Second-harmonic generation (SHG) response and birefringence are two critically important properties of nonlinear optical (NLO) materials. However, the simultaneous optimization of these two key properties remains a major challenge because of their contrasting microstructure requirements. Herein, we report the first tetravalent rare-earth metal fluorinated sulfate, CeF2(SO4). Its structure features novel net-like layers constructed by highly distorted [CeO4F4] polyhedra, which are further interconnected by [SO4] tetrahedra to form a three-dimensional structure. CeF2(SO4) exhibits the strongest SHG effect (8 times that of KH2PO4) and the largest birefringence for sulfate-based NLO materials, the latter exceeding the birefringent limit for oxides. Theoretical calculations and crystal structure analysis reveal that the unusually large SHG response and giant birefringence can be attributed to the introduction of the highly polarizable fluorinated [CeO4F4] polyhedra as well as the favorable alignment of [CeO4F4] polyhedra and [SO4] tetrahedra. This research affords a new paradigm for the designed synthesis of high-performance NLO materials.

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Astrocyte activation, associated with the release of pro-inflammatory cytokines interleukin 1-β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), is a hallmark of multiple brain diseases, including mesial temporal lobe epilepsy. In recent years, several microRNAs have emerged as important controllers of Toll-like receptor (TLR) signaling. In this study, we investigated the effect of miR-132, miR-146a, and miR-155 on myeloid-related protein-8 (MRP8) induced astrocyte-related inflammation. Using quantitative polymerase chain reaction (qPCR) and western blot, we found clear upregulation of TLR4 and downstream inflammatory cytokines, along with dysregulation of miR-132, miR-146a, and miR-155 in in vitro astrocytes after exposing them to different concentrations of MRP8. In addition, we focused on the effect of miR-132 on astrocyte-related inflammation induced by MRP8 via lentiviral infection then evaluated the expression of its possible target genes: acetylcholinesterase (AChE) and interleukin-1 receptor-associated kinase (IRAK4). Our results show that miR-132 is a negative feedback regulator of IL-1β and IL-6, but not TNF-α, by targeting IRAK4. Together, our findings demonstrate the novel role of TLR4-related microRNAs, especially miR-132, in the regulation of MRP8-induced astrocyte activation and highlight the importance of miR-132 in the modulation of innate immune response induced by endogenous ligands in neurological diseases.

The targeted synthesis of deep-ultraviolet (deep-UV) nonlinear optical (NLO) materials, especially those with non-π-conjugated sulfates, has experienced considerable difficulties due to the need to reconcile the oft-competing requirements for deep-UV transparency and strong second-harmonic generation (SHG). We report herein the designed synthesis of the first rare-earth metal-based deep-UV sulfate La(NH 4 )-(SO 4 ) 2 by a double-salt strategy involving introduction of complementary cations, together with optical studies that reveal a short-wavelength deep-UV absorption edge (below 190 nm) and the strongest SHG response among deep-UV NLO sulfates (2.4 × KDP). Theoretical calculations and crystal structure analysis suggest that the excellent balance between SHG response and deep-UV transparency can be attributed to a synergistic interaction of the hetero-cations La 3 + and [NH 4 ] + , which optimize alignment of the [SO 4 ] tetrahedra and highly polarizable [LaO 8 ] polyhedra.

Recent study showed that inflammation was related to lung cancer. However, the exact cause of lung inflammation leading to carcinogenesis is unknown. MicroRNAs (miRNAs) are a group of endogenous non-coding small RNAs that regulate the activity of targeted mRNAs by inflammatory response in many diseases. MiR-451 was reported to relate to the development of lung cancer and metastasis of glioma. But the effect of miR-451 on cell proliferation, migration, and invasion of lung cancer is not really clear. In order to explore the molecular mechanism of the occurrence and development of lung cancer, we investigated the effect of human miR-451 on the proliferation, invasion, and metastasis in lung cancer cell line A549. The miR-451 expression construct was generated into pGenesil-1.1 and transfected into A549 cells. Results showed that the recombinant vectors were verified by sequencing. And miR-451 was over-expressed in A549 by real-time RT PCR. Furthermore, the proliferation, invasion, and metastasis of the cells in miR-451 group were inhibited significantly compared with those in control and A549 groups by MTT assay, Transwell invasion assay, and wound-healing assay. And the lung cancer metastasis factors (MMP-2, MMP-9, VEGF, and CXCR4) were decreased in miR-451 group by Western blot. Moreover, it was proved that inflammation-related gene-PSMB8 was a target for miR-451 by bioinformatics analysis and dual-luciferase reporter assay. And the protein expressions of PSMB8 and NOS2 were decreased in miR-451 group compared with those in control and A549 groups. Therefore, our findings indicated that miR-451 related to PSMB8/NOS2 inflammatory factors may suppress the development and migration of lung cancer, providing evidence for the role of miR-451 in lung cancer.

Treating children with steroid-resistant nephrotic syndrome (SRNS) has been a clinical challenge for pediatricians. We recruited 24 children (18 boys and six girls) with steroid-resistant idiopathic nephrotic syndrome (SRINS) who were <2 years. All patients were administered prednisone 2 mg/kg per day prior to mycophenolate mofetil (MMF). By the end of the eighth week, MMF was initiated at 25-30 mg/kg daily for 6- 12 months. Prednisone dose was reduced stepwise. Biochemical assays were performed every 2 months. Complete remission was achieved in 15 patients, partial remission in six, and no response to MMF was noted in three. With MMF treatment, the levels of urinary protein and serum cholesterol decreased and that of serum albumin increased in a time-dependant manner. We demonstrated the MMF could reduce proteinuria in SRINS children <2 years. Our study suggests that MMF therapy might be an effective strategy for treating SRINS in children <2 years.

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus (DM). However, the exact mechanism is not clearly understood. In this study, our results showed that 24 h urinary protein, kidney index, and glomerular area were decreased, while creatinine clearance ratio was increased in DN rats when the rats were treated with NAR 50 mg/d for 6 weeks. Mesangial cell (MMCs) proliferation was inhibited in the NAR group by 3,(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and the cell cycle analysis showed that cells stayed in G2 phase in NAR group. And NAR treatment attenuated the deposition of ECM in DN rats and MMCs. Moreover, our data showed that let-7a was downexpressed in both DN rats and MMCs under high glucose condition. Surprisingly, NAR affected the expressions of Col4 and FN through upregulating let-7a in MMCs. In addition, we found that let-7a negatively regulated the expression of transforming growth factor-β1 receptor 1 (TGFBR1), and TGFBR1 was required for the let-7a-mediated downregulation of TGF-β1/smad signaling. Interestingly, NAR inhibited TGF-β1/smads signaling activation by upregulating let-7a. Therefore, our findings indicated that NAR ameliorated kidney injury by regulating let-7a/TGFBR1 signaling.

Second-harmonic-generation (SHG) efficiency and birefringence are two crucial parameters for nonlinear optical (NLO) crystals. However, the simultaneous optimization of these two key parameters remains a great challenge due to their contrasting microstructure prerequisites. In this paper, the first example of tetravalent rare-earth iodate-sulfate Ce­(IO3)2(SO4) (CISO) was designed by a defluorinated homovalent substitution strategy based on the parent compound CeF2(SO4)·H2O (CFSO) from the centrosymmetric to the noncentrosymmetric structure, which shows a large SHG effect of 3.5 × KDP in metal sulfates and a significant birefringence (0.259 at 546 nm) in hetero-oxyanion tetrahedral-group-based optical crystals. In the structure of CISO, both [IO3] and [SO4] groups are in the cis-position to each other, while [CeO8] polyhedra are highly distorted due to the different coordination environments of two kinds of oxyanions in one structure, which displays optimized optical anisotropy and polarizability attributed to their synergistic effect, leading to the strong SHG efficiency and sufficient birefringence. First-principles simulations for CISO have been employed to rationalize the correlations between the molecular structure and optical properties.