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Background Chitosan (Chi) is a natural material which has been widely used in neural applications due to possessing better biocompatibility. In this research study, a novel of nanocomposites film based on Chitosan (Chi) with Hyaluronic Acid (HA), combined with varying amounts of gold nanoparticles (AuNPs) was created resulting in pure Chi, Chi-HA, Chi-HA-AuNPs (25 ppm) and Chi-HA-AuNPs (50 ppm). Methods This study focused on evaluating their effects on Mesenchymal Stem Cell (MSC) viability, colony formation and biocompatibility. The surface morphology and chemical position was characterized through UV-Visible spectroscopy (UV-Vis), Fourier-transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and contact-angle assessment. Results When seeding MSCs on Chi-HA-AuNPs (50 ppm), the results showed high cell viability, biocompatibility, and the highest colony formation ability. Meanwhile, the evidence showed that Chi-HA-Au nano film was able to inhibit Nestin and β-Tubulin expression of MSCs, as well as inhibit the ability of neurogenic differentiation. Furthermore, the results of Matrix Metalloproteinase 2/9 (MMP2/9) expression in MSCs were also significantly higher in the Chi-HA-AuNP (50 ppm) group, guiding with angiogenesis and wound healing abilities. In addition, in our rat model, both capsule thickness and collagen deposition were the lowest in Chi-HA-AuNPs (50 ppm). Conclusion Thus, in view of the in vitro and in vivo results, Chi-HA-AuNPs (50 ppm) could not only maintain the greatest stemness properties and regulate the neurogenic differentiation ability of MSCs, but was able to also induce the least immune response. Herein, Chi-HA-Au 50 ppm nano film holds promise as a suitable material for nerve regeneration engineering.

Lung cancer is the leading cause of death from cancer in Taiwan and throughout the world. Immunotherapy has revealed promising and significant efficacy in NSCLC, through immune checkpoint inhibition by blocking programmed cell death protein (PD)-1/PD-1 ligand (PD-L1) signaling pathway to restore patients’ T-cell immunity. One novel type of long, non-coding RNAs, circular RNAs (circRNAs), are endogenous, stable, and widely expressed in tissues, saliva, blood, urine, and exosomes. Our previous results revealed that the plasma level of hsa_circ_0000190 can be monitored by liquid-biopsy-based droplet digital PCR and may serve as a valuable blood-based biomarker to monitor the disease progression and the efficacy of immunotherapy. In this study, hsa_circ_0000190 was shown to increase the PD-L1 mRNA-mediated soluble PD-L1 (sPD-L1) expression, consequently interfering with the efficacy of anti-PD-L1 antibody and T-cell activation, which may result in immunotherapy resistance and poor outcome. Our results unraveled that hsa_circ_0000190 facilitated the tumorigenesis and immune evasion of NSCLC by upregulating sPD-L1 expression, potentially developing a different aspect in elucidating the molecular immunopathogenesis of NSCLC. Hsa_circ_0000190 upregulation can be an effective indicator for the progression of NSCLC, and hsa_circ_0000190 downregulation may possess a potential therapeutic value for the treatment of NSCLC in combination with immunotherapy.

Lung cancer is the leading cause of cancer-related mortality worldwide, and its tumorigenesis involves the accumulation of genetic and epigenetic events in the respiratory epithelium. Epigenetic modifications, such as DNA methylation, RNA modification, and histone modifications, have been widely reported to play an important role in lung cancer development and in other pulmonary diseases. Whereas the functionality of DNA and chromatin modifications referred to as epigenetics is widely characterized, various modifications of RNA nucleotides have recently come into prominence as functionally important. N6-methyladosine (m6A) is the most prevalent internal modification in mRNAs, and its machinery of writers, erasers, and readers is well-characterized. However, several other nucleotide modifications of mRNAs and various noncoding RNAs have also been shown to play an important role in the regulation of biological processes and pathology. Such epitranscriptomic modifications play an important role in regulating various aspects of RNA metabolism, including transcription, translation, splicing, and stability. The dysregulation of epitranscriptomic machinery has been implicated in the pathological processes associated with carcinogenesis including uncontrolled cell proliferation, migration, invasion, and epithelial-mesenchymal transition. In recent years, with the advancement of RNA sequencing technology, high-resolution maps of different modifications in various tissues, organs, or disease models are being constantly reported at a dramatic speed. This facilitates further understanding of the relationship between disease development and epitranscriptomics, shedding light on new therapeutic possibilities. In this review, we summarize the basic information on RNA modifications, including m6A, m1A, m5C, m7G, pseudouridine, and A-to-I editing. We then demonstrate their relation to different kinds of lung diseases, especially lung cancer. By comparing the different roles RNA modifications play in the development processes of different diseases, this review may provide some new insights and offer a better understanding of RNA epigenetics and its involvement in pulmonary diseases.

Hydrogels are widely used in tissue engineering owing to their high water retention and soft characteristics. It remains a challenge to develop hydrogels with tunable degradation rates, proper environmental responsiveness, and injectability. In this study, biodegradable difunctional polyurethane (DFPU) nanoparticle dispersions are synthesized from an eco‐friendly waterborne process involving the use of glyoxal. Such DFPU is used to crosslink chitosan (CS). Schiff base linkages between DFPU and CS successfully produce self‐healing hydrogels at room temperature. Moreover, cryogels are generated after being frozen at −20 °C. These gels are found to be sensitive to low pH and amine‐containing molecules owing to the property of Schiff bases. Furthermore, the degradation rates can be adjusted by the type of the component oligodiols in DFPU. Rheological evaluation verifies the excellent self‐healing properties (≈100% recovery after damage). Both the self‐healing gels and cryogels are injectable (through 26‐gauge and 18‐gauge needles, respectively) and biocompatible. Rat implantation at 14 d shows the low immune responses of cryogels. The functionalized biodegradable polyurethane nanoparticles represent a new platform of crosslinkers for biomacromolecules such as chitosan through the dynamic Schiff reaction that may give rise to a wide variety of self‐healing gels and cryogels for biomedical applications., A new biodegradable waterborne difunctional polyurethane (DFPU) crosslinker is obtained by modifying waterborne polyurethane (PU) with glyoxal. Adding the crosslinker to glycol chitosan (CS) produces CS‐PU self‐healing hydrogel at room temperature and generates CS‐PU cryogel after being temporally frozen at −20 °C. Both gels are featured with injectability (26‐gauge and 18‐gauge needles, respectively), multiresponsiveness, tunable degradation rates, good cell proliferation, and biocompatibility.

The present work develops an atomic layer reduction (ALR) method to accurately tune oxidation level, electrical conductance, band-gap structure, and photoluminescence (PL) response of graphene oxide (GO) sheets. The ALR route is carried out at 200 °C within ALR cycle number of 10–100. The ALR treatment is capable of striping surface functionalities (e.g., hydroxyl, carbonyl, and carboxylic groups), producing thermally-reduced GO sheets. The ALR cycle number serves as a controlling factor in adjusting the crystalline, surface chemistry, electrical, optical properties of GO sheets. With increasing the ALR cycle number, ALR-GO sheets display a high crystallinity, a low oxidation level, an improved electrical conductivity, a narrow band gap, and a tunable PL response. On the basis of the results, the ALR technique offers a great potential for accurately tune electrical and optical properties of carbon materials through the cyclic removal of oxygen functionalities, without any complicated thermal and chemical desorption processes.

Electric field stimulation is known to affect various cellular processes, including cell fate specification and differentiation, particularly towards neuronal lineages. This makes it a promising therapeutic strategy to stimulate regeneration of neuronal tissues. Retinal ganglion cells (RGCs) is a type of neural cells of the retina responsible for transduction of visual signals from the retina to the brain cortex, and is often degenerated in various blindness-causing retinal diseases. The organic photovoltaic materials such as poly-3-hexylthiophene (P3HT) can generate electric current upon illumination with light of the visible spectrum, and possesses several advantageous properties, including light weight, flexibility and high biocompatibility, which makes them a highly promising tool for electric stimulation of cells in vitro and in vivo. In this study, we tested the ability to generate photocurrent by several formulations of blend (bulk heterojunction) of P3HT (which is electron donor material) with several electron acceptor materials, including Alq3 and bis(10-hydroxybenzo[h]quinolinato)beryllium (Bebq2). We found that the photovoltaic device based on bulk heterojunction of P3HT with Bebq2 could generate photocurrent when illuminated by both green laser and visible spectrum light. We tested the growth and differentiation capacity of human induced pluripotent stem cells (hiPSC)-derived RGCs when grown in interface with such photostimulated device, and found that they were significantly increased. The application of P3HT:Bebq2-formulation of photovoltaic device has a great potential for developments in retinal transplantation, nerve repair and tissue engineering approaches of treatment of retinal degeneration.

Age-related macular degeneration (AMD) is the eye disease with the highest epidemic incidence, and has great impact on the aged population. Wet-type AMD commonly has the feature of neovascularization, which destroys the normal retinal structure and visual function. So far, effective therapy options for rescuing visual function in advanced AMD patients are highly limited, especially in wet-type AMD, in which the retinal pigmented epithelium and Bruch&rsquo, s membrane structure (RPE-BM) are destroyed by abnormal angiogenesis. Anti-VEGF treatment is an effective remedy for the latter type of AMD, however, it is not a curative therapy. Therefore, reconstruction of the complex structure of RPE-BM and controlled release of angiogenesis inhibitors are strongly required for sustained therapy. The major purpose of this study was to develop a dual function biomimetic material, which could mimic the RPE-BM structure and ensure slow release of angiogenesis inhibitor as a novel therapeutic strategy for wet AMD. We herein utilized plasma-modified polydimethylsiloxane (PDMS) sheet to create a biomimetic scaffold mimicking subretinal BM. This dual-surface biomimetic scaffold was coated with laminin and dexamethasone-loaded liposomes. The top surface of PDMS was covalently grafted with laminin and used for cultivation of the retinal pigment epithelial cells differentiated from human induced pluripotent stem cells (hiPSC-RPE). To reach the objective of inhibiting angiogenesis required for treatment of wet AMD, the bottom surface of modified PDMS membrane was further loaded with dexamethasone-containing liposomes via biotin-streptavidin linkage. We demonstrated that hiPSC-RPE cells could proliferate, express normal RPE-specific genes and maintain their phenotype on laminin-coated PDMS membrane, including phagocytosis ability, and secretion of anti-angiogenesis factor PEDF. By using in vitro HUVEC angiogenesis assay, we showed that application of our membrane could suppress oxidative stress-induced angiogenesis, which was manifested in decreased secretion of VEGF by RPE cells and suppression of vascularization. In conclusion, we propose modified biomimetic material for dual delivery of RPE cells and liposome-enveloped dexamethasone, which can be potentially applied for AMD therapy.

ZnO/Ag/ZnO (ZAZ) and ZnO/Cu/ZnO (ZCZ) were prepared. The dependence of crystalline, electrical, and optical properties for the multilayer on the postdeposition annealing (PDA) was studied. After PDA of 300°C for 20 min, the diffusion of Cu in ZnO occurs; this result is responsible for the increasing resistance of the annealed ZCZ. Ag with a thickness of 10 nm was deposited upon ZnO. The interface of ZnO and Ag is clearly revealed by high resolution transmission electron microscopy. The crystalline of ZnO and Ag films in the ZAZ with a sheet resistance (Rs) down to 4.17 Ω/sq. The ZAZ layer shows a better thermal stability (up to 400°C) than that of the ZCZ ones. The PDA degraded slightly the optical transmittance and increases the conductivity of ZAZ layer. The figure of merit (FOM) is applied to analysis of the ZAZ layer. The PDA can enhance the FOM of the ZAZ with Ag thickness >8 nm. The resultingRsand the transmittance ZAZ layers were analyzed by the Taguchi method to obtain the appropriate parameters. The optimized ZAZ has been verified with aRsof 2.3 Ω/sq, a high transmittance (71%), and the optimal FOM of 1.41 × 10−2 Ω−1.

Linear metal string complexes of [MnL4(NCS)2] (Scheme 1, M = NiII, CoII, or CrII; n = 3 or 5; L = dpa- or tpda2- where dpa- is dipyridylamido anion and tpda2- is tripyridyldiamido dianion) are studied for the fundamental understanding of the effect of inter-nuclei interactions on electron transfer (ET). The metal strings are isolated within n-alkanethiol monolayers and the properties of ET through various metal strings are differentiated by scanning tunneling microscopy. Although very similar in physical dimension, their apparent heights against the same alkanethiol background are significantly different. The discrepancy is ascribed to electron localization−delocalization among the metal centers.

The synthesis of two new bifunctional oligo-α-aminopyridine ligands, N-(6-{6-[3-(6-amino-pyridin-2-ylamino)-phenylamino]-pyridin-2-ylamino}-pyridin-2-yl)-4-methylbenzenesulfonamide (apppm) and N-(6-{6-[3-(6-bromo-pyridin-2-ylamino)-phenylamino-pyridin-2-yl-amino]-pyridin-2-yl)-4-methylbenzenesulfonamide (bpppm), by double aminated couplings and Pd-catalization is presented in this paper. NaNH2 was used as a critical base in the first step of the aminated coupling for synthesizing the key building block N-(6-bromo-pyridin-2-yl)-pyridine-2,6-diamine (bppd) in 96% yield. Pyridine was then used in the second step of the aminated coupling for 4-toluenesulphonyl chloride and bppd. Finally, the monoamination was facilitated by the palladium-catalyzed Buchwald's coupling reaction, and subsequently the corresponding metal complexes of these bifunctional ligands were constructed. The single-crystal X-ray crystallographic data of the complex [Cu(apppm)(ClO4)(H2O)](ClO4)·2THF (1), [Cu(bpppm)](ClO4)2·(H2O)5/3·(CH3CN)1/3 (3), and the related salt [H(appm)](ClO4)·THF (2), were prepared and characterized. In complex 1, Cu(II) coordinates with the three nitrogen atoms of the pyridine rings, with the oxygen atom of the p-toluenesulphonyl group, strongly with the oxygen of the water molecule, and weakly with the oxygen atom of the perchlorate anion, and shows a distorted octahedral geometry. However, in the complex 3, Cu(II) bonds to N(1), N(3), N(5), and N(7) of the ligand bpppm toughly and exhibits a twisted square planar geometry.

Holographic recordings in a LiNbO3 crystal using ordinary and extraordinary light in transmission-type geometry were performed. The system parameters of storage capacity (M/#), sensitivity, and signal-to-noise ratio were measured. Although extraordinary light will induce stronger fanning light (nonlinear enhanced scattered light) in LiNbO3, our experimental results indicate that the system using extraordinary light is superior to that using ordinary light. Our demonstrations and results can help to optimize the holographic recording in some applications of volume holographic optical element (VHOE), such as wavelength division multiplexing (WDM) filters in optical communication.

The linear pentanuclear chromium complexes [CrII5(μ5-tpda)4Cl2] (1), [CrII5(μ5-tpda)4(NCS)2] (2), [CrIIICrII4(μ5-tpda)4F2](BF4) (3), and [CrIIICrII4(μ5-tpda)4F(OTf)](OTf) (4), with four all-syn tri(α-pyridyl)diamido dianion (tpda2–) ligands, have been prepared and structurally characterized. Compounds 1 and 2 possess a delocalized Cr(II)–Cr(II)–Cr(II)–Cr(II)–Cr(II) five-centred metal–metal bond of order 1.5. In both 1 and 2 two values for CrII–CrII bond lengths are found both; the outer ones connected with axial ligands are 2.284(1) and 2.285(2) A, and the inner ones are 2.2405(8) and 2.246(1) A, for 1 and 2, respectively. When compound 1 reacts with 2 equiv. of AgBF4 or Ag(OTf), a oxidation reaction takes place and one of the terminal chromium(II) ions is oxidized to produce [CrIIICrII4(μ5-tpda)4F2]BF4 (3) or [CrIIICrII4(μ5-tpda)4F(OTf)](OTf) (4). Two short Cr–Cr distances [1.969(2) and 2.138(2) A for 3, 1.846(1) and 1.922(1) A for 4] are found, with the presence of two quadruple bonds among four adjacent CrII ions. The fifth CrIII ion, which is separated from the neighboring CrII ion by 2.487(2) A for 3 and 2.610(1) A for 4, is simply a square pyramidal unit with no metal–metal bonding interaction.

A series of aluminum complexes incorporating substituted symmetrical and asymmetrical tridentate pyrrolyl ligands are synthesized conveniently and the treatment of the derivatives with small organic molecules are analyzed. The reaction of lithiated [C4H2NH(2-CH2NH(t)Bu)(5-CH2NR1R2)], where for 1, R1 = R2 = Me; 2, R1 = H, R2 = (t)Bu, with AlCl3 in diethyl ether affords Al[C4H2N(2-CH2NH(t)Bu)(5-CH2NMe2)]Cl2 (3) and Al[C4H2N(2,5-CH2NH(t)Bu)2]Cl2 (4), respectively, in high yields. Furthermore, subjecting 3 and 4 to reaction with one equiv. of LiNMePh in diethyl ether generates Al[C4H2N(2-CH2NH(t)Bu)(5-CH2NMe2)][NMePh]Cl (5) and Al[C4H2N(2,5-CH2NH(t)Bu)2][NMePh]Cl (6), respectively, while eliminating one equiv. of LiCl. The reaction between compound 4 with two equiv. of LiO-Ph-4-Me in diethyl ether yields the aluminum di-phenoxide compound Al[C4H2N(2,5-CH2NH(t)Bu)2](O-Ph-4-Me)2 (7) whereas the combination of 3 and two equiv. of LiNH(t)Bu, produces Al[C4H2N(2-CH2N(t)Bu)(5-CH2NMe2)](NH(t)Bu)(NH2(t)Bu) (8). Additionally, the mixing of 1 and one equiv. of AlMe3 renders Al[C4H2N(2-CH2NH(t)Bu)(5-CH2NMe2)]Me2 (9). Adding one more equiv. of AlMe3 with 9 affords {Al[C4H2N(2-CH2NH(t)Bu)(5-CH2NMe2)AlMe3]Me2} (10), which can also be obtained by treating 1 with two equiv. of AlMe3 directly. The treatment of 9 with one equiv. of 2,6-dimethylphenol in diethyl ether gives the aluminum alkoxide derivative, Al[C4H2N(2-CH2NH(t)Bu)(5-CH2NMe2)](O-C6H3-2,6-Me2)Me (11). Furthermore, the reaction between 9 and one equiv. of 1-ethyl-1-phenyl ketene, initiates the aluminum dimethyl complex Al{C4H2N[2-CH2CEtPh-C(=O)-NH(t)Bu](5-CH2NMe2)}Me2 (12) with a C-N bond breakage and a C-C bond formation. All the Al-derivatives are characterized by (1)H and (13)C NMR spectroscopy and the molecular structures are determined by single crystal X-ray diffractometry in solid state.

Glioblastoma (GBM) is the most aggressive malignant brain tumor in adults. TDP-43 (TARDBP), a DNA and RNA binding protein, is well known to play a key role in RNA processing, including involving in the pathogenesis of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Recent reports suggested that TDP-43 participate to the regulation of metabolic glycolysis in cancer. Overcoming metabolic stress is critical for cancer cell survival and growth in nutrient deprivation condition. Herein we found protein level of TDP-43 was increased in nutrient deprivation. Overexpression TDP-43 promotes glioblastoma cell survival and suppressed the activated-form levels of caspase 3 protein under nutrient deprivation. Overexpression of TDP-43 increased the tumorigenicity as determined by anchorage-independent growth assay and xenografts in immunocompromised mice model. Under nutrient deprivation, we also found that TDP-43-overexpression induced autophagy. Recent evidence suggests that autophagy is a cell survival mechanism in cancer cells. Finally, treatment of autophagy inhibitor blocks the survival of TDP-43 overexpressing GBM cells in nutrient deprivation condition. By this study, we presume TDP-43 enhanced GBM cells tumorigincity, activated autophagy and inhibited cell death under nutrient deprivation condition. TDP-43 is potentially the new aspects for understanding the tumorigenicity and metablolic regulation for malignant brain tumors and GBM. Citation Format: Tzu-Wei Lin, Chen-Wen Wu. The TDP-43 confers resistance to metabolic stress condition via activating autophagy in GBM cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1145. doi:10.1158/1538-7445.AM2015-1145

Three novel oligo-α-pyridylamino ligands, tripyridyldi-amine (H2tpda), tetrapyridyltriamine (H3teptra), pentapyridyltetramine (H4peptea) are synthesized; the crystal structures of their metal complexes with the all-anti configuration of the chelating ligands are reported.