Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Measuring Light and Geometry Data of Roadway Environments with a Camera

Evaluation of the conspicuity of roadway environments for their environmental impact on driving performance is vital for roadway safety. Existing meters and tools for roadway measurements cannot record light and geometry data simultaneously in a high resolution. This study introduced a new method that adopted recently developed high dynamic range (HDR) photogrammetry to measure the luminance and XYZ coordinates of millions of points across a road scene with the same device—a camera, and a MatLab code for data treatment and visualization. To validate this method, the roadway environments of a straight and flat section of Jayhawk Boulevard (482.8 m long) at Lawrence, KS and a roundabout (15.3 m in diameter) at its end were measured under clear and cloudy sky in the daytime and at nighttime with dry and wet pavements. Eight HDR images of the roadway environments under different viewing conditions were generated using the HDR photogrammetric techniques and calibrated. From each HDR image, synchronous light and geometry data were extracted in Radiance and further analyzed to identify potential roadway environmental hazards using the MatLab code (http://people.ku.edu/~h717c996/research.html). The HDR photogrammetric measurement with current equipment had a margin of errors for geometry measurement that varied with the measuring distance, averagely 23.1% - 27.5% for the Jayhawk Boulevard and 9.3% - 16.2% for the roundabout. The accuracy of luminance measurement was proven in the literature as averagely 1.5% - 10.1%. The camera-aided measurement is fast, non-contact, non-destructive, and off the road, thus, it is deemed more efficient and safer than conventional ways using meters and tools. The HDR photogrammetric techniques with current equipment still need improvements on accuracy and speed of the data treatment.

潜艇运动激发的表面波

A moving submarine can generate internal waves,as well as extremely small free surface waves,in a fluid with density stratification.In this study,the internal and free surface wave wakes caused by a moving submarine in two layers of constant density fluid were studied numerically using the commercial software STAR-CCM+.The realizable k–εturbulence model was used to solve the Reynolds-averaged Navier–Stokes equation,and the volume of the fluid method was used to monitor the fluctuations of the internal interface and free surface.Different cases of a moving submarine with different cruising speeds and relative diving depths were studied.Results showed that the maximum fluctuation amplitude of the free surface increased as the speed of the submarine increased;however,the maximum fluctuation amplitude of the internal interface first decreased and then increased.When the submarine moved at the maximum cruising speed,the maximum fluctuation amplitude of the free surface decreased as the diving depth increased,while the wavelength of the free surface wave was basically the same.If the submarine moved at the minimum cruising speed,then the wave elevation in the free surface was extremely small,but the internal surface had obviously large-amplitude internal waves,and the relative diving depth had a great influence on internal waves.

燃烧源氨排放对灰霾期间北京大气铵的重要贡献

Aerosol ammonium(NH_(4)^(+)),mainly produced from the reactions of ammonia(NH_(3))with acids in the atmosphere,has significant impacts on air pollution,radiative forcing,and human health.Understanding the source and formation mechanism of NH_(4)^(+)can provide scientific insights into air quality improvements.However,the sources of NH_(3)in urban areas are not well understood,and few studies focus on NH_(3)/NH_(4)^(+)at different heights within the atmospheric boundary layer,which hinders a comprehensive understanding of aerosol NH_(4)^(+).In this study,we perform both field observation and modeling studies(the Community Multiscale Air Quality,CMAQ)to investigate regional NH_(3)emission sources and vertically resolved NH_(4)^(+)formation mechanisms during the winter in Beijing.Both stable nitrogen isotope analyses and CMAQ model suggest that combustion-related NH_(3)emissions,including fossil fuel sources,NH_(3)slip,and biomass burning,are important sources of aerosol NH_(4)^(+)with more than 60%contribution occurring on heavily polluted days.In contrast,volatilization-related NH_(3)sources(livestock breeding,N-fertilizer application,and human waste)are dominant on clean days.Combustion-related NH_(3)is mostly local from Beijing,and biomass burning is likely an important NH_(3)source(~15%–20%)that was previously overlooked.More effective control strategies such as the two-product(e.g.,reducing both SO_(2)and NH_(3))control policy should be considered to improve air quality.

Global Profiling of 2-hydroxyisobutyrylome in Common Wheat

As a novel post-translational modification(PTM),lysine 2-hydroxyisobutyrylation(Khib)is considered to regulate gene transcriptional activities in eukaryotic cells;however,the functions of Khib-modified proteins in plants remain unknown.Here,we report that Khib is an evolutionarilyconserved PTM in wheat and its progenitors.A total of 3348 Khib sites on 1074 proteins are identified in common wheat(Triticum aestivum L.)by using affinity purification and mass spectroscopy of 2-hydroxyisobutyrylome.Bioinformatic data indicate that Khib-modified proteins participate in a wide variety of biological and metabolic pathways.Immunoprecipitation confirms that Khibmodified proteins are present endogenously.A comparison of Khib and other main PTMs shows that Khib-modified proteins are simultaneously modified by multiple PTMs.Using mutagenesis experiments and co-immunoprecipitation assays,we demonstrate that Khib on K206 of phosphoglycerate kinase(PGK)is a key regulatory modification for its enzymatic activity,and mutation on K206 affects the interactions of PGK with its substrates.Furthermore,Khib modification of low-molecular-weight proteins is a response to the deacetylase inhibitors nicotinamide and trichostatin.This study provides evidence to promote our current understanding of Khib in wheat plants,including the cooperation between Khib and its metabolic regulation.

Natural Variation in OsPRR37 Regulates Heading Date and Contributes to Rice Cultivation at a Wide Range of Latitudes

Heading date and photoperiod sensitivity are fundamental traits that determine rice adaptation to a wide range of geographic environments. By quantitative trait locus （QTL） mapping and candidate gene analysis using whole- genome re-sequencing, we found that Oryza sativa Pseudo-Response Regulator37 （OsPRR37; hereafter PRR37） is respon- sible for the Early heading7-2 （EH7-2）/Heading date2 （Hd2） QTL which was identified from a cross of late-heading rice ＇Milyang23 （M23）＇ and early-heading rice ＇H143＇. H143 contains a missense mutation of an invariantly conserved amino acid in the CCT （CONSTANS, CO-like, and TOC1） domain of PRR37 protein. In the world rice collection, different types of nonfunctional PRR37 alleles were found in many European and Asian rice cultivars. Notably, the japonica varieties harboring nonfunctional alleles of both Ghd7/Hd4 and PRR37/Hd2 flower extremely early under natural long-day condi- tions, and are adapted to the northernmost regions of rice cultivation, up to 53~ N latitude. Genetic analysis revealed that the effects of PRR37 and Ghd7 alleles on heading date are additive, and PRR37 down-regulates Hd3a expression to suppress flowering under long-day conditions. Our results demonstrate that natural variations in PRR37/Hd2 and GhdT/ Hd4 have contributed to the expansion of rice cultivation to temperate and cooler regions.

Crystal structure of the African swine fever virus core shell protein p15

African swine fever virus(ASFV)is the causative agent of African swine fever,a highly fatal hemorrhagic disease of pigs,which has resulted in great economic losses to the global pork industry,especially in Asia.ASFV particles are comprised ofmultiple layers encompassing the genomic DNA.Though the capsid structure has been determined,very little is known about the structure of the core shell.The precursor polyprotein pp62 is the structural component of the core shell that gives rise to the p35 and p15 proteins.Herein,we describe the crystal structure of p15 at a resolution of 2.2Å.The structure of p15 exhibits as a trimeric conformation that is mainly mediated by intermolecular disulfide bonds and supported bymultiple hydrogen bond interactions.The button conformation on the surface of adjacentmolecules may also play a role in trimeric formation of the ASFV p15.The center of the p15 trimer exhibits opposite electrostatic characteristics on each side.These findings benefit our understanding of ASFV core shell assembly and will aid in the design of antiviral drugs and vaccines.

Anisotropic MOF-on-MOF Growth of Isostructural Multilayer Metal–Organic Framework Heterostructures

Isostructural MOFs with similar crystallographic parameter are easily available for MOF-on-MOF growth and possible to form core–shell structure by isotropic growth.However,due to well-matched cell lattice,selective growth in isostructural MOF heterostructures remains a great challenge for engineering atypical MOF heterostructures.Herein,an anisotropic MOF-onMOF growth strategy was developed to structure a range of multilayer sandwich-like ZIF-L heterostructures via stacking isostructural ZIF-L-Zn and ZIF-L-Co alternately with three-,five-,seven-,and more layer structures.Moreover,these heterostructures with highly designable feature were fantastic precursors for fabricating derivatives with tunable magnetic and catalytic properties.Such strategy explores a novel way of achieving anisotropic MOF-on-MOF growth between isostructural MOFs and opens up new horizons for regulating the properties by MOF modular assembly in versatile functional nanocomposites.

Anisotropic MOF-on-MOF Growth of Isostructural Multilayer Metal–Organic Framework Heterostructures

Isostructural MOFs with similar crystallographic parameter are easily available for MOF-on-MOF growth and possible to form core–shell structure by isotropic growth.However,due to well-matched cell lattice,selective growth in isostructural MOF heterostructures remains a great challenge for engineering atypical MOF heterostructures.Herein,an anisotropic MOF-onMOF growth strategy was developed to structure a range of multilayer sandwich-like ZIF-L heterostructures via stacking isostructural ZIF-L-Zn and ZIF-L-Co alternately with three-,five-,seven-,and more layer structures.Moreover,these heterostructures with highly designable feature were fantastic precursors for fabricating derivatives with tunable magnetic and catalytic properties.Such strategy explores a novel way of achieving anisotropic MOF-on-MOF growth between isostructural MOFs and opens up new horizons for regulating the properties by MOF modular assembly in versatile functional nanocomposites.