Systemic whole transcriptome analysis identified underlying molecular characteristics and regulatory networks implicated in the retina following optic nerve injury.

Optic nerve injuries are severely disrupt the structural and functional integrity of the retina, often leading to visual impairment or blindness. Despite the profound impact of these injuries, the molecular mechanisms involved remain poorly understood. In this study, we performed a comprehensive whole-transcriptome analysis of mouse retina samples after optic nerve crush (ONC) to elucidate changes in gene expression and regulatory networks. Transcriptome analysis revealed a variety of molecular alterations, including 256 mRNAs, 530 lncRNAs, and 37 miRNAs, associated with metabolic, inflammatory, signaling, and biosynthetic pathways in the injured retina. The integrated analysis of co-expression and protein-protein interactions identified an active interconnected module comprising 5 co-expressed proteins (Fga, Serpina1a, Hpd, Slc38a4, and Ahsg) associated with the complement and coagulation cascades. Finally, 2 mRNAs (Slc38a4 and Fga), 2 miRNAs (miR-671-5p and miR-3057-5p), and 6 lncRNAs (MSTRG.1830.1, Gm10814, A530013C23Rik, Gm40634, MSTRG.9514.1, A330023F24Rik) were identified by qPCR in 661W and HEK293T cells, and some of them were validated as critical components of a ceRNA network active in the injured retina through dual-luciferase reporter assays. In conclusion, our study provides comprehensive insight into the complex and dynamic biological mechanisms involved in retinal injury responses and highlights promising potential targets to enhance neuroprotection and restore vision.

Effect of gold-conjugated resveratrol nanoparticles on glioma cells and its underlying mechanism.

BACKGROUND:  Glioblastoma is the most aggressive brain tumor with poor prognosis. Although Resveratrol (Rsv) is known to have therapeutic effects on glioma, the effects of gold-conjugated resveratrol nanoparticles (Rsv-AuNPs) on glioma cells are rarely reported. OBJECTIVE: We aimed to investigate the effects of Rsv-AuNPs on glioma cells and its underlying mechanism. METHOD: Human glioma cell line U87 was treated with different concentrations of Rsv-AuNPs. CCK-8, transwell, and wound healing assay were performed to measure the effects of Rsv-AuNPs on cell proliferation, invasion, and migration ability, respectively. Flow cytometry assay was used to detect the effects of Rsv-AuNPs on apoptosis. Changes of protein expressions related to proliferation, invasion, migration, and apoptosis were measured by Western blot assay. In addition, the inhibitory role of Rsv-AuNPs in the PI3K/AKT/mTOR signaling pathway was verified by using PI3K inhibitor LY294002. RESULTS: Rsv-AuNPs treatment significantly suppressed proliferation, migration, and invasion of U87 cells (all P < 0.05) and increased the apoptosis rate (P < 0.05). The changes of proteins related to proliferation, migration, invasion and apoptosis were consistent (all P < 0.05). Moreover, Rsv-AuNPs treatment significantly inhibited the phosphorylation of PI3K, AKT and mTOR proteins in U87 cells (P < 0.05). CONCLUSION: The present study found that Rsv-AuNPs inhibited the proliferation, migration, and invasion of U87 cells and induced apoptosis by inhibiting the activation of PI3K/AKT/mTOR signaling pathway. In the future, Rsv-AuNPs might be applied to the clinical treatment of glioma through more in-depth animal and clinical research.

Retraction: An MSN-PEG-IP drug delivery system and IL13Rα2 as targeted therapy for glioma.

Retraction of 'An MSN-PEG-IP drug delivery system and IL13Rα2 as targeted therapy for glioma' by Jinlong Shi et al., Nanoscale, 2017, 9, 8970-8981, https://doi.org/10.1039/C6NR08786H.

4D Printing of Butterfly Scale-Inspired Structures for Wide-Angle Directional Liquid Transport.

Unidirectional liquid transport has been extensively explored for water/fog harvesting, electrochemical sensing, and desalination. However, current research mainly focuses on linear liquid transport (transport angle α = 0°), which exhibits hindered lateral liquid spreading and low unidirectional transport efficiency. Inspired by the wide-angle (0° < α < 180°) liquid transport on butterfly wings, this work successfully achieves linear (α = 0°), wide-angle, and even ultra-wide-angle (α = 180°) liquid transport by four-dimensional (4D) printing of butterfly scale-inspired re-entrant structures. These asymmetric re-entrant structures can achieve unidirectional liquid transport, and their layout can control the Laplace pressure in the forward (structure-tilting) and lateral directions to adjust the transport angle. Specifically, high transport efficiency and programmable forward/lateral transport paths are simultaneously achieved by the ultra-wide-angle transport, where liquid fills the lateral path before being transported forward. Moreover, the ultra-wide-angle transport is also validated in 3D space, which provides an innovative platform for advanced biochemical microreaction, large-area evaporation, and self-propelled oil-water separation.

Phosphatase and Tensin Homology Deleted on Chromosome 10 Inhibitors Promote Neural Stem Cell Proliferation and Differentiation.

Phosphatase and tensin homology deleted on chromosome 10 (PTEN) is a tumor suppressor gene. Its encoded protein has phosphatase and lipid phosphatase activities, which regulate the growth, differentiation, migration, and apoptosis of cells. The catalytic activity of PTEN is crucial for controlling cell growth under physiological and pathological conditions. It not only affects the survival and proliferation of tumor cells, but also inhibits a variety of cell regeneration processes. The use of PTEN inhibitors is being explored as a potentially beneficial therapeutic intervention for the repair of injuries to the central nervous system. PTEN influences the proliferation and differentiation of NSCs by regulating the expression and phosphorylation of downstream molecular protein kinase B (Akt) and the mammalian target of rapamycin (mTOR). However, the role of PTEN inhibitors in the Akt/mTOR signaling pathway in NSC proliferation and differentiation is unclear. Dipotassium bisperoxo (picolinoto) oxovanadate (V) [bpv(pic)] is a biologically active vanadium compound that blocks PTEN dephosphorylation and suppresses its activity, and has been used as a PTEN lipid phosphatase inhibitor. Here, bpv(pic) intervention was found to significantly increase the number of rat NSCs, as determined by bromodeoxyuridine staining and the cell counting kit-8, and to increase the percentage of neurons undergoing differentiation, as shown by immunofluorescence staining. Bpv(pic) intervention also significantly increased PTEN and mTOR expression, as shown by real-time PCR analysis and western blotting. In conclusion, PTEN inhibitor bpv(pic) promotes the proliferation and differentiation of NSCs into neurons.

3D-Printed Anisotropic Polymer Materials for Functional Applications.

Anisotropy is the characteristic of a material to exhibit variations in its mechanical, electrical, thermal, optical properties, etc. along different directions. Anisotropic materials have attracted great research interest because of their wide applications in aerospace, sensing, soft robotics, and tissue engineering. 3D printing provides exceptional advantages in achieving controlled compositions and complex architecture, thereby enabling the manufacture of 3D objects with anisotropic functionalities. Here, a comprehensive review of the recent progress on 3D printing of anisotropic polymer materials based on different techniques including material extrusion, vat photopolymerization, powder bed fusion, and sheet lamination is presented. The state-of-the-art strategies implemented in manipulating anisotropic structures are highlighted with the discussion of material categories, functionalities, and potential applications. This review is concluded with analyzing the current challenges and providing perspectives for further development in this field.

Wide-Gamut Biomimetic Structural Colors from Interference-Assisted Two-Photon Polymerization.

Two-photon polymerization (TPP) is an emerging direct laser writing technique for the fabrication of structural colors. However, its coloration ability is suppressed as the vertical resolution is up to several microns. To solve this issue, an interference-assisted TPP technique was employed. Laser interference at a highly reflective interface produced the periodic energy redistribution along the vertical direction, turning the laser voxel into multilayer structures and confirming this technology as a facile and robust method for precise control of its vertical feature size. Biomimetic structural colors (BSCs) inspired from the ridge-lamella configurations in the Morph butterflies were fabricated using this improved TPP technique. The coloration mechanisms of the multilayer interference from the lamella layers, the thin-film interference from the fusion of multilayers, and the hybrid situations were systematically studied. These BSC colors were grouped as pixel palettes with various TPP parameters corresponding to each other, and they spanned almost the entire standard red-green-blue color space. Moreover, under optimized conditions, it was possible to fabricate a 1 cm2 area within 2.5 h. These features make interference-assisted TPP an ideal coloration method for practical applications, such as display, decoration, sensing, and so on.

Facile Surface Functionalization Strategy for Two-Photon Lithography Microstructures.

Two-photon lithography (TPL) is a powerful tool to construct small-scale objects with complex and precise 3D architectures. While the limited selection of chemical functionalities on the printed structures has restricted the application of this method in fabricating functional objects and devices, this study presents a facile, efficient, and extensively applicable method to functionalize the surfaces of the objects printed by TPL. TPL-printed objects, regardless of their compositions, can be efficiently functionalized by combining trichlorovinylsilane treatment and thiol-ene chemistry. Various functionalities can be introduced on the printed objects, without affecting their micro-nano topographies. Hence, microstructures with diverse functions can be generated using non-functional photoresists. Compared to existed strategies, this method is fast, highly efficient, and non photoresist-dependent. In addition, this method can be applied to various materials, such as metals, metal oxides, and plastics that can be potentially utilized in TPL or other 3D printing technologies. The applications of this method on the biofunctionalization of microrobots and cell scaffolds are also demonstrated.

Robust Carbonated Structural Color Barcodes with Ultralow Ontology Fluorescence as Biomimic Culture Platform.

Photonic crystal (PC) barcodes are a new type of spectrum-encoding microcarriers used in multiplex high-throughput bioassays, such as broad analysis of biomarkers for clinical diagnosis, gene expression, and cell culture. Unfortunately, most of these existing PC barcodes suffered from undesired features, including difficult spectrum-signal acquisition, weak mechanical strength, and high ontology fluorescence, which limited their development to real applications. To address these limitations, we report a new type of structural color-encoded PC barcodes. The barcodes are fabricated by the assembly of monodisperse polydopamine- (PDA-) coated silica (PDA@SiO2) nanoparticles using a droplet-based microfluidic technique and followed by pyrolysis of PDA@SiO2 (C@SiO2) barcodes. Because of the templated carbonization of adhesive PDA, the prepared C@SiO2 PC beads were endowed with simultaneous easy-to-identify structural color, high mechanical strength, and ultralow ontology fluorescence. We demonstrated that the structural colored C@SiO2 barcodes not only maintained a high structural stability and good biocompatibility during the coculturing with fibroblasts and tumor cells capture but also achieved an enhanced fluorescent-reading signal-to-noise ratio in the fluorescence-reading detection. These features make the C@SiO2 PC barcodes versatile for expansive application in fluorescence-reading-based multibioassays.

Capillary-Force-Driven Self-Assembly of 4D-Printed Microstructures.

Capillary-force-driven self-assembly is emerging as a significant approach for the massive manufacture of advanced materials with novel wetting, adhesion, optical, mechanical, or electrical properties. However, academic value and practical applications of the self-assembly are greatly restricted because traditional micropillar self-assembly is always unidirectional. In this work, two-photon-lithography-based 4D microprinting is introduced to realize the reversible and bidirectional self-assembly of microstructures. With asymmetric crosslinking densities, the printed vertical microstructures can switch to a curved state with controlled thickness, curvature, and smooth morphology that are impossible to replicate by traditional 3D-printing technology. In different evaporating solvents, the 4D-printed microstructures can experience three states: (I) coalesce into clusters from original vertical states via traditional self-assembly, (II) remain curved, or (III) arbitrarily self-assemble (4D self-assembly) toward the curving directions. Compared to conventional approaches, this 4D self-assembly is distance-independent, which can generate varieties of assemblies with a yield as high as 100%. More importantly, the three states can be reversibly switched, allowing the development of many promising applications such as reversible micropatterns, switchable wetting, and dynamic actuation of microrobots, origami, and encapsulation.

Correlation Analysis Among the Level of IL-35, Microvessel Density, Lymphatic Vessel Density, and Prognosis in Non-Small Cell Lung Cancer.

The aim of this study was to determine the expression of IL-35 and the lymphatic vessel density (LVD) and microvessel density (MVD) in the pathological tissues from patients with non-small cell lung cancer (NSCLC) and to analyze their correlation with other common clinical prognostic factors, as well as patients' overall survival and progression-free survival. We analyzed the pathological characteristics of 130 patients with NSCLC and determined the IL-35 expression, MVD, and LVD changes in the pathological tissues by immunohistochemistry. The results showed that IL-35 expression was significantly correlated with tumor differentiation, lymph node metastasis, T staging, LVD, and MVD (P < 0.05) but was not associated with age, sex, smoking, and other factors. Univariate analysis of risk models showed that age, lymph node metastasis, T stage, and high IL-35 expression, LVD, and MVD were significantly associated with NSCLC prognosis (P < 0.05), whereas sex, smoking, and high differentiation were not correlated with prognosis. Multivariate analysis of the proportional risk model showed that the IL-35 expression, lymph node metastasis, high LVD, and high MVD were significantly correlated with NSCLC prognosis (P < 0.05). In conclusion, IL-35, MVD, and LVD may be independent prognostic markers. In addition, IL-35 might represent a promising clinical drug target for the treatment of NSCLC.

Mechanism and kinetics characteristic of self-discharge of FeS2 cathodes for thermal batteries.

The service life of FeS2 thermal batteries is significantly affected by self-discharge of the cathode. Herein, SEM, XRD and XPS were employed to characterize the mechanism of self-discharge of the FeS2 cathode. A novel combined-discharge method, in which a tiny current (5 mA cm-2) was applied to minimize the effect of polarization on discharge capacity, was conducted to study the kinetics characteristic of self-discharge of FeS2 cathode upon discharge. Then, the self-discharge kinetics parameters which are related to the current density (20, 50 and 200 mA cm-2) and temperature (400, 450, 500 and 550 °C) were determined by the Serin-Ellickson model. Characterizations of the cells standing at 500 °C confirm that the decomposition product of the FeS2 cathode is FeS. The quantitative analysis of self-discharge rate constants (SRC) demonstrates that the reaction is a diffusion-controlling process. The kinetics process can conform to the Serin-Ellickson model. Specifically, the values of SRC increase when the cell is carried by a heavier load, since more breakage would form in FeS2 particles at the larger current density. Besides, the SRC increase at a higher temperature, and the relationship of SRC and temperature can be fitted by the Arrhenius equation. Consequently, the apparent activation energy decreases with the increase of current density.

3D-printed cellular tips for tuning fork atomic force microscopy in shear mode.

Conventional atomic force microscopy (AFM) tips have remained largely unchanged in nanomachining processes, constituent materials, and microstructural constructions for decades, which limits the measurement performance based on force-sensing feedbacks. In order to save the scanning images from distortions due to excessive mechanical interactions in the intermittent shear-mode contact between scanning tips and sample, we propose the application of controlled microstructural architectured material to construct AFM tips by exploiting material-related energy-absorbing behavior in response to the tip-sample impact, leading to visual promotions of imaging quality. Evidenced by numerical analysis of compressive responses and practical scanning tests on various samples, the essential scanning functionality and the unique contribution of the cellular buffer layer to imaging optimization are strongly proved. This approach opens new avenues towards the specific applications of cellular solids in the energy-absorption field and sheds light on novel AFM studies based on 3D-printed tips possessing exotic properties.

3D Bioinspired Microstructures for Switchable Repellency in both Air and Liquid.

In addition to superhydrophobicity/superoleophobicity, surfaces with switchable water/oil repellency have also aroused considerable attention because of their potential values in microreactors, sensors, and microfluidics. Nevertheless, almost all those as-prepared surfaces are only applicable for liquids with higher surface tension (γ > 25.0 mN m-1) in air. In this work, inspired by some natural models, such as lotus leaf, springtail skin, and filefish skin, switchable repellency for liquids (γ = 12.0-72.8 mN m-1) in both air and liquid is realized via employing 3D deformable multiply re-entrant microstructures. Herein, the microstructures are fabricated by a two-photon polymerization based 3D printing technique and the reversible deformation is elaborately tuned by evaporation-induced bending and immersion-induced fast recovery (within 30 s). Based on 3D controlled microstructural architectures, this work offers an insightful explanation of repellency/penetration behavior at any three-phase interface and starts some novel ideas for manipulating opposite repellency by designing/fabricating stimuli-responsive microstructures.

Berberine inhibits proliferation and induces G0/G1 phase arrest in colorectal cancer cells by downregulating IGF2BP3.

AIMS: Berberine (BBR) is one of isoquinoline alkaloids from Coptidis Rhizoma and possesses extensive pharmacological activities, including anti-colorectal cancer (CRC) activity. However, the detailed mechanisms remain to be determined. The current study aims to investigate the ability and the potential mechanism of BBR against CRC. MAIN METHODS: By mining recognized CRC datasets and RNA-seq results of cells and tumors treated with BBR for perform bioinformatics analysis to find key targets IGF2BP3. Overexpression and knockdown of IGF2BP3 assays were used to explore the biological role of IGF2BP3 in the process of BBR against CRC. KEY FINDINGS: Our results showed that BBR inhibits proliferation and induces G0/G1 phase arrest in CRC cells by downregulating IGF2BP3. Specifically, Knockdown of IGF2BP3 could suppress the PI3K/AKT pathway to inhibit cell proliferation and cycle transition. The negative effects of BBR in CRC cells could be rescued by overexpressing IGF2BP3. SIGNIFICANCE: Our data might provide a theoretical basis for the future use of BBR in colorectal cancer prevention.

A highly colorimetric photonic film composed of non-close-packed melanin-like colloidal arrays.

HOTHESIS: Because of their flexible structure and adjustable color, structural colors with non-close-packed colloidal crystal arrays (NCCAs) have broad applications. However, most of these structural colors are limited by an approximate refractive index or high background scattering, and they present an unsatisfactory color that seriously hinders their practical application. Preparation of particles with a high refractive index or adsorption coefficient may be an effective approach to construct highly colorimetric NCCA structural colors in a nonaqueous solvent. The aim of this study was to explore the formation process of NCCA by the assembly of colloidal particles in a nonaqueous solvent, so as to fabricate NCCAs with a high refractive index and high adsorption. EXPERIMENTS: An attempt was made to fabricate the NCCA structural color by dispersing the desired particles in a 2-hydroxyethyl methacrylate (HEMA) solvent. Surface-functionalized poly(methyl methacrylate) (PMMA) particles were developed by emulsifier-free emulsion polymerization. The formation of NCCA was studied by comparing the dispersion of three classes of surface-functionalization of colloidal particles in the HEMA solvent. The melanin-like particles with a high refractive index and a high adsorption coefficient were synthesized by doping polydopamine (PDA) into good surface-functionalization particles by emulsifier-free emulsion polymerization. A highly colorimetric poly(2-hydroxyethyl methacrylate) (pHEMA) optical film with NCCA was fabricated by dispersing the melanin-like particles in a pHEMA hydrogel. FINDINGS: PMMA-HEMA colloidal particles could successfully construct a NCCA structure in a nonaqueous HEMA solvent because of the solvation. Based on the "good particles," PMMA-HEMA-PDA colloidal particles, an initial 3-hydroxytyramine hydrochloride (DA·HCl) concentration of 1.926 mM was shown to significantly improve the colorimetric value of the final solidified NCCA hydrogel. These results provided an important reference for the construction of surfactant-free HEMA non-close-packed colloidal crystals. This highly colorimetric structurally colored hydrogel may be widely used in the design of a variety of colored intelligent sensors and soft devices.

Palmatine induces G2/M phase arrest and mitochondrial-associated pathway apoptosis in colon cancer cells by targeting AURKA.

Studies have shown that palmatine (PAL) has anti-cancer effects. However, the activity and potential mechanisms of PAL against colorectal cancer remain elusive. The results showed that PAL significantly inhibited the proliferation of colon cancer cells in vitro and in vivo without significant effect on non-tumorigenic colon cells. Target prediction and clinical sample database analysis suggested that PAL may contribute to colon cancer cells phase arrest and apoptosis by targeting aurora kinase A (AURKA). Inhibition and overexpression of AURKA proved that PAL induces G2/M phase arrest and apoptosis in colon cancer cells by targeting AURKA. Moreover, PAL promoted intracellular Reactive oxygen species (ROS) production and decreased mitochondrial membrane potential (ΔΨm). PAL reduced the levels of AURKA, Bcl-xl and Bcl2 proteins, and promoted the expression of pro-apoptotic proteins P53, P73, Caspase3 and Caspase9, as well as the increase of cytochrome c (cyt. c) in cell lysates in vitro and in vivo. Together, our study confirmed that PAL induced G2/M phase arrest and mitochondrial-associated pathway apoptosis in colon cancer cells by targeting AURKA. PAL may provide a novel solution for the treatment of colon cancer by serving as a new AURKA inhibitor.

Magnoflorine from Coptis chinese has the potential to treat DNCB-induced Atopic dermatits by inhibiting apoptosis of keratinocyte.

AIMS: In Sheng Nong's herbal classic in China, Rhizoma coptidisa(RC) could be used to treat Atopic dermatitsb(AD), but its core ingredient(s) and mechanism remains unknown. The present study aimed to find out the ingredients against AD and expound its mechanisms. MATERIALS AND METHODS: Seven alkaloids were isolated from RC to compare the inhibition against HaCaT cells by MTT assays and apoptosis of cells stimulated with TNF-α/IFN-γ by flow cytometry. The effects of target alkaloids against AD were evaluated on DNCBc (2,4-dinitrochlorobenzene)-induced atopic dermatitis in mice. KEY FINDINGS: Seven alkaloids were isolated from RC successfully. The results from MTT and flow cytometry indicated that among these alkaloids, only magnoflorine d(MAG) had no obvious toxicity on cells, but could inhibit the apoptosis of the cells stimulated with TNF-α/IFN-γ. Further animal experiments confirmed that MAG significantly attenuated the AD-like symptom and inhibited the AD-induced increases in IgE/IL-4, as compared with control (P < 0.01). Moreover, MAG reduced the low Δψme(mitochondrial membrane potential) in HaCaT cells. The results of western blotting proved that MAG inhibited apoptosis of keratinocytes through decreasing the expressions of CTSBf (cathepsin B), Cyte Cg (cytochrome C), Bid and caspase-3/7/8/9. SIGNIFICANCE: Overall, MAG inhibited apoptosis by decreasing the expression of apoptotic pathway-related proteins, and laid a foundation for the study of AD mechanisms.

S-equol inhibits proliferation and promotes apoptosis of human breast cancer MCF-7 cells via regulating miR-10a-5p and PI3K/AKT pathway.

S-equol is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora, which has strong anti-cancer activity. Based on this, the purpose of this study was to investigate the anti-breast cancer mechanism of S-equol. We examined the effects of S-equol on proliferation and apoptosis of MCF-7 cells by cell counting kit-8 assay and flow cytometry. Screening for microRNAs and predicting their target genes using the starBase and Targetscan website, respectively. Protein expression was detected by Western blot. The microRNA level were quantified by real-time PCR. The results showed that S-equol inhibited the proliferation of breast cancer MCF-7 cells in a time- and dose-dependent manner and promoted apoptosis of MCF-7 cells. The expression of miR-10a-5p was significantly decreased in breast cancer tissues and breast cancer cell lines, and the expression of miR-10a-5p was negatively correlated with the proliferation of MCF-7 cells. Luciferase reporter experiments demonstrated that miR-10a-5p directly targets PIK3CA 3'UTR to function. It was further found that S-equol exerts an anti-breast cancer effect by up-regulating miR-10a-5p and inhibiting the PI3K/AKT pathway. Our study revealed the mechanism of S-equol against breast cancer, and miR-10a-5p may be a potential target for the treatment of breast cancer.

Programmable Liquid Adhesion on Bio-Inspired Re-Entrant Structures.

Surfaces combining antispreading and high adhesion can find wide applications in the manipulation of liquid droplets, generation of micropatterns and liquid enrichment. To fabricate such surfaces, almost all the traditional methods demand multi-step processes and chemical modification. And even so, most of them cannot be applied for some liquids with extremely low surface energy. In the past decade, multiply re-entrant structures have aroused much attention because of their universal and modification-independent antiadhesion or antipenetration ability. Unfortunately, theories and applications about their liquid adhesion behavior are still rare. In this work, inspired by the springtail skin and gecko feet in the adhered state, it is demonstrated that programmable liquid adhesion is realized on the 3D-printed micro doubly re-entrant arrays. By arranging the arrays reasonably, three different Cassie adhesion behaviors can be obtained: I) no residue adhesion, II) tunable adhesion, and III) absolute adhesion. Furthermore, various arrays are designed to tune macro/micro liquid droplet manipulation, which can find applications in the transportation of liquid droplets, liquid enrichment, generation of tiny droplets, and micropatterns.