Stereochemically Active Lone-Pair Containing Metal Substitution in Polar Axis toward a Giant Phase-Matchable Optical Nonlinear Silicate Crystal Li3(OH)PbSiO4.

Atoms in special lattice sites can play a crucial role in realizing materials properties, which is long pursued but difficult to control. Herein, by adopting a stereochemically active lone-pair-containing metal substitution strategy, a nonlinear-optical (NLO) silicate crystal Li3(OH)PbSiO4 was successfully synthesized, featuring [PbSiO4]∞ layers with the perfect orientation of the stereochemically active lone-pair Pb(II) cation in the polar-axis lattice. Li3(OH)PbSiO4 overcomes the long-standing problem of silicates, that is, poor nonlinear properties because it exhibits both the largest birefringence of 0.082 and the largest phase-matchable second-harmonic-generation (SHG) efficiency of 21 × KDP among the known silicates. The successful polar-axis lattice substitution could offer a new direction for realizing the rational control of materials structures and properties.

Panax notoginseng alleviates oxidative stress through miRNA regulations based on systems biology approach.

BACKGROUND: Herbal medicine Sanqi (SQ), the dried root or stem of Panax notoginseng (PNS), has been reported to have anti-diabetic and anti-obesity effects and is usually administered as a decoction for Chinese medicine. Alternative to utilizing PNS pure compound for treatment, we are motivated to propose an unconventional scheme to investigate the functions of PNS mixture. However, studies providing a detailed overview of the transcriptomics-based signaling network in response to PNS are seldom available. METHODS: To explore the reasoning of PNS in treating metabolic disorders such as insulin resistance, we implemented a systems biology-based approach with RNA sequencing (RNA-seq) and miRNA sequencing data to elucidate key pathways, genes and miRNAs involved. RESULTS: Functional enrichment analysis revealed PNS up-regulating oxidative stress-related pathways and down-regulating insulin and fatty acid metabolism. Superoxide dismutase 1 (SOD1), peroxiredoxin 1 (PRDX1), heme oxygenase-1 (Hmox1) and glutamate cysteine ligase (GCLc) mRNA and protein levels, as well as related miRNA levels, were measured in PNS treated rat pancreatic ß cells (INS-1). PNS treatment up-regulated Hmox1, SOD1 and GCLc expression while down-regulating miR-24-3p and miR-139-5p to suppress oxidative stress. Furthermore, we verified the novel interactions between miR-139-5p and miR-24-3p with GCLc and SOD1. CONCLUSION: This work has demonstrated the mechanism of how PNS regulates cellular molecules in metabolic disorders. Therefore, combining omics data with a systems biology strategy could be a practical means to explore the potential function and molecular mechanisms of Chinese herbal medicine in the treatment of metabolic disorders.

PbBe2B2O6: an ultraviolet nonlinear-optical crystal with unprecedented π-π interacting BeBO5 group.

π-Conjugated-group systems are fascinating and have been pursued for nonlinear materials owing to their superior optical and electronic properties, but are so far quite limited. Here, we report a new ultraviolet (UV) nonlinear-optical (NLO) beryllium borate crystal PbBe2B2O6 that manifests an unprecedented π-π interacting BeBO5 group, constructed by interconnected π-conjugated BeO3 and BO3 units. The PbBe2B2O6 crystal has a short UV cutoff wavelength of 249 nm, phase-matching behavior in the whole transmission region from UV to IR light region (249-3166 nm), and remarkably the largest NLO effect (18.5 × KDP) among the π-conjugated UV NLO crystal materials. Theoretical calculation unravels that the highly NLO-active BeBO5 group has strong π-π interactions. This work offers an innovative source of BeO3-participating NLO materials and expands the frontier of NLO research.

PbBi(SeO3)2F and Pb2Bi(SeO3)2Cl3: Coexistence of Three Kinds of Stereochemically Active Lone-Pair Cations Exhibiting Excellent Nonlinear Optical Properties.

Stereochemically active lone-pair (SCALP) cations are one attractive type of nonlinear optical (NLO)-active units because of their large microcosmic polarizability and anisotropy. Currently, the single and/or dual lone-pair cation-based noncentrosymmetric (NCS) oxides have been extensively investigated and verified to be one class of outstanding NLO materials. From the perspective of function optimization, the integration of three kinds of SCALP cations into one crystal may synergistically improve the NLO properties, which is greatly expected but unexplored to date. Herein, by introducing flexible metal halide bonds to guarantee the stereochemical activity and overcome the energetically favorable antiparallel arrangements of lone-pair cations, the first type of three lone-pair-cation (Pb2+, Bi3+, and Se4+)-coexisting NCS oxides PbBi(SeO3)2F (I) and Pb2Bi(SeO3)2Cl3 (II) was obtained. As expected, both compounds show outstanding NLO properties, such as the strong second-harmonic-generation signal (10.5× and 13.5 × KDP), large birefringence (0.103 and 0.186), relatively wide energy band gaps (3.75 and 3.45 eV), and good physicochemical stability. Theoretical calculations demonstrated the effect of three lone-pair-cation-based polyhedra and the halide anion on NLO properties.

Lead Tellurite Crystals BaPbTe2O6 and PbVTeO5F with Large Nonlinear-/Linear-Optical Responses due to Active Lone Pairs and Distorted Octahedra.

The exploration of nonlinear-/linear-optical crystal materials with high performance is an extremely difficult research project. Herein, the two new lead tellurite crystals BaPbTe2O6 and PbVTeO5F were successfully obtained through a facile hydrothermal synthesis strategy. BaPbTe2O6 lies in the noncentrosymmetric (NCS) and chiral orthorhombic space group P212121, featuring a unique ∞1[PbTe2O6] chain consisting of the PbO4 and TeO3 building units, while PbVTeO5F belonging to the centrosymmetric (CS) orthorhombic space group Pbca manifests a 2D layer made up of ∞1[PbO4F2] chains and novel [V2Te2O10F2] clusters. Further, a systematic analysis of lead tellurites finds that the coordination geometries of the Pb atom exert a considerable influence on the connection modes of Pb-O and Te-O building units. BaPbTe2O6 shows a great second-harmonic-generation (SHG) effect of ∼5× the benchmark KH2PO4 (KDP) and a large optical birefringence of 0.086 at 590 ± 3 nm. PbVTeO5F demonstrates a remarkably larger birefringence of 0.142 at 590 ± 3 nm, benefiting from the introduction of the VO5F octahedral unit. Theoretical studies reveal that the large SHG and birefringence in BaPbTe2O6 can be attributed to TeO3 and PbO4 polyhedra with active lone pairs, while the remarkably enlarged birefringence in PbVTeO5F is attributable to the highly distorted octahedral VO5F. The functional orientations of active building units may offer a practical insight into the design of the desired optical functional materials.

A phase II study of perioperative treatment in gastric cancer with No.16a2/b1 lymph node metastasis: DRAGON-06 trial.

Although gastric cancer with para-aortic lymph node (PAN) metastasis is commonly regarded as unresectable, surgeons have explored the optimal treatment for patients with PAN metastases limited to No.16a2/b1 in the past few decades. Preoperative systemic therapy combined with D2 gastrectomy plus PAN dissection may improve the prognosis of these patients. In this multicenter phase II trial, 29 gastric cancer patients with PAN metastasis limited to No.16a2/b1 will receive preoperative treatment with nab-paclitaxel, oxaliplatin, S-1 (nab-POS: nab-paclitaxel, oxaliplatin, S-1) and sintilimab followed by D2 gastrectomy plus PAN dissection; and postoperative treatment with oral S-1, intravenous sintilimab and intraperitoneal paclitaxel. The end points for the study are 3-year overall survival, 3-year disease-free survival, pathological response rate, incidence of postoperative complications and adverse events.

Stomach cancer with metastases in the para-aortic lymph nodes is usually considered inoperable. Chemotherapy combined with resection of the stomach and more extensive lymph node dissection may prolong the life of these patients. In this multicenter study, 29 stomach cancer patients with para-aortic lymph node metastases will receive preoperative treatment with nab-paclitaxel, oxaliplatin, S-1 and sintilimab, followed by resection of the stomach combined with para-aortic lymph node dissection and use of continued oral, intravenous and intraperitoneal chemotherapy. The study's end points are 3-year overall survival, 3-year disease-free survival, pathological response rate, incidence of postoperative complications and adverse events. Clinical Trial Registration: ChiCTR2200061125 (ChiCTR.org.cn).

Sr2Pb(BeB5O10)(BO3): An Excellent Ultraviolet Nonlinear-Optical Beryllium Borate by the Pb-Modified Construction of a Conjugated System and Lone-Pair Effect.

The design of material by chemical and/or crystalline modification of a classic structure model benefits not only the optimized physical properties but also the controllability and efficiency. Herein, a new nonlinear-optical (NLO) beryllium borate crystal, Sr2Pb(BeB5O10)(BO3) (SPBBO), is successfully designed and synthesized by chemical and crystalline modification of the perovskite-like K3B6O10Cl NLO crystal. SPBBO displays a 3D BeB5O103- open-framework structure composed of interconnecting BeB5O13 groups with filled cationic Sr/Pb and anionic BO3 groups, which exhibits the striking enhancement of the second-harmonic-generation (SHG) response (8 × KDP) and birefringence (0.10) compared to the parent model. Replacement of K by Sr and Pb with a lone pair and replacement of Cl by conjugated BO3 result in the synergistic conjugation of Pb with host BeB5O103- and filled BO3 groups, contributing to the striking enhancement of the SHG and birefringence. Single-crystal measurements show that SPBBO has a short UV absorption edge of 280 nm with a wide energy band gap of 4.35 eV and an outstanding laser-induced resistant behavior with a remarkably high laser-induced damage threshold of 2100 MW cm-2. The excellent properties indicate that the SPBBO crystal is a very promising UV NLO functional material.

miR-29b restrains cholangiocarcinoma progression by relieving DNMT3B-mediated repression of CDKN2B expression.

Numerous studies have reported the important role of microRNAs (miRNAs) in human cancers. Although abnormal miR-29b expression has been linked to tumorigenesis in several cancers, its role in cholangiocarcinoma remains largely unknown. We found that miR-29b expression is frequently downregulated in human cholangiocarcinoma QBC939 cells and in clinical tumor samples. In cholangiocarcinoma patients, low miR-29b expression predicts poor overall survival. Overexpression of miR-29b in QBC939 cells inhibited proliferation, induced G1 phase cycle arrest, and promoted apoptosis. Methylation-specific PCR (MSP) analysis revealed a decreased methylation imprint at the promoter of the cell cycle inhibitor gene CDKN2B in cells overexpressing miR-29b. After identifying the DNA methyltransferase DNMT3B as a putative miR-29b target, luciferase reporter assays confirmed a suppressive effect of miR-29b on DNMT3B expression. Accordingly, we detected an inverse correlation between miR-29b and DNMT3B expression in clinical cholangiocarcinoma specimens. In QBC939 cells, DNMT3B overexpression promoted proliferation and inhibited apoptosis. DNMT3B silencing, in turn, led to increased CDKN2B expression. We also observed significant growth arrest in subcutaneous tumors formed in nude mice by QBC939 cells overexpressing miR-29b. These findings suggest miR-29b functions as a tumor suppressor in cholangiocarcinoma by relieving DNMT3B-mediated repression of CDKN2B expression.

MethHC 2.0: information repository of DNA methylation and gene expression in human cancer.

DNA methylation is an important epigenetic regulator in gene expression and has several roles in cancer and disease progression. MethHC version 2.0 (MethHC 2.0) is an integrated and web-based resource focusing on the aberrant methylomes of human diseases, specifically cancer. This paper presents an updated implementation of MethHC 2.0 by incorporating additional DNA methylomes and transcriptomes from several public repositories, including 33 human cancers, over 50 118 microarray and RNA sequencing data from TCGA and GEO, and accumulating up to 3586 manually curated data from >7000 collected published literature with experimental evidence. MethHC 2.0 has also been equipped with enhanced data annotation functionality and a user-friendly web interface for data presentation, search, and visualization. Provided features include clinical-pathological data, mutation and copy number variation, multiplicity of information (gene regions, enhancer regions, and CGI regions), and circulating tumor DNA methylation profiles, available for research such as biomarker panel design, cancer comparison, diagnosis, prognosis, therapy study and identifying potential epigenetic biomarkers. MethHC 2.0 is now available at http://awi.cuhk.edu.cn/∼MethHC.

M4LiBe4P7O24 and M4Li(Li3P)P7O24 (M = Cs, Rb): deep-ultraviolet nonlinear-optical phosphates with a tetrahedra-substituted paracelsian-like framework.

New paracelsian-like beryllophosphates M4LiBe4P7O24 and their tetrahedra-substituted phases M4Li(Li3P)P7O24 (MLiP2O6, M = Cs, Rb) were designed and synthesized. Interestingly, two types of phases undergo a structural transformation, resulting from the radius and valence charge number of tetrahedral cations. Four crystals demonstrate potential deep-UV NLO properties such as short absorption edges (<190 nm) and phase-matching SHG response.

BaLiTe2O5X (X = Cl, Br): mixed alkali/alkaline-earth metal tellurite halides with [Te2O5]∞ chains.

Isostructural mixed alkali/alkaline-earth metal tellurite halides BaLiTe2O5X (X = Cl, Br) have been successfully synthesized by a mild hydrothermal method, which possess the [Te2O5]∞ chains formed by the corner-sharing connections of the TeO3 and TeO4 polyhedra. The [Te2O5]∞ chains are bridged via the LiO3 polyhedra to form the [LiTe2O5]∞ layers with 4- and 6-membered rings. The adjacent [LiTe2O5]∞ layers are linked via the BaO9 polyhedra to form the [BaLiTe2O5]∞ double layers, which are further connected via weak Ba-X-Li interactions to generate a 3D framework. Analysis of different lithium tellurites shows that the different arrangements of the Te-O and Li-O units in the lithium tellurites can be attributed to the cation-cation repulsion and lone-pair effect. Both compounds display good thermal stability, wide optical bandgaps (4.25 and 4.13 eV), and large birefringence. First-principles calculations indicate that the TeOn groups and X- determine the optical properties of BaLiTe2O5X (X = Cl, Br).

miRTarBase 2020: updates to the experimentally validated microRNA-target interaction database.

MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18-25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA-target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA-target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.

LiMII (IO3 )3 (MII =Zn and Cd): Two Promising Nonlinear Optical Crystals Derived from a Tunable Structure Model of α-LiIO3.

Excellent nonlinear optical materials simultaneously meet the requirements of large SHG response, phase-matching capability, wide transparency windows, considerable energy band-gap, good thermal stability and structure stability. Herein, two new promising nonlinear optical (NLO) crystals LiMII (IO3 )3 (MII =Zn and Cd) are rationally designed by the aliovalent substitution strategy from the commercialized α-LiIO3 with the perfect parallel alignment of IO3 groups. Compared with parent α-LiIO3 and related AI 2 MIV (IO3 )6 , the title compounds exhibit more stable covalent 3D structure, and overcome the racemic twinning problem of AI 2 MIV (IO3 )6 . More importantly, both compounds inherit NLO-favorable structure merits of α-LiIO3 and show larger SHG response (≈14× and ≈12×KDP), shorter absorption edge (294 and 297 nm) with wider energy band-gap (4.21 and 4.18 eV), good thermal stability (460 and 430 °C), phase-matching behaviors, wider optical transparency window and good structure stability, achieving an excellent balance of NLO properties.

KBi(IO3)3(OH) and NaBi(IO3)4: from the centrosymmetric chain to a noncentrosymmetric double layer.

Two new alkali-metal bismuth iodates KBi(IO3)3(OH) (1) and NaBi(IO3)4 (2) have been synthesized by a hydrothermal method via tuning of alkali-metal ions. Compound 1 crystallizes in the space group P1[combining macron] and features a [Bi(IO3)3(OH)]n chain with eight-membered Bi-O-I-O-Bi-O-I-O rings. The [Bi(IO3)3(OH)]n chain consists of paddlewheel-like dimeric Bi2(OH)2(IO3)4 units linked by IO3 pairs. Compound 2 in the polar space group Cc features a [Bi(IO3)4]- double layer with Bi4I4 eight-membered rings (8-MRs). NaBi(IO3)4 exhibits a strong second harmonic generation (SHG) response of ∼5.0 × KDP (KH2PO4) and a wide transmittance window (0.4-12 µm), and structure analyses and theoretical calculations reveal that polarization results mainly from the proper alignment of the IO3 groups. The calculated electronic structure based on the DFT method indicates that the BiOn and IO3 groups dominate their optical properties.

BeO6 Trigonal Prism with Ultralong Be-O Bonds Observed in a Deep Ultraviolet Optical Crystal Li13BeBe6B9O27.

Beryllium (Be) has high ionization energy (9.32 eV) with the greatest degree of covalency in the group IIA elements, and BeO4 tetrahedra (and BeO3 triangles) with covalent character are generally presented in beryllates. An unprecedented BeO6 trigonal prism with ultralong Be-O bonds as well as a BeO4 common tetrahedron is discovered in a new deep ultraviolet crystal Li13BeBe6B9O27 (LBeBBO) with a ∞2[Be6B9O33] double-layer framework. The BeO6 unit and its bond character are verified by an isostructural crystal Li13(Mg0.45Be0.55)Be6B9O27, while the orbital theory and charge density difference further clarify the ionic character of the BeO6 unit. Phonon dispersion confirms the structural stability of LBeBBO.

Research Progress in the Pathogenesis of Alzheimer's Disease.

OBJECTIVE: Alzheimer's disease (AD) is a kind of chronic degenerative disease of the central nervous system, characteristics of cognitive dysfunction, and behavioral disability. The pathological changes include the formation of senile plaques-containing beta-amyloid (Aß), neurofibrillary tangles (NFTs), loss of neurons, and synapses. So far, the pathogenesis of AD is still unclear. This study was aimed to review the major pathogenesis of AD-related to the published AD studies in recent 20 years. DATA SOURCES: The author retrieved information from the PubMed database up to January 2018, using various search terms and their combinations, including AD, Aß, NFTs, pathogenesis, and genetic mutation. STUDY SELECTION: The author included data from peer-reviewed journals printed in English and Chinese on pathophysiological factors in AD. He organized these informations to explain the possible pathogenesis in AD. RESULTS: There are many amounts of data supporting the view that AD pathogenesis so far there mainly are Aß toxicity, tau protein, gene mutation, synaptic damages, intermediate neurons and network abnormalities, changes in mitochondrial function, chemokines, etc., Its nosogenesis may be involved in multiple theories and involved in multiple molecular signaling pathways, including Aß, tau protein, and synaptic anomaly; mutual relationship between the mechanisms urge jointly neuronal degeneration. CONCLUSIONS: This review highlights the research advances in the pathogenesis of AD. Future research has needed to fully disclose the association between multiple pathogenesis at the same time to interdict multiple signaling pathways, etc.

Synergetic Influence of Alkali-Metal and Lone-Pair Cations on Frameworks of Tellurites.

Four new tellurites were hydrothermally synthesized by the adjustment of different alkali-metal ions, and all of the compounds demonstrate 2D layer structures. Rb2Te4O9·2H2O in centrosymmetric space group Pccn features a new [Te4O9]∞2- anion sheet consisting of rare [Te8O22]12- groups. RbNaTe8O14(OH)6·8H2O in CS space group P1̅ exhibits a [Te4O9]∞2- anion layer by linkage of the TeO3 and TeO4 units. NaPb4Te4O12F located in CS space group P4/ n displays an unusual [PbTeO3]∞ neutral layer made up of PbO3 and TeO3 trigonal pyramids. RbK3Te8O18·5H2O lying in noncentrosymmetric (NCS) space group Cc shows a [Te4O9]∞2- anion layer composed of the TeO3 and TeO4 units; its second-harmonic-generation response is about 0.2 times that of KH2PO4; structure analysis and local dipole moment calculation verify that the weak polarization mostly from the [Te4O9]∞2- layer results from the inverse arrangement of TeO n units, and further theoretical calculation confirms that TeO n groups dominate the band gap of RbK3Te8O18·5H2O and optical properties. Meanwhile, systematic analyses of a series of metal tellurites reveal that the alkali-metal cations exert a considerable impact on polarization of the crystal structures, which puts forward a feasible idea about the design of new NCS materials.

Li6Na3Sr14Al11P22O90: an oxo-centered Al3 cluster based phosphate constructed from two types of (3,6)-connected kgd layers.

A novel and thermally stable aluminum phosphate Li6Na3Sr14Al11P22O90 (1) has been achieved by using a solid-state molten method, which contains an oxo-centered trinuclear cluster and an anti-Lowenstein's rule Al-O-Al linkage and is constructed from two types of (3,6)-connected kgd layers [Al(Al3O)(PO4)7]25- and [Al(PO4)2]3-. The good optical transparency in the whole UV range and excellent thermal stability make the title compound a potential optical window material.

Modified-FOLFIRINOX in metastatic pancreatic cancer: A prospective study in Chinese population.

FOLFIRINOX chemotherapy has shown remarkable responses in patients with metastatic pancreatic cancer (MPC), and has significantly improved prognosis. However, FOLFIRINOX is currently not frequently applied in China because of its high incidence of adverse events, and there is no recognized optimization for this therapy in Chinese population. Modification of FOLFIRINOX may be better for its acceptance in China. In this study, we evaluated the efficacy and safety of modified-FOLFIRINOX in patients with MPC. A total of 62 MPC patients were treated with modified-FOLFIRINOX (no Fluorouracil bolus, 85% Oxaliplatin and 75% Irinotecan) between April 2014 and April 2017 in our institute. 40 of them were evaluated, with a response rate of 32.5% (13/40). The frequent grade 3/4 adverse events are neutropenia (29%) and alanine aminotransferase elevation (14.5%). No treatment-related death was observed. The median overall survival and median progression-free survival are 10.3 months and 7.0 months, respectively. In conclusion, modified-FOLFIRINOX had significantly improved tolerance with similar efficacy to FOLFIRINOX. These findings may provide evidence for the use of FOLFIRINOX in Chinese patients with MPC.