2'-O-methylation at internal sites on mRNA promotes mRNA stability.

2'-O-methylation (Nm) is a prominent RNA modification well known in noncoding RNAs and more recently also found at many mRNA internal sites. However, their function and base-resolution stoichiometry remain underexplored. Here, we investigate the transcriptome-wide effect of internal site Nm on mRNA stability. Combining nanopore sequencing with our developed machine learning method, NanoNm, we identify thousands of Nm sites on mRNAs with a single-base resolution. We observe a positive effect of FBL-mediated Nm modification on mRNA stability and expression level. Elevated FBL expression in cancer cells is associated with increased expression levels for 2'-O-methylated mRNAs of cancer pathways, implying the role of FBL in post-transcriptional regulation. Lastly, we find that FBL-mediated 2'-O-methylation connects to widespread 3' UTR shortening, a mechanism that globally increases RNA stability. Collectively, we demonstrate that FBL-mediated Nm modifications at mRNA internal sites regulate gene expression by enhancing mRNA stability.

Low RNA stability signifies strong expression regulatability of tumor suppressors.

RNA expression of a gene is determined by not only transcriptional regulation, but also post-transcriptional regulation of RNA decay. The precise regulation of RNA stability in the cell plays an important role in normal development. Dysregulation of RNA stability can lead to diseases such as cancer. Here we found tumor suppressor RNAs tended to decay fast in normal cell types when compared with other RNAs. Consistent with a negative effect of m6A modification on RNA stability, we observed preferential deposition of m6A on tumor suppressor RNAs. Moreover, abundant m6A and fast decay of tumor suppressor RNAs both tended to be further enhanced in prostate cancer cells relative to normal prostate epithelial cells. Further, knockdown of m6A methyltransferase METTL3 and reader YTHDF2 in prostate cancer cells both posed stronger effect on tumor suppressor RNAs than on other RNAs. These results indicated a strong post transcriptional expression regulatability mediated by abundant m6A modification on tumor suppressor RNAs.

Low RNA stability signifies increased post-transcriptional regulation of cell identity genes.

Cell identity genes are distinct from other genes with respect to the epigenetic mechanisms to activate their transcription, e.g. by super-enhancers and broad H3K4me3 domains. However, it remains unclear whether their post-transcriptional regulation is also unique. We performed a systematic analysis of transcriptome-wide RNA stability in nine cell types and found that unstable transcripts were enriched in cell identity-related pathways while stable transcripts were enriched in housekeeping pathways. Joint analyses of RNA stability and chromatin state revealed significant enrichment of super-enhancers and broad H3K4me3 domains at the gene loci of unstable transcripts. Intriguingly, the RNA m6A methyltransferase, METTL3, preferentially binds to chromatin at super-enhancers, broad H3K4me3 domains and their associated genes. METTL3 binding intensity is positively correlated with RNA m6A methylation and negatively correlated with RNA stability of cell identity genes, probably due to co-transcriptional m6A modifications promoting RNA decay. Nanopore direct RNA-sequencing showed that METTL3 knockdown has a stronger effect on RNA m6A and mRNA stability for cell identity genes. Our data suggest a run-and-brake model, where cell identity genes undergo both frequent transcription and fast RNA decay to achieve precise regulation of RNA expression.

A Non-π-Conjugated Molecular Crystal with Balanced Second-Harmonic Generation, Bandgap, and Birefringence.

Traditional nonlinear optical (NLO) crystals are exclusively limited to ionic crystals with π-conjugated groups and it is a great challenge to achieve a subtle balance between second-harmonic generation, bandgap, and birefringence for them, especially in the deep-UV spectrum region (Eg  > 6.20 eV). Herein, a non-π-conjugated molecular crystal, NH3 BH3 , which realizes such balance with a large second-harmonic generation response (2.0 × KH2 PO4 at 1064 nm, and 0.45 × ß-BaB2 O4 at 532 nm), deep-UV transparency (Eg > 6.53 eV), and moderate birefringence (Δn = 0.056@550 nm) is reported. As a result, NH3 BH3 exhibits a large quality factor of 0.32, which is evidently larger than those of non-π-conjugated sulfate and phosphate ionic crystals. Using an unpolished NH3 BH3 crystal, effective second-harmonic generation outputs are observed at different wavelengths. These attributes indicate that NH3 BH3 is a promising candidate for deep-UV NLO applications. This work opens up a new door for developing high-performance deep-UV NLO crystals.

Designing a Hybrid Perovskite with Enlarged Birefringence and Bandgap for Modulation of Light Polarization.

Birefringent crystals have important applications in optoelectronics areas due to their ability to modulate and polarize light. Despite increasing discovery of the birefringence potential of new crystals, it remains a great challenge to optimize both birefringence and bandgap simultaneously. Herein, a 1D chain-like hybrid perovskite birefringent crystal designed by 3D-to-1D dimensional tailoring, (GAM)2 PbI7 ·H2 O (GAM = C5 N10 H10 ), is presented, showing enlarged birefringence of 0.49@550 nm and enlarged optical bandgap (2.48 eV). Consequently, the birefringent quality factor of (GAM)2 PbI7 ·H2 O is up to 2.8 times that of the template MAPbI3 . In particular, the birefringence is much larger than those of commercial birefringent crystals and surpasses that of the vast majority of hybrid perovskite known to date. Theoretical calculations reveal that the strongly anisotropic arrangement of (GAM)2.5+ π-conjugated cations and ordered PbI6 octahedra contributes to the large birefringence and wide bandgap of (GAM)2 PbI7 ·H2 O. It is believed that this work will provide a new pathway toward the rational design and synthesis of hybrid perovskite birefringent crystals for compact wide-bandgap polarization dependent devices.

Deep-Ultraviolet Bialkali-Rare Earth Metal Anhydrous Sulfate Birefringent Crystal.

Birefringence is an important linear optical property of anisotropic crystals that plays a significant role in regulating light polarization. A new bialkali-rare earth metal sulfate, NaRbY2(SO4)4 compound, consisting of non-π-conjugated alkali metals and rare earth metal-centered dodecahedral YO8 has been synthesized. The structure analysis suggests that the three-dimensional (3D) structure of the compound is found to be attributable to the combination of dodecahedral YO8 and tetrahedral SO4 groups with Na+ and Rb+ located in the cavities. The ultraviolet, visible, and near-infrared (UV-vis-NIR) spectra reveal that the compound exhibits transparency at a wavelength of less than 200 nm. The observed birefringence of the compound is 0.045@550 nm, which is comparatively larger than that of most deep-ultraviolet (DUV) birefringent crystals. The birefringence mainly originated from the YO8 dodecahedron, which is suggested by first-principles calculations. This research work can provide a useful perspective to explore new DUV sulfates with excellent birefringence.

CHD6 promotes broad nucleosome eviction for transcriptional activation in prostate cancer cells.

Despite being a member of the chromodomain helicase DNA-binding protein family, little is known about the exact role of CHD6 in chromatin remodeling or cancer disease. Here we show that CHD6 binds to chromatin to promote broad nucleosome eviction for transcriptional activation of many cancer pathways. By integrating multiple patient cohorts for bioinformatics analysis of over a thousand prostate cancer datasets, we found CHD6 expression elevated in prostate cancer and associated with poor prognosis. Further comprehensive experiments demonstrated that CHD6 regulates oncogenicity of prostate cancer cells and tumor development in a murine xenograft model. ChIP-Seq for CHD6, along with MNase-Seq and RNA-Seq, revealed that CHD6 binds on chromatin to evict nucleosomes from promoters and gene bodies for transcriptional activation of oncogenic pathways. These results demonstrated a key function of CHD6 in evicting nucleosomes from chromatin for transcriptional activation of prostate cancer pathways.

Boosting the Electrocatalytic Performance of CoPt Alloy with Enhanced Electron Transfer via Atomically Dispersed Cobalt Sites.

Designing electrocatalysts with strong electronic metal-support interaction can effectively regulate the electronic properties of metal active centers, therefore maximizing the catalytic performance. As a proof of concept, heteroatoms doped carbon with CoPt alloy and isolated Co single atoms (CoPtCoSA@NSC) are synthesized using CoPt bimetallic metal-organic framework as the precursor in this work. The existence of CoSA on the carbon substrate leads to more electron transfer between CoPt and the support, and appropriate upward shift of the d band center of the catalysts, which can effectively reduce the reaction barrier of rate determine step and boost the catalytic performance of CoPt alloy. The enhanced catalytic activity and stability of CoPtCoSA@NSC are demonstrated experimentally. Remarkably, the overpotential for hydrogen evolution reaction is only 23 mV at 10 mA cm-2 and the half-wave potential for oxygen reduction reaction is 0.90 V, both exceeding the commercial Pt/C benchmark. In addition, CoPtCoSA@NSC also exhibits great potential as a cathode electrocatalyst for Zn-air battery, in terms of large open circuit potential of 1.53 V, high power density of 184 mW cm-2 , as well as superior cycling stability. This work provides a novel strategy for regulating the electronic structure and catalytic performance of alloy based electrocatalysts.

Designing a Dimension Reduced Hybrid Perovskite with Robust Large Birefringence by Expanding Cationic π-Delocation.

It is in great demand to discover new materials with large birefringence for the miniaturization of optical communication devices. In this work, a new one-dimensional hybrid halide perovskite, (C6 N10 H8 )Pb2 Br6 , is obtained successfully through structural design of dimension reduction from the notable three-dimensional halide perovskite CsPbBr3 . Remarkably, (C6 N10 H8 )Pb2 Br6 exhibits a significantly enhanced birefringence of ∆n = 0.42@550 nm, which is the largest among halide perovskites so far. Furthermore, its birefringence performance is robust in a wide temperature range of 300-440 K. Theoretical calculations reveal that this outstanding birefringence results from the synergistic effect of [PbBr6 ]4- octahedra and [C6 N10 H8 ]2+ cations with expanding π-delocation. According to further structural analyses, the structural dimension reduction cooperating with the increase of [PbBr6 ]4- octahedral distortion leads to the enhanced birefringence. This work uncovers the great promise of hybrid halide perovskites as robust birefringent crystals in future optical communication and would shed useful insights on the design and synthesis of new birefringent crystals.

Local Polarity-Induced Assembly of Second-Order Nonlinear Optical Materials.

ConspectusSecond-order nonlinear optical (NLO) materials, producing coherent light by the cascaded frequency conversion, are current hot topics in material chemistry and optics, as they play an important role in diverse fields, such as laser technology, precision measurements, and quantum information as well as future space propulsion. The prerequisite for a second-order NLO material is that it must crystallize in a noncentrosymmetric space group, but it tends to be centrosymmetric in terms of thermodynamical stability. Furthermore, it should simultaneously satisfy strict requirements on second-order NLO coefficients, birefringence, optical transmittance windows, crystal growth, and so on. Therefore, it is still an urgent challenge to rationally assemble high-performance second-order NLO materials. In this Account, we first review the significance and background of second-order NLO materials and some strategies to design new second-order NLO materials controllably. After that, we mainly present our recent studies on the rational assembly of second-order NLO materials by the so-called strategy of "local polarity-induced assembly", including: (1) making use of the coordination habit between specific cations like Li+ or Mg2+ and tetrahedral (PO4)3-, (P2O7)4-, and (SO4)2- units to generate the local polarity, and further inducing the assembly of second-order NLO materials of superb optical properties; (2) by virtue of self-condensation of weakly polarizable units, condensation of different weakly polarizable units and partial substitution of O atoms by F or S atoms in weakly polarizable units of tetrahedral MO4 or octahedral MO6 configuration, enhancing the local polarity to induce the assembly of second-order NLO materials; and (3) introducing strongly polarizable units of stereoactive lone pair electrons into π-conjugated systems to afford the local polarity and inducing second-order NLO materials with enhanced NLO responses. Based on this strategy, we successfully assembled a variety of excellent second-order NLO materials and expanded new sources of second-order NLO materials, like fluorooxosilicophosphates, thiosulfates, and borosulfates. Finally, we will conclude the topic and give some prospects for exploring new excellent second-order NLO materials. We believe that the "local polarity-induced assembly" strategy will not only be useful for understanding the structure-property relationships of second-order NLO materials but also provide researchers with insights into obtaining noncentrosymmetric structures that are essential to other functional materials in piezoelectricity, ferroelectricity, and pyroelectricity, etc.

Selection of surgical modality for massive splenomegaly in children.

BACKGROUND: Laparoscopic splenectomy (LS), a treatment for both benign and malignant splenic diseases, can prove technically challenging in patients with massive splenomegaly. In particular, the optimal surgical modality for treating massive splenomegaly in children remains controversial. METHODS: The clinicopathologic data of 289 pediatric patients undergoing splenectomy for massive splenomegaly were studied in a retrospective analysis. Accordingly, the patients were classified into the LS surgery group and open splenectomy (OS) surgery group. In the laparoscopy cohort, they were separated into two subgroups according to the method of surgery: the multi-incision laparoscopic splenectomy (MILS) and the single-incision laparoscopic splenectomy (SILS) surgery groups, respectively. Patient demographics, clinical data, surgery, complications, and postoperative recovery underwent analysis. Concurrently, we compared the risk of adverse laparoscopic splenectomy outcomes utilizing univariable and multivariable logistic regression. RESULTS: The total operation time proved remarkably shorter in the OS group in contrast to the LS group (149.87 ± 61.44 versus 188.20 ± 52.51 min, P < 0.001). Relative to the OS group, the LS group exhibited lowered postoperative pain scores, bowel recovery time, and postoperative hospitalization time (P < 0.001). No remarkable difference existed in post-operation complications or mortality (P > 0.05). Nevertheless, the operation duration was remarkably longer in the SILS surgery group than in the MILS surgery group (200 ± 46.11 versus 171.39 ± 40.30 min, P = 0.02). Meanwhile, the operative duration of MILS and SILS displayed a remarkable positive association with splenic length. Moreover, the operative duration of SILS displayed a remarkable positive association with the age, weight, and height of the sick children. Splenic length proved an independent risk factor of adverse outcomes (P < 0.001, OR 1.378). CONCLUSIONS: For pediatric patients with massive splenomegaly who can tolerate prolonged anesthesia and operative procedures, LS surgery proves the optimal treatment regimen. SILS remains a novel surgery therapy which may be deemed a substitutional surgery approach for treating massive splenomegaly.

A High-Performance Nonlinear Optical Crystal with a Building Block Containing Expanded π-Delocalization.

Common nonlinear optical (NLO) crystals consist of traditional functional building blocks with inherent optical limitation. Herein, inspired by traditional (B3 O6 )3- inorganic building block, we theoretically identified a new type of organic functional building blocks and then successfully synthesized the first cyamelurate NLO crystal, Ba(H2 C6 N7 O3 )2 ⋅ 8 H2 O. To our surprise, the constituent (H2 C6 N7 O3 )- building block is not in structurally optimal arrangement, but Ba(H2 C6 N7 O3 )2 ⋅ 8 H2 O exhibits excellent optical properties including wide band gap of 4.10 eV, very large birefringence of 0.24@550 nm, and exceptionally strong second-harmonic generation (SHG) response of about 12×KH2 PO4 . Both the SHG response and birefringence are much larger than those of commercial NLO crystal ß-BaB2 O4 with optimally aligned (B3 O6 )3- building block. Theoretical calculations suggest that the expanded π-conjugation delocalization within (H2 C6 N7 O3 )- vs (B3 O6 )3- should be responsible to the enhanced performance. This work implies that there is still much room to develop new NLO crystals with excellent functional building blocks that may be longly neglected.

A Hydrogen Bonded Supramolecular Framework Birefringent Crystal.

Birefringent crystals could modulate the polarization of light and are widely used as polarizers, waveplates, optical isolators, etc. To date, commercial birefringent crystals have been exclusively limited to purely inorganic compounds such as α-BaB2 O4 with birefringence of about 0.12. Herein, we report a new hydrogen bonded supramolecular framework, namely, Cd(H2 C6 N7 O3 )2 ⋅8 H2 O, which exhibits exceptionally large birefringence up to about 0.60. To the best of our knowledge, the birefringence of Cd(H2 C6 N7 O3 )2 ⋅8 H2 O is significantly larger than those of all commercial birefringent crystals and is the largest among hydrogen bonded supramolecular framework crystals. First-principles calculations and structural analyses reveal that the exceptional birefringence is mainly ascribed to strong covalent interactions within (H2 C6 N7 O3 )- organic ligands and the perfect coplanarity between them. Given the rich structural diversity and tunability, hydrogen bonded supramolecular frameworks would offer unprecedented opportunities beyond the traditional purely inorganic oxides for birefringent crystals.

A Two-Dimensional Hybrid Perovskite With Heat Switching Birefringence.

Birefringent crystals that can switch light polarization have important applications in optoelectronics. In the last decades, birefringence is mostly optimized by chemical strategies. Recently, switching birefringence by physical means has attracted much attention. Here, this work reports the observation of heat switching birefringence in a 2D layered hybrid halide perovskite (C2 N3 H4 )2 PbCl4 ((C2 N3 H4 )+ =1,2,4-triazolium). This heat switching birefringence leads to a significant change in the interference color for the crystal plate under the illumination of orthogonal polarized light. Structure analyses reveal a heat dependent structure transition in (C2 N3 H4 )2 PbCl4 , whose birefringence is switched by the change in the distortion degree of PbCl6 octahedron. This discovery may be beneficial to the further development of stimuli-responsive polarization optical devices.

A Functional Allele of CsFUL1 Regulates Fruit Length through Repressing CsSUP and Inhibiting Auxin Transport in Cucumber.

Fruit length is a prominent agricultural trait during cucumber (Cucumis sativus) domestication and diversifying selection; however, the regulatory mechanisms of fruit elongation remain elusive. We identified two alleles of the FRUITFULL (FUL)-like MADS-box gene CsFUL1 with 3393C/A Single Nucleotide Polymorphism variation among 150 cucumber lines. Whereas CsFUL1A was specifically enriched in the long-fruited East Asian type cucumbers (China and Japan), the CsFUL1C allele was randomly distributed in cucumber populations, including wild and semiwild cucumbers. CsFUL1A knockdown led to further fruit elongation in cucumber, whereas elevated expression of CsFUL1A resulted in significantly shorter fruits. No effect on fruit elongation was detected when CsFUL1C expression was modulated, suggesting that CsFUL1A is a gain-of-function allele in long-fruited cucumber that acts as a repressor during diversifying selection of East Asian cucumbers. Furthermore, CsFUL1A binds to the CArG-box in the promoter region of SUPERMAN, a regulator of cell division and expansion, to repress its expression. Additionally, CsFUL1A inhibits the expression of auxin transporters PIN-FORMED1 (PIN1) and PIN7, resulting in decreases in auxin accumulation in fruits. Together, our work identifies an agriculturally important allele and suggests a strategy for manipulating fruit length in cucumber breeding that involves modulation of CsFUL1A expression.

Sub-chronic ecotoxicity of triphenyl phosphate to earthworms (Eisenia fetida) in artificial soil: Oxidative stress and DNA damage.

As a flame retardant, triphenyl phosphate (TPHP) is commonly added to various daily products. Due to its easy diffusion, TPHP pollution has become a global concern. Despite the wide focus on environmental risk, the sub-chronic ecotoxicity of TPHP in soil organisms remains unclear. In this study, the artificial soil exposure method was used to analyze the oxidative stress and DNA damage in earthworms with 0, 20, 40, 60 and 80 mg/kg TPHP treatments through the response of reactive oxygen species (ROS), antioxidant and detoxifying enzymes, malondialdehyde (MDA) and olive tail moment (OTM) at 7, 14, 21 and 28 days. Throughout the experimental period, the results showed that the ROS content in earthworms treated with 20, 40, 60 and 80 mg/kg TPHP treatments increased by 9.43-18.37 %, 6.07-25.73 %, 7.71-42.61 % and 8.22-46.70 %, respectively, compared to the control treatment. Meanwhile, the activities of antioxidant and detoxification enzymes in earthworms with all TPHP treatments were significantly activated after exposure for 7 and 14 days, and then inhibited at 21 and 28 days. Despite the protection of antioxidant enzymes and detoxification enzymes, MDA content in earthworms with the 20 mg/kg treatment still significantly increased at 7 and 14 days of exposure, as well as in the other three treatments. Compared to the control treatment, the obviously higher OTM values in earthworms with TPHP treatments possibly indicated a genotoxicity of TPHP in earthworms. Furthermore, the integrated biomarker response index (IBRv2) revealed that earthworms showed an obvious biochemical response TPHP-contaminated soil, which was strongly correlated with TPHP concentrations and exposure time. This study provides insights into the TPHP hazard in the soil environment and offers a reference to assess its environmental risk to soil ecosystems.

A Hybrid Halide Perovskite Birefringent Crystal.

Birefringent crystals that can modulate the polarization of light play a significant role in modern optical devices including polarizing microscopes, optical isolators, and achromatic quarter-wave plates. To date, commercial birefringent crystals are exclusively limited to purely inorganic compounds. Here we report a new organic-inorganic hybrid halide, MLAPbBr4 (MLA=melamine), which features a (110)-oriented layered perovskite structure. Although the 6s2 lone-pair electrons of Pb2+ cations are stereochemically inert, MLAPbBr4 exhibits a birefringence of 0.322@550 nm, which exceeds those of all commercial birefringent crystals. The first-principles calculations reveal that this birefringence should be ascribed to the highly dislocated π-conjugation of MLA cations and high distortion of PbBr6 octahedra. This work highlights the persistently neglected great potential of hybrid halide perovskites as birefringent crystals.

A Hybrid Antiperovskite with Strong Linear and Second-Order Nonlinear Optical Responses.

Antiperovskites have been studied since the 1980s because of their rich physical and chemical properties, but their linear and second-order nonlinear optical responses remain largely unknown. Here we report a new polar crystal, Cs3 Cl(HC3 N3 S3 ) (I), which features a quasi-one-dimensional antiperovskite structure composed of ClCs6 polyhedra and A-site [HC3 N3 S3 ]2- rings. To our best knowledge, this kind of antiperovskite structure is reported for the first time. Remarkably, I exhibits a very strong nonlinear optical response up to 11.4 times that of the benchmark KH2 PO4 and exceptionally large birefringence of 0.52. The first-principles calculations and structural analyses reveal that [HC3 N3 S3 ]2- is the "material gene" while the antiperovskite structural feature making it in a favorable arrangement. This work provides a new structural platform for the rational design of integrated optoelectronic materials with linear and second-order nonlinear optical responses.

An Optically Anisotropic Crystal with Large Birefringence Arising from Cooperative π Orbitals.

Birefringent materials are highly demanded for high-performance polarized optics. As compared with artificial anisotropic metamaterials, anisotropic crystals have advantages of low optical losses and easy processing, but their birefringence is still limited. Herein, based on first-principles studies, we identified a new type of functional anion units, (Hx C6 N9 )(3-x)- (x=0, 1, 2), and then successfully synthesized a new anisotropic crystal, namely, CsH2 C6 N9 ⋅H2 O (I), whose crystal structure consists of (H2 C6 N9 )- anions. Remarkably, I is ultraviolet transparent and exhibits very large birefringence of about 0.55@550 nm, which is much larger than those of commercial birefringent crystals. These results make I a candidate for highly efficient manipulation of optics and light in optical modulation devices. Theoretical calculations reveal that large birefringence mainly arises from the cooperative π orbitals in (H2 C6 N9 )- anions. This work provides a new insight on the underlying structure-property relationships of anisotropic crystals.

A New Nonlinear Optical Material with N(CN)2 - Anion.

Discovering new functional genes and developing high-performance materials are the goals being pursued by scientists. In this work, we successfully obtained a second-order nonlinear optical (NLO) material via the aqueous solution method, Y[N(CN)2 ]4 [NH(C2 H5 )3 ] ⋅ 3H2 O, which is the first NLO material with the anionic group N(CN)2 - . Remarkably, this material is not only strongly NLO-active at 1064 nm with a response of about 2.8 × KH2 PO4 , but also possesses a short UV absorption edge of 250 nm. In-depth first-principles calculations illustrate well that the optical properties are mainly from the strong interaction of N, C and Y atoms. This result indicates that the N(CN)2 - anion may be a new NLO functional gene. This work enriches the diversity of NLO functional genes and materials.