Recent development of organic small-molecule and nanomaterial fluorescent probes for hydrazine

Hydrazine,an essential chemical,has been used within a wide spectrum of industries,including pesticides,pharmaceuticals and even satellite-launching systems.However,the excessive consumption of hydrazine raised the risk of environmental pollution accidents and occurrence of diseases because of its high toxicity and volatility.This led to the discovery of diverse fluorescent probes for the monitoring of the dangerous substance,including those based on organic small molecules and emerging nanomaterials.Herein,we are going to present a comprehensive review of recently reported hydrazine fluorescent probes,and discuss their structure design strategies and detection mechanisms.In particular,both organic small-molecule and nanomaterial fluorescent probes for hydrazine will be discussed together for the first time.

Recent Progress in Endoplasmic Reticulum-Targetable Small-Molecule Probes for Fluorescence Sensing and Phototherapy

The endoplasmic reticulum(ER)is the most widespread organelle within eukaryotic cells,performing various essential functions such as protein synthesis,post-translational modifications,and lipid metabolism.Abnormal fluctuations of biologically active species and microenvironments in the ER can disrupt homeostasis and eventually lead to ER stress,which is closely linked to the occurrence and progression of many human diseases.Therefore,the ER has been regarded as an important analytical object as well as a promising therapeutic target in both bio sensing and biomedicine.Recently,there has been a growing interest in developing photon-excited molecular tools to uncover the physio pathological roles of ER and treat ERrelated disorders.This review presents a comprehensive summary of recent advances in ER-targeted small-molecule probes and their applications for fluorescent sensing and phototherapy,mainly focusing on targeting strategies and probe design principles.Last,we discuss the challenges involved with ER-targeted probes and highlight potential prospects in this field.

英汉笔译课程PROBE教学模式探究

作为本科翻译专业的一门核心课程,英汉笔译课程在培养学生英汉双语运用能力、翻译能力和跨文化能力,尤其是学生英译汉翻译实践能力作用明显。文章对“PROBE教学模式”进行概念诠释,从教学目标、课程设计、教学过程和学习评价四个方面探讨了“PROBE教学模式”在英汉笔译课程中的应用,最后提出几点建议,以期提高英汉笔译课程的教学效果。

Discovery of a small-molecule bromodomain-containing protein 4 inhibitor that induces AMP-activated protein kinase-modulated autophagy-associated cell death in breast cancer

OBJECTIVE To discover a small-molecule bromodomain-containing protein 4(BRD4)inhibitor that induces AMP-activated protein kinase-modulated autophagy-associated cell death in breast cancer and exploreits potential mechanisms.METHODS BRD4 interactors were analyzed by PPI network prediction and The Cancer Genome Atlas(TCGA)analysis.The interaction between BRD4 and AMPK was confirmed by co-immunoprecipitation assay.Novel BRD4 inhibitors were designed and synthesized based upon pharmacophore analysis of BRD4(1),then screened by antiproliferative activity and Alpha Screen of BRD4(1).The selectivity of the best candidate compound 8f was validated by co-crystallization,FRET assay and co-immuno precipitation assay.The mechanisms of 8f were investigated by fluorescence microscopy,electron microscopy,Western blotting,immunocytochemistry,si RNA and GFP-m RFP-LC3 plasmid transfections,as well as immunohistochemistry and immunofluorescence.Potential mechanisms were discovered by i TRAQ-based proteomics analysis and the therapeutic effect of 8f was assessed by xenograft breast cancer mouse and zebrafish models.RESULTS We identified that BRD4 interacted with AMPK,which was remarkably downregulated in breast cancer.We next designed and synthesized 49 candidate compounds,and eventually discovered a selective small-molecule inhibitor of BRD4(8f).Subsequently,8f was discovered to induce autophagyassociated cell death(ACD)by BRD4-AMPK interaction,and thus activating AMPK-m TOR-ULK1-modulated autophagic pathway in breast cancer cells.Interestingly,the i TRAQ-based proteomics analyses revealed that 8f induced ACD pathways,involved in HMGB1,VDAC1/2 and e EF2.Moreover,8f displayed a therapeutic potential on both xenograft breast cancer mouse and zebrafish models.CONCLUSION We discovered a novel small-molecule inhibitor of BRD4 that induces BRD4-AMPK-modulated ACD in breast cancer,which may provide a candidate drug for future cancer therapy.

Transient Folate Deprivation in Combination with Small-molecule Compounds Facilitates the Generation of Somatic Cell-derived Pluripotent Stem Cells in Mice

Induced pluripotent stem cells （iPSCs） can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for the extra-embryonic tissues. This iPSC technology not only represents a new way to use individual-specific stem cells for regenerative medicine but also constitutes a novel method to obtain large numbers of disease-specific cells for biomedical re- search. However, the low efficiency of reprogramming and genomic integration of oncogenes and viral vectors limit the potential application of iPSCs. Chemical-induced reprogramming offers a novel ap- proach to generating iPSCs. In this study, a new combination of small-molecule compounds （SMs） （so- dium butyrate, A-83-01, CHIR99021, Y-27632） under conditions of transient folate deprivation was used to generate iPSC. It was found that transient folate deprivation combined with SMs was sufficient to permit reprogramming from mouse embryonic fibroblasts （MEFs） in the presence of transcription factors, Oct4 and Klf4, within 25 days, replacing Sox2 and c-Myc, and accelerated the generation of mouse iPSCs The resulting cell lines resembled mouse embryonic stem （ES） cells with respect to proliferation rate, morphology, pluripotency-associatedmarkers and gene expressions. Deprivation of folic acid, combined with treating MEFs with SMs, can improve the inducing efficiency of iPSCs and reduce their carcino- genicity and the use of exogenous reprogramming factors.

Efficient small-molecule donor with improved structural order and molecular aggregation enabled by side-chain modification

Side-chain modification is a proven effective approach for morphology manipulation in organic solar cells(OSCs).However,in-depth analysis and investigation involving side-chain modification towards morphology improvement,including molecular microstructure,orientating packing and aggregation are urgent for all-small-molecule(ASM)systems.Herein,employing a fluorine-modified two-dimension benzodithiophene(BDT)as central unit,we contrastively synthesized two small-molecule donors,namely BDT-F-SR and BDT-F-R,each welding alkylthio side-chains on thienyl of central BDT unit and the other grafted non-sulfuric alkyl side-chains.As predicted,the synergetic side-chain modification of fluorination and alkyl changeover triggers diverse molecular dipole moments and orientations,resulting in different molecular energy levels,thermal stabilities,molecular planarity and order.Eventually,together with the preeminent small-molecule acceptor Y6,BDT-F-R-based ASM OSCs obtain enhanced power conversion efficiency(PCE)of 13.88%compared to BDT-F-SR-based devices(PCE of 12.75%)with more suitable phase-separation and balanced carrier mobilities.The contrast results reveal that alkyl sidechains seem to be a more satisfactory partner for fluorine-modified 2D BDT-based small-molecule donors compared to alkylthio pendants,and highlight the significance of subtle side-chain modification for molecular structural order fun-tuning and morphology control,laying the foundation for efficient ASM OSCs.

Design,synthesis,and evaluation of fluoroquinolone derivatives as microRNA-21 small-molecule inhibitors

MicroRNA-21(miRNA-21)is highly expressed in various tumors.Small-molecule inhibition of miRNA-21 is considered to be an attractive novel cancer therapeutic strategy.In this study,fluoroquinolone derivatives A1eA43 were synthesized and used as miRNA-21 inhibitors.Compound A36 showed the most potent inhibitory activity and specificity for miRNA-21 in a dual-luciferase reporter assay in HeLa cells.Compound A36 significantly reduced the expression of mature miRNA-21 and increased the protein expression of miRNA-21 target genes,including programmed cell death protein 4(PDCD4)and phosphatase and tensin homology deleted on chromosome ten(PTEN),at 10 μM in HeLa cells.The Cell Counting Kit-8 assay(CCK-8)was used to evaluate the antiproliferative activity of A36;the results showed that the IC_(50) value range of A36 against six tumor cell lines was between 1.76 and 13.0 μM.Meanwhile,A36 did not display cytotoxicity in BEAS-2B cells(lung epithelial cells from a healthy human donor).Furthermore,A36 significantly induced apoptosis,arrested cells at the G_(0)/G_(1) phase,and inhibited cell-colony formation in HeLa cells.In addition,mRNA deep sequencing showed that treatment with A36 could generate 171 dysregulated mRNAs in HeLa cells,while the expression of miRNA-21 target gene dual-specificity phosphatase 5(DUSP5)was significantly upregulated at both the mRNA and protein levels.Collectively,these findings demonstrated that A36 is a novel miRNA-21 inhibitor.

Tb^(3+)-nucleic acid probe-based label-free and rapid detection of mercury pollution in food

Mercury is a threatening pollutant in food,herein,we developed a Tb^(3+)-nucleic acid probe-based label-free assay for mix-and-read,rapid detection of mercury pollution.The assay utilized the feature of light-up fluorescence of terbium ions(Tb^(3+))via binding with single-strand DNA.Mercury ion,Hg^(2+)induced thymine(T)-rich DNA strand to form a double-strand structure(T-Hg^(2+)-T),thus leading to fluorescence reduction.Based on the principle,Hg^(2+)can be quantified based on the fluorescence of Tb^(3+),the limit of detection was 0.0689μmol/L and the linear range was 0.1-6.0μmol/L.Due to the specificity of T-Hg^(2+)-T artificial base pair,the assay could distinguish Hg^(2+)from other metal ions.The recovery rate was ranged in 98.71%-101.34%for detecting mercury pollution in three food samples.The assay is low-cost,separation-free and mix-to-read,thus was a competitive tool for detection of mercury pollution to ensure food safety.

Small-Molecule Ligands as Challenge for Positron Emission Tomography of Peptide Receptors in Neurons and Microglia of the Brain

Neuropeptide and chemokine receptors of the G protein-coupled receptor (GPCR) family belong to different classes and subgroups providing different docking sites and special binding behavior at extracellular and also transmembrane domains for small molecules potentially suitable for positron emission tomography (PET). The contribution gives an overview updating developments of small-molecule, nonpeptide ligands at a selection of peptide and chemokine receptors, expressed in neurons and microglia of the brain, regarding the last five years. Orexin 1 and orexin 2 receptors (OX1R;OX2R) and neuropeptide Y1 and Y2 receptors (NPY1R, NPY2R) were chosen as representatives of Class A neuropeptide receptors, chemokine receptor CX3C (CX3CR1) as Class A, protein-activated receptor, highly expressed in activated microglia, and corticotropin releasing factor receptor 1 (CRFR1) as representative Class B1 receptor. Structural differences between binding domains and their endogenous ligands as well as parallel expression in different types of cells and generally low density of these receptors in brain tissue are factors making the search for selective and sensitive ligands more difficult than for classical GPCR receptors. Main progress in ligand development is observed for NPY receptor antagonists and orexin receptor antagonists. For orexin receptors, search for suitable ligands can be supported with modelling approaches, as recently the complete molecular structure of these receptors is available. Small molecules, binding at CRFR1, as for other Class B1 receptor ligands, in PET and investigations of pharmacodynamics revealed rather allosteric binding modes, although, the complete crystal structure of CRFR1 as prototype of Class B1 provides, hitherto, improved possibilities for understanding binding mechanisms. Highly specific as a marker of microglia among?the GPCRs, CX3CR1 is focused as target of PET during inflammation of brain and spinal cord.

An exo Probe-based Reverse Transcription and Recombinase Polymerase Amplification for Rapid Detection of Feline Calicivirus in Cats

Feline calicivirus(FCV)was a highly prevalent RNA virus causing upper respiratory tract infections in cats through the mouth and nose around the world,result in the death of cats especially under 1 year old with upper respiratory tract disease(URTD)and virulent systemic disease(FCV-VSD)[1].Infected cats usually presented with mouth ulcers,salivation and gingivitis-stomatitis.Furthermore,both recovered cats and asymptomatic carriers can still carry and spread the FCV virus for extended periods of time,contributing to the potential for outbreak.This presented a significant threat to the health and lives of cats,and rare wildlife and took a heavy financial loss on the pet industry,making the prevention and control of the virus difficult.Hence,rapid identification of FCV in clinical samples was necessary to prevent the spread of FCV and avoid financial loss.

Lift-Off Effect of Koch and Circular Differential Pickup Eddy Current Probes

A flexible or planar eddy current probe with a differential structure can suppress the lift-off noise during the inspection of defects.However,the extent of the lift-off effect on differential probes,including different coil structures,varies.In this study,two planar eddy current probes with differential pickup structures and the same size,Koch and circular probes,were used to compare lift-off effects.The eddy current distributions of the probes perturbed by 0°and 90°cracks were obtained by finite element analysis.The analysis results show that the 90°crack can impede the eddy current induced by the Koch probe even further at relatively low lift-off distance.The peak-to-peak values of the signal output from the two probes were compared at different lift-off distances using finite element analysis and experimental methods.In addition,the effects of different frequencies on the lift-off were studied experimentally.The results show that the signal peak-to-peak value of the Koch probe for the inspection of cracks in 90°orientation is larger than that of the circular probe when the lift-off distance is smaller than 1.2 mm.In addition,the influence of the lift-off distance on the peak-to-peak signal value of the two probes was studied via normalization.This indicates that the influence becomes more evident with an increase in excitation frequency.This research discloses the lift-off effect of differential planar eddy current probes with different coil shapes and proves the detection merit of the Koch probe for 90°cracks at low lift-off distances.

Cryogenic Digital Image Correlation as a Probe of Strain in Iron-Based Superconductors

Uniaxial strain is a powerful tuning parameter that can control symmetry and anisotropic electronic properties in iron-based superconductors.However,accurately characterizing anisotropic strain can be challenging and complex.Here,we utilize a cryogenic optical system equipped with a high-spatial-resolution microscope to characterize surface strains in iron-based superconductors using the digital image correlation method.Compared with other methods such as high-resolution x-ray diffraction,strain gauge,and capacitive sensor,digital image correlation offers a non-contact full-field measurement approach,acting as an optical virtual strain gauge that provides high spatial resolution.The results measured on detwinned BaFe_(2)As_(2)are quantitatively consistent with the distortion measured by x-ray diffraction and neutron Larmor diffraction.These findings highlight the potential of cryogenic digital image correlation as an effective and accessible tool for probing the isotropic and anisotropic strains,facilitating applications of uniaxial strain tuning in research of quantum materials.

Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

Plasma potential measurements using an emissive probe made of oxide cathode

A novel emissive probe consisting of an oxide cathode coating is developed to achieve a low operating temperature and long service life.The properties of the novel emissive probe are investigated in detail,in comparison with a traditional tungsten emissive probe,including the operating temperature,the electron emission capability and the plasma potential measurement.Studies of the operating temperature and electron emission capability show that the tungsten emissive probe usually works at a temperature of 1800 K-2200 K while the oxide cathode emissive probe can function at about 1200 K-1400 K.In addition,plasma potential measurements using the oxide cathode emissive probe with different techniques have been accomplished in microwave electron cyclotron resonance plasmas with different discharge powers.It is found that a reliable plasma potential can be obtained using the improved inflection point method and the hot probe with zero emission limit method,while the floating point method is invalid for the oxide cathode emissive probe.

Distal-scanning common path probe for optical coherence tomography

In this paper,we present a distal-scanning common path probe for optical coherence tomography(OCT)equipped with a hollow ultrasonic motor and a simple and specially designed beam-splitter.This novel probe proves to be able to effectively circumvent polarization and dispersion mismatch caused by fiber motion and is more robust to a variety of interfering factors during the imaging process,experimentally compared to a conventional noncommon path probe.Furthermore,our design counteracts the attenuation of backscattering with depth and the fall-off of the signal,resulting in a more balanced signal range and greater imaging depth.Spectral-domain OCT imaging of phantom and biological tissue is also demonstrated with a sensitivity of∼100dB and a lateral resolution of∼3μm.This low-cost probe offers simplified system configuration and excellent robustness,and is therefore particularly suitable for clinical diagnosis as one-off medical apparatus.

Design of compact integrated diamond nitrogen-vacancy center quantum probe

An integrated quantum probe for magnetic field imaging is proposed,where the nitrogen–vacancy(NV)center fixed at the fiber tip is located on the periphery of flexible ring resonator.Using flexible polyimide(PI)as the substrate medium,we design a circular microstrip antenna,which can achieve a bandwidth of 140 MHz at Zeeman splitting frequency of 2.87 GHz,specifically suitable for NV center experiments.Subsequently,this antenna is seamlessly fixed at a three-dimensional-printed cylindrical support,allowing the optical fiber tip to extend out of a dedicated aperture.To mitigate errors originating from processing,precise tuning within a narrow range can be achieved by adjusting the conformal amplitude.Finally,we image the microwave magnetic field around the integrated probe with high resolution,and determine the suitable area for placing the fiber tip(SAP).

Temperature-controlled DCP Fluorescent Probe Based on Hydrogel-immobilized Quantum Dots Composite

A composite was created by incorporating the quantum dot-enhanced SiO_(2)nanoparticles within this hydrogel.Based on this composite,a temperature-controlled fluorescent probe for DCP was developed.A meticulous examination of this probe revealed its attributes and factors affecting its performance.By using temperature modulation,the probe was adept at detecting DCP concentrations ranging between 1.0×10^(-6)and 9.0×10^(-6)mol/L.Such a probe offers remarkable selectivity,repeatability,and robust stability,so that the detection of DCP can be carried out at different temperatures,and a fast,reliable,sensitive and low-cost intelligent detection method is realized.

Progress in Mechanical Modeling of Implantable Flexible Neural Probes

Implanted neural probes can detect weak discharges of neurons in the brain by piercing soft brain tissue,thus as important tools for brain science research,as well as diagnosis and treatment of brain diseases.However,the rigid neural probes,such as Utah arrays,Michigan probes,and metal microfilament electrodes,are mechanically unmatched with brain tissue and are prone to rejection and glial scarring after implantation,which leads to a significant degradation in the signal quality with the implantation time.In recent years,flexible neural electrodes are rapidly developed with less damage to biological tissues,excellent biocompatibility,and mechanical compliance to alleviate scarring.Among them,the mechanical modeling is important for the optimization of the structure and the implantation process.In this review,the theoretical calculation of the flexible neural probes is firstly summarized with the processes of buckling,insertion,and relative interaction with soft brain tissue for flexible probes from outside to inside.Then,the corresponding mechanical simulation methods are organized considering multiple impact factors to realize minimally invasive implantation.Finally,the technical difficulties and future trends of mechanical modeling are discussed for the next-generation flexible neural probes,which is critical to realize low-invasiveness and long-term coexistence in vivo.

RNA SNP Detection Method With Improved Specificity Based on Dual-competitive-padlock-probe

Objective The detection of RNA single nucleotide polymorphism(SNP)is of great importance due to their association with protein expression related to various diseases and drug responses.At present,splintR ligase-assisted methods are important approaches for RNA direct detection,but its specificity will be limited when the fidelity of ligases is not ideal.The aim of this study was to create a method to improve the specificity of splintR ligase for RNA detection.Methods In this study,a dualcompetitive-padlock-probe(DCPLP)assay without the need for additional enzymes or reactions is proposed to improve specificity of splintR ligase ligation.To verify the method,we employed dual competitive padlock probe-mediated rolling circle amplification(DCPLP-RCA)to genotype the CYP2C9 gene.Results The specificity was well improved through the competition and strand displacement of dual padlock probe,with an 83.26%reduction in nonspecific signal.By detecting synthetic RNA samples,the method demonstrated a dynamic detection range of 10 pmol/L-1 nmol/L.Furthermore,clinical samples were applied to the method to evaluate its performance,and the genotyping results were consistent with those obtained using the qPCR method.Conclusion This study has successfully established a highly specific direct RNA SNP detection method,and provided a novel avenue for accurate identification of various types of RNAs.

A Study of Radiation-Induced Telomere Instability Using Multiplex Ligation-Dependent Probe Amplification (MLPA)

The integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation was analyzed by Multiplex Ligation-Dependent Probe Amplification (MLPA). The TK6 cell line has the native p53 tumor-suppressor gene, whereas WTK1 cells contain a p53 mutation. Each cell line was isolated pre- and post-irradiation (2 and 3 Gy) and analyzed by MLPA. The impact of irradiation on these two cell lines was investigated using probes that target specific regions on chromosomes associated with subtelomeric regions. Results indicate that WTK1 and TK6 are impacted differently after irradiation, and that each cell line presents its own unique MLPA profile. The most notable differences are the appearance of a number of probes in the post-irradiated MLPA profile that are not present in the controls, and two unique probe signals only seen in WTK1 cells. These results build on our previous studies that indicate how different human cell lines can be affected by radiation in significantly different ways depending on the presence or absence of wild type p53.