction in diseases associated with poor circulation.

Much evidence now indicates a direct crosstalk between thyroid hormones (THs) and the immune system. We previously showed that THs behave as anti-inflammatory agents in human leukemic THP-1 monocytes, but a potential neuroprotective effect of THs in microglia have been under-investigated. Microglia, the primary innate immune cells of the brain, play a pivotal role in the regulation of neuroinflammation and nongenomic integrin αvβ3-mediated action of THs appear to be involved. Integrin αvβ3 was highly expressed in activated BV-2 cells, while it was decreased by THs. In addition, THs facilitated wound healing in BV-2 murine microglia cells activated by lipopolysaccharide (LPS), through integrin αvβ3 and reactive oxygen species (ROS), with tetrac (a metabolite of TH) potentiated the inhibition of migration. Nitric oxide (NO) played a role with different mechanisms in the presence of either T3 or T4. Our data showed the capability of TH and analogues to modulate the M1-to-M2 microglial transition and suggest a new spectrum of actions in the central nervous system (CNS).

The endocannabinoid signalling system (ECS) plays a critical role from the very beginning of embryogenesis. Accordingly, the ECS is engaged early-on in nervous system development, starting from neurulation, supported by the identification of ECS components - both receptors and enzymes controlling endocannabinoid metabolism – at these early stages. In particular, regarding the brain, the ECS is involved in the tightly regulated sequence of events that comprise brain development, from neurogenesis to neuronal migration, morphological guidance for neuronal connectivity, and synaptic circuitry refinement. The importance of this broad role of the ECS across various brain development processes is further underscored by the growing understanding of the consequences of cannabis exposure at different developmental stages. Despite the considerable knowledge we have on the role of the ECS in brain development, significant gaps in our understanding remain, particularly regarding the long-term impact and underlying mechanisms of cannabis exposure at different developmental stages. This review provides an overview of the current state of knowledge on the role of the ECS throughout brain development, from embryogenesis to adulthood, and discusses the impact of cannabis exposure, especially during adolescence—a critical period of circuitry maturation and refinement coinciding with an increased risk of cannabis use.