Boosted Second Harmonic Generation of a Chiral Hybrid Lead Halide Resonant to Charge Transfer Exciton from Metal Halide Octahedra to Ligand.

Chiral hybrid organic-inorganic metal halides (HOMHs) offer an ideal platform for the advancement of second-order nonlinear optical (NLO) materials owing to their inherent noncentrosymmetric structures. The enhancement of optical nonlinearity of chiral HOMHs could be achieved by matching the free exciton and/or self-trapped exciton energy levels with desired NLO frequencies. However, the current scarcity of resonance modes and low resonance ratio hamper the further improvements of NLO performance. Herein, we propose a new resonant channel of charge transfer (CT) excited states from metal halide polyhedra to organic ligand to boost the second-order optical nonlinearity of chiral HOMHs. The model lead halide (C7H10N)PbBr3 (C7H10N=1-ethylpyridinium) exhibits a drastically enhanced second harmonic generation in resonance to the deep CT exciton energy, with intensity of up to 111.0 times that of KDP and 10.9 times that of urea. The effective NLO coefficient has been determined to be as high as ~40.2 pm V-1, balanced with a large polarization ratio and high laser damage threshold. This work highlights the contribution of organic ligands in the construction of a resonant channel for enhancing second-order NLO coefficients of metal halides, and thus provides guidelines for designing new chiral HOMHs materials for advanced nonlinear photonic applications.

Free Halogen Substitution of Chiral Hybrid Metal Halides for Activating the Linear and Nonlinear Chiroptical Properties.

Halogen substitution has been proven as an effective approach to the band gap engineering and optoelectronic modulation of organic-inorganic hybrid metal halide (OIHMH) materials. Various high-performance mixed halide OIHMH film materials have been primarily obtained through the substitution of coordinated halogens in their inorganic octahedra. Herein, we propose a new strategy of substitution of free halogen outside the inorganic octahedra for constructing mixed halide OIHMH single crystals with chiral structures, resulting in a boost of their linear and nonlinear chiroptical properties. The substitution from DMA4[InCl6]Cl (DMA = dimethylammonium) to DMA4[InCl6]Br crystals through a facile antisolvent vaporization method produces centimeter-scale single crystals with high thermal stability along with high quantum yield photoluminescence, conspicuous circularly polarized luminescence, and greatly enhanced second harmonic generation (SHG). In particular, the obtained DMA4[InCl6]Br single crystal features an intrinsic chiral structure, exhibiting a significant SHG circular dichroism (SHG-CD) response with a highest reported anisotropy factor (gSHG-CD) of 1.56 among chiral OIHMH materials. The enhancements in both linear and nonlinear chiroptical properties are directly attributed to the modulation of octahedral distortion. The mixed halide OIHMH single crystals obtained by free halogen substitution confine the introduced halogens within free halogen sites of the lattice, thereby ensuring the stability of compositions and properties. The successful employment of such a free halogen substitution approach may broaden the horizon of the regulation of structures and the optoelectronic properties of the OIHMH materials.

A novel NEDD4L-TXNIP-CHOP axis in the pathogenesis of nonalcoholic steatohepatitis.

Background: Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver diseases worldwide. There is a pressing clinical need to identify potential therapeutic targets for NASH treatment. Thioredoxin interacting protein (Txnip) is a stress responsive gene that has been implicated in the pathogenesis of NASH, but its exact role is not fully understood. Here, we investigated the liver- and gene-specific role of Txnip and its upstream/downstream signaling in the pathogenesis of NASH. Methods and Results: Using four independent NASH mouse models, we found that TXNIP protein abnormally accumulated in NASH mouse livers. A decrease in E3 ubiquitin ligase NEDD4L resulted in impaired TXNIP ubiquitination and its accumulation in the liver. TXNIP protein levels were positively correlated with that of CHOP, a major regulator of ER stress-mediated apoptosis, in NASH mouse liver. Moreover, gain- and loss-of-function studies showed that TXNIP increased protein not mRNA levels of Chop both in vitro and in vivo. Mechanistically, the C-terminus of TXNIP associated with the N-terminus of the α-helix domain of CHOP and decreased CHOP ubiquitination, thus increasing the stability of CHOP protein. Lastly, selective knockdown of Txnip by adenovirus-mediated shRNA (not targets Txnip antisense lncRNA) delivery in the livers of both young and aged NASH mice suppressed the expression of CHOP and its downstream apoptotic pathway, and ameliorated NASH by reducing hepatic apoptosis, inflammation, and fibrosis. Conclusions: Our study revealed a pathogenic role of hepatic TXNIP in NASH and identified a novel NEDD4L-TXNIP-CHOP axis in the pathogenesis of NASH.

Regulating the solvation chemistry of non-flammable high voltage electrolyte through salt-solvent ratio modulation.

Boosting the energy density and safety issue of lithium-ion batteries has become ever more important to satisfy the diverse applications such as energy storage and mobile electronic devices. Herein, we present a new high voltage polyether-based electrolyte (HVPEE) by solvation structure design that can endure high-voltage operations and also possess non-flammable features. Especially, HVPEEs show better compatibility and stability with electrode than conventional electrolyte. We find that the solvent separated ion pair (SSIP) and contact ion pair (CIP) dominate the ion-solvent structure of HVPEEs, rather than the free solvent and ions. In this way, the oxidative decomposition of HVPEE on the cathode interface can be suppressed significantly due to the reduced highest occupied molecular orbital of SSIP complex structure than that of free TFSI-. As a result, the oxidation voltage can achieve as high as 5.35 V when the ether group/Li is optimized at 10/1 in the HVPEE, enabling the LiFePO4//Li full cells deliver a capacity of 165 mA h g-1 with a capacity retention of 98 % after 200 cycles. Moreover, when the cut-off voltage is 4.5 V, the discharge capacity of the LiNi0.6Mn0.2Co0.2O2//Li full cell can reach 170 mA h g-1.

Structurally integrated asymmetric polymer electrolyte with stable Janus interface properties for high-voltage lithium metal batteries.

Solid-state polymer electrolytes are outstanding candidates for next-generation lithium metal batteries in the realm of high specific energy densities, high safeties and tight contact with electrodes. However, their applications are still hindered by the limitations that no single polymer is electrochemically stable with the oxidizing high-voltage cathode and the highly reductive Li anode, simultaneously. Herein, a bilayer asymmetric polymer electrolyte (SL-SPE) without accessional interface resistance that using poly (ethylene glycol) diacrylate (PEGDA) as a "bridge" to connect the sulfonyl (OS = O)-contained oxidation-tolerated layer and polyether-derived reduction-tolerated layer (SPE), is proposed and synthesized by sequential two-step UV polymerizations. SL-SPE can provide widened electrochemical stability window up to 5 V, while simultaneously deploying a stable Janus interface property. Eventually, the superior high-voltage (4.4 V) cycling durability can be displayed in LiNi0.6Co0.2Mn0.2O2|SL-SPE|Li batteries. This finding provides a bran-new idea for designing multifunctional polymer electrolytes in the application of solid-state batteries.

Second-order nonlinear optical properties of copper-based hybrid organic-inorganic perovskites induced by chiral amines.

Recently, chiral hybrid organic-inorganic perovskites (HOIPs) are drawing wide attention due to their intrinsic noncentrosymmetric structures which result in fascinating properties such as ferroelectronics and second-order nonlinear optics (NLO). However, previous research mainly focused on chiral lead-based halide perovskites ignoring that the toxic Pb element is harmful to humans and the environment. Herein, we successfully synthesized block-like (R-/S-NEA)2CuCl4 (NEA = 1-naphthylethylamine) and needle-like (R-/S-CYHEA)6Cu3Cl12 (CYHEA = 1-cyclohexylethylamine) single crystals, which crystallize in the Sohncke P21 and I2 space group, respectively. Each pair of chiral perovskite enantiomers shows mirror circular dichroism (CD) signals. The thin films show an efficient second harmonic generation (SHG) response and the NLO coefficients of (R-NEA)2CuCl4 and (R-CYHEA)6Cu3Cl12 are 11.74 and 3.04 pm V-1, respectively, under 920 nm excitation with Y-cut quartz as a reference, which shows that the chiral amine has a significant effect on the SHG behavior. The high SHG response of (R-NEA)2CuCl4 is perhaps due to the rigidity of the aromatic amine, which leads to highly asymmetrical space groups. Our results provide guidelines for designing and tuning the SHG response in chiral HOIPs.

Self-Healing, Reconfigurable, Thermal-Switching, Transformative Electronics for Health Monitoring.

Soft, deformable electronic devices provide the means to monitor physiological information and health conditions for disease diagnostics. However, their practical utility is limited due to the lack of intrinsical thermal switching for mechanically transformative adaptability and self-healing capability against mechanical damages. Here, the design concepts, materials and physics, manufacturing approaches, and application opportunities of self-healing, reconfigurable, thermal-switching device platforms based on hyperbranched polymers and biphasic liquid metal are reported. The former provides excellent self-healing performance and unique tunable stiffness and adhesion regulated by temperature for the on-skin switch, whereas the latter results in liquid metal circuits with extreme stretchability (>900%) and high conductivity (3.40 × 104  S cm-1 ), as well as simple recycling capability. Triggered by the increased temperature from the skin surface, a multifunctional device platform can conveniently conform and strongly adhere to the hierarchically textured skin surface for non-invasive, continuous, comfortable health monitoring. Additionally, the self-healing and adhesive characteristics allow multiple multifunctional circuit components to assemble and completely wrap on 3D curvilinear surfaces. Together, the design, manufacturing, and proof-of-concept demonstration of the self-healing, transformative, and self-assembled electronics open up new opportunities for robust soft deformable devices, smart robotics, prosthetics, and Internet-of-Things, and human-machine interfaces on irregular surfaces.

Enabling high-capacity Li metal battery with PVDF sandwiched type polymer electrolyte.

Polyvinylidene difluoride (PVDF) is one of the most attractive electrolyte materials for solid-state batteries due to its high ionic conductivity, however, the battery performance is limited by the high electrolyte-electrode interfacial resistance. Herein, PVDF polymer mixed with ceramic Li7La3Zr2O12 is coated on cellulose support membrane (PLCSM) through a simple slurry-casting method. The ionic transport of PLCSM is originated from dimethyl formamide (DMF)-Li+ solvation structure, which plays a critical role in conducting lithium ions. ß-PVDF after dehydrofluorination offers a high dielectric constant and enhances the dissociation of lithium salt. As a result, PLCSM with a total thickness of 85 µm presents an oxidation voltage of 4.9 V. Li-Li symmetric cells by employing PLCSM reveal that the critical current density (CCD) is increased to 1 mA cm-2. A full cell of LiFePO4 |PLCSM |Li with high mass loading (1.2 mA h cm-2) shows a first-cycle discharge capacity of 160 mA h g-1. With LiNi0.6Mn0.2Co0.2O2 as the cathode, the initial discharge capacity is 153 mA h g-1, and the capacity retention after 80 cycles is 80 %. The sandwiched PLCSM provides an effective strategy to achieve high-performance dendrite-free Li metal batteries.

Knockdown of lncRNA TP53TG1 Enhances the Efficacy of Sorafenib in Human Hepatocellular Carcinoma Cells.

The multikinase inhibitor, sorafenib, is a first-line treatment for hepatocellular carcinoma (HCC), but its limited efficacy, drug resistance and toxicity are a concern. In this study, we investigated the role of lncRNA TP53TG1 in the efficacy of sorafenib in HCC cells. We found that treatment with sorafenib increased the expression of TP53TG1 in HCC cells. Knockdown of TP53TG1 sensitized tumor cells to the antiproliferative effects of sorafenib. Furthermore, TP53TG1 knockdown had an additive inhibitory effect on HCC cell proliferation and migration in the presence of sorafenib. The combination of TP53TG1 knockdown and sorafenib drastically inhibited the activation of the ERK pathway. This work demonstrates that TP53TG1 deficiency enhances the efficacy of sorafenib in HCC. Combining TP53TG1 knockdown with sorafenib may be an optimal form of therapy for HCC treatment.

0D chiral hybrid indium(III) halides for second harmonic generation.

Chiral metal halides have shown great potential for application in next generation nonlinear optical (NLO) devices owing to their intrinsic non-centrosymmetry. However, the structures and properties of chiral hybrid indium halides have been rarely reported, especially when it comes to second-harmonic generation (SHG) in NLO. In this work, we have synthesized a pair of new zero-dimensional (0D) chiral hybrid indium halides, (R-MPEA)6InCl9 and (S-MPEA)6InCl9, and studied their NLO properties. The as-prepared chiral hybrid indium halides crystallize in non-centrosymmetric P3221 and P3121 space groups, respectively. NLO studies show that 0D chiral hybrid indium halide crystals exhibit strong SHG responses with high polarization ratio and high laser damage threshold (LDT). This work enriches the family of chiral hybrid metal halide materials and offers a feasible strategy for the targeted design and synthesis of intrinsically non-centrosymmetric metal halide materials for NLO applications.

Identification of Gm15441, a Txnip antisense lncRNA, as a critical regulator in liver metabolic homeostasis.

BACKGROUND: The majority of mammalian genome is composed of non-coding regions, where numerous long non-coding RNAs (lncRNAs) are transcribed. Although lncRNAs have been identified to regulate fundamental biological processes, most of their functions remain unknown, especially in metabolic homeostasis. Analysis of our recent genome-wide screen reveals that Gm15441, a thioredoxin-interacting protein (Txnip) antisense lncRNA, is the most robustly induced lncRNA in the fasting mouse liver. Antisense lncRNAs are known to regulate their sense gene expression. Given that Txnip is a critical metabolic regulator of the liver, we aimed to investigate the role of Gm15441 in the regulation of Txnip and liver metabolism. METHODS: We examined the response of Gm15441 and Txnip under in vivo metabolic signals such as fasting and refeeding, and in vitro signals such as insulin and key metabolic transcription factors. We investigated the regulation of Txnip expression by Gm15441 and the underlying mechanism in mouse hepatocytes. Using adenovirus-mediated liver-specific overexpression, we determined whether Gm15441 regulates Txnip in the mouse liver and modulates key aspects of liver metabolism. RESULTS: We found that the expression levels of Gm15441 and Txnip showed a similar response pattern to metabolic signals in vivo and in vitro, but that their functions were predicted to be opposite. Furthermore, we found that Gm15441 robustly reduced Txnip protein expression in vitro through sequence-specific regulation and translational inhibition. Lastly, we confirmed the Txnip inhibition by Gm15441 in vivo (mice) and found that Gm15441 liver-specific overexpression lowered plasma triglyceride and blood glucose levels and elevated plasma ketone body levels. CONCLUSIONS: Our data demonstrate that Gm15441 is a potent Txnip inhibitor and a critical metabolic regulator in the liver. This study reveals the therapeutic potential of Gm15441 in treating metabolic diseases.

LncRNA TP53TG1 Promotes the Growth and Migration of Hepatocellular Carcinoma Cells via Activation of ERK Signaling.

Long non-coding RNA (lncRNA) TP53 target 1 (TP53TG1) was discovered as a TP53 target gene. TP53TG1 has been reported as having dual roles by exerting tumor-suppressive and oncogenic activities that vary depending on the cancer type. Yet, the role of TP53TG1 in hepatocellular carcinoma (HCC) is not fully understood. In this study, we performed both gain- and loss-of-function studies to determine the biological role of TP53TG1 in HCC. We found that the knockdown of TP53 in HCC cells caused the upregulation of TP53TG1. Furthermore, we found that the knockdown of TP53TG1 not only suppressed HCC cell proliferation and migration, but also reduced intrinsic ERK signaling. In contrast, the overexpression of TP53TG1 increased ERK activation and enhanced HCC proliferation. In conclusion, our study reveals an oncogenic role of TP53TG1 in HCC, which provides a novel insight into the cell-type-specific function of TP53TG1 in HCC.

Lymphotoxin ß receptor-mediated NFκB signaling promotes glial lineage differentiation and inhibits neuronal lineage differentiation in mouse brain neural stem/progenitor cells.

BACKGROUND: Lymphotoxin (LT) is a lymphokine mainly expressed in lymphocytes. LTα binds one or two membrane-associated LTß to form LTα2ß1 or LTα1ß2 heterotrimers. The predominant LTα1ß2 binds to LTß receptor (LTßR) primarily expressed in epithelial and stromal cells. Most studies on LTßR signaling have focused on the organization, development, and maintenance of lymphoid tissues. However, the roles of LTßR signaling in the nervous system, particularly in neurogenesis, remain unknown. Here, we investigated the role of LTßR-mediated NFκB signaling in regulating neural lineage differentiation. METHODS: The C57BL/6J wild-type and GFAP-dnIκBα transgenic mice were used. Serum-free embryoid bodies were cultured from mouse embryonic stem cells and further induced into neural stem/progenitor cells (NSCs/NPCs). Primary neurospheres were cultured from embryonic and adult mouse brains followed by monolayer culture for amplification/passage. NFκB activation was determined by adenovirus-mediated NFκB-firefly-luciferase reporter assay and p65/RelB/p52 nuclear translocation assay. LTßR mRNA expression was evaluated by quantitative RT-PCR and LTßR protein expression was determined by immunohistochemistry and Western blot analysis. Multilabeled immunocytochemistry or immunohistochemistry followed by fluorescent confocal microscopy and quantitative analysis of neural lineage differentiation were performed. Graphing and statistical analysis were performed with GraphPad Prism software. RESULTS: In cultured NSCs/NPCs, LTα1ß2 stimulation induced an activation of classical and non-classical NFκB signaling. The expression of LTßR-like immunoreactivity in GFAP+/Sox2+ NSCs was identified in well-established neurogenic zones of adult mouse brain. Quantitative RT-PCR and Western blot analysis validated the expression of LTßR in cultured NSCs/NPCs and brain neurogenic regions. LTßR expression was significantly increased during neural induction. LTα1ß2 stimulation in cultured NSCs/NPCs promoted astroglial and oligodendrocytic lineage differentiation, but inhibited neuronal lineage differentiation. Astroglial NFκB inactivation in GFAP-dnIκBα transgenic mice rescued LTßR-mediated abnormal phenotypes of cultured NSCs/NPCs. CONCLUSION: This study provides the first evidence for the expression and function of LTßR signaling in NSCs/NPCs. Activation of LTßR signaling promotes glial lineage differentiation. Our results suggest that neurogenesis is regulated by the adaptive immunity and inflammatory responses.