Highly Active Single-Atom Nanozymes with High-Loading Iridium for Sensitive Detection of Pesticides.

Single-atom nanozymes (SAzymes) are novel mimic-enzyme materials with atomically doped active sites. They play a pivotal role in the field of nanozymes because of their excellent catalytic activities, high utilization efficiency of the metal atoms, and simple model of active sites. Herein, the peroxidase (POD)-like SAzymes with high-loading iridium (Ir) (5.31%) on graphene oxide (GO) nanosheets [Ir(III)/GO] were prepared through a coordination reaction between the Ir(III) complex and the oxygen-containing groups in GO. The preparation strategy avoids nitrogen doping and pyrolysis procedures which are the usually used strategies to improve the GO-based enzyme mimic activity. Ascribed to the highly active Ir atoms, Ir(III)/GO SAzymes demonstrate outstanding POD-like activity without the oxidase-like activity. In advantage of the excellent POD-like activity, a simple and sensitive colorimetric pesticide detection platform is established. The developed sensing platform offers an excellent "switch-on" pirimicarb (PIB) detection in the linear range of 10-300 nM with a limit of detection (LOD) of 2.81 nM. Moreover, the detection platform was fabricated into a portable test kit, which is composed of a test swab and sample processing tube. In the aid of a color-reading APP, the test kit can detect PIB with the LOD of 3.31 nM. It is astonishing to get this excellent detection sensitivity just using the simple colorimetric strategy. This work not only provides a novel strategy to synthesize Ir-based SAzymes but also exhibits the super capability of Ir(III)/GO in the biosensing field.

All-solution-processed perovskite/gallium nitride particles hybrid visible-blind ultraviolet photodetectors.

Last decades have witnessed the rapid development of ultraviolet (UV) photodetectors in diversity of applications. The III-nitride semiconductor and metal halide perovskite have both performed promising UV-sensing optoelectronic properties. However, they are still suffering from either the high temperature epitaxial-growth or low photocurrent generated in UV range. In this work, we demonstrate an innovative MAPbCl3/GaN particle hybrid device with all-solution-processed deposition methods. Comparing to the control MAPbCl3photoconductors, the photo-sensing ability of the hybrid device with the optimal concentration of GaN particles is more than one order of magnitude enhanced, and report a responsivity of 86 mA W-1, a detectivity of 3.1 × 1011Jones and a rise/fall time of 1.1/10.7 ms at 360 nm. The photocurrent increment could be attributed to the enhanced UV absorption of GaN particles and facilitated charge separation and photoconductive gain at MAPbCl3/GaN heterojunction. This work paves a pathway towards the large-scale low-cost UV photodetectors in versatile applications.

Ultrasonographic classification of 26 cases of fetal umbilical-portal-systemic venous shunts and the correlations with fetal chromosomal abnormalities.

OBJECTIVE: To investigate the ultrasonographic classification of fetal umbilical-portal-systemic venous shunts (UPSVS) and the correlations with fetal chromosomal abnormalities. METHODS: We retrospectively analyzed the ultrasound characteristics and the corresponding chromosomal abnormalities of 26 cases of fetal UPSVS prenatally diagnosed. RESULTS: A total of 26 fetuses diagnosed as UPSVS were included, including four cases of type I UPSVS, ten of type II, three of type IIIA, and nine of type IIIB. Four cases of type I were all complicated by fetal heart enlargement and heart insufficiency, of which one case had multiple malformations, and all four cases terminated pregnancies. Six of ten cases of type II terminated pregnancies, including four of Down's syndrome, one of twin reversed arterial perfusion sequence, one of fetal edema but with normal copy number variation (CNV) by chorionic villus sampling. The other four of ten cases were isolated type II with normal chromosomes, which were delivered at full term and were normal in growth and development when followed up 34 months after birth. Three cases of type IIIA all terminated pregnancies, of which one had multiple malformations, one had right multicystic dysplastic kidney, and one had fetal heart enlargement and heart failure. Among nine of type IIIB, seven with chromosomal abnormalities and/ or complicated malformations terminated pregnancies, and two with isolated type IIIB and normal chromosomes were delivered at full term, and were normal in growth and development (one was followed up to 33 months after birth and the other 20 months after birth). CONCLUSION: Fetal UPSVS can be clearly diagnosed and typed by prenatal ultrasonography. Fetal prognosis is determined by the types of UPSVS and complicated malformations and/ or chromosomal abnormalities. The probability of fetal chromosomal abnormalities in UPSVS fetuses is related to the ultrasonographic classification.

Circular RNA circ_0006948 Promotes Esophageal Squamous Cell Carcinoma Progression by Regulating microRNA-3612/LASP1 Axis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the most prevalent malignancy worldwide. Circular RNAs (circRNAs) circ_0006948 is reported to be upregulated in ESCC cells. AIMS: This study is designed to explore the role and mechanism of circ_0006948 in ESCC progression. METHODS: Circ_0006948, linear FNDC3B, microRNA-3612 (miR-3612), and LIM and SH3 protein 1 (LASP1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, colony number, migration, invasion, and apoptosis were examined by Cell Counting Kit-8 (CCK-8), colony formation, transwell, and flow cytometry assays, severally. Glucose consumption, lactate production, and ATP level were measured by the corresponding kits. Protein levels of hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA), and LASP1 were assessed by western blot assay. The cytoplasmic localization of circ_0006948 was identified by the subcellular fractionation assay. The binding relationship between miR-3612 and circ_0006948 or LASP1 was predicted by starBase or TargetScan and then verified by a dual-luciferase reporter assay. The biological role of circ_0006948 on ESCC tumor growth was examined by the xenograft tumor model in vivo. RESULTS: Circ_0006948 and LASP1 were increased, and miR-3612 was decreased in ESCC tissues and cells. Furthermore, circ_0006948 knockdown could suppress cell viability, colony number, migration, invasion, glycolysis, and boost apoptosis in ESCC cells. Mechanically, circ_0006948 could act as a sponge of miR-3612 to regulate LASP1 expression. In addition, circ_0006948 silencing inhibited ESCC tumor growth in vivo. CONCLUSION: Circ_0006948 boosted ESCC progression partly by regulating the miR-3612/LASP1 axis, providing an underlying therapeutic target for the ESCC treatment.

A low-background fluorescent aptasensor for acetamiprid detection based on DNA three-way junction-formed G-quadruplexes and graphene oxide.

A simple fluorescence detection platform has been established for acetamiprid assay based on DNA three-way junctions (TWJs), which can triple the fluorescence signal without any other amplification. It is designed with three single-stranded DNAs (ssDNA), each of which contains one-third or two-thirds of the G-quadruplex sequence at each end. Upon the addition of acetamiprid, the conformation of the aptamer-containing double-stranded DNA (dsDNA) changes from its original conformation and releases a strand of ssDNA. This ssDNA, with the other two ssDNAs, can assemble into DNA TWJs, and the three pairs of the branched ends of the DNA TWJs are adjacent to each other, allowing them to form three units of G-quadruplexes. Hence, the fluorescence of N-methyl mesoporphyrin IX (NMM) is lighted by the nascent G-quadruplexes. Graphene oxide (GO) is then added to minimize the detection background by absorbing the free NMM and non-target-induced ssDNA. The proposed strategy can assay acetamiprid in a wide linear range of 0-500 nM with a detection limit of 5.73 nM. More importantly, this assay platform demonstrates high potential for acetamiprid assay in food control and environmental monitoring.

Effect of Prescription Tongxin on Endothelial Progenitor Cells in Peripheral Blood.

CONTEXT: Coronary heart disease (CHD) refers to a disease where coronary atherosclerosis induces stenosis or obstruction of the blood vessels. Endothelial progenitor cells (EPCs) function to protect and repair the vascular endothelium, and their functional activity state reflects the ability of the body to repair vascular damage. In the peripheral blood of patients with CHD, the density of EPCs decreases, and the function of EPCs is low. OBJECTIVE: This study aimed to investigate the effects of a China Food and Drug Administration (CFDA)-approved prescription medicine, Tongxin, on the density and function of endothelial progenitor cells (EPCs) in peripheral blood. DESIGN: In this study, a randomized, single blind, parallel controlled clinical trial was used. The single blind subjects were subjects. SETTING: The study took place in the Cardiology and Emergency Departments at Shanghai Municipal Hospital of Traditional Chinese Medicine in Shanghai, China. PARTICIPANTS: Participants were 48 patients with coronary heart disease at the hospital. INTERVENTION: Participants were randomly divided into 2 groups (n = 24 each): a control group and an intervention group. Both groups received routine drug treatments, such as platelet inhibitors, nitrates, ß-receptor blockers, statins, angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARBs), and calcium blockers. The control group was treated with the Shexiang Baoxin Pill, while the intervention group was treated with prescription Tongxin. The course of treatment was 3 months for both groups. OUTCOME MEASURES: Changes in the density and function of EPCs in the peripheral blood of the 2 groups were measured at baseline and postintervention, and the clinical efficacy of the 2 treatments was statistically analyzed. RESULTS: The density of EPCs was significantly higher in both groups after 3 months of treatment, compared to the densities at baseline (P < .05). The change in density between baseline and postintervention was significantly greater for the intervention group than for the control group (P < .05). For the control group, the proliferative vitality [optical density (OD)] value of the EPCs was significantly higher than that at baseline from the fourth day of treatment (P < .05). In the intervention group, the OD value was significantly higher than that at baseline from the first day of treatment (P < .05). Furthermore, the intervention group's cells began to enter the logarithmic growth phase of increase from the fifth day of treatment, and the group's increase as significantly higher than the control group's from the fifth to the seventh dayof treatment (P < .05 for all 3 days). Moreover, the total effective rate was higher in the intervention group than in the control group (P < .05). CONCLUSIONS: Prescription Tongxin can stimulate the release of EPCs from the bone marrow to the peripheral blood of patients with CHD, can significantly increase the proliferation of EPCs in the peripheral blood, and can improve the clinical symptoms of patients. Its curative effect was greater than that of the control treatment.

RLIM: a recursive and latent infection model for the prediction of US COVID-19 infections and turning points.

Initially found in Hubei, Wuhan, and identified as a novel virus of the coronavirus family by the WHO, COVID-19 has spread worldwide at exponential speed, causing millions of deaths and public fear. Currently, the USA, India, Brazil, and other parts of the world are experiencing a secondary wave of COVID-19. However, the medical, mathematical, and pharmaceutical aspects of its transmission, incubation, and recovery processes are still unclear. The classical susceptible-infected-recovered model has limitations in describing the dynamic behavior of COVID-19. Hence, it is necessary to introduce a recursive, latent model to predict the number of future COVID-19 infection cases in the USA. In this article, a dynamic recursive and latent infection model (RLIM) based on the classical SEIR model is proposed to predict the number of COVID-19 infections. Given COVID-19 infection and recovery data for a certain period, the RLIM is able to fit current values and produce an optimal set of parameters with a minimum error rate according to actual reported numbers. With these optimal parameters assigned, the RLIM model then becomes able to produce predictions of infection numbers within a certain period. To locate the turning point of COVID-19 transmission, an initial value for the secondary infection rate is given to the RLIM algorithm for calculation. RLIM will then calculate the secondary infection rates of a continuous time series with an iterative search strategy to speed up the convergence of the prediction outcomes and minimize the maximum square errors. Compared with other forecast algorithms, RLIM is able to adapt the COVID-19 infection curve faster and more accurately and, more importantly, provides a way to identify the turning point in virus transmission by searching for the equilibrium between recoveries and new infections. Simulations of four US states show that with the secondary infection rate ω initially set to 0.5 within the selected latent period of 14 days, RLIM is able to minimize this value at 0.07 and reach an equilibrium condition. A successful forecast is generated using New York state's COVID-19 transmission, in which a turning point is predicted to emerge on January 31, 2021. Supplementary Information: The online version contains supplementary material available at 10.1007/s11071-021-06520-1.

Crocin inhibits the migration, invasion, and epithelial-mesenchymal transition of gastric cancer cells via miR-320/KLF5/HIF-1α signaling.

The biological activities of crocin, one of the main bioactive compounds of saffron, include anti-inflammatory, antioxidant, antidepressant, and anticancer effects. Crocin has been shown to trigger the apoptosis of gastric cancer cells, but its effect on the metastasis of gastric cancer cells remains unclear. Krüppel-like factor 5 (KLF5) and hypoxia-inducible factor-1α (HIF-1α) are important transcription factors in the development of gastric cancer. KLF5 and HIF-1α expression were analyzed in gastric cancer tissues and cells. Following exposure to crocin, AGS and HGC-27 gastric cancer cells were assessed with regard to migration, invasion, and epithelial-mesenchymal transition (EMT) as well as the expression of KLF5, HIF-1α, and microRNA-320 (miR-320). The miR-320/KLF5/HIF-1α signaling pathway became the focus for further investigation of the mechanism of crocin in gastric cancer cell migration, invasion, and EMT. KLF5 and HIF-1α expression were elevated in gastric cancer tissues and cells, and KLF5 expression was positively correlated with the HIF-1α level in gastric cancer tissues. Crocin was associated with reduced expression of KLF5 and HIF-1α, whereas miR-320 expression was increased. Crocin also inhibited the migration, invasion, and EMT of gastric cancer cells. Upregulation of KLF5 attenuated crocin's function and elevated HIF-1α expression. Dual-luciferase reporter assay demonstrated that KLF5 was a target gene of miR-320. Crocin modulated KLF5 expression via elevation of miR-320 expression. In conclusion, crocin inhibits the EMT, migration, and invasion of gastric cancer cells, and this activity is mediated through miR-320/KLF5/HIF-1α signaling.

Contribution of structured self-monitoring of blood glucose to self-efficacy in poorly controlled diabetes patients in China.

AIM: To investigate the association between structured self-monitoring of blood glucose (SMBG) and diabetes self-efficacy in Chinese patients. METHODS: This study was a single-centre, open-label, prospective, randomized controlled trial. A total of 250 type 1 and type 2 diabetes patients were recruited and randomly assigned to the structured SMBG group and the control group in a 1:1 ratio. The main outcome observed in this subgroup analysis was a change in the diabetes self-efficacy scale (DSES) scores. A multivariate generalized estimating equation was used to evaluate factors affecting the DSES scores. RESULTS: We found that the DSES scores tended to decrease significantly with the follow-up time in the intervention group (Wald ß = 7.882, P < .001; Wald ß = 3.130, P = .003; Wald ß = 7.879, P < .001). However, no significant differences in the DSES scores were detected in the control group. Glycaemic control improved in both the intervention and control groups at the third month (P < .05). In the intervention group, sustained improvement of the DSES scores maintained the improvement in glycaemic control through the sixth month. In the control group, glycaemic control tended to deteriorate in the sixth month without the support of an improved DSES scores (P = .056). CONCLUSION: Structured SMBG could contribute to the effective and persistent improvement of diabetes self-efficacy. (ClinicalTrials.gov, NCT02225691).

A luminescent microRNA nanoprobe based on the target-triggered release of an iridium(III)-solvent complex from mesoporous silica nanoparticles.

A luminescent microRNA nanoprobe based on the target-triggered Ir(III)-solvent complex release has been fabricated. The complex is initially embedded into mesoporous silica nanoparticles (MSNs), and then is capped by single-stranded (ss) DNA. In the presence of the target microRNA, the ssDNA hybridize with the microRNA forming a rigid DNA/RNA heteroduplexes and leaving the surface of MSN. Thus, the capped Ir(III) solvent complex is released and re-coordinated with histidine (His) to form a new luminescent complex. The luminescence intensity of the nascent complex (with excitation/emission maxima at 340/570 nm) is positively correlated with the concentrations of the target microRNA in the range from 0.05 to 2 nM, and the detection limit of microRNA is estimated as 0.2 pM (S/N = 3). The ability of this nanoprobe to detect microRNA in cell extract further demonstrates its potential in practical application. Graphical abstractSchematic of a luminescent microRNA nanoprobe based on the target-triggered release of an Ir(III)-solvent complex from mesoporous silica nanoparticles.

γ-Aminobutyric acid-modified graphene oxide as a highly selective and low-toxic fluorescent nanoprobe for relay recognition of copper(II) and cysteine.

A sensitive and selective graphene oxide (GO)-based fluorescent nanoprobe has been developed for the relay recognition of Cu2+ and cysteine (Cys) by covalently grafting γ-aminobutyric acid (GABA) onto GO. The fluorescence of the probe (with excitation/emission maxima at 360/445 nm) is selectively quenched by Cu2+ via static fluorescence quenching. Fluorescence drops linearly as the concentration of Cu2+ is increased from 50 nM to 1.0 µM, and the detection limit for Cu2+ is calculated as 15 nM. By virtue of the strong interaction between Cys and Cu2+, the GO-GABA/Cu2+ complex can further sensitively recognize Cys in a "switch-on" mode. The linear range for Cys detection is from 50 nM to 1.0 µM, and the detection limit is 38 nM. The probe has low cytotoxicity, and it works well inside living cells, which is verified by the successful application in imaging of LLC-PK1 cells. Graphical abstract Gamma-Aminobutyric Acid (GABA) modified graphene oxide (GO) is a highly selective nanoprobe for the fluorometric relay recognition of Cu2+ and Cys.

Development of a Luminescent Dinuclear Ir(III) Complex for Ultrasensitive Determination of Pesticides.

To improve the G-quadruplex specificity of Ir(III) complexes, a novel dinuclear Ir(III) complex (Din Ir(III)-1) was designed and synthesized through connecting two mononuclear Ir(III) complexes via a diphenyl bridge. Din Ir(III)-1 presents 3.4-4.1-fold enhancements for G-quadruplex relative to ssDNA and 4.3-5.3-fold enhancements relative to dsDNA in luminescence intensity, respectively, demonstrating an excellent G-quadruplex selectivity. Ascribed to its superior specificity to G-quadruplex, Din Ir(III)-1 was employed to construct a highly sensitive luminescent pesticides' detection platform. The detection is based on acetylcholinesterase (AChE)-catalyzed hydrolysis product-induced DNA conformational transformation and subsequent terminal deoxynucleotidyl transferase (TdT) directed G-quadruplex formation. The assay exhibited a linear response between the emission intensity of Din Ir(III)-1 and the pesticide concentration in the range of 0.5-25 µg/L ( R2 = 0.994), and the limit of detection for the pesticide was as low as 0.37 µg/L when using aldicarb as the model pesticide. Moreover, this strategy demonstrates good applicability for the pesticide detection in real samples. It is also versatile for the detection of other organophosphate or carbamate pesticides, which have the inhibition ability toward AChE. Therefore, the proposed approach is scalable for practical application in food safety and environmental monitoring fields and will provide promising solutions for the assay of pesticide residues.

AMP-activated protein kinase activation in mediating phenylalanine-induced neurotoxicity in experimental models of phenylketonuria.

Phenylketonuria (PKU), one of the most prevalent autosomal recessive disorders of amino acid metabolism, is characterized by abnormal accumulation of phenylalanine, which can lead to intellectual disability. The main pathologic changes in the central nervous system of untreated phenylketonuric patients are reductions in the number of axons, dendrites, and synapses in the brain. Such alterations are thought to be mainly associated with the toxic effects caused by phenylalanine. However, the underlying molecular mechanisms have not been fully elucidated. The present study shows that a high concentration of phenylalanine remarkably inhibited neuronal neurite formation in vitro. Interestingly, AMP-activated protein kinase (AMPK), the energy status sensor, was activated in cultured cerebral cortical neurons upon phenylalanine treatment. Pretreatment with an AMPK inhibitor ameliorated the reduction of neurite formation caused by phenylalanine. In addition, the levels of the phosphorylated AMPK, the active form of AMPK, were significantly higher in the cerebral cortices of PKU mice with elevated phenylalanine levels in this brain region compared to those in wild-type control mice, whereas the density of dendritic spines on basal secondary dendrites of pyramidal neurons in prefrontal cortices of PKU mice was significantly decreased. Collectively, these findings indicate that AMPK activation is a key event in impaired neuronal dendritic development in PKU and consequently, a potential therapeutic target for developing neuroprotective strategies against phenylalanine-evoked brain injury in PKU.

Volatile Terpenes and Terpenoids from Workers and Queens of Monomorium chinense (Hymenoptera: Formicidae).

Twenty-one volatile terpenes and terpenoids were found in Monomorium chinense Santschi (Hymenoptera: Formicidae), a native Chinese ant, by using headspace solid-phase microextraction (HS-SPME) coupled with gas-phase chromatography and mass spectrometry (GC-MS), which makes this ant one of the most prolific terpene producers in insect. A sesquiterpene with unknown structure (terpene 1) was the main terpene in workers and neocembrene in queens. Terpenes and terpenoids were detected in poison, Dufour's and mandibular glands of both workers and queens. Worker ants raised on a terpene-free diet showed the same terpene profile as ants collected in the field, indicating that de novo terpene and terpenoid synthesis occurs in M. chinense.

Ultrasensitive Homogeneous Electrochemical Detection of Transcription Factor by Coupled Isothermal Cleavage Reaction and Cycling Amplification Based on Exonuclease III.

The assay and monitoring of transcription factors (TFs) has attracted extensive attention due to their important roles in regulation of gene expressions. Herein, a simple, low cost, rapid, and highly sensitive homogeneous electrochemical method utilizing the coupled isothermal cleavage reaction and cycling amplification based on exonuclease III (Exo III) was explored for the analysis of transcription factor NF-κB p50 in aqueous solution. In the assay, a 3'-methylene blue (MB)-labeled hairpin probe is designed, which can be opened up by the single stranded DNA (ssDNA) protected by NF-κB p50 from the Exo III cleavage, to trigger the subsequent Exo III-assisted digestion, thus a large amount of MB-labeled mononucleotides are liberated to result in the greatly amplified electrochemical signal. By virtue of this Exo III-assisted target recycling, the present assay allows the detection of NF-κB p50 at the picomolar level, which is an exciting level for TFs detection. Furthermore, this detection possesses excellent selectivity, demonstrating high application potential in biological system and convenient TFs' inhibitors screening. Comparing with the other reported strategies for TFs detection, this Exo III-assisted homogeneous electrochemical detection platform was just composed of one kind of enzyme and two DNA probes, offered a really simple and low-cost electrochemical detection for TFs assay.

A G-quadruplex-selective luminescent iridium(III) complex and its application by long lifetime.

BACKGROUND: The G-quadruplex motif has been widely used for the construction of analytical detection platforms due to its rich structural polymorphism and flexibility. Luminescent assays are often limited due to the interference from endogenous fluorophores in biological samples. METHODS: To address this challenge, a novel long lifetime iridium(III) complex 1 was synthesized and used to construct a G-quadruplex-based assay for detecting prostate specific antigen (PSA) in aqueous solution. PSA is a common biomarker in serum and used as a model for demonstration in this work. RESULTS: The PSA assay has achieved a detection limit of 40.8pg·mL-1, and shows high selectivity towards PSA over other proteins. Additionally, the assay could function in diluted human serum by using time-resolved luminescent spectroscopy, with good linearity from 1 to 10ng·mL-1 of PSA, which is adequate to detect the PSA levels for physiological (<4ng·mL-1) and clinical (4-10ng·mL-1) applications. CONCLUSIONS: The assay was successfully constructed. As revealed from time-resolved method, the long lifetime property of iridium(III) complex 1 plays an important role in distinguishing phosphorescence signals from short-life auto-fluorescence of human serum. GENERAL SIGNIFICANCE: Luminescent transition metal complexes offer several advantages over other widely used organic fluorophores, such as long phosphorescence lifetime, large Stokes shift and modular syntheses. In addition, the assay could work effectively in diluted human serum using time-resolved luminescent spectroscopy, it therefore could be potentially developed to monitor PSA in biological samples. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.

Silencing of a lipase maturation factor 2-like gene by wheat-mediated RNAi reduces the survivability and reproductive capacity of the grain aphid, Sitobion avenae.

Lipase maturation factor (LMF) family proteins are required for the maturation and transport of active lipoprotein lipases. However, the specific roles of LMF2 remain unknown. In this study, a grain aphid lmf2-like gene fragment was cloned and was highly similar in sequence to a homologous gene in the pea aphid, Acyrthosiphon pisum. An RNAi vector was constructed with this fragment and used for wheat transformation. The expression of the lmf2-like gene in aphid, as well as the growth and reproduction of the aphids, was analyzed after feeding on the transgenic wheat. There were no significant differences in the expression of the lmf2-like gene over development. The expression of the lmf2-like gene was significantly reduced by 27.6% on the fifth day, and 57.6% on the 10th day after feeding. The total number of aphids produced on the transgenic plants was less than the number produced on control plants, and the difference became significant or after 2 weeks. The molting numbers were also reduced in the aphids reared on the transgenic plants. Our findings indicate that lmf2-like genes may have potential as a target gene for the control of grain aphids and show that feeding aphids with wheat expressing lmf2-like RNAi resulted in significant reductions in survival and reproduction.

Interaction of an Iridium(III) Complex with G-Quadruplex DNA and Its Application in Luminescent Switch-On Detection of Siglec-5.

Sialic acid (Sia) binding immunoglobulin (Ig)-like lectin-5 (Siglec-5) is a type-I transmembrane protein, and it has been demonstrated as a biomarker of granulocytic maturation and acute myeloid leukemia phenotype. Herein we aimed to construct a method that could sensitively detect Siglec-5 by taking advantage of the high affinity and selectivity of the K19 aptamer for its cognate target, and the selective interaction of luminescent iridium(III) transition metal complexes with G-quadruplex DNA. The iridium(III) complex 1 [Ir(tpyd)2(2,9-dmphen)]PF6 (where tpyd =2-(m-tolyl)pyridine; 2,9-dmphen =2,9-dimethyl-1,10-phenanthroline) was synthesized, and it displayed high luminescence for G-quadruplex DNA compared to dsDNA and ssDNA. Additionally, complex 1 exhibited a blue shift luminescence response to c-kit2 G-quadruplex, and the interaction between 1 and G-quadruplexes was discussed based on the results of G-tetrad assay, loop effect assay, and other assays. Then complex 1 was utilized to develop a G-quadruplex-based sensing platform for Siglec-5 in aqueous solution. Upon the addition of Siglec-5, the specific binding of the K19 aptamer sequence results in a conformational change that generates a split G-quadruplex structure, which is then recognized by the G-quadruplex-specific iridium(III) complex with an enhanced luminescent response. Futhermore, the use of the assay for detecting Siglec-5 in cellular debris was demonstrated.

In silico identification of natural product inhibitors of JAK2.

Emodic acid (1) and 6-chloroemodic acid (2) have been identified from a natural product database as useful scaffolds for the future development of novel JAK2 inhibitors using structure-based high-throughput virtual screening. Low-energy binding conformations of 1 and 2 in the JAK2 PTK domain were generated by virtual ligand docking and were found to overlap considerably with the binding pose of CMP6, a known JAK2 inhibitor. Compounds 1 and 2 displayed low micromolar efficacies against JAK2 enzyme activity and JAK2 autophosphorylation in human erythroleukemia cells, and inhibited STAT3 DNA-binding activity in a human hepatocarcinoma cell line.

Discovery of a small-molecule inhibitor of STAT3 by ligand-based pharmacophore screening.

STAT3 modulates the transcription of a wide variety of regulatory genes involved in cell proliferation, differentiation, migration, apoptosis, and other critical cellular functions. Constitutive activation of STAT3 has been detected in a wide spectrum of human malignancies. A pharmacophore model constructed from a training set of STAT3 inhibitors binding to the SH2 domain was used to screen an in-house database of compounds, from which azepine 1 emerged as a top candidate. Compound 1 inhibited STAT3 DNA-binding activity in vitro and attenuated STAT3-directed transcription in cellulo with comparable potency to the well-known STAT3 inhibitor S3I-201. A fluorescence polarization assay revealed that compound 1 targeted the SH2 domain of STAT3. Furthermore, compound 1 inhibited STAT3 phosphorylation in cells without affecting the total expression of STAT3. This study also validates the use of pharmacophore modeling to identify inhibitors of protein-protein interactions.