Towards 1D Transport in 3D Materials: SOC-Induced Charge-Transport Anisotropy in Sm3ZrBi5.

One-dimensional (1D) charge transport offers great insight into strongly correlated physics, such as Luttinger liquids, electronic instabilities, and superconductivity. Although 1D charge transport is observed in nanomaterials and quantum wires, examples in bulk crystalline solids remain elusive. In this work, we demonstrate that spin-orbit coupling (SOC) can act as a mechanism to induce quasi-1D charge transport in the Ln3MPn5 (Ln = lanthanide; M = transition metal; Pn = Pnictide) family. From three example compounds, La3ZrSb5, La3ZrBi5, and Sm3ZrBi5, density functional theory calculations with SOC included show a quasi-1D Fermi surface in the bismuthide compounds, but an anisotropic 3D Fermi surface in the antimonide structure. By performing anisotropic charge transport measurements on La3ZrSb5, La3ZrBi5, and Sm3ZrBi5, we demonstrate that SOC starkly affects their anisotropic resistivity ratios (ARR) at low temperatures, with an ARR of ∼4 in the antimonide compared to ∼9.5 and ∼22 (∼32 after magnetic ordering) in La3ZrBi5 and Sm3ZrBi5, respectively. This report demonstrates the utility of spin-orbit coupling to induce quasi-low-dimensional Fermi surfaces in anisotropic crystal structures, and provides a template for examining other systems. This article is protected by copyright. All rights reserved.

Modeling 5-FU-Induced Chemotherapy Selection of a Drug-Resistant Cancer Stem Cell Subpopulation.

(1) Background: Cancer stem cells (CSCs) are a subpopulation of cells in a tumor that can self-regenerate and produce different types of cells with the ability to initiate tumor growth and dissemination. Chemotherapy resistance, caused by numerous mechanisms by which tumor tissue manages to overcome the effects of drugs, remains the main problem in cancer treatment. The identification of markers on the cell surface specific to CSCs is important for understanding this phenomenon. (2) Methods: The expression of markers CD24, CD44, ALDH1, and ABCG2 was analyzed on the surface of CSCs in two cancer cell lines, MDA-MB-231 and HCT-116, after treatment with 5-fluorouracil (5-FU) using flow cytometry analysis. A machine learning model (ML)-genetic algorithm (GA) was used for the in silico simulation of drug resistance. (3) Results: As evaluated through the use of flow cytometry, the percentage of CD24-CD44+ MDA-MB-231 and CD44, ALDH1 and ABCG2 HCT-116 in a group treated with 5-FU was significantly increased compared to untreated cells. The CSC population was enriched after treatment with chemotherapy, suggesting that these cells have enhanced drug resistance mechanisms. (4) Conclusions: Each individual GA prediction model achieved high accuracy in estimating the expression rate of CSC markers on cancer cells treated with 5-FU. Artificial intelligence can be used as a powerful tool for predicting drug resistance.

Anticancer assessment and antibiofilm potential of Laetiporus sulphureus mushroom originated from Serbia.

Laetiporus sulphureus (Bull.) Murrill is a well-known edible mushroom consumed in nutrition as delicacy. It has been used in traditional medicine because of its beneficial effects on human wellness, such as antimicrobial, antioxidant, and anticancer potential. The present study determined the phenolic profile of Laetiporus sulphureus ethanolic extract (LSE) by high-performance liquid chromatographic method. Tolerance of two probiotic bacterial strains Lactiplantibacillus plantarum 229v, Bifidobacterium animalis subsp. lactis and probiotic yeast Saccharomyces boulardii on LSE was analyzed in terms of viability and biofilm formation. Effects of extract on colorectal (HCT-116) and cervical (HeLa) cancer cells viability was determined using MTT test in concentration range: 1-500 µg/mL after 24 and 72 h. Redox parameters (superoxide anion radicals, nitrites, and reduced glutathione) were evaluated using NBT, Griess, and GSH assays in the concentration range of 1-500 µg/mL after 24 and 72 h. Antimigratory activity was determined by wound healing method using selected concentrations of 10 and 50 µg/mL after 24 h. Untreated cells were considered as control. As control cell line, we used healthy fibroblasts (MRC-5). Our results demonstrated abundance of LSE in phenolics, with rosmarinic acid as the main component. LSE induced low tolerance of tested planktonic probiotic strains, with no affection on their ability to form biofilm. No significant cytotoxicity on tested cancer cells was observed, with prooxidative and antimigratory effects noticed. Extract exerted significant antimigratory activity on cancer cells without effect on planktonic and probiotic cultures in biofilm. These results indicate potential application of Laetiporus sulphureus ethanolic extract as natural protector of probiotics with prominent ability to suppress cancer cell motility.

Colossal magnetoresistance in the multiple wave vector charge density wave regime of an antiferromagnetic Dirac semimetal.

Colossal negative magnetoresistance is a well-known phenomenon, notably observed in hole-doped ferromagnetic manganites. It remains a major research topic due to its potential in technological applications. In contrast, topological semimetals show large but positive magnetoresistance, originated from the high-mobility charge carriers. Here, we show that in the highly electron-doped region, the Dirac semimetal CeSbTe demonstrates similar properties as the manganites. CeSb0.11Te1.90 hosts multiple charge density wave modulation vectors and has a complex magnetic phase diagram. We confirm that this compound is an antiferromagnetic Dirac semimetal. Despite having a metallic Fermi surface, the electronic transport properties are semiconductor-like and deviate from known theoretical models. An external magnetic field induces a semiconductor metal-like transition, which results in a colossal negative magnetoresistance. Moreover, signatures of the coupling between the charge density wave and a spin modulation are observed in resistivity. This spin modulation also produces a giant anomalous Hall response.

Porphene and porphite as porphyrin analogs of graphene and graphite.

Two-dimensional materials have unusual properties and promise applications in nanoelectronics, spintronics, photonics, (electro)catalysis, separations, and elsewhere. Most are inorganic and their properties are difficult to tune. Here we report the preparation of Zn porphene, a member of the previously only hypothetical organic metalloporphene family. Similar to graphene, these also are fully conjugated two-dimensional polymers, but are composed of fused metalloporphyrin rings. Zn porphene is synthesized on water surface by two-dimensional oxidative polymerization of a Langmuir layer of Zn porphyrin with K2IrCl6, reminiscent of known one-dimensional polymerization of pyrroles. It is transferable to other substrates and bridges µm-sized pits. Contrary to previous theoretical predictions of metallic conductivity, it is a p-type semiconductor due to a predicted Peierls distortion of its unit cell from square to rectangular, analogous to the appearance of bond-length alternation in antiaromatic molecules. The observed reversible insertion of various metal ions, possibly carrying a fifth or sixth ligand, promises tunability and even patterning of circuits on an atomic canvas without removing any π centers from conjugation.

Combined Biological and Numerical Modeling Approach for Better Understanding of the Cancer Viability and Apoptosis.

Nowadays, biomedicine is a multidisciplinary science that requires a very broad approach to the study and analysis of various phenomena essential for a better understanding of human health. This study deals with the use of numerical simulations to better understand the processes of cancer viability and apoptosis in treatment with commercial chemotherapeutics. Starting from many experiments examining cell viability in real-time, determining the type of cell death and genetic factors that control these processes, a lot of numerical results were obtained. These in vitro test results were used to create a numerical model that gives us a new angle of observation of the proposed problem. Model systems of colon and breast cancer cell lines (HCT-116 and MDA-MB-231), as well as a healthy lung fibroblast cell line (MRC-5), were treated with commercial chemotherapeutics in this study. The results indicate a decrease in viability and the appearance of predominantly late apoptosis in the treatment, a strong correlation between parameters. A mathematical model was created and employed for a better understanding of investigated processes. Such an approach is capable of accurately simulating the behavior of cancer cells and reliably predicting the growth of these cells.

Absence of TRIC-B from type XIV Osteogenesis Imperfecta osteoblasts alters cell adhesion and mitochondrial function - A multi-omics study.

Osteogenesis Imperfecta (OI) is a heritable collagen-related bone dysplasia characterized by bone fractures, growth deficiency and skeletal deformity. Type XIV OI is a recessive OI form caused by null mutations in TMEM38B, which encodes the ER membrane intracellular cation channel TRIC-B. Previously, we showed that absence of TMEM38B alters calcium flux in the ER of OI patient osteoblasts and fibroblasts, which further disrupts collagen synthesis and secretion. How the absence of TMEM38B affects osteoblast function is still poorly understood. Here we further investigated the role of TMEM38B in human osteoblast differentiation and mineralization. TMEM38B-null osteoblasts showed altered expression of osteoblast marker genes and decreased mineralization. RNA-Seq analysis revealed that cell-cell adhesion was one of the most downregulated pathways in TMEM38B-null osteoblasts, with further validation by real-time PCR and Western blot. Gap and tight junction proteins were also decreased by TRIC-B absence, both in patient osteoblasts and in calvarial osteoblasts of Tmem38b-null mice. Disrupted cell adhesion decreased mutant cell proliferation and cell cycle progression. An important novel finding was that TMEM38B-null osteoblasts had elongated mitochondria with altered fusion and fission markers, MFN2 and DRP1. In addition, TMEM38B-null osteoblasts exhibited a significant increase in superoxide production in mitochondria, further supporting mitochondrial dysfunction. Together these results emphasize the novel role of TMEM38B/TRIC-B in osteoblast differentiation, affecting cell-cell adhesion processes, gap and tight junction, proliferation, cell cycle, and mitochondrial function.

CaMKII inhibition due to TRIC-B loss-of-function dysregulates SMAD signaling in osteogenesis imperfecta.

Ca2+ is a second messenger that regulates a variety of cellular responses in bone, including osteoblast differentiation. Mutations in trimeric intracellular cation channel B (TRIC-B), an endoplasmic reticulum channel specific for K+, a counter ion for Ca2+flux, affect bone and cause a recessive form of osteogenesis imperfecta (OI) with a still puzzling mechanism. Using a conditional Tmem38b knock out mouse, we demonstrated that lack of TRIC-B in osteoblasts strongly impairs skeleton growth and structure, leading to bone fractures. At the cellular level, delayed osteoblast differentiation and decreased collagen synthesis were found consequent to the Ca2+ imbalance and associated with reduced collagen incorporation in the extracellular matrix and poor mineralization. The impaired SMAD signaling detected in mutant mice, and validated in OI patient osteoblasts, explained the osteoblast malfunction. The reduced SMAD phosphorylation and nuclear translocation were mainly caused by alteration in Ca2+ calmodulin kinase II (CaMKII)-mediated signaling and to a less extend by a lower TGF-ß reservoir. SMAD signaling, osteoblast differentiation and matrix mineralization were only partially rescued by TGF-ß treatment, strengthening the impact of CaMKII-SMAD axes on osteoblast function. Our data established the TRIC-B role in osteoblasts and deepened the contribution of the CaMKII-SMAD signaling in bone.

The Cross-Sectional Study of attitudes towards risk factors of viral infections transmitted by blood-borne pathogens.

OBJECTIVE: The objective of this paper was threefold: To assess risk factors of blood-borne pathogen exposure and viral infection for employees at their workplace, to spot the differences between groups of respondents without exposure and those exposed to blood-borne infections, and to identify main risk predictors. METHOD: The Cross-Sectional Study was conducted, surveying 203 employees, at the Institute for Emergency Medical Services in Serbia, which were eligible to enter the study and surveyed by Previously Developed Questionnaire. RESULTS: A total of 97.60% of respondents have perceived risk at their workplace, but there were low numbers of HIV, HbcAg, and Anti-HCV testing and poor percent of vaccination for hepatitis B. There were no statistically significant differences between spotted groups of respondents in their attitudes. Three variables were predictors: accidental usedneedle stick injuries (OR = 90.34; 95% CI, 8.79-928.03), contact with the blood of patientsthrough the skin (OR = 176.94; 95% CI, 24.95-1254.61), and the years of service (OR = 0.92; 95% CI, 0.86-1.00). CONCLUSION: The significance of this study is that it points to a double risk, because not only health workers are endangered, but also citizens who receive first aid.

The Cross-Sectional Study of attitudes towards risk factors of viral infections transmitted by blood-borne pathogens / Estudo transversal das atitudes em relação aos fatores de risco para infecções virais transmitidas pelo sangue / Estudio cruzado sobre las actitudes hacia los factores del riesgo de las infecciones virales que se transmiten por la sangre

ABSTRACT Objective: The objective of this paper was threefold: To assess risk factors of blood-borne pathogen exposure and viral infection for employees at their workplace, to spot the differences between groups of respondents without exposure and those exposed to blood-borne infections, and to identify main risk predictors. Method: The Cross-Sectional Study was conducted, surveying 203 employees, at the Institute for Emergency Medical Services in Serbia, which were eligible to enter the study and surveyed by Previously Developed Questionnaire. Results: A total of 97.60% of respondents have perceived risk at their workplace, but there were low numbers of HIV, HbcAg, and Anti-HCV testing and poor percent of vaccination for hepatitis B. There were no statistically significant differences between spotted groups of respondents in their attitudes. Three variables were predictors: accidental usedneedle stick injuries (OR = 90.34; 95% CI, 8.79-928.03), contact with the blood of patientsthrough the skin (OR = 176.94; 95% CI, 24.95-1254.61), and the years of service (OR = 0.92; 95% CI, 0.86-1.00). Conclusion: The significance of this study is that it points to a double risk, because not only health workers are endangered, but also citizens who receive first aid.

RESUMO Objetivo: O objetivo deste estudo foi triplo: avaliar os fatores de risco de exposição a patógenos transmitidos pelo sangue e infecções virais para funcionários no local de trabalho, perceber diferenças entre grupos de indivíduos que não foram expostos e aqueles que estavam expostos a infeções transmitidas pelo sangue e identificar os principais preditores de risco. Método: Foi realizado um estudo transversal, entrevistando 203 funcionários do Instituto de Assistência Médica de Emergência da Sérvia, que cumpriram as condições para fazer parte do estudo e foram entrevistados por meio de um questionário previamente elaborado. Resultados: Um total de 97,60% dos entrevistados percebeu risco em seu local de trabalho, mas houve um pequeno número de testes de HIV, HbcAg e Anti-HCV e um baixo percentual de vacinação contra hepatite B. Não houve diferenças estatisticamente significativas entre os grupos observados de entrevistados em termos de suas atitudes. Três variáveis foram preditores: lesões acidentais da punção com agulha (OR = 90,34; 95% Cl, 8,79-928,03), contato com o sangue dos pacientes através da pele (OR = 176,94; 95% Cl, 24,95-1254,61) e tempo de serviço (OR = 0,92; 95% Cl, 0,86-1,00). Conclusão: O significado deste estudo é que indica um duplo risco, tendo em vista que não apenas os profissionais de saúde estão em risco, mas também os cidadãos que recebem primeiros socorros.

RESUMEN Objetivo: El objetivo de este trabajo fue triple: estimar los factores del riesgo de la exposición de los patógenos transmitidos por la sangre y infecciones virales para los empleados en el puesto de trabajo, advertir las diferencias de los grupos de los examinados que no fueron expuestos y los que fueron expuestos a las infecciones que se transmiten por la sangre e identificar los mayores predictores del riesgo. Método: Fue hecho el estudio de la sección, con una encuesta de 203 empleados en la Institución para los primeros auxilios de Serbia, que cumplieron las condiciones para ser la parte del estudio y encuestado a través del cuestionario. Resultados: Total de 97,60% de los examinados mostró el riesgo en su puesto de trabajo, pero existía el pequeño número de testes a VIH, HbcAg y Anti - HCV y bajo porciento de vacunación contra Hepatitis B. No hubo diferencias estadísticas significantes entre grupos reconocidos de los cuestionados según sus opiniones. Tres variables fueron los predictores: las lesiones de pinchazo con la aguja accidentales (OR = 90,34; 95% CI, 8,79-928,03), contacto con la sangre dentro de la piel (OR = 176,94; 95% CI, 24,95-1254,61) y experiencia laboral (OR = 0,92; 95%CI, 0,86-1,00). Conclusión: El significado de este estudio es lo que muestra riesgo doble, teniendo en la cuenta que no son amenazados solo los trabajadores sanitarios, sino y los ciudadanos que reciben primeros auxilios.

Numerical modelling of WNT/ß-catenin signal pathway in characterization of EMT of colorectal carcinoma cell lines after treatment with Pt(IV) complexes.

BACKGROUND AND OBJECTIVE: Colorectal cancer (CRC) is at the top of the most common cancer types in the world, with significant mortality rates among both men and women. Deregulation of Wnt/ß-catenin pathway and cell-cell junctions' components, acquisition of invasive phenotype, epithelial-mesenchymal transition (EMT) and invasion are important for development and progression of colorectal cancer. Numerical simulation presents method for estimation of the Wnt pathway via its individual components in cells, thus providing information about EMT, migratory and invasive potential. By using this numerical model, the effectiveness of treatment in EMT suppression can be assessed. Furthermore, the model can be adapted to ``every'' cell type, application time or duration of treatment can be also modified. METHODS: We characterized colorectal cancer (CRC) cell lines (HCT-116, SW-480) from the aspect of EMT, via markers ß-catenin and E-cadherin using numerical modeling. To confirm the numerical model, cells were treated with sublethal concentrations of platinum(IV) complexes and their ligands. We confirmed ß-catenin regulated expression of mesenchymal markers: N-cadherin, Vimentin and MMP-9, and decreased E-cadherin expression. Treatment-induced changes were determined in the protein expression of tested markers and results showed cell-specific responses. Molecular docking was performed to investigate exact effects of treatments on E-cadherin and ß-catenin in cell-cell junctions and individually in tested cells. RESULTS: The application of the numerical model via ß-catenin and E-cadherin (experimentally measured), is largely valid for the categorization of EMT progression in cells. This numerical modeling better characterizes cells with single cell migration, higher expression of mesenchymal markers, and advanced mesenchymal phenotype like HCT-116 cell line. The model was validated for the treatments and results show HCT-116 cells as more sensitive to applied compounds, among which ligands were more potent in reducing migration and invasiveness. Anti-migratory/invasive effects were due to increased E-cadherin, cytoplasmic ß-catenin expression and suppressed mesenchymal markers. In silico methods showed higher affinity of tested chemicals towards free ß-catenin, which is the key for regulation of migratory/invasive potential. CONCLUSIONS: Our study shows that, no matter individual properties of cell lines and EMT degree, de novo formation of intercellular junctions stands in the basis of anti-migratory/invasive process.

Royal Jelly and trans-10-Hydroxy-2-Decenoic Acid Inhibit Migration and Invasion of Colorectal Carcinoma Cells.

Research background: Acquisition of migratory potential is pivotal for cancer cells, enabling invasion and metastasis of colorectal carcinoma. Royal jelly and its bioactive component trans-10-hydroxy-2-decenoic acid (10H2DA) showed remarkable antimetastatic potential, but the molecular mechanism underlying this activity is unclear. Experimental approach: Identification and quantification of 10H2DA in royal jelly originating from Serbia was done by HPLC method. Cytotoxicity of 10H2DA was measured by tetrazolium dye MTT test in concentration range 1-500 µg/mL after 24 and 72 h. Its effect on the collective and single-cell migration was measured by wound healing and transwell migration assays. Invasive potential of cancer cells was evaluated by a transwell method modified with collagen. Immunofluorescence was used for migratory and invasive protein expression, while the gene expression of these markers was evaluated by quantitative real time polymerase chain reaction (qRT-PCR). All assays were applied on human colorectal carcinoma HCT-116 and SW-480 cell lines and, except for MTT, evaluated after 24 h of treatment with two selected concentrations of royal jelly and 10H2DA. Results and conclusions: According to HPLC, the mass fraction of 10H2DA in royal jelly was 0.92% (m/m). Treatment with 10H2DA showed no cytotoxic effect; however, significant inhibitory potential of royal jelly and 10H2DA on the motility and invasiveness of colorectal cancer cells was observed. More pronounced effect was exerted by 10H2DA, which significantly suppressed collective cell migration and invasiveness of SW-480 cells, as well as single- and collective cell migration and invasive potential of HCT-116 cell line. Treatments increased epithelial markers E-cadherin and cytoplasmic ß-catenin in HCT-116 cells, thus stabilizing intercellular connections. In SW-480 cells, 10H2DA increased E-cadherin on protein and gene level, and suppressed epithelial-mesenchymal transition (EMT) markers. In both cell lines, treatments induced significant suppression of promigratory/proinvasive markers: N-cadherin, vimentin and Snail on protein and gene level, which explains decreased migratory and invasive potential of HCT-116 and SW-480 cells. Novelty and scientific contribution: Our study presents new findings and elucidation of royal jelly and 10H2DA molecular mechanism that underlies their antimigratory/antiinvasive activity on colorectal cancer cells. These findings are shown for the first time indicating that these natural products are a valuable source of anticancer potential and should be reconsidered for further antitumour therapy.

SMAD3 mutation in LDS3 causes bone fragility by impairing the TGF-ß pathway and enhancing osteoclastogenesis.

Loss-of-function mutations in SMAD3 cause Loeys-Dietz syndrome type 3 (LDS3), a rare autosomal-dominant connective tissue disorder characterized by vascular pathology and skeletal abnormalities. Dysregulation of TGF-ß/SMAD signaling is associated with abnormal skeletal features and bone fragility. To date, histomorphometric and ultrastructural characteristics of bone with SMAD3 mutations have not been reported in humans and the exact mechanism by which SMAD3 mutations cause the LDS3 phenotype is poorly understood. Here, we investigated bone histomorphometry and matrix mineralization in human bone with a SMAD3 mutation and explored the associated cellular defect in the TGF-ß/SMAD pathway in vitro. The index patient had recurrent fractures, mild facial dysmorphism, arachnodactyly, pectus excavatum, chest asymmetry and kyphoscoliosis. Bone histomorphometry revealed markedly reduced cortical thickness (-68 %), trabecular thickness (-32 %), bone formation rate (-50 %) and delayed mineralization. Quantitative backscattered electron imaging demonstrated undermineralized bone matrix with increased heterogeneity in mineralization. The patient's SMAD3 mutation (c.200 T > G; p.I67S), when expressed from plasmid vectors in HEK293 cells, showed reduced phosphorylation and transcription factor activity compared to normal control and SMAD3 (p.S264Y), a gain-of-function mutation, somatic mosaicism of which causes melorheostosis. Transfection study of the patients' SMAD3 (p.I67S) mutation displayed lower luciferase reporter activity than normal SMAD3 and reduced expression of TGF-ß signaling target genes. Patient fibroblasts also demonstrated impaired SMAD3 protein stability. Osteoclastogenic differentiation significantly increased and osteoclast-associated genes, including ACP5 (encoding TRAP), ATP6V0D2, and DCSTAMP, were up-regulated in CD14 (+) peripheral blood mononuclear cells (PBMCs) with the SMAD3 (p.I67S) mutation. Upregulation of osteoclastogenic genes was associated with decreased expression of TGF-ß signaling target genes. We conclude that bone with the SMAD3 (p.I67S) mutation features reduced bone formation, and our functional studies revealed decreased SMAD3 activation and protein stability as well as increased osteoclastogenesis. These findings enhance our understanding of the pathophysiology of LDS3 caused by SMAD3 mutations. Emerging therapies targeting in the TGF-ß/SMAD pathway also raise hope for treatment of LDS3.

Simple Chemical Rules for Predicting Band Structures of Kagome Materials.

Compounds featuring a kagome lattice are studied for a wide range of properties, from localized magnetism to massless and massive Dirac Fermions. These properties come from the symmetry of the kagome lattice, which gives rise to Dirac cones and flat bands. However, not all compounds with a kagome sublattice show properties related to it. We derive chemical rules predicting if the low-energy physics of a material is determined by the kagome sublattice and bands arising from it. After sorting out all known crystals with the kagome lattice into four groups, we use chemical heuristics and local symmetry to explain additional conditions that need to be met to have kagome bands near the Fermi level.

A Class of Magnetic Topological Material Candidates with Hypervalent Bi Chains.

The link between crystal and electronic structure is crucial for understanding structure-property relations in solid-state chemistry. In particular, it has been instrumental in understanding topological materials, where electrons behave differently than they would in conventional solids. Herein, we identify 1D Bi chains as a structural motif of interest for topological materials. We focus on Sm3ZrBi5, a new quasi-one-dimensional (1D) compound in the Ln3MPn5 (Ln = lanthanide; M = metal; Pn = pnictide) family that crystallizes in the P63/mcm space group. Density functional theory calculations indicate a complex, topologically nontrivial electronic structure that changes significantly in the presence of spin-orbit coupling. Magnetic measurements show a quasi-1D antiferromagnetic structure with two magnetic transitions at 11.7 and 10.7 K that are invariant to applied field up to 9 T, indicating magnetically frustrated spins. Heat capacity, electrical, and thermoelectric measurements support this claim and suggest complex scattering behavior in Sm3ZrBi5. This work highlights 1D chains as an unexplored structural motif for identifying topological materials, as well as the potential for rich physical phenomena in the Ln3MPn5 family.

Specific inflammatory osteoclast precursors induced during chronic inflammation give rise to highly active osteoclasts associated with inflammatory bone loss.

Elevated osteoclast (OC) activity is a major contributor to inflammatory bone loss (IBL) during chronic inflammatory diseases. However, the specific OC precursors (OCPs) responding to inflammatory cues and the underlying mechanisms leading to IBL are poorly understood. We identified two distinct OCP subsets: Ly6ChiCD11bhi inflammatory OCPs (iOCPs) induced during chronic inflammation, and homeostatic Ly6ChiCD11blo OCPs (hOCPs) which remained unchanged. Functional and proteomic characterization revealed that while iOCPs were rare and displayed low osteoclastogenic potential under normal conditions, they expanded during chronic inflammation and generated OCs with enhanced activity. In contrast, hOCPs were abundant and manifested high osteoclastogenic potential under normal conditions but generated OCs with low activity and were unresponsive to the inflammatory environment. Osteoclasts derived from iOCPs expressed higher levels of resorptive and metabolic proteins than those generated from hOCPs, highlighting that different osteoclast populations are formed by distinct precursors. We further identified the TNF-α and S100A8/A9 proteins as key regulators that control the iOCP response during chronic inflammation. Furthermore, we demonstrated that the response of iOCPs but not that of hOCPs was abrogated in tnf-α-/- mice, in correlation with attenuated IBL. Our findings suggest a central role for iOCPs in IBL induction. iOCPs can serve as potential biomarkers for IBL detection and possibly as new therapeutic targets to combat IBL in a wide range of inflammatory conditions.

Catalogue of flat-band stoichiometric materials.

Topological electronic flattened bands near or at the Fermi level are a promising route towards unconventional superconductivity and correlated insulating states. However, the related experiments are mostly limited to engineered materials, such as moiré systems1-3. Here we present a catalogue of the naturally occuring three-dimensional stoichiometric materials with flat bands around the Fermi level. We consider 55,206 materials from the Inorganic Crystal Structure Database catalogued using the Topological Quantum Chemistry website4,5, which provides their structural parameters, space group, band structure, density of states and topological characterization. We combine several direct signatures and properties of band flatness with a high-throughput analysis of all crystal structures. In particular, we identify materials hosting line-graph or bipartite sublattices-in either two or three dimensions-that probably lead to flat bands. From this trove of information, we create the Materials Flatband Database website, a powerful search engine for future theoretical and experimental studies. We use the database to extract a curated list of 2,379 high-quality flat-band materials, from which we identify 345 promising candidates that potentially host flat bands with charge centres that are not strongly localized on the atomic sites. We showcase five representative materials and provide a theoretical explanation for the origin of their flat bands close to the Fermi energy using the S-matrix method introduced in a parallel work6.

Platismatia glauca-Lichen species with suppressive properties on migration and invasiveness of two different colorectal carcinoma cell lines.

Platismatia glauca is a popular lichen traditionally used as a spice and possesses significant anti-cancer potential, whose anti-migratory/anti-invasive properties were mostly disregarded. Migration/invasion of cancer cells is processed in cancer metastasis and targeting their markers is an important strategy in anti-cancer treatment. We examined the anti-migratory/anti-invasive properties of P. glauca extract on two colorectal carcinoma cell lines (HCT-116 and SW-480) and elucidated possible mechanisms underlying these properties. Cell migration was evaluated by wound healing and RTCA methods. Immunofluorescent assay was used for the analysis of protein, while qRT-PCR for gene expression of migratory/invasive markers. ELISA assay was applied for the determination of MMP-9 concentration. P. glauca extract inhibited the motility of tested cells, by reducing pro-migratory/pro-invasive markers and potentially retaining intercellular connections. Treatment showed cell-selective effects, and HCT-116 cells were more responsive. Our study presents important scientific novelty, thus these lichen properties should be furtherly examined regarding the amelioration of anti-cancer treatment. PRACTICAL APPLICATIONS: Based on the evidence we provided in the present study, we have demonstrated that lichen species Platismatia glauca possess important biological activity, which has not been sufficiently investigated so far. It is of great importance to explore its anti-cancer potential, not only from a cytotoxic point of view but especially anti-migratory and anti-invasive. Herein, we showed that this species expresses significant suppressive effects on migration and invasiveness of colorectal carcinoma cells. This tested lichen has the potential to be used as a natural complementary anti-cancer treatment, with special reference on the dose applied and type of carcinoma. Our study represents a significant novelty in the field of scientific investigation of lichens and natural products, and further detailed studies are needed on in vitro and in vivo model systems.

Pseudevernia furfuracea inhibits migration and invasion of colorectal carcinoma cell lines.

ETHNOPHARMACOLOGICAL RELEVANCE: Pseudevernia furfuracea (L.) Zopf is common lichen species, traditionally used worldwide in treating various medical conditions, among which are intestinal issues and cancer. Most studies are focused mainly on cytotoxic potential of lichens, whilst their antimigratory and antiinvasive properties are often disregarded. Migration and invasion of cancer cells are pivotal processes in cancer metastasis, wherein cancer cells are able to migrate individually or in form of a coherent mass. One of successful strategies in anticancer treatments is targeting Wnt/ß-catenin signal pathway, that is aberrantly activated in colorectal carcinoma, as well as lowering level of migratory/invasive markers. AIM OF THE STUDY: Present study aimed to show antimigratory/invasive potential of Pseudevernia furfuracea methanol extract on HCT-116 and SW-480 colorectal carcinoma cell lines and to elucidate possible mechanism of its action. MATERIALS AND METHODS: Collective cell migration was assessed by Wound healing assay and single cell migration in real time by RTCA method. Analysis of anti- and promigratory protein expression was performed using immunofluorescent staining. Additionally, gene expression of antimigratory/promigratory and invasive (E-cadherin, ß-catenin, N-cadherin, Vimentin, Snail and MMP-9) markers were investigated by qRT-PCR method. Concentration of MMP-9 was determined colorimetrically by ELISA test. RESULTS: P. furfuracea extract was able to suppress both collective and single cancer cell migration, by inhibiting expression of promigratory/invasive markers and possibly re-establishing cell-cell adhesions. The present study indicates at P. furfuracea as effective antimigratory treatment, and HCT-116 cells were proved to be a more sensitive cell line to applied treatment. CONCLUSIONS: This lichen species is a promising candidate for application in treatment of cancer in order to prevent metastasis.