1,2-BF2 Shift and Photoisomerization Induced Multichromatic Response.

Adaptive materials that exhibit a multichromatic response as a function of applied stimulus are highly desirable, as they can result in applications ranging from smart surfaces to anticounterfeit devices. Here we report on such a system based on an intriguing thermal 1,2-BF2 shift that transforms a visible-light-activated azo-BF2 photoswitch into a BF2-hydrazone fluorophore (BODIHY) in both solution and the solid-state. Structure-property analysis, in conjunction with DFT calculations, reveals that the shift is catalyzed by the spatial proximity of an oxygen atom next to the BF2 group and that the activation originates from an electronic and not steric effect. Theoretical calculations also show that while the energy barrier for the trans → BODIHY transformation is accessible at room temperature (thermal half-life of 30 h), the cis → BODIHY transformation has a much higher barrier, which is why the 1,2-BF2 shift is not observed for the cis form. The photoswitching of the azo-BF2, in conjunction with the 1,2-BF2 shift, was then used in the multicolor modulation of a switch-containing cross-linked polydimethylsiloxane film using light and/or heat stimuli, elaborating the usefulness of the sophisticated reaction cascade that can be accessed from this simple system.

The influence of short-range molecular order in gelatinized starch on the formation of starch-lauric acid complexes.

A model system of gelatinized wheat starch (GWS) and lauric acid (LA) was used to examine the effect of residual short-range molecular order in GWS on the formation of starch-lipid complexes. The extent of residual short-range molecular order, as determined by Raman spectroscopy, decreased with increasing water content or heating duration of gelatinization. The enthalpy changes, crystallinity, short-range molecular order and the in vitro enzymic digestion of GWS-LA complexes increased initially to a maximum and then declined as the short-range molecular order in GWS decreased, showing that there was an optimal amount of residual short-range molecular order in GWS for maximizing GWS-LA complexes formation. Below this optimum amount, the limited disruption of short-range molecular order may constrain the mobility of amylose chains for complexation with LA, whereas with excessive disruption above this amount the amylose chains may be too disorganized or entangled to form complexes with LA. The susceptibility of GWS-LA complexes to enzymatic hydrolysis was influenced by both long- and short-range structural order, and to a lesser extent the amounts of complexes. This study showed clearly the role of short-range molecular order in gelatinized starch in influencing the formation of GWS-LA complexes.

Synthesis and Photophysical Properties of Silole-Fused Cycloparaphenylenes.

Herein, we report the introduction of a silole unit into cycloparaphenylenes (CPPs), and two compounds [12]Si3CPP and [16]Si4CPP are obtained by a platinum- and gold-mediated cyclooligomerization strategy. Their optical and electronic properties are studied by UV-vis absorption and fluorescence spectra, which show red shifts and higher photoluminescence quantum yields (PLQYs) compared with the corresponding CPPs.

Photoinduced Phosphination of Arenes Enabled by an Electron Donor-Acceptor Complex Using Thianthrenium Salts.

Herein, we describe a metal-free approach for the cross-coupling of arenes or styryl-thianthrenium salts (TTs) with diarylphosphines via an electron donor-acceptor (EDA) complex. Various tertiary phosphines were obtained with high site selectivity and good functional group tolerance. This method enables straightforward construction of C-P bonds via C-H activation of arenes and allows the late-stage functionalization of natural products or pharmaceutical molecules. Mechanistic studies support the approach involving a photoinduced EDA complex.

Rational design of supramolecular self-assembly sensor for living cell imaging of HDAC1 and its application in high-throughput screening.

Supramolecular chemistry offers new insights in bioimaging, but specific tracking of enzyme in living cells via supramolecular host-guest reporter pair remains challenging, largely due to the interference caused by the complex cellular environment on the binding between analytes and hosts. Here, by exploiting the principle of supramolecular tandem assay (STA) and the classic host-guest reporter pair (p-sulfonatocalix[4]arene (SC4A) and lucigenin (LCG)) and rationally designing artificial peptide library to screen sequence with high affinity of the target enzyme, we developed a "turn-on" fluorescent sensing system for intracellular imaging of histone deacetylase 1 (HDAC1), which is a potential therapeutic target for various diseases, including cancer, neurological, and cardiovascular diseases. Based on computational simulations and experimental validations, we verified that the deacetylated peptide by HDAC1 competed LCG, freeing it from the SC4A causing fluorescence increase. Enzyme kinetics experiments were further conducted to prove that this assay could detect HDAC1 specifically with high sensitivity (the LOD value is 0.015 µg/mL, ten times lower than the published method). This system was further applied for high-throughput screening of HDAC1 inhibitors over a natural compound library containing 147 compounds, resulting in the identification of a novel HDAC1 down-regulator (Ginsenoside RK3). Our results demonstrated the sensitivity and robustness of the assay system towards HDAC1. It should serve as a valuable tool for biochemical studies and drug screening.

Visualizing Drug Release from a Stimuli-Responsive Soft Material Based on Amine-Thiol Displacement.

In this research, we developed a photoluminescent platform using amine-coupled fluorophores, generated from a single conjugate acceptor containing bis-vinylogous thioesters. Based on the experimental and computational results, the fluorescence turn-on mechanism was proposed to be charge separated induced energy radiative transition for the amine-coupled fluorophore, while the sulfur-containing precursor was not fluorescent since the energy internal conversion occurred through vibrational 2RS- (R represents alkyl groups) as energy acceptor(s). Further utilizing the conjugate acceptor, we establish a new fluorogenic approach via a highly cross-linked soft material to selectively detect cysteine under neutral aqueous conditions. Turn-on fluorescence emission and macroscopic degradation occurred in the presence of cysteine as the stimuli, which can be visually tracked due to the generation of an optical indicator and the cleavage of linkers within the matrix. Furthermore, a novel drug delivery system was constructed, achieving controlled release of sulfhydryl drug (6-mercaptopurine) which was tracked by photoluminescence and high-performance liquid chromatography. The photoluminescent molecules developed herein are suitable for visualizing polymeric degradation, making them suitable for additional "smart" material applications.

Comprehensive bioinformatics analysis on exportins in lung adenocarcinoma and lung squamous cell carcinoma.

Background: Lung cancer is one of the most common malignant tumors in the world. Exportins are closely associated with the cellular activity and disease progression in a variety of different tumors. However, the expression level, genetic variation, immune infiltration, and biological function of different exportins in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), as well as their relationship with the prognosis of patients with LUAD and LUSC have not been fully clarified. Methods: To analyze the differential expression, prognostic value, genetic variation, biological function, and immune cell infiltration of exportins in patients with LUAD and LUSC, the ONCOMINE; UALCAN; Human Protein Atlas (HPA); Kaplan-Meier plotter; cBioPortal; Search Tool for the Retrieval of Interacting Genes/Proteins (STRING); Database for Annotation, Visualization, and Integrated Discovery (DAVID); Tumor Immune Estimation Resource (TIMER); and LinkedOmics databases were used in this study. Results: The transcriptional and protein expression levels of CSE1L and XPO1/5/6/7 were increased in patients with LUAD and LUSC, and the increased transcriptional levels of CSE1L and XPO5/6/7 were related to worse prognosis. An increased transcriptional level of XPO1 was associated with a better prognosis. These results indicated that CSE1L and XPO1/5/6/7 may be potential prognostic biomarkers for the survival of patients with LUAD and LUSC. Moreover, the high mutation rate of exportins in non-small cell lung cancer was 50.48%, and the largest proportion of mutations included high messenger RNA expression. The expression of exportins was significantly correlated with the infiltration of various immune cells. Differentially expressed exportins could regulate the occurrence and development of LUAD and LUSC by involving a variety of microRNAs and transcription factor E2F1. Conclusions: Our study provides novel insights into the selection of prognostic biomarkers of exportins in LUAD and LUSC.

Small peptide LINC00511-133aa encoded by LINC00511 regulates breast cancer cell invasion and stemness through the Wnt/ß-catenin pathway.

LINC00511 is an long non-coding RNA (lncRNA) of ncRNAs,This study aimed to investigate whether the lncRNA LINC00511 could encode a small peptide, LINC00511-133aa, and whether this peptide could promote breast cancer cell metastasis and stemness by activating the wnt/ß-catenin pathway. The LINC00511-133aa coding sequence vector and control vector were transfected into MCF-7 and MDA-MB-231 breast cancer cells, with subsequent assessment of peptide expression using PCR, western blotting, and immunofluorescence assays. Cell proliferation, invasion, and apoptosis were evaluated using CCK8, apoptotic, wound healing, and transwell invasion assays, while the characteristic changes of tumor stem cells were detected through sphere-forming assay and western blot analyses of the stemness markers Oct4, Nanog, and SOX2. Results showed that LINC00511-133aa was indeed encoded by LINC00511 and promoted the invasiveness and stemness of breast cancer cells while limiting apoptosis by modulating the expression levels of wnt/ß-catenin pathway-related proteins Bax, c-myc, and CyclinD1, as well as facilitating ß-catenin protein entry into the nucleus. This study provides evidence for the potential involvement of lncRNA LINC00511 and its peptide product in breast cancer progression via the regulation of the wnt/ß-catenin pathway.

Ground-state intramolecular proton transfer inhibits the selective methylation on quinoline and pyridine derivatives.

Methylation is one of the crucial steps for drug discovery, organic synthesis, and catalysis. Despite being a versatile and well-known chemical reaction, its chemoselectivity has not been well addressed. In this paper, we reported a thorough experimental and computational investigation of the selective N-methylation of N-heterocyclic compounds, mainly quinolines and pyridines. These reactions were conducted in a base-free manner under ambient conditions using iodomethane as the methylating reagent, exhibited good chemoselectivity, and were tolerant of other amine, carboxyl, or hydroxyl functional groups without needing protection. To this end, 13 compounds were synthesized as a proof-of-concept and 7 crystal structures were obtained. However, the chemoselectivity failed in the presence of a thiol group. Detailed quantum chemical calculations provided insights into the N-methylation mechanism and its selectivity and demonstrated that the isomerization induced by ground-state intramolecular proton transfer (GSIPT) in the presence of a thiol group inhibits the N-methylation.

Rational Design to Activate Tetrafluoromethane by Two-Coordinate Borinium.

The activation of tetrafluoromethane (CF4) is quite challenging. The current methods have a high decomposition rate but are expensive, and therefore, their widespread use is limited. Here, inspired by the successful C-F activation within saturated fluorocarbons, we have designed a rational approach based on two-coordinate borinium for activating CF4 using density functional theory (DFT) calculations. Our calculations predict that this approach is both thermodynamically and kinetically favorable.

Ferroptosis Inhibitor Regulates the Disease Progression of Systematic Lupus Erythematosus Mice Model Through Th1/Th2 Ratio.

BACKGROUND: Systematic lupus erythematosus (SLE) is an autoimmunemediated disease. So far, there is no relevant report on ferroptosis in SLE research, and the role of T helper 1 (Th1) and T helper 2 (Th2) cells in SLE is still unclear. METHODS: This study employed SLE mice models with and without ferroptosis inhibitors (Liproxstatin­1) and normal control mice. Treated mice were analyzed with hematoxylin and eosin (H&E) staining, immunohistochemical detection of glutathione peroxidase 4 (GPX4), malondialdehyde (MDA) detection, ELISA(enzyme-linked immunosorbent assay) detection of Th1 and Th2 cytokines and flow cytometry detection of Th1 and Th2 ratio. RESULTS: The results showed that compared with the normal group, the SLE group exhibited significantly higher expression of anti-double-stranded deoxyribonucleic acid (anti-dsDNA), MDA and Th1 cytokines, significantly lower expression of GPX4 and Th2 cytokines and increased Th1/Th2 ratio. Similarly, compared with the SLE group, the SLE + liproxstatin-1 group showed significantly low expression of anti-dsDNA, MDA and Th1 cytokines, significantly high expression of GPX4 and Th2 cytokines and reduced Th1/Th2 ratio. CONCLUSION: These results demonstrate that ferroptosis may be involved in promoting SLE development. Therefore, inhibiting ferroptosis may be a potential treatment for SLE. Similarly, the Th1/Th2 ratio may have a role in promoting SLE development.

Distinguishing functional and structural MRI abnormalities between bipolar and unipolar depression.

Background: This study aims to investigate the underlying characteristics of spontaneous brain activity by analyzing the volumes of the hippocampus and parahippocampal gyrus, as well as the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo), in order to differentiate between bipolar disorder (BD) and unipolar depressive disorder. Methods: A total of 46 healthy controls, 58 patients with major depressive disorder (MDD), and 61 patients with BD participated in the study and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. The researchers calculated the differences in volume, fALFF, and ReHo values among the three groups. Additionally, they conducted correlation analyses to examine the relationships between clinical variables and the aforementioned brain measures. Results: The results showed that the BD group exhibited increased fALFF in the hippocampus compared to the healthy control (HC) and MDD groups. Furthermore, the ReHo values in the hippocampus and parahippocampal gyrus were significantly higher in the BD group compared to the HC group. The findings from the person correlation analysis indicated a positive relationship between ReHo values in the hippocampus and both HAMD and HAMA scores. Moreover, there was no correlation between the volumes, fALFF, and ReHo values in the hippocampus and parahippocampal gyrus, and cognitive function levels (RBANS). Conclusion: Taken together, these aberrant patterns of intrinsic brain activity in the hippocampus and parahippocampal gyrus may serve as quantitative indicators for distinguishing between BD and unipolar depression.

Effects of Typical Solvents on the Structural Integrity and Properties of Activated Kaolinite by Wet Ball Milling.

The influence of organic solvents on the structural integrity and properties of activated kaolinite were compared and analyzed via characterization techniques and molecular dynamics (MD) simulation. The results revealed that the organic intercalators can be easily inserted into the interlayer spaces of activated kaolinite within a short time of the wet ball milling. The DMSO intercalated kaolinites maintained structural integrity due to the high intercalation rate and the excellent buffering effect against the crushing force of milling during the delamination/exfoliation process. The delaminated layers of the DMSO-kaolinite complex exhibited a high specific surface area of 99.12 m2/g and a low average thickness of 35.21 nm. The calculated elastic properties of the organo-kaolinite complex manifested the intercalation of DMSO into a kaolinite interlayer, which could improve the compressibility and structural integrity of kaolinite nanosheets. The DMSO-kaolinite complex was easier to peel off when compared to the other organic intercalators due to its more intercalated molecules.

Cyberbullying definitions and measurements in children and adolescents: Summarizing 20 years of global efforts.

Despite numerous instruments existing to assist in the measurement of specific cyberbullying behaviors or cyberbullying in general, it is still unclear their purpose, corresponding scenarios, and their effectiveness. This study, therefore, aims to provide a comprehensive review of academic efforts on cyberbullying definitions, measurements, and their effectiveness in children and adolescents in the past two decades. A systematic review was performed using ASReview, an open source machine learning systematic review system. Three bibliographic citation databases, including Web of Science core collection, PubMed, and EBSCO were adopted for all relevant literature published from January 2001 to August 2021. In total, twenty-five studies, mentioning seventeen cyberbullying measurement scales, met the study collection criteria. The results found that most failed to provide a clear definition of cyberbullying, often providing unclear and inconsistent descriptions for the youth. Similarly, studies found it difficult to clearly reflect the three key elements of bullying, namely: harmfulness, repetitiveness, and the power imbalance between bullies and victims. With regard to cyberbullying types, most presented two or three categories, including victimization, perpetration, and bystanding, while some suggested four types based on the nature of the cyberbullying behavior, including written or verbal, visual or sexual, character impersonation, and exclusion. If characteristics are considered, cyberbullying becomes more specific with multiple categories being proposed, including flaming (or roasting), harassment, denigration, defamation, outing, jokes, online sexual harassment, and cyberstalking. With regard to measurements, many scales have been proposed and frequently refined to capture specific cyberbullying experience of the youth. This study emphasizes the value and importance of providing clear cyberbullying definitions and helps scholars in youth cyberbullying choose appropriate measurement scales.

A web-based database server using 43,710 public RNA-seq samples for the analysis of gene expression and alternative splicing in livestock animals.

BACKGROUND: Livestock animals is of great significance in agricultural production. However, the role of specific gene expression, especially alternative splicing in determining phenotype, is not well understood. The livestock research community needs a gene expression and alternative splicing database contributing to livestock genetic improvement. DESCRIPTION: We report the construction of LivestockExp ( https://bioinfo.njau.edu.cn/livestockExp ), a web-based database server for the exploration of gene expression and alternative splicing using 43,710 uniformly processed RNA-seq samples from livestock animals and several relative species across six orders. The database is equipped with basic querying functions and multiple online analysis modules including differential/specific expression analysis, co-expression network analysis, and cross-species gene expression conservation analysis. In addition to the re-analysis of public datasets, users can upload personal datasets to perform co-analysis with public datasets. The database also offers a wide range of visualization tools and diverse links to external databases enabling users to efficiently explore the results and to gain additional insights. CONCLUSION: LivestockExp covers by far the largest number of livestock animal species and RNA-seq samples and provides a valuable data resource and analysis platform for the convenient utilization of public RNA-seq datasets.

Scaling up ultrathin boat-graphane with the non-classical stiffness relation to macroscopic metamaterials.

Scaling up ultrathin nanosheets with unusual mechanical properties to macroscopic metamaterials is an intriguing topic considering the significant gap of their characteristic scales. In this regard, we investigate the relation between the in- and out-of-plane stiffness of monolayer boat-graphane in two principal axis directions by quantum mechanical calculations. A non-classical relation between the two types of stiffness is found, in opposition to the classical one for orthotropic thin plates. Analytical lattice dynamics models are proposed and suggest that the two kinds of stiffness stem from different covalent interaction sources, giving rise to the discrepancy. Guided by the geometry of boat-graphane and the model predictions, the non-classical relation successfully scales to macroscopic metamaterial plates, as justified by finite element simulations. The key structural parameters for successful scaling are also explored. The present work not only enriches our understanding of the nanomechanics of ultrathin nanosheets but also suggests a novel approach to construct mechanical metamaterials.

LncRNA AC098934 promotes proliferation and invasion in lung adenocarcinoma cells by combining METTL3 and m6A modifications.

Background: Long non-coding RNA (lncRNA) regulates the tumorigenesis as well as the development of lung adenocarcinoma (LUAD), which is one of the high-mortality cancers. We explored the influence of lncRNA AC098934 on the malignant biological behavior of LUAD and potential underlying molecular mechanisms. Methods: The expression level of AC098934 in either the LUAD or the normal tissues was identified in the TCGA database. Two AC098934 knockdown siRNAs were infected into cells of LUAD, including A549 as well as H1299 cells, using the lentivirus. Real-time Quantitative polymerase chain reaction (QPCR) helped to determine the knockdown efficiency of AC098934. CCK-8, cell cloning, wound healing combined with transwell assays tested the role of AC098934 in the cell proliferation, migration as well as the invasion. Tumor formation experiment in nude mice subcutaneously confirmed the promoting effect of AC098934 in vivo. In addition, combinations of METTL3 and AC098934, as well as m6A and AC098934 were identified through the RIP assay. Results: Compared to the normal tissues, AC098934 was more highly expressed in LUAD tissues. After AC098934 was knocked down by siRNA, the proliferation, invasion, migration as well as tumorigenesis abilities of both A549 and H1299 cells were reduced. Mechanistically, AC098934 could bind to the m6A antibody and METTL3 protein. METTL3 overexpression promoted the m6A modification on AC098934, thereby increasing the interaction of m6A modification. Conclusion: The highly expressed lncRNA AC098934 in LUAD facilitates the cell proliferation as well as invasion either in vitro or in vivo. METTL3 binds, furthermore, modulates the m6A modification of AC098934. Our research revealed a new molecular mechanism, through which AC098934 promoted the malignant behavior of LUAD tumors under the m6A modification induced by METTL3. This indicates that AC098934 is possible to be a promising biomarker as well as a therapeutic target for the patients with LUAD.

Synthesis, Characterization and Photophysical Properties of Mesoionic N-Heterocyclic Imines.

N-heterocyclic imines are widely used in transition-metal chemistry, main-group chemistry as well as catalysis, due to their enhanced basicity and nucleophilicity which benefit from their ylidic form. As their analogs, mesoionic N-heterocyclic imines, which feature more highly ylidic form, is still in its infancy though excellent works also achieved. Here we reported the synthesis, characterization and photophysical properties of mesoionic N-heterocyclic imines. TD-DFT are employed to get deeper insight into the mechanism of the photophysical behaviors. The unsubstituted mesoionic N-heterocyclic imines (4-6) displayed considerable quantum yields (QY: up to 43.8%) and could be potentially applied as luminescent materials.

CYP2D6 Gene Polymorphisms and Variable Metabolic Activity in Schizophrenia Patients of Han and Tibetan Populations.

Background: It has been suggested that the pharmacogenomic response to antipsychotics in schizophrenia patients partially contributed by drug metabolism enzyme polymorphism, including P450 2D6 (CYP2D6). However, CYP2D6 gene polymorphism across populations is largely unknown. Materials and Methods: Here, we investigated the differences of CYP2D6 gene polymorphism between Chinese Han and Tibetan schizophrenia patients. We analyzed five CYP2D6 gene related polymorphic locus in 103 patients with schizophrenia, including 60 Han ethnicity and 43 of Tibetan ethnicity, by nucleic acid MALDI-TOF. Results: Polymorphisms of rs1065852, rs1135840 and rs16947 were significantly different between Han and Tibetan patients. rs1065852 AA genotype had a low frequency of 9.3% in Tibetan patients in comparison with a frequency of 41.7% in Han patients, whereas rs16947 AA genotype had a low frequency of 3.3% in Han patients in comparison with a frequency of 34.9% in Tibetan patients. Additionally, the two patient groups showed distinct distribution of CYP2D6 haplotypes, with the highest frequency of *10/*10 and *1/*2 in Han and Tibetan patients, respectively. Furthermore, Han and Tibetan patients showed differential CYP2D6 metabolic activity. Discussion: Taken together, this exploratory study showed the differences of CYP2D6 gene and metabolic polymorphism between Han and Tibetan schizophrenia patients, and therefore may improve our understanding of the pharmacogenomic response to antipsychotics in schizophrenia patients across populations.

DNMT3B regulates proliferation of A549 cells through the microRNA-152-3p/NCAM1 pathway.

The purpose of the present study was to examine the epigenetic mechanism by which microRNA (miR)-152-3p regulates proliferation in non-small cell lung cancer A549 cells via neural cell adhesion molecule 1 (NCAM1). Bisulfite sequencing PCR (BSP), the gold standard for methylation detection, uses bisulfite-treated DNA to determine its pattern of methylation. Treatment of DNA with bisulfite converts cytosine residues to uracil, but leaves 5-methylcytosine residues unaffected. It was conducted and demonstrated a relatively high level of methylation in the miR-152-3p promoter region. Chromatin immunoprecipitation was combined with PCR to detect the binding of DNA methyltransferase 3B (DNMT3B) protein to miR-152-3p, which tends to occur in the core region of the miR-152-3p gene in A549 cells. Luciferase assay identified NCAM1 as the target gene of miR-152-3p. MTT, colony formation and Transwell assays indicated that miR-152-3p could decrease cell proliferation and invasion and in addition to reducing the expression level of NCAM1. Overexpression of NCAM1 could attenuate the effect of miR-152-3p. DNMT3B knockdown decreased the proliferative ability of A549 cells and increased the expression of miR-152-3p, while decreased that of NCAM1. After treatment with miR-152-3p inhibitor, these effects were attenuated and the NCAM1 expression level was upregulated. The results indicated that miR-152-3p may suppress the proliferation of A549 cells by downregulating NCAM1. In addition, DNMT3B negatively regulated the expression of miR-152-3p via modulation of the methylation level in the miR-152-3p core region, thus mediating the proliferation of lung tumor cells.