Low Migration Rates Research Articles

A Systematic Review and Meta-Analysis of Factors Associated with Esophageal Stent Migration and a Comparison of Anti-Migration Techniques.

Esophageal stents are efficacious in managing many different pathologies. However, they are limited by their common complication of migration. We present the largest comprehensive review of the risk factors associated with stent migration and interventions leveraged to prevent it. A systematic review was conducted following PRISMA guidelines. Inclusion criteria were primary data sources (no systematic reviews), ≥18 years of age, esophageal stent placement, and reported indication for intervention, site of placement, and migration rate. 162 papers met this criterion. Proportions experiencing migration were pooled using a random effects model with a DerSimonian-Laird estimator to account for potential heterogeneity and forest plots were used to visualize the treatment effects across studies. There were 14,092 patients included in the analysis. The mean migration rate across all studies and stent types was 17.2% and the mean reintervention rate was 83.2%. Cancerous indications, benign strictures, history of esophageal surgery, stent diameter <20mm, plastic stents, and fully covered stents were associated with significantly higher migration rates. There was a trend towards stents using anti-migration technology having lower migration rates (effect size (ES)=0.15, 95% confidence interval (CI) 0.10-0.20) compared to those that did not (ES=0.33, 95% CI 0.18-0.48), however this difference was not significant. There were no statistically significant differences between stent fixation strategies (clips, sutures, wire hooks, Shim's technique). There are several risk factors associated with stent migration; however no current solutions confer significantly reduced stent migration. Further optimization of these devices or creation of new technology to prevent migration is indicated.

Effects of domesticated-to-wild gene flow on the genetic structure and diversity of wild papaya (Carica papaya L.) in its Mesoamerican diversity area.

Due to the increase in demand for food production worldwide, the cultivation of improved varieties is used as a strategy in order to maximize production. The improved Maradol papaya variety was introduced to the Yucatan Peninsula (YP), Mexico, the Mesoamerican diversity area of papaya, in the 1990s. The domesticated and wild papaya belong to the same species (Carica papaya L.), which promotes gene flow from crops to their wild relatives, threatening the genetic diversity of wild papaya populations in the region. In this study, we used a population genomic approach to evaluate the impact of domesticated-to-wild gene flow on the genetic structure and diversity of wild papaya in the YP. We used 2054 SNP markers for 227 wild individuals from 15 collection sites and 127 domesticated individuals from 13 Maradol papaya plantations. We found, (a) the presence of individuals that may be the result of a hybridization process between wild and domesticated papaya; (b) a higher genetic diversity in the wild group (HE = 0.18) in comparison to the domesticated group (HE = 0.09); and (c) low migration rates from domesticated to wild plants (m = 0.005). The domesticated-to-wild gene flow in C. papaya can have a negative effect on the genetic diversity and adaptive potential of wild populations from this region. The conservation of crop wild relatives should be a priority since they are part of various ecological processes and are considered natural reservoirs of genetic diversity for crops.

Efficacy and safety of a novel multisegmented fully covered self-expanding metal stent for malignant esophageal obstruction: a prospective pilot study with historical control.

Self-expanding metal stents (SEMSs) are effective for symptom palliation in patients with esophageal obstruction. However, their placement can lead to adverse events such as stent migration and restenosis. A novel fully covered SEMS (FCSEMS) with antimigration properties has been developed to address these issues. This study aimed to evaluate the feasibility and safety of this novel stent in treating malignant esophageal obstruction. This prospective pilot study enrolled patients with malignant esophageal obstruction treated with the novel stent at a tertiary referral center. Primary outcomes included technical and clinical efficacy, whereas secondary outcomes were adverse events. Treatment outcomes were compared between the novel stent and historical control groups. 137 patients were analyzed, comprising 32 in the novel stent group and 105 in the historical control group. In the novel stent group, technical success was achieved in 100% of patients and clinical success in 96.9%. No stent placement-related events, including bleeding or perforation, were observed. Though no significant differences in adverse events were found, the novel stent group had a lower migration rate than the historical control group (9.4% vs. 14.3%, p = 0.565). Median stent patency was similar between the groups (70.5 vs. 43.0days, p = 0.185). The novel multisegmented FCSEMS demonstrated high technical and clinical efficacy with a low migration rate, presenting a promising treatment option for malignant esophageal obstruction. Further studies with larger samples are needed to confirm these findings.

Deficiencies of Inducible Costimulator (ICOS) During Chronic Infection with Toxoplasma gondii Upregulate the CD28-Dependent Cytotoxicity of CD8+ T Cells and Their Effector Function Against Tissue Cysts of the Parasite.

We recently identified that the cerebral mRNA expression of inducible costimulator (ICOS) and its ligand, ICOSL, both significantly increase during the elimination of Toxoplasma gondii cysts from the brains of infected mice by the perforin-mediated cytotoxic activity of CD8+ T cells. In the present study, we examined the role of ICOS in activating the effector activity of CD8+ T cells in response to the presence of cysts in infected mice. Following the adoptive transfer of splenic CD8+ T cells from chronically infected ICOS-deficient (ICOS-/-) and wild-type (WT) mice to infected SCID mice, fewer CD8+ T cells were detected in the brains of the recipients of ICOS-/- CD8+ T cells than the recipients of WT CD8+ T cells. Interestingly, even with the lower migration rate of the ICOS-/- CD8+ T cells, those T cells eliminated T. gondii cysts more efficiently than WT CD8+ T cells did in the brains of the recipient mice. Consistently, the ICOS-/- CD8+ T cells secreted greater amounts of granzyme B in response to T. gondii antigens in vitro than WT CD8+ T cells did. We identified that CD8+ T cells of infected ICOS-/- mice express significantly greater levels of CD28 on their surface than CD8+ T cells of infected WT mice, and the relative expression of CD28 mRNA to CD8β mRNA levels in the brains of the recipients of those CD8+ T cells were strongly correlated with their relative expression levels of mRNA for T-bet transcription factors and perforin. Furthermore, blocking CD28 signaling using a combination of anti-CD80 and anti-CD86 antibodies eliminated the increased cytotoxic activity of the ICOS-/- CD8+ T cells in vitro. The present study uncovered notable compensatory interactions between ICOS and CD28, which protected the cytotoxic effector activity of CD8+ T cells against microbial infection in a murine model of chronic infection with T. gondii.

Hill-Robertson interference may bias the inference of fitness effects of new mutations in highly selfing species.

The accurate estimation of the distribution of fitness effects (DFE) of new mutations is critical for population genetic inference but remains a challenging task. While various methods have been developed for DFE inference using the site frequency spectrum of putatively neutral and selected sites, their applicability in species with diverse life history traits and complex demographic scenarios is not well understood. Selfing is common among eukaryotic species and can lead to decreased effective recombination rates, increasing the effects of selection at linked sites, including interference between selected alleles. We employ forward simulations to investigate the limitations of current DFE estimation approaches in the presence of selfing and other model violations, such as linkage, departures from semidominance, population structure, and uneven sampling. We find that distortions of the site frequency spectrum due to Hill-Robertson interference in highly selfing populations lead to mis-inference of the deleterious DFE of new mutations. Specifically, when inferring the distribution of selection coefficients, there is an overestimation of nearly neutral and strongly deleterious mutations and an underestimation of mildly deleterious mutations when interference between selected alleles is pervasive. In addition, the presence of cryptic population structure with low rates of migration and uneven sampling across subpopulations leads to the false inference of a deleterious DFE skewed towards effectively neutral/mildly deleterious mutations. Finally, the proportion of adaptive substitutions estimated at high rates of selfing is substantially overestimated. Our observations apply broadly to species and genomic regions with little/no recombination and where interference might be pervasive.

DDR1 promotes metastasis of cervical cancer and downstream phosphorylation signal via binding GRB2

Cervical cancer is a leading cause of cancer-related death among women and its recurrence and metastasis poses challenges to treatment. Discoidin domain receptor 1 (DDR1) was associated with cellular migration and invasion in several types of cancers. However, its function in cervical cancer is still unclear. In this study, we found that DDR1 was significantly more expressed in cervical cancer samples than in normal tissues. SRY-Box transcription factor 2 (SOX2), a known oncogene in cervical cancer, showed a positive correlation with DDR1 and regulated DDR1 transcription, contributing to the elevated expression of DDR1 in cervical cancer. Regarding the function of DDR1 in cervical cancer, the overexpression of DDR1 caused an increase in the migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells. In contrast, cervical cancer cells with reduced DDR1 expression exhibited a lower migration rate, fewer invasive cells, and decreased levels of EMT markers. In vivo, mice injected with cervical cancer cells with overexpressed DDR1 showed more pulmonary metastasis and nodule number. Opposite results were found in mice injected with DDR1 silenced cervical cancer cells. Since DDR1 can cause phosphorylation of downstream targets, a phosphorylation omics was employed to reveal the downstream targets of DDR1, including eukaryotic translation initiation factor 4E binding protein 1 and EPH receptor A2. Furthermore, DDR1 bound directly with Src homology 2 domain of growth factor receptor bound protein 2 (GRB2) which mediated the function of DDR1 in the malignant behaviors of cervical cancer and the phosphorylation of downstream targets. In conclusion, DDR1 binds directly to GRB2 and then affects downstream phosphorylation signals, ultimately exacerbating the metastasis of cervical cancer cells. This work sheds light on the mechanism by which DDR1 functions in cervical cancer cells, providing therapeutic strategy for the treatment of cervical cancer.

Unilateral-access vs. bilateral-access in transfemoral transcatheter aortic valve replacement: A slim fit approach

BackgroundVascular complications remain prevalent on transfemoral transcatheter aortic valve replacement (TF-TAVR) with a significant proportion related to the secondary arterial access. We hypothesized that placing the second sheath ipsilateral and distal to the delivery sheath could reduce vascular complications with similar safety and efficacy. ObjectivesComparing vascular complications and clinical outcomes when placing the secondary arterial sheath in the ipsilateral (unilateral-access) versus in the contralateral (bilateral-access) femoral artery during TF-TAVR. MethodsPatients who underwent TF-TAVR using unilateral-access as first-choice approach were retrospectively compared with a contemporaneous bilateral-access group. The primary endpoint was the incidence of vascular complications related to femoral access according to the VARC-3 criteria. A propensity-score analysis was performed accounting for the differences in clinical, vascular, and procedural characteristics. ResultsA total of 217 patients were included, of whom 150 (69.1 %) underwent TF-TAVR through bilateral- and 67 (30.9 %) through unilateral-access. Vascular complications occurred in 16.0 % of the bilateral-access group and 10.4 % of the unilateral-access group (p = 0.280). The unilateral-access group achieved high procedural success with normalization of peak aortic velocity and low rates of paravalvular leaks, valve migration and pacemaker requirement. After propensity-score matching, the overall complications rate was superior in the bilateral-access group (54.4 % vs 35.1 %, p = 0.038) due to a trend of higher vascular complications (26.3 % vs 12.3 %, p = 0.058) and a significant higher occurrence of bleeding complications (17.5 % vs 1.8 %, p = 0.008). ConclusionsUnilateral-access TF-TAVR is feasible, safe, and potentially enhances procedural efficiency and patient satisfaction while maintaining the capacity for bailout interventions in managing vascular complications.

Protective Effect of Resveratrol Against Non-Small Cell Lung Cancer: In-Vitro and In-Silico Studies

Resveratrol, a non-flavone polyphenol molecule, has been shown to be both chemotherapeutic and chemopreventive in the treatment of several forms of cancer, including lung cancer. 80% of cancers of the lungs are non-small cell lung cancers. The study was carried out to see the effects of Resveratrol in non-small cell lung cancer cells (A549) and to observe its binding as an inhibitor to Akt protein using in-vitro and in-silico studies, respectively. As per the results of Cell viability assay, which used Doxorubicin and Dexamethasone as standard drugs, Resveratrol (p = 0.01, p = 0.0051) could significantly stop lung cancer cells from growing, with IC50 values of 37.32 ± 0.8 μM. It was discovered that Resveratrol was about six times more effective than Dexamethasone, suggesting that it has a significantly higher anti-proliferative potential than this standard drug. During the Wound-closure assay, the rate of migration in the Resveratrol treatment group showed a lower migration rate at a higher concentration of 500 μM together with a change in the shape of the cell, demonstrating the concentration-dependent behavior of A549 cell growth. In the current study, it was demonstrated using Cell viability assay and Wound closure assay that Resveratrol exhibits anti-proliferative activity on A549 lung cancer cells and inhibits cancer cell proliferation in a concentration and time-dependent manner. It was also observed that Resveratrol binds to Akt protein and it inhibits the activity of Akt by interacting with the ATP-binding region of Akt protein. However, the molecular mechanism behind resveratrol’s anti-cancer benefits remains unknown. Finally, the current study may lay the groundwork for future research into the tumor suppressor resveratrol.

Why Are Children of Immigrants Less Geographically Mobile? Examining the Role of Economic Disadvantage and Family Networks

Previous work has found that adult children of international migrants in Western Europe have lower internal migration rates than individuals of native origin. This gap is important for differences in well-being, educational opportunities, and labor market outcomes. So far, however, little is known about the reasons for the greater geographical stability of migrant children. Theories suggest that structural differences such as economic resources as well as preferences for living near family may explain their lower internal migration rates. The current study tests these explanations by examining unique longitudinal register data from the Netherlands in which we follow the internal migration trajectories of people aged 18–50 in an observation window of 16 years between 2006 and 2022. We compare individuals of native origin with children of immigrants from Turkey and Morocco, two of the largest migrant populations in the country. Event history models confirmed that once socio-demographic characteristics were controlled for, children of migrants were less likely to migrate internally than individuals of native origin. Mediation analysis showed that economic resources did not explain the negative association; instead, the lower migration rates observed among children of migrants were mediated by geographical proximity to kin. Because migrant family networks are more geographically concentrated, children of migrants are more often discouraged from moving away. These findings highlight the pivotal role of family networks in explaining migrant-native differences in migration decision-making.

Hill-Robertson interference may bias the inference of fitness effects of new mutations in highly selfing species.

The accurate estimation of the distribution of fitness effects (DFE) of new mutations is critical for population genetic inference but remains a challenging task. While various methods have been developed for DFE inference using the site frequency spectrum of putatively neutral and selected sites, their applicability in species with diverse life history traits and complex demographic scenarios is not well understood. Selfing is common among eukaryotic species and can lead to decreased effective recombination rates, increasing the effects of selection at linked sites, including interference between selected alleles. We employ forward simulations to investigate the limitations of current DFE estimation approaches in the presence of selfing and other model violations, such as linkage, departures from semidominance, population structure, and uneven sampling. We find that distortions of the site frequency spectrum due to Hill-Robertson interference in highly selfing populations lead to mis-inference of the deleterious DFE of new mutations. Specifically, when inferring the distribution of selection coefficients, there is an overestimation of nearly neutral and strongly deleterious mutations and an underestimation of mildly deleterious mutations when interference between selected alleles is pervasive. In addition, the presence of cryptic population structure with low rates of migration and uneven sampling across subpopulations leads to the false inference of a deleterious DFE skewed towards effectively neutral/mildly deleterious mutations. Finally, the proportion of adaptive substitutions estimated at high rates of selfing is substantially overestimated. Our observations apply broadly to species and genomic regions with little/no recombination and where interference might be pervasive.

Variation in spatial population structure in the Anopheles gambiae species complex.

Anopheles gambiae, Anopheles coluzzii, and Anopheles arabiensis are three of the most widespread vectors of malaria parasites, with geographical ranges stretching across wide swaths of Africa. Understanding the population structure of these closely related species, including the extent to which populations are connected by gene flow, is essential for understanding how vector control implemented in one location might indirectly affect vector populations in other locations. Here, we assessed the population structure of each species based on a combined data set of publicly available and newly processed whole-genome sequences. The data set included single nucleotide polymorphisms from whole genomes of 2,410 individual mosquitoes sampled from 128 locations across 19 African countries. We found that A. gambiae sampled from several countries in West and Central Africa showed low genetic differentiation from each other according to principal components analysis (PCA) and ADMIXTURE modeling. Using Estimated Effective Migration Surfaces (EEMS), we showed that this low genetic differentiation indicates high effective migration rates for A. gambiae across this region. Outside of this region, we found eight groups of sampling locations from Central, East, and Southern Africa for which A. gambiae showed higher genetic differentiation, and lower effective migration rates, between each other and the West/Central Africa group. These results indicate that the barriers to and corridors for migration between populations of A. gambiae differ across the geographical range of this malaria vector species. Using the same methods, we found higher genetic differentiation and lower migration rates between populations of A. coluzzii in West and Central Africa than for A. gambiae in the same region. In contrast, we found lower genetic differentiation and higher migration rates between populations of A. arabiensis in Tanzania, compared to A. gambiae in the same region. These differences between A. gambiae, A. coluzzii, and A. arabiensis indicate that migration barriers and corridors may vary, even between very closely related species. Overall, our results demonstrate that migration rates vary both within and between species of Anopheles mosquitoes, presumably based on species-specific responses to the ecological or environmental conditions that may impede or facilitate migration, and the geographical patterns of these conditions across the landscape. Together with previous findings, this study provides robust evidence that migration rates between populations of malaria vectors depend on the ecological context, which should be considered when planning surveillance of vector populations, monitoring for insecticide resistance, and evaluating interventions.

Genomic analysis of conservation status, population structure, and admixture in local Czech and Slovak dairy goat breeds

While dairy goat production, characterized by traditional production on small farms, is an important source of income in the Czech Republic and Slovakia, locally adapted breeds have not been fully consolidated over the last 100 years due to large fluctuations in population size and inconsistent breeding programs that allowed for different crossbreeding strategies. Our main objective in this study was therefore to assess the conservation status of 4 Czech (Alpine Goat, White Shorthair, Brown Shorthair and Czech Landrace) and one Slovak (Slovak White Shorthair) local goat breeds, to analyze their population structure and admixture, and to estimate their relatedness to several neighboring breeds. Our analyses included 142 goats belonging to 5 local breeds genotyped with the Illumina 50K BeadChip and 618 previously genotyped animals representing 15 goat breeds from Austria and Switzerland (all analyses based on 46,862 autosomal SNPs and 760 animals). In general, the conservation status of the Czech and Slovak local goat breeds was satisfactory, with the exception of the Brown Shorthair goat, as the analyzed parameters (heterozygosity, haplotype richness, ROH-based inbreeding and effective population size) were mostly above the median of 20 breeds. However, for all 5 Czech and Slovakian breeds, an examination of historical effective population size indicated a substantial decline about 8 to 22 generations ago. In addition, our study revealed that the Czech and Slovakian breeds are not fully consolidated; for instance, White Shorthair and Brown Shorthair were not clearly distinguishable. Considerable admixture, especially in Czech Landrace (effective number of parental clusters equal to 4.2), and low but numerous migration rates from other Austrian and Swiss breeds were found. These results provide valuable insights for future breeding programs and genetic diversity management of local Czech and Slovak goat breeds.

Can magnetic nanoparticles enhance adoptive cell therapy via driving migration of lymphocytes into tumors?

Therapy of malignant tumors still represents a huge problem for healthcare, since these diseases lead to a high rate of disability and premature death of the population. The main problems of adoptive cell therapy for malignant tumors are a low rate of migration of effector lymphocytes into tumors, as well as their low activity in tumors due to suppressive tumor microenvironment. In addition, it should be noted that systemic intravenous administration of a large number of activated lymphocytes may be accompanied by a pronounced cytokine release syndrome, which leads to significant negative side effects, including high temperature, blood clotting disorders, aggression of immune cells against their own tissues, even neurotoxicity. Functional nanomaterials, such as magnetic nanoparticles with various surface modifications (PEG, PEI, DMSA, citrate, etc.) are highly promising agents for targeted delivery of different anti-tumor substances. Magnet-driven enrichment of effector anti-tumor lymphocytes in tumors would highly increase the effectiveness and enhance safety of adoptive lymphocyte therapy. However, different research groups obtained opposing data about the feasibility and efficiency of such approach. Thus, this review is focused on experimental details of the contradicting studies and aims to elucidate the possible reasons of these controversies and the best practices to efficiently target lymphocytes into tumors.

An Intersectional Analysis of Precarity and Exploitation: Women and LGBTQIA+ Workers in Substate Neoliberal Systems

The intersection of gender and ethnicity or race lies at the root of structural discrimination and racist practices for accessing the labor market and in the workplace. This discrimination is particularly evident for women and LGBTQIA+ individuals who either belong to ethnic minorities or are migrants. However, numerous other social drivers (e.g., age, class, origins) and external factors (e.g., prejudices, gender‐based violence) further hinder their participation in the work domain and their attainment of fair labor conditions. This article explores how gender, ethnicity, and race intersect and operate with other conditions and factors to perpetuate the precarity and exploitation of women and LGBTQIA+ individuals who find themselves at the nexus of varied intersectional axes. The discussion centers around two neoliberal substate units in the Global North (South Tyrol, in Italy, and Catalonia, Spain) that register low unemployment rates and high rates of migration and that are home to historical, linguistic, and ethnic minorities. This empirical article provides for an informed debate on the lived experience of precarity and exploitation of women and LGBTQIA+ workers, and an analysis of how neoliberal substate units’ labor and gender policies could be reformed.

Effects of Norflurazon and UV Radiation on Symbiotic and Free-Living Hydra

In this study, we aimed to document the freshwater symbiotic interactions along with the impact of the abiotic environment and anthropogenic effects on the functionality of freshwater organisms. Symbiotic green hydra (Z) and free-living brown hydra (S), either separately or both species together, were treated with the herbicide norflurazon in concentrations of 2 × 10−6 mol/L (N6) and 2 × 10−7 mol/L (N7) for 72 h. Also, hydras were treated with both norflurazon and UV radiation at a wavelength of 254 nm for 2 min or were irradiated only. The next part of the experiment was performed in the same way but with added suspensions of isolated endosymbiotic alga, free-living alga, or both algae together. Mortality, migration, tentacle and tissue damage, changes in the thickness of the mesoglea of hydras, and clustering of algae were monitored. Green hydra generally showed lower rates of migration, and mortality was observed only in green hydra exposed to UV radiation. Tentacle damage was more pronounced in green hydra and included a specific fork-like structure. The use of cryofixation and TEM enabled us to partly elucidate the effect of clustering of algae. In summary, our study provides new insights into the influence of different environmental stressors and their combination on symbiotic and free-living freshwater hydras and algae and a better understanding of interactions in freshwater ecosystems.

Kinetic migration of PBS and PBSA biopolymers prepared by cast film extrusion and biaxial stretching: A combined experimental and modeling approach

AbstractThe kinetic migration of poly(butylene succinate) (PBS) and poly(butylene succinate‐co‐adipate) (PBSA) biopolymers, prepared by cast film extrusion (thin film) and biaxial stretching (biaxially oriented [BO] film) techniques, were investigated based on experimental and mathematical modeling. MATLAB coding was used to fit the migration data to a diffusion model. BO films significantly reduced the migration rate compared with thin films, with reductions of 29% and 41% for BO‐PBS and BO‐PBSA, respectively, due to the increased degree of molecular crystallinity. Higher ethanol content increased the quantity of substance diffusing from plastic film. PBS and PBSA are more suitable for packaging hydrophilic foods than alcoholic beverages. PBS exhibited a lower migration rate than PBSA due to its more rigid polymer matrix. Remarkably, BO‐films exhibited 31% and 41% lower diffusion coefficients (D) compared with thin films, but significantly higher partition coefficients (KP,F) by 44% and 267% for BO‐PBS and BO‐PBSA, respectively. This suggests a stronger affinity of migrant for BO film matrix. However, at 70°C, PBSA films may be hydrolyzed with a high ethanol, resulting in an inadequate diffusion model. The diffusion–reaction concept should be implemented for a better fit. These findings provide valuable insights for selecting appropriate packaging materials and predicting migration under diverse conditions, ultimately promoting consumer safety.

Anti-tumor therapy of glycyrrhetinic acid targeted liposome co-delivery of doxorubicin and berberine for hepatocellular carcinoma.

During the development of hepatocellular carcinoma (HCC), hepatic stellate cells undergo activation and transform into cancer-associated fibroblasts (CAFs) due to the influence of tumor cells. The interaction between CAFs and tumor cells can compromise the effectiveness of chemotherapy drugs and promote tumor proliferation, invasion, and metastasis. This study explores the potential of glycyrrhetinic acid (GA)-modified liposomes (lip-GA) as a strategy for co-delivery of berberine (Ber) and doxorubicin (Dox) to treat HCC. The characterizations of liposomes, including particle size, zeta potential, polydispersity index, stability and in vitro drug release, were investigated. The study evaluated the anti-proliferation and anti-migration effects of Dox&Ber@lip-GA on the Huh-7 + LX-2 cell model were through MTT and wound-healing assays. Additionally, the in vivo drug distribution and anti-tumor efficacy were investigated using the H22 + NIH-3T3-bearing mouse model. The results indicated that Dox&Ber@lip-GA exhibited a nanoscale particle size, accumulated specifically in the tumor region, and was efficiently taken up by tumor cells. Compared to other groups, Dox&Ber@lip-GA demonstrated higher cytotoxicity and lower migration rates. Additionally, it significantly reduced the deposition of extracellular matrix (ECM) and inhibited tumor angiogenesis, thereby suppressing tumor growth. In conclusion, Dox&Ber@lip-GA exhibited superior anti-tumor effects both in vitro and in vivo, highlighting its potential as an effective therapeutic strategy for combating HCC.

Atomic-scale smoothing of semiconducting oxides via plasma-enabled atomic-scale reconstruction

β-Ga2O3, known as a next-generation wide-bandgap transparent semiconducting oxide (TSO), has considerable application potential in ultra-high-power and high-temperature devices. However, fabricating a smooth β-Ga2O3 substrate is challenging owing to its strong mechanical strength and chemical stability. In this study, an atomic-scale smoothing method named plasma-enabled atomic-scale reconstruction (PEAR) is proposed. We find that three reconstruction modes, namely, 2D-island, step-flow, and step-bunching, can be identified with the increase in the input power; only the step-flow mode can result in the formation of an atomically smooth β-Ga2O3 surface (Sa = 0.098 nm). Various surface and subsurface characterizations indicate that the smooth β-Ga2O3 surface shows excellent surface integrity, high crystalline quality, and remarkable photoelectric properties. The atomic-scale density functional theory-based calculations show that the diffusion energy barrier of a Ga atom is only 0.46 eV, thereby supporting the atomic mass migration induced by high-energy plasma irradiation in the experiment. Nanoscale molecular dynamics simulations reveal that O atoms firstly migrate to crystallization sites, followed by Ga atoms with a lower migration rate; reconstruction mainly proceeds along the <010> direction and then expands along the <100> and <001> directions. The millimeter-scale numerical simulations based on the finite element method demonstrate that the coupling of the thermal and flow fields of plasma is the impetus for PEAR of β-Ga2O3. Furthermore, the smoothing generality of PEAR is demonstrated by extending it to other common TSOs (α-Al2O3, ZnO, and MgO). As a typical plasma-based atomic-scale smoothing method, PEAR is expected to enrich the theoretical and technological knowledge on atomic-scale manufacturing.

Lateral meander migration of a medium-sized lowland river: Case study on the Rába river, Hungary

Engineering works greatly influence the lateral channel migration (LCM) of meandering rivers. We aimed to characterise the spatiotemporal characteristics of LCM during the last 174 years of the almost freely meandering Upper Rába (Hungary) and to identify units with distinctive LCM histories. The studied Rába's reach has been regulated just at some points. Due to the free meandering, its length varied between 119 and 133 km. The most intensive length increase (+291 m/y) took place between 2005 and 2008, and by the end of the process , the sinuosity had reached its historical maximum (SI 2018 = 1.93). The mean LCM was 3.3 m/y (1844-2018). The periods with intensive channel migration (max: 24-27 m/y) were followed by periods with low migration rates. Based on local channel morphology and LCM rates, 14 units were identified. The highest LCM rate was measured in the freely migrating units (R5: 5.8 m/y; R3: 4.4 m/y and R6 4.0 m/y).

Pine needles and soil as bioindicators of forest ecosystems in the anthropogenically disturbed areas of the Baikal region

Forest ecosystems of Baikal region were chosen a subject of comprehensive research conducted on the basis of the monitoring network created. Recommendations of the international manual ICP Forests, as well as the authors’ developments were used for the research. The study was focused on toxicological, physiological-biochemical, and biogeochemical indicators that adequately reflect the state and manifestation of the protective properties of the forest ecosystem main components (tree-stand and soil) under the influence of anthropogenic factors – air pollution, urbanization, and irrational forest management. The assessment of the vital state of tree-stands of Scots pine (indicator species) was carried out on the basis of representative indicators: pigments, the level of enzymatic and non-enzymatic components of antioxidant protection, the content and ratio of biogenic elements, changes in morphometric parameters. When studying soil in anthropogenically disturbed territories, an increase in soil density, a decrease in natural moisture, aeration, and humus content were found, alkalization of the upper horizons and accumulation of pollutants with a low migration rate in the upper horizons of the soil profile. Air pollution and high recreational load were shown to produce the greatest stressful impact on the forest ecosystems.