Migratory Properties Research Articles

Ex vivo expansion in a clinical grade medium, containing growth factors from human platelets, enhances migration capacity of adipose stem cells.

Adipose tissue mesenchymal stem/stromal cells (ASC) can be used as advanced therapy medicinal product in regenerative and cancer medicine. We previously demonstrated Supernatant Rich in Growth Factors (SRGF) can replace fetal bovine serum (FBS) to expand ASC by a clinical grade compliant protocol. The therapeutic potential of ASC is based also on their homing capacity toward inflammatory/cancer sites: oriented cell migration is a fundamental process in this scenario. We investigated the impact of SRGF on ASC migration properties. The motility/migration potential of ASC expanded in 5% SRGF was analyzed, in comparison to 10% FBS, by standard wound healing, bidimensional chemotaxis and transwell assays, and by millifluidic transwell tests. Mechanisms involved in the migration process were investigated by transient protein overexpression. In comparison to standard 10% FBS, supplementation of the cell culture medium with 5% SRGF, strongly increased migration properties of ASC along the chemotactic gradient and toward cancer cell derived soluble factors, both in static and millifluidic conditions. We showed that, independently from applied migratory stimulus, SRGF expanded ASC were characterized by far lower expression of α-smooth muscle actin (αSMA), a protein involved in the cell migration machinery. Overexpression of αSMA induced a significant and marked decrease in migration capacity of SRGF expanded ASC. In conclusion, 5% SRGF addition in the cell culture medium increases the migration potential of ASC, reasonably through appropriate downregulation of αSMA. Thus, SRGF could potentially improve the therapeutic impact of ASC, both as modulators of the immune microenviroment or as targeted drug delivery vehicles in oncology.

Targeted Anthocyanin Enrichment of Cranberry Juice by Electrodialysis with Filtration Membranes: Impact of Filtration Membrane Physicochemical Properties and Predictive Statistical Models.

To optimize cranberry juice enrichment, correlation between physicochemical properties of filtration membranes (FM) and anthocyanin migration was investigated during electrodialysis with filtration membranes (EDFM) using redundancy (RDA) and multivariate regression (MRGA) analyses. Six polyether sulfone (PES) and polyvinylidene fluoride (PVDF) membranes with molecular weight cut-offs between 150 and 500 kDa, commercially available at large scale, were characterized in terms of nine physicochemical characteristics and used for EDFM. The highest migration of total anthocyanin was obtained with PVDF 250 kDa, with a global migration rate of 3.5 ± 0.4 g/m2·h. RDA showed that two FM properties (mesopore porosity and hydrophilic porosity) were significantly negatively correlated to the anthocyanin's migration and explained 67.4% of their total variation in migration. Predictive MRGA models were also developed for each anthocyanin based on these significant FM properties. A combination of intermolecular interactions may lead to binding in a cooperative and synergistic mode and hinder the anthocyanin migration.

Tumor- and Fibroblast-Derived Cell-Free DNAs Differently Affect the Progression of B16 Melanoma In Vitro and In Vivo.

It is widely postulated that the majority of pathologically elevated extracellular or cell-free DNA (cfDNA) in cancer originates from tumor cells; however, evidence has emerged regarding the significant contributions of other cells from the tumor microenvironment. Here, the effect of cfDNA originating from murine B16 melanoma cells and L929 fibroblasts on B16 cells was investigated. It was found that cfDNAL929 increased the viability and migration properties of B16 cells in vitro and their invasiveness in vivo. In contrast, cfDNAB16 exhibited a negative effect on B16 cells, reducing their viability and migration in vitro, which in vivo led to decreased tumor size and metastasis number. It was shown that cell treatment with both cfDNAs resulted in an increase in the expression of genes encoding DNases and the oncogenes Braf, Kras, and Myc. cfDNAL929-treated cells were shown to experience oxidative stress. Gene expression changes in the case of cfDNAB16 treatment are well correlated with the observed decrease in proliferation and migration of B16 cells. The obtained data may indicate the possible involvement of fibroblast DNA in the tumor microenvironment in tumor progression and, potentially, in the formation of new tumor foci due to the transformation of normal cells.

Effects of starch gelatinisation and water migration on the hardness of parboiled rice

SummaryParboiled rice is well known for its high nutritional value, while its firm texture is still challenging to accept by consumers. In this study, the effects of starch gelatinisation and water migration on the increased hardness of parboiled rice were investigated. The hardness of parboiled rice was affected by starch gelatinisation, displaying an increasing trend with an increasing degree of starch gelatinisation (DSG). Examination of the water migration characteristics during soaking showed that the water uptake capacity of parboiled rice was significantly enhanced. Compared to white rice soaked at 90 °C, the water molecules in parboiled rice were restricted to the outer layer of starch. Significant correlations between rice hardness, DSG and moisture absorption‐related parameters were established, indicating that gelatinised starch limits the migration of water to the inside of the rice kernel, resulting in a firm rice grain. These results enhance the understanding of starch gelatinisation by parboiling and water migration properties during the cooking process of parboiled rice. This study provided new insights into the regulation of hardness by parboiled rice processing.

Concurrent inhibition of IR, ITGB1, and CD36 perturbated the interconnected network of energy metabolism and epithelial-to-mesenchymal transition in breast cancer cells.

Altered energy metabolism is an emerging hallmark of cancer and plays a pivotal in cell survival, proliferation, and biosynthesis. In a rapidly proliferating cancer, energy metabolism acts in synergism with epithelial-to-mesenchymal transition (EMT), enabling cancer stemness, dissemination, and metastasis. In this study, an interconnected functional network governing energy metabolism and EMT signaling pathways was targeted through the concurrent inhibition of IR, ITGB1, and CD36 activity. A novel multicomponent MD simulation approach was employed to portray the simultaneous inhibition of IR, ITGB1, and CD36 by a 2:1 combination of Pimozide and Ponatinib. Further, in-vitro studies revealed the synergistic anticancer efficacy of drugs against monolayer as well as tumor spheroids of breast cancer cell lines (MCF-7 and MDA-MB-231). In addition, the combination therapy exerted approximately 40% of the apoptotic population and more than 1.5- to 3-fold reduction in the expression of ITGB1, IR, p-IR, IRS-1, and p-AKT in MCF-7 and MDA-MB-231 cell lines. Moreover, the reduction in fatty acid uptake, lipid droplet accumulation, cancer stemness, and migration properties were also observed. Thus, targeting IR, ITGB1, and CD36 in the interconnected network with the combination of Pimozide and Ponatinib represents a promising therapeutic approach for breast cancer.

Characterization of intestinal mononuclear phagocyte subsets in young ruminants at homeostasis and during Cryptosporidium parvum infection.

Cryptosporidiosis is a poorly controlled zoonosis caused by an intestinal parasite, Cryptosporidium parvum, with a high prevalence in livestock (cattle, sheep, and goats). Young animals are particularly susceptible to this infection due to the immaturity of their intestinal immune system. In a neonatal mouse model, we previously demonstrated the importance of the innate immunity and particularly of type 1 conventional dendritic cells (cDC1) among mononuclear phagocytes (MPs) in controlling the acute phase of C. parvum infection. These immune populations are well described in mice and humans, but their fine characterization in the intestine of young ruminants remained to be further explored. Immune cells of the small intestinal Peyer's patches and of the distal jejunum were isolated from naive lambs and calves at different ages. This was followed by their fine characterization by flow cytometry and transcriptomic analyses (q-RT-PCR and single cell RNAseq (lamb cells)). Newborn animals were infected with C. parvum, clinical signs and parasite burden were quantified, and isolated MP cells were characterized by flow cytometry in comparison with age matched control animals. Here, we identified one population of macrophages and three subsets of cDC (cDC1, cDC2, and a minor cDC subset with migratory properties) in the intestine of lamb and calf by phenotypic and targeted gene expression analyses. Unsupervised single-cell transcriptomic analysis confirmed the identification of these four intestinal MP subpopulations in lamb, while highlighting a deeper diversity of cell subsets among monocytic and dendritic cells. We demonstrated a weak proportion of cDC1 in the intestine of highly susceptible newborn lambs together with an increase of these cells within the first days of life and in response to the infection. Considering cDC1 importance for efficient parasite control in the mouse model, one may speculate that the cDC1/cDC2 ratio plays also a key role for the efficient control of C. parvum in young ruminants. In this study, we established the first fine characterization of intestinal MP subsets in young lambs and calves providing new insights for comparative immunology of the intestinal MP system across species and for future investigations on host-Cryptosporidium interactions in target species.

Abstract PO5-24-09: Optimizing the Therapeutic Treatment of Breast Cancer Through a Dual Data-driven Theoretical Model

Abstract Despite rapid advancements in treatments and technology, breast cancer remains the second leading cause of cancer related morbidity in women in the US. As a heterogeneous disease, the unique genetic and phenotypic profile of each tumor complicates the prediction of treatment responses and optimized treatment strategies. One primary manifestation of phenotypic plasticity and concomitant intra-tumoral heterogeneity is the Epithelial-Mesenchymal Transition (EMT). The acquisition of migratory and invasive properties through EMT facilitates tumor metastasis and results in worse patient outcomes. As a result, the EMT and its reverse process (MET) often influence treatment response. However, the different mechanisms through which these therapeutic drugs affect the EMT-related phenotypic switching rates as well as each phenotype’s replication rates are unclear, and further investigation is required for better understanding their precise effect for directing optimal treatment strategies and improved patient outcomes. Here, we compile an atlas of publicly available metastatic and non-metastatic RNA sequencing data of breast cancer cell lines treated with therapeutic and chemotherapeutic drugs and propose a dual data-driven theoretical framework for understanding the effects of each drug on breast cancer treatment response. We infer the cell fractions, EMT phenotypic transition rates and phenotypic replication rates of each case through an extension of our previously developed hybrid data-driven and theoretical model, COMET. We infer single-cell RNA sequencing-derived EMT-related trajectories and apply a continuous time Markov chain model to infer inter-state transition rates. By analyzing the atlas of RNA sequencing data and integration with our framework, we gain novel insights into the context-specific mechanisms by which therapeutic drugs affect the phenotypic transition rates. This comprehensive understanding will contribute to optimizing breast cancer therapy and ultimately improving patient outcomes. Citation Format: A. Najafi. Optimizing the Therapeutic Treatment of Breast Cancer Through a Dual Data-driven Theoretical Model [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-24-09.

LINC01572 promotes the malignant progression of lung adenocarcinoma by modulating p53 mediated by miRNA-338-5p/TTK axis.

Lung cancer is one of the malignant tumors that threaten human health seriously. Long non-coding RNA (lncRNA) is an important factor affecting tumorigenesis and development. However, the mechanism of lncRNA in lung cancer progression remains to be further explored. In this study, the TCGA database was analyzed, and LINC01572 was found to be increased in lung adenocarcinoma (LUAD) tissues. Thereafter, with the help of databases including lncBase, TargetScan, and mirDIP, as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, LINC01572/miRNA-338-5p/TTK regulatory axis and downstream p53 signaling pathway were excavated. qRT-PCR was adopted to detect levels of LINC01572, miRNA-338-5p, and TTK in LUAD cells. The role that LINC01572 played in LUAD cells was validated by CCK-8 assay, flow cytometry, colony formation, Transwell, and scratch healing assays. The binding ability between LINC01572/TTK and miRNA-338-5p was then verified by dual-luciferase and RIP analysis. The results of this study demonstrated that LINC01572 was elevated in LUAD cells compared with normal cells. The overexpression of LINC01572 promoted the proliferative and migratory properties of LUAD cells but inhibited cell apoptosis. The inhibition of LINC01572 resulted in the opposite result. In addition, rescue experiments revealed that LINC01572, as a molecular sponge of miRNA-338-5p, targeted TTK to manipulate p53 for facilitating LUAD cell malignant progression. Apart from this, we constructed a mouse xenograft model and confirmed that the knockdown of LINC01572 hindered the growth of LUAD solid tumors in vivo. Our findings illuminated the molecular mechanism of LINC01572 influencing LUAD and provided new insights for targeted therapy of LUAD cells.

Abstract PO5-27-08: Cytotoxicity and motility inhibitory effect of FA-Hep-CuS nanoparticles on breast cancer cells

Abstract In spite of a decreased rate of cancer onset, by about 33%, since 1991, it is still as dreadful and a major cause of death globally. After heart disease, cancer continues to be the second most prevalent cause of death in the US. According to the American Cancer Society, there will be around 2 million new cases of cancer identified in Americans in 2023, along with approximately 610,000 cancer-related deaths. Breast cancer will continue to be the most common invasive cancer diagnosed in women. Each year about 2.3 million women are diagnosed with breast cancer. In consideration of the severity of breast cancer, herein we designed and synthesized a multimode photothermal agent, FA-Hep-CuS, for the advancement of photothermal therapy of cancer. CuS nanoparticles deposited on heparin-conjugated folic acid (FA-Hep-CuS) were prepared by gently heating unfractionated heparin in dimethyl formamide (DMF), then adding N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC), and finally adding the aminated folic acid in DMF and stirring for four days. Further, FA-Hep was dispersed in DI water, then citrated CuS nanoparticles dispersed in DI water were added, and the mixture was stirred for 8 hours to prepare FA-Hep-CuS. Moreover, the activation of the nanoparticles by non-ionizing radiation (NIR; l= 808 nm) was also evaluated for increased anti-cancer efficiency. In MDA-MB-231 (Triple-negative or TNBC or ER⁻/PR⁻/Her2⁻) breast cancer cell lines, the cytotoxic effects of FA, CuS, and FA-Hep-CuS, as well as their ability to impede motility, have been investigated. They have also been examined to determine how they affect the expression of mesenchymal indicators and clonogenicity. All these demonstrated significant dose-dependent in-vitro cytotoxicity against MDA-MB- 231 breast cancer cells. The cell viability assay showed that the FA-CuS was more effective than FA and CuS. Activation of the nanoparticles with NIR resulted in the significantly enhanced dose-dependent inhibitory potential of the nanoparticles against the migratory properties of the aggressive TNBC cells. In agreement, the clonogenicity of the TNBC cells was also inhibited dose-dependently. We are now focusing on its inhibitory potential on the EMT markers of the TNBC cells. We further aim to investigate the effects of FA-Hep-CuS in in-vivo models of breast cancers. Citation Format: David Arreola. Cytotoxicity and motility inhibitory effect of FA-Hep-CuS nanoparticles on breast cancer cells [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-08.

The role of CXCR4-CXCL12 in the development and migration of human natural killer cells

Abstract Natural killer (NK) cells play a critical role in controlling viral infection and malignancy and undergo differentiation from multipotent progenitors in secondary lymphoid tissue. Despite dependence on the microenvironment for differentiation, little is known about the cell-cell interactions that promote NK cell precursor trafficking and maturation in tissue. We have identified the chemokine receptor CXCR4 and its ligand CXCL12 as regulators of the cellular interactions between human NK cell precursors and stromal cells that support NK cell differentiation. Using in-vitro NK cell differentiation, we found that treatment of CD34+ precursors with CXCR4 antagonist AMD3100 leads to a lower efficiency of NK cell generation. Since previous work demonstrates the association of cell migration with NK cell development, we interrogated the effect of AMD3100 on NK cell migration. Using live cell imaging we found that AMD3100 treatment of NK cells or progenitor cells results in altered migratory properties and decreased arrest of cells on CXCL12+ stromal cells. Additional experiments using high resolution microscopy and flow cytometry suggest that integrins are interacting with CXCR4 in NK cells. Our data suggests that the CXCR4-CXCL12 interaction is critical for the migration and proper development of NK cells. Future studies will focus on the necessity for CXCR4-CXCL12 in specific key transitions in development and interrogate the cell biological mechanisms of this process.

Expression of ZKSCAN3 protein suppresses proliferation, migration, and invasion of pancreatic cancer through autophagy.

Elevated autophagy activity enhances the malignancy of pancreatic cancer (PaCa), and autophagy is recognized as a novel therapeutic target. Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) is a transcription factor that suppresses autophagy, but its association with PaCa is unknown. We analyzed the function of ZKSCAN3 in PaCa and investigated whether autophagy regulation through ZKSCAN3 could become a new therapeutic target for PaCa. Using reverse transcription-quantitative polymerase chain reaction and western blotting, we observed that ZKSCAN3 expression was upregulated in several PaCa cell lines compared with normal pancreatic ductal epithelial cells. Additionally, comparing ZKSCAN3 expression with the prognosis of PaCa patients using web databases, we found that higher ZKSCAN3 expression in PaCa was associated with extended overall survival. Knocking down ZKSCAN3 promoted the proliferation of PaCa cells. Moreover, following ZKSCAN3 knockdown, PaCa cells exhibited significantly enhanced migratory and invasive properties. Conversely, overexpression of ZKSCAN3 significantly suppressed the proliferation, migration and invasion of PaCa cells. Additionally, the knockdown of ZKSCAN3 increased the expression of LC3-II, a marker of autophagy, whereas ZKSCAN3 overexpression decreased LC3-II expression. In a xenograft mouse model, tumors formed by MIA PaCa-2 cells in which ZKSCAN3 was knocked down significantly increased in size compared with the control group. In conclusion, ZKSCAN3 expression was upregulated in several pancreatic cancer cells. Additionally, it was revealed that ZKSCAN3 is negatively correlated with the malignancy of PaCa through autophagy. These results suggest that autophagy regulation via ZKSCAN3 may be a new therapeutic target for PaCa.

Enhancing the Photocatalytic Activity of Halide Perovskite Cesium Bismuth Bromide/Hydrogen Titanate Heterostructures for Benzyl Alcohol Oxidation.

Halide perovskite Cs3Bi2Br9 (CBB) has excellent potential in photocatalysis due to its promising light-harvesting properties. However, its photocatalytic performance might be limited due to the unfavorable charge carrier migration and water-induced properties, which limit the stability and photocatalytic performance. Therefore, we address this constraint in this work by synthesizing a stable halide perovskite heterojunction by introducing hydrogen titanate nanosheets (H2Ti3O7-NS, HTiO-NS). Optimizing the weight % (wt%) of CBB enables synthesizing the optimal CBB/HTiO-NS, CBHTNS heterostructure. The detailed morphology and structure characterization proved that the cubic shape of CBB is anchored on the HTiO-NS surface. The 30 wt% CBB/HTiO-NS-30 (CBHTNS-30) heterojunction showed the highest BnOH photooxidation performance with 98% conversion and 75% benzoic acid (BzA) selectivity at 2 h under blue light irradiation. Detailed optical and photoelectrochemical characterization showed that the incorporating CBB and HTiO-NS widened the range of the visible-light response and improved the ability to separate the photo-induced charge carriers. The presence of HTiO-NS has increased the oxidative properties, possibly by charge separation in the heterojunction, which facilitated the generation of superoxide and hydroxyl radicals. A possible reaction pathway for the photocatalytic oxidation of BnOH to BzH and BzA was also suggested. Furthermore, through scavenger experiments, we found that the photogenerated h+, e- and •O2- play an essential role in the BnOH photooxidation, while the •OH have a minor effect on the reaction. This work may provide a strategy for using HTiO-NS-based photocatalyst to enhance the charge carrier migration and photocatalytic performance of CBB.

The Influence Mechanism of Quantum Well Growth and Annealing Temperature on In Migration and Stress Modulation Behavior.

This study explores the effects of growth temperature of InGaN/GaN quantum well (QW) layers on indium migration, structural quality, and luminescence properties. It is found that within a specific range, the growth temperature can control the efficiency of In incorporation into QWs and strain energy accumulated in the QW structure, modulating the luminescence efficiency. Temperature-dependent photoluminescence (TDPL) measurements revealed a more pronounced localized state effect in QW samples grown at higher temperatures. Moreover, a too high annealing temperature will enhance indium migration, leading to an increased density of non-radiative recombination centers and a more pronounced quantum-confined Stark effect (QCSE), thereby reducing luminescence intensity. These findings highlight the critical role of thermal management in optimizing the performance of InGaN/GaN MQWs in LEDs and other photoelectronic devices.

Phosphatidylinositol 4-Kinase III Alpha Governs Cytoskeletal Organization for Invasiveness of Liver Cancer Cells

High expression of phosphatidylinositol 4-kinase III alpha (PI4KIIIα) correlates with poor survival rates in patients with hepatocellular carcinoma. In addition, hepatitis C virus (HCV) infections activate PI4KIIIα and contribute to hepatocellular carcinoma progression. We aimed at mechanistically understanding the impact of PI4KIIIα on the progression of liver cancer and the potential contribution of HCV in this process. Several hepatic cell culture and mouse models were used to study the functional importance of PI4KIIIα on liver pathogenesis. Antibody arrays, gene silencing, and PI4KIIIα-specific inhibitor were applied to identify the involved signaling pathways. The contribution of HCV was examined by using HCV infection or overexpression of its nonstructural protein. High PI4KIIIα expression and/or activity induced cytoskeletal rearrangements via increased phosphorylation of paxillin and cofilin. This led to morphologic alterations and higher migratory and invasive properties of liver cancer cells. We further identified the liver-specific lipid kinase phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (PIK3C2γ) working downstream of PI4KIIIα in regulation of the cytoskeleton. PIK3C2γ generates plasma membrane phosphatidylinositol 3,4-bisphosphate-enriched, invadopodia-like structures that regulate cytoskeletal reorganization by promoting Akt2 phosphorylation. PI4KIIIα regulates cytoskeleton organization via PIK3C2γ/Akt2/paxillin-cofilin to favor migration and invasion of liver cancer cells. These findings provide mechanistic insight into the contribution of PI4KIIIα and HCV to the progression of liver cancer and identify promising targets for therapeutic intervention.

BDAPbI4 Dion Jacobson hybrid perovskite-based artificial nociceptors on biodegradable substrate

With the current evolution in artificial intelligence technology, biodegradable biomimetic devices are essential to execute increasingly complicated tasks and respond to challenging work environments. Consequently, the integration of artificial nociceptors holds considerable importance in enhancing the capabilities of humanoid robots. Low-dimensional Hybrid organic–inorganic Perovskites (HOIPs) show promise in emulating biological neurons owing to their inherent ion migration properties. In this work, we present Dion-Jacobson hybrid perovskite (BDAPbI4 (BDA=NH3C4H8NH3)) diffusive memristor on a paper substrate to serve as an artificial nociceptor. The symmetric electrode configuration as Paper/Ag/PCBM/BDAPbI4/PMMA/Ag demonstrates low operating voltage diffusive memristor with an ON/OFF ratio of ∼103. The surface investigation of device before top electrode deposition via X-ray photoelectron spectroscopy XPS and electrical characteristics of the complete device reveal the interplay between Schottky barrier at BDAPbI4/Ag interface and conductive filament formation/rupture within active layer as the origin of the abrupt resistive switching. The characteristics of the diffusive memristor resemble those of biological nociceptors, displaying sensitivity to external stimuli and key attributes such as threshold response, lack of adaptation, and relaxation. These findings underscore the potential application of Dion-Jacobson hybrid perovskites (BDAPbI4) as diffusive memristors in future neuromorphic intelligence systems.

Effect of NASCION‐Type ceramic dispersion in PAN/PVA‐based blend polymer electrolyte: A structural, thermal, and electrical study

AbstractSolid flexible separators having adequate ion conductivity at ambient temperature along with good thermal and voltage stability are potential candidates for separators in all solid‐state ion batteries. In the present work, zirconium and niobium‐doped Li1.3Al0.3Ti1.7 (PO4)3 ceramic particles have been incorporated into a polyvinyl alcohol (PVA) and polyacrylonitrile (PAN)‐based blend that served as a flexible matrix to create a flexible polymer–ceramic framework and have been examined for conductivity, dielectric properties, voltage stability, thermal stability, and electrochemical performance. The flexible polymer–ceramic framework shows high thermal stability, improved conductivity, and a high‐voltage window. Optimized dc conductivity of 9.8 × 10−5 S cm−1 has been observed among all investigated samples, with an improved voltage stability of 4.94 V. Further, the Trukhan model has been used to understand the effect of filler loading on ion migration properties. The optimized solid polymer electrolyte (SPE) shows improved ion mobility (μ) of 5.13 × 10−2 cm2 V−1 s, number density (n) = 2.39 × 1015 cm3, and diffusion coefficient (D) of 2.09 × 10−3 cm2 s−1. It also shows a very high specific capacitance of ~10−4 Fg−1, excellent cycling stability, and 93.75% capacity retention after 100 cycles.

Apolipoprotein L1 is a tumor suppressor in clear cell renal cell carcinoma metastasis.

The 5-year survival rate of kidney cancer drops dramatically from 93% to 15% when it is metastatic. Metastasis constitutes for 30% of kidney cancer cases, in which clear cell renal cell carcinoma (ccRCC) is the most prominent subtype. By sequencing mRNA of ccRCC patient samples, we found that apolipoprotein L1 (APOL1) was highly expressed in tumors compared to their adjacent normal tissues. This gene has been previously identified in a large body of kidney disease research and was reported as a potential prognosis marker in many types of cancers. However, the molecular function of APOL1 in ccRCC, especially in metastasis, remained unknown. In this study, we modulated the expression of APOL1 in various renal cancer cell lines and analyzed their proliferative, migratory, and invasive properties. Strikingly, APOL1 overexpression suppressed ccRCC metastasis both in vitro and in vivo. We then explored the mechanism by which APOL1 alleviated ccRCC malignant progression by investigating its downstream pathways. APOL1 overexpression diminished the activity of focal adhesive molecules, Akt signaling pathways, and EMT processes. Furthermore, in the upstream, we discovered that miR-30a-3p could inhibit APOL1 expression. In conclusion, our study revealed that APOL1 play a role as a tumor suppressor in ccRCC and inhibit metastasis, which may provide novel potential therapeutic approaches for ccRCC patients.

Effectiveness of autologous growth factor concentrates combined with topical minoxidil in patients of androgenic alopecia

Abstract Background: Concentrated growth factor (CGF) is a form of platelet concentrate. CGF contains abundant autologous growth factors that can promote cell proliferation, migration, osteogenic differentiation, and angiogenic properties in wound healing and bone regeneration. Recent studies revealed that CGF injection in hairless scalp could enhance hair density and optimize hair growth in androgenic alopecia (AGA) patients. Objective: The objective of this study was to study the effectiveness of autologous growth factor concentrate (GFC) combined with topical minoxidil in patients of AGA. Materials and Methods: A prospective nonrandomized interventional study with before and after comparison was carried out among 22 patients diagnosed with AGA. They were treated with deep intradermal injections of GFC in scalp. Four injections were administered 4 weeks apart, and patients were followed for 16 weeks. Treatment outcomes were assessed by taking photographs, using Global Aesthetic Improvement Scale (GAIS), and by performing a hair pull test after 16 weeks of therapy and compared to baseline. Incidence of adverse events was recorded. Patient’s self-satisfaction was assessed using a survey-based questionnaire at the end of the study. Results: Global macroscopic photographs showed a significant improvement in hair growth post-GFC therapy in all 22 patients. GAIS suggested that GFC treatments were effective in treating AGA, and the majority of patients were satisfied with their improvement. Hair pull test was negative in 100% of patients 4 months posttherapy. Therapy was found to be well tolerated with high patient satisfaction (100%). In addition, treatments resulted in a faster rate of hair growth and a decrease in greasy and unpleasant sensation of hair. Conclusion: GFC was found to have a promising role in the management of AGA in both males and females.

Customizing superior surface insulation properties of polymeric dielectric via in-plane molecular chain orientation

Surface flashover is a common breakdown phenomenon on material surfaces for which surface charge migration property, determined by surface composition and molecular chain structure, is crucial. Precise modulation of charge migration property by simple and efficient methods to improve surface flashover voltage is the goal in industry. Here, in-plane molecular chain orientation (MCO) modulation by uniaxial stretching was proposed to achieve this goal and investigate the intrinsic mechanism of charge migration on flashover. Flashover voltage and accompanying leakage current, performed with electrodes oriented at varying angles to the MCO direction, show a consistent trend, which skillfully reveals that the facilitated charge migration is favorable for improving flashover voltage. When the stretching ratio is 3.5, the flashover voltage along the stretching direction (SD) increases by up to 48.7%, while the in-plane minimum flashover voltage remains essentially unchanged with the change in stretching ratio. Molecular chain segment motion properties along different directions further elucidate that the surprising improvement of flashover voltage along SD is primarily due to the MCO that promotes intra-chain charge migration. This work provides a new perspective on anti-flashover modification of polymeric dielectric and will promote the development of surface flashover mechanisms.

MiR-199a-5p targets DUSP14 to regulate cell proliferation, invasion and stemness in non-small cell lung cancer

BackgroundNon-small cell lung cancer (NSCLC) shows the highest morbidity among malignant tumors worldwide. Despite improvements of diagnosis and treatment, patient prognosis remains unfavorable. Therefore, there is a need to discover a novel treatment strategy for NSCLC. DUSP14 is related to various cancers as the regulatory factor for cellular processes. However, its specific roles in NSCLC and the upstream modulator remain largely unclear. MethodsDUSP14 expression patterns within the lung cancer patient cohort from TCGA database were analyzed using UALCAN online tool. Different databases including miRDB, starbase, and Targetscan were employed to screen the upstream regulator of DUSP14. DUSP14 and miR-199a-5p expression was determined by qRT-PCR and Western blot techniques. To confirm binding interaction of DUSP14 with miR-199a-5p, we conducted a dual-luciferase reporter assay. Cell viability, migration, and stemness properties were assessed using CCK-8, EdU (5-ethynyl-2′-deoxyuridine) incorporation, transwell invasion, and sphere formation assays. The effect of DUSP14 silencing on tumorigenesis was assessed with the NSCLC cell xenograft mouse model. ResultsOur study discovered that DUSP14 exhibited high expression within NSCLC tumor samples, which is related to the dismal prognostic outcome in NSCLC patients. Silencing DUSP14 impaired NSCLC cell proliferation, migration, and tumor sphere formation. Besides, we identified miR-199a-5p as the upstream regulatory factor for DUSP14, and its expression was negatively related to DUSP14 level within NSCLC tissues. Introducing miR-199a-5p recapitulated the function of DUSP14 silencing in NSCLC cell aggressiveness and stemness. Moreover, knocking down DUSP14 efficiently inhibited tumor formation in NSCLC cells of the xenograft model. ConclusionsOur study suggests that DUSP14 is negatively regulated by miR-199a-5p within NSCLC, whose overexpression is required for sustaining NSCLC cell proliferation, invasion and stemness.