PnMYB4 negatively modulates saponin biosynthesis in Panax notoginseng through interplay with PnMYB1

Saponins are the main triterpenoid ingredients from Panax notoginseng,a well-known Chinese medicine,and are important sources for producing drugs to prevent and treat cerebrovascular and cardiovascular diseases.However,the transcriptional regulatory network of saponin biosynthesis in P.notoginseng is largely unknown.In the present study we demonstrated that one R2R3-MYB transcription factor,designated PnMYB4,acts as a repressor of saponin accumulation.Suppression of PnMYB4 in P.notoginseng calli significantly increased the saponin content and the expression level of saponin biosynthetic genes.PnMYB4 directly bound to the promoters of key saponin biosynthetic genes,including PnSS,PnSE,and PnDS,to repress saponin accumulation.PnMYB4 and the activator PnMYB1 could inter-acted with PnbHLH,which is a positive regulator of saponin biosynthesis,to modulate the biosynthesis of saponin.PnMYB4 competed with PnMYB1 for binding to PnbHLH,repressing activation of the promoters of saponin structural genes induced by the PnMYB1-PnbHLH complex.Our study reveals that a complex regulatory module of saponin biosynthesis is associated with positive and negative MYB transcriptional regulators and provides a theoretical basis for improving the content of saponins and efficacy of P.notoginseng.

Novel modelling strategies for high‑frequency stock trading data

Full electronic automation in stock exchanges has recently become popular,generat-ing high-frequency intraday data and motivating the development of near real-time price forecasting methods.Machine learning algorithms are widely applied to mid-price stock predictions.Processing raw data as inputs for prediction models(e.g.,data thinning and feature engineering)can primarily affect the performance of the prediction methods.However,researchers rarely discuss this topic.This motivated us to propose three novel modelling strategies for processing raw data.We illustrate how our novel modelling strategies improve forecasting performance by analyzing high-frequency data of the Dow Jones 30 component stocks.In these experiments,our strategies often lead to statistically significant improvement in predictions.The three strategies improve the F1 scores of the SVM models by 0.056,0.087,and 0.016,respectively.

A variational solution of 2-D sound-structure interaction problems

Based on the fluid-structure coupling theory, a localized variational principle for analyzing the sound radiation from elastic structure submerged in water due to harmonic excitations is presented. It will be a powerful tool to formulate various numerical methods for steady response of structural-acoustic systems. By means of this variational principle a hybrid element method, in which an analytical solution valid in most of the surrounding water is incorporated with finite elements distributed in the structure and its neighboring water, is devised. Computational examples are then given to demonstrate its high accuracy and time saving.

HTR2A agonists play a therapeutic role by restricting ILC2 activation in papain-induced lung inflammation

Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been reported.Previous studies have shown that type 2 cytokines,such as IL-5 and IL-13,are related to depression.Here,we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression.Interestingly,serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation.Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs.Furthermore,an HTR2A selective agonist(DOI)impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro.Mice with ILC2-specific depletion of HTR2A(Il5^(cre/+)·Htr2a^(flox/flox)mice)abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation.In conclusion,serotonin and DOI could restrict the type 2 lung immune response,indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ILC2s.

Vitamin B6 regulates IL-33 homeostasis to alleviate type 2 inflammation

Interleukin-33(IL-33)is a crucial nuclear cytokine that induces the type 2 immune response and maintains immune homeostasis.The fine-tuned regulation of IL-33 in tissue cells is critical to control of the type 2 immune response in airway inflammation,but the mechanism is still unclear.Here,we found that healthy individuals had higher phosphate-pyridoxal(PLP,an active form of vitamin B6)concentrations in the serum than asthma patients.Lower serum PLP concentrations in asthma patients were strongly associated with worse lung function and inflammation.In a mouse model of lung inflammation,we revealed that PLP alleviated the type 2 immune response and that this inhibitory effect relied on the activity of IL-33.A mechanistic study showed that in vivo,pyridoxal(PL)needed to be converted into PLP,which inhibited the type 2 response by regulating IL-33 stability.In mice heterozygous for pyridoxal kinase(PDXK),the conversion of PL to PLP was limited,and IL-33 levels were increased in the lungs,aggravating type 2 inflammation.Furthermore,we found that the mouse double minute 2 homolog(MDM2)protein,an E3 ubiquitin-protein ligase,could ubiquitinate the N-terminus of IL-33 and sustain IL-33 stability in epithelial cells.PLP reduced MDM2-mediated IL-33 polyubiquitination and decreased the level of IL-33 through the proteasome pathway.In addition,inhalation of PLP alleviated asthma-related effects in mouse models.In summary,our data indicate that vitamin B6 regulates MDM2-mediated IL-33 stability to constrain the type 2 response,which might help develop a potential preventive and therapeutic agent for allergy-related diseases.

A human antibody potently neutralizes RSV by targeting the conserved hydrophobic region of prefusion F

Respiratory syncytial virus(RSV) continues to pose serious threats to pediatric populations due to the lack of a vaccine and effective antiviral drugs. RSV fusion(F) glycoprotein mediates viral-host membrane fusion and is a key target for neutralizing antibodies. We generated 23 full-human monoclonal antibodies(hm Abs) against prefusion F protein(pre-F) from a healthy adult with natural RSV infection by single B cell cloning technique. A highly potent RSV-neutralizing hm Ab, named as 25-20, is selected, which targets a new site Φ-specific epitope. Site-directed mutagenesis and structural modelling analysis demonstrated that 25-20 mainly targets a highly conserved hydrophobic region located at the a4 helix and a1 helix of pre-F, indicating a site of vulnerability for drug and vaccine design. It is worth noting that 25-20 uses an unreported inferred germline(i GL) that binds very poorly to pre-F, thus high levels of somatic mutations are needed to gain high binding affinity with pre-F. Our observation helps to understand the evolution of RSV antibody during natural infection. Furthermore, by in silico prediction and experimental verification, we optimized 25-20 with KD values as low as picomolar range. Therefore, the optimized 25-20 represents an excellent candidate for passive protection against RSV infection.

An amphiphilic[2]biphenyl-extended pillar[6]arene:Synthesis,controllable self-assembly in water and application in cell-imaging

Synthesis and functionalization of novel macrocyclic host molecules are important topics in supramolecular chemistry.In this work,the first amphiphilic[2]biphenyl-extended pillar[6]arene(AM-[2]BP-ExP6)was designed and synthesized with poly(ethylene glycol)chains as the hydrophilic tails and a rigid cavity as the hydrophobic core.Due to its amphiphilic nature,AM-[2]BP-ExP6 could self-assemble to stable fibers in water.What’s more,AM-[2]BP-ExP6 could associate with quaternary ammonium modified tetraphenylethylene guest(QTPE)to form a 2:1 host-guest complex,accompanied by significant enhanced fluorescence.Interestingly,different like AM-[2]BP-ExP6,AM-[2]BP-ExP6⊃QTPE host-guest complex selfassembled into fluorescent particles with diameter about 310 nm,the obtained fluorescent particles can be further employed in living cell imaging.

Occurrence of bisphenol A in surface and drinking waters and its physicochemical removal technologies

Bisphenol A （BPA）, an endocrine disrupting compound, has caused wide public concerns due to its wide occurrence in environment and harmful effects. BPA has been detected in many surface waters and drinking water with the maximum concentrations up to tens of μg · L-1. The physicochemical technology options in eliminating BPA can be divided into four categories： oxidation, advanced oxidation, adsorption and membrane filtration. Each removal option has its own limitation and merits in removing BPA. Oxidation and advanced oxidation generally can remove BPA efficiently while they also have some drawbacks, such as high cost, the generation of a variety of transformation products that are even more toxic than the parent compound and difficult to be mineralized. Only few advanced oxidation methods have been reported to be able to mineralize BPA completely. Therefore, it is important not only to identify the major initial transformation products but also to assess their estrogenic activity relative to the parent compounds when oxidation methods are employed to remove BPA. Without formation of harmful by-products, physical separation methods such as activated carbon adsorption and membrane processes are able to remove BPA in water effluents and thus have potential as BPA removal technologies. However, the necessary regeneration of activated carbon and the low BPA removal efficiency when the membrane became saturated may limit the application of activated carbon adsorption and membrane processes for BPA removal. Hybrid processes, e.g. combining adsorption and biologic process or combining membrane and oxidation process, which can achieve simultaneous physical separation anddegradation of BPA, will be highly preferred in future.

TRANSFER MATRIX METHOD FOR ANALYZING VIBRATION AND DAMPING CHARACTERISTICS OF ROTATIONAL SHELL WITH PASSIVE CONSTRAINED LAYER DAMPING TREATMENT

The first order differential matrix equations of the host shell and constrained layer for a sandwich rotational shell are derived based on the thin shell theory.Employing the layer wise principle and first order shear deformation theory, only considering the shearing deformation of the viscoelastic layer, the integrated first order differential matrix equation of a passive constrained layer damping rotational shell is established by combining with the normal equilibrium equation of the viscoelastic layer.A highly precise transfer matrix method is developed by extended homogeneous capacity precision integration technology.The numerical results show that present method is accurate and effective.

MODELING AND DYNAMICS ANALYSIS OF SHELLS OF REVOLUTION BY PARTIALLY ACTIVE CONSTRAINED LAYER DAMPING TREATMENT

A new model for a smart shell of revolution treated with active constrained layer damping （ACLD） is developed, and the damping effects of the ACLD treatment are discussed. The motion and electric analytical formulation of the piezoelectric constrained layer are presented first. Based on the authors~ recent research on shells of revolution treated with passive constrained layer damping （PCLD）, the integrated first-order differential matrix equation of a shell of revolution partially treated with ring ACLD blocks is derived in the frequency domain. By virtue of the extended homogeneous capacity precision integration technology, a stable and simple numerical method is further proposed to solve the above equation. Then, the vibration responses of an ACLD shell of revolution are measured by using the present model and method. The results show that the control performance of the ACLD treatment is complicated and frequency-dependent. In a certain frequency range, the ACLD treatment can achieve better damping characteristics compared with the conventional PCLD treatment.

Influence of crystal materials on the synchrotron X-ray fluorescence analysis:a study of crystal and amorphous clinopyroxene

Synchrotron X-ray fluorescence analyses of crystal and amorphous clinopyroxene were compared. The results showed that using the synchrotron X-ray as a source of energy, the diffraction X-ray of crystal materials will seriously affect the X-ray fluorescence analysis. In order to avoid the influence of diffraction, the best way to solve it is to use the monochromatic source, or to have a collimating slit between sample and Si(Li) detector.

Quantum phase transition and destruction of Kondo effect in pressurized SmB6

SmB_6 has been a well-known Kondo insulator for decades, but recently attracts extensive new attention as a candidate topological system. Studying SmB_6 under pressure provides an opportunity to acquire the much-needed understanding about the effect of electron correlations on both the metallic surface state and bulk insulating state. Here we do so by studying the evolution of two transport gaps(low temperature gap E_l and high temperature gap E_h) associated with the Kondo effect by measuring the electrical resistivity under high pressure and low temperature(0.3 K) conditions. We associate the gaps with the bulk Kondo hybridization, and from their evolution with pressure we demonstrate an insulator-tometal transition at ~4 GPa. At the transition pressure, a large change in the Hall number and a divergence tendency of the electron-electron scattering coefficient provide evidence for a destruction of the Kondo entanglement in the ground state. Our results raise the new prospect for studying topological electronic states in quantum critical materials settings.