A simple "turn-on" fluorescence sensor for salicylaldehyde skeleton based on switch of PET-AIE effect.

The selective detection of salicylaldehyde skeleton is of great significance in phytochemistry and biological research but rarely reported. In this research, a simple and highly selective "turn-on" fluorescence sensor (CDB-Am) for salicylaldehyde skeleton was developed based on switch of photoinduced electron transfer (PET) and aggregation-induced emission (AIE). CDB-Am bearing amino-cyanodistyrene structure responded to salicylaldehyde in the range of 3.1 to 40 µM with a detection limit of 0.94 µM. The sensing process of formation of Schiff-base adduct CDB-SA was confirmed by 1H NMR, MS, and FT-IR spectra, revealing that a recovered AIE property accounted for the turn-on fluorescence response of CDB-Am and the intramolecular hydrogen bonding played a crucial role in the disruption of PET process. This sensing ability was successfully applied for both fluorescence qualitative test of salicylaldehyde skeleton on TLC analysis and quantitative detection of salicylaldehyde skeleton with good accuracy in the root bark of Periploca sepium, suggesting the extensive applications in phytochemistry and traditional Chinese herbal medicine. Furthermore, CDB-Am exhibited the first excellent fluorescence imaging ability in detecting salicylaldehyde skeleton in a living system. This work supplied a new strategy of preparing a novel "turn-on" fluorescence probe for detecting salicylaldehyde skeleton in complex environments and living bodies.

HOXA9 is critical in the proliferation, differentiation, and malignancy of leukaemia cells both in vitro and in vivo.

Progress in the understanding of the molecular mechanism for acute myeloid leukaemia is of great significance to generate new potential targets for treatment. Recent studies showed that HOXA9, a homeodomain-containing transcription factor, is commonly deregulated in acute leukaemia. In this study, we elucidated the direct correlation between HoxA9 expression and progression of leukaemia using 2 different types of leukaemia cells HL-60 and MOLT-3. The HoxA9 expression level was decreased in leukaemia cells with the treatment of all-trans retinoic acid or arsenic trioxide (As2 O3 ). Downregulation of HoxA9 could impair the proliferation and promote the leukaemia cell death. HoxA9 silencing also potentiated the differentiation of leukaemia cells, and in vivo studies demonstrated that HoxA9 downregulation could interfere the tumour growth. Interestingly, HoxA9 silencing also led to the alteration in miRNA expression, mediating the promoting effect on the leukaemia cell differentiation. Therefore, this work provided a promising and potentially efficient target to leukaemia treatment, indicating that HoxA9 is likely to be an ideal candidate in the gene therapy against acute myeloid leukaemia. In this study, we elucidated the critical role of HoxA9 in the proliferation and differentiation of leukaemia cells both in vitro and in vivo. The effect of HoxA9 modulation was correlated with the clinical effect of all-trans retinoic acid and As2 O3 . Furthermore, HoxA9 also regulated the miRNA expression, controlling the leukaemia cell differentiation. Therefore, this work provided new insights into molecular mechanism underlying the leukaemia treatment, potentially putting forward a brand new target to the gene therapy against leukaemia.

High-Temperature Tensile Characteristics of an Al-Zn-Mg-Cu Alloy: Fracture Characteristics and a Physical Mechanism Constitutive Model.

High-temperature tensile tests were developed to explore the flow features of an Al-Zn-Mg-Cu alloy. The fracture characteristics and microstructural evolution mechanisms were thoroughly revealed. The results demonstrated that both intergranular fractures and ductile fractures occurred, which affected the hot tensile fracture mechanism. During high-temperature tensile, the second phase (Al2CuMg) at the grain boundaries (GBs) promoted the formation and accumulation of dimples. With the continual progression of high-temperature tensile, the aggregation/coarsening of dimples along GBs appear, aggravating the intergranular fracture. The coalescence and coarsen of dimples are reinforced at higher tensile temperatures or lower strain rates. Considering the impact of microstructural evolution and dimple formation/coarsening on tensile stresses, a physical mechanism constitutive (PMC) equation is herein proposed. According to the validation and analysis, the predictive results were in preferable accordance with the testing data, showing the outstanding reconfiguration capability of the PMC model for high-temperature tensile features in Al-Zn-Mg-Cu alloys.

Hot Deformation Behavior of Hastelloy C276 Alloy: Microstructural Variation and Constitutive Models.

Isothermal deformation experiments of the Hastelloy C276 alloy were executed using the Gleeble-3500 hot simulator at a temperature range of 1000-1150 °C and a strain rate range of 0.01-10 s-1. Microstructural evolution mechanisms were analyzed via transmission electron microscope (TEM) and electron backscatter diffraction (EBSD). Results reveal that the influences of hot compression parameters on the microstructure variation features and flow behaviors of the Hastelloy C276 alloy were significant. The intense strain hardening (SH) effects caused by the accumulation of substructures were promoted when the strain rates were increased, and true stresses exhibited a notable increasing tendency. However, the apparent DRV effects caused by the annihilation of substructures and the increasingly dynamic recrystallization (DRX) behaviors occurred at high compressed temperature, inducing the reduction in true stresses. In addition, a physical-based (PB) constitutive model and a long short-term memory (LSTM) model optimized using the particle swarm optimization (PSO) algorithm were established to predict the flow behavior of Hastelloy C276 alloy. The smaller average absolute relative error and greater relation coefficient suggest that the LSTM model possesses a higher forecasting accuracy than the PB model.

"Turn-on" fluorescent sensor for Th4+ in aqueous media based on a combination of PET-AIE effect.

Previously reported fluorescent sensors for Th4+ experienced emission quenching or generated false positive signal upon aggregate formation in aqueous media. Herein, a simple and novel thorium sensor (CDB-BA) based on cyanodistyrene structure was designed and synthesized, which integrated the highly emitting characteristic of AIE effect and off-on response of PET modulation for the first time to construct the "turn-on" fluorescent probe for Th4+. Besides excellent selectivity, CDB-BA exhibited remarkable fluorescent enhancement which was linearly related to the concentration of Th4+ in the range of 0.25-8 µM. The detection limit was attained 0.074 µM, which was lower than that of most previously reported sensors. The mechanism of tris-chelate complex of CDB-BA with Th4+ was confirmed by mass spectra, IR spectra and DFT calculation. The excellent Th4+ sensing ability of CDB-BA was successfully applied to detecting Th4+ on TLC plates, in real water samples and living-cell imaging. This work suggested that the combination of AIE and PET photophysical mechanism could offer the merits of minimized background and enhanced signal fidelity to develop novel "turn-on" fluorescent probe in complicated aqueous environment and biological research.

Chinese Traditional Medicine NiuBeiXiaoHe (NBXH) Extracts Have the Function of Antituberculosis and Immune Recovery in BALB/c Mice.

BACKGROUND: The Traditional Chinese Medicine NiuBeiXiaoHe (NBXH) is a valid antituberculosis (TB) prescription from the experience of clinical practice. However, the mechanism of NBXH extracts' immunotherapy has been poorly understood. Herein, the immunotherapeutic efficacy and the differentially expressed (DE) genes of NBXH extracts were evaluated and identified in BALB/c mice. METHODS: The total RNA was extracted from peripheral blood mononuclear cells, and the DE genes were identified by gene chip. The enrichment and signaling pathway analyses were performed using Gene Ontology (GO) and KEGG database. RESULTS: It was shown that the treatment of NBXH extracts (high dose) significantly reduced mycobacteria loads and histopathological lesions in mice infected by Mycobacterium tuberculosis and resulted in 3,454 DE upregulated genes and 3,594 downregulated DE genes. Furthermore, NBXH extracts killed mycobacteria by inhibiting the supply of necessary ingredients for their growth and proliferation. They restored the disordered immune microenvironments by up- or downregulating immune and inflammation-related pathways. CONCLUSIONS: Taken together, NBXH extracts not only efficiently decreased the mycobacteria loads but also balanced the immune disorders in mice. These new findings provide a fresh perspective for elucidating the immunotherapeutic mechanism of NBXH extracts and pointed out the direction for improving the treatment efficacy of NBXH extracts.

Dual-responding circularly polarized luminescence based on mechanically and thermally induced assemblies of cyano-distyrylbenzene hydrogen bonding liquid crystals.

Circularly polarized luminescence controlled by both mechanics and temperature was observed for the first time. The cyano-distyrylbenzene-cholesterol liquid crystals exhibited not only mechanochromism and thermochromism but also mechanically induced and thermally induced circularly polarized.

Double-detecting fluorescent sensor for ATP based on Cu2+ and Zn2+ response of hydrazono-bis-tetraphenylethylene.

Although all kinds of sensors with unique detecting ability for one guest were reported, the fluorescence sensor with multiple detecting abilities was seldom presented. This work designed and synthesized a novel AIE fluorescence probe bearing double detecting for ATP based on Cu2+ and Zn2+ response of hydrazono-bis-tetraphenylethylene (Bis-TPE). Bis-TPE was prepared in 82% yield with simple procedure. It exhibited strong red AIE fluorescence based on the large conjugated electron effect in aqueous media. It showed outstanding selective sensing abilities for Cu2+ by strong fluorescence quenching and for Zn2+ by red-orange fluorescence change. The sensing mechanism of 1:1 stoichiometric ratios was confirmed by 1H NMR and MS study. The strong red fluorescence of Bis-TPE + Cu2+ system could be recovered by adding ATP. The orange fluorescence of Bis-TPE + Zn2+ system could be quenched by adding Cu2+ and then was recovered by adding ATP. These double detecting abilities for ATP with the "off-on" red fluorescence in Bis-TPE + Cu2+ system and "allochroic-off-on" orange fluorescence in Bis-TPE + Zn2++Cu2+ system were successfully applied to test Cu2+, Zn2+ and ATP in test paper and living cell imaging, displaying the good application prospects for sensing Cu2+, Zn2+ and double detecting ATP in the complicated environment.

miR-423-5p serves as a diagnostic indicator and inhibits the proliferation and invasion of ovarian cancer.

MicroRNA (miR)-423-5p is a potential target for the diagnosis and therapy of heart failure and cancer. The present study aimed to investigate the expression and role of miR-423-5p in ovarian cancer. miR-423-5p expression in ovarian tissues and plasma collected from ovarian cancer patients and healthy volunteers was analyzed by polymerase chain reaction analysis. In addition, a cell proliferation assay, clonogenic assay and Matrigel-based assay were performed to evaluate the role of miR-423-5p in ovarian cancer cells. The results demonstrated that miR-423-5p was downregulated in ovarian cancer tissues and plasma from ovarian cancer patients, compared with healthy individuals. Of note, miR-423-5p expression in ovarian tissues and plasma was demonstrated to be inversely correlated with ovarian cancer progression. Transfection with miR-423-5p efficiently increased miR-423-5p expression in A2780-s and A2780-cp cells, which had low miR-423-5p expression. Ectopic overexpression of miR-423-5p reduced cell proliferation, colony formation and invasion of ovarian cancer cells. In conclusion, the present study indicated that miR-423-5p may serve as a diagnostic indicator and functions as a tumor suppressor in ovarian cancer.

Promiscuity and selectivity of small-molecule inhibitors across TAM receptor tyrosine kinases in pediatric leukemia.

The TAM receptor tyrosine kinase family member Mer has been recognized as an attractive therapeutic target for pediatric leukemia. Beside Mer the family contains other two kinases, namely, Tyro3 and Axl, which are highly homologues with Mer and thus most existing small-molecule inhibitors show moderate or high promiscuity across the three kinases. Here, the structural basis and energetic property of selective binding of small-molecule inhibitors to the three kinases were investigated at molecular level. It is found that the selectivity is primarily determined by the size, shape and configuration of kinase's ATP-binding site; the Mer and Axl possess a small, closed active pocket as compared to the bulky, open pocket of Tyro3. The location and conformation of active-site residues of Mer and Axl are highly consistent, suggesting that small-molecule inhibitors generally have a low Mer-over-Axl selectivity and a high Mer-over-Tyro3 selectivity. We demonstrated that the difference in ATP binding potency to the three kinases is also responsible for inhibitor selectivity. We also found that the long-range interactions and allosteric effect arising from rest of the kinase's active site can indirectly influence inhibitor binding and selectivity.