Spatially resolved metabolomics visualizes heterogeneous distribution of metabolites in lung tissue and the anti-pulmonary fibrosis effect of Prismatomeris connate extract

Pulmonary fibrosis (PF) is a chronic progressive end-stage lung disease. However, the mechanisms underlying the progression of this disease remain elusive. Presently, clinically employed drugs are scarce for the treatment of PF. Hence, there is an urgent need for developing novel drugs to address such diseases. Our study found for the first time that a natural source of Prismatomeris connata Y. Z. Ruan (Huang Gen, HG) ethyl acetate extract (HG-2) had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic (TGF-β1/Smad) pathway. Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation, cellular response to reactive oxygen species, and extracellular matrix (ECM) disassembly. Moreover, mass spectrometry imaging (MSI) was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2, which was related to arginine biosynthesis and alanine, asparate and glutamate metabolism, the downregulation of arachidonic acid metabolism, and the upregulation of glycerophospholipid metabolism. In conclusion, we elaborated on the relationship between metabolite distribution and the progression of PF, constructed the regulatory metabolic network of HG-2, and discovered the multi-target therapeutic effect of HG-2, which might be conducive to the development of new drugs for PF.

Haplotype-resolved and chromosome-scale genomes provide insights into co-adaptation between the Amur tiger and Amur leopard

DEAR EDITOR,Big cats,such as Amur tigers(Panthera tigris altaica)and Amur leopards(P.pardus orientalis),are apex predator and have evolved specialized traits for hunting and carnivory(Moya et al.,2022),thus playing a crucial role in maintaining biodiversity and ecosystem integrity by regulating prey-predator dynamics.However,human-induced pressures,habitat fragmentation,and environmental alterations have restricted these species in small and isolated populations.Currently,all extant big cats are categorized as endangered or threatened according to their conservation status.Amur tigers and Amur leopards share overlapping geographic ranges,habitats,and certain prey species in the forests of Northeast Asia(Jiang et al.,2015).To reduce interspecies conflict,these carnivores exhibit differentiated dietary and temporal niches.Amur tigers predominantly prey on large ungulates,while Amur leopards hunt small to medium-sized animals(Sugimoto et al.,2016).Additionally,they occupy different temporal niches,with tigers being active at night and leopards more active during the day.Despite spatial and temporal niche partitioning,interspecific competition between these two species is inevitable.Tigers,benefiting from their greater size,have a competitive advantage over leopards,which can manifest in occasional leopard predation by tigers and declines in leopard populations with increasing tiger density(Jiang et al.,2015).Tigers also displace leopards from marginal habitats in nature reserves where they coexist.

Time-resolved ultra-small-angle X-ray scattering beamline(BL10U1)at SSRF

The construction of a new beamline,BL10U1,was completed at the Shanghai synchrotron radiation facility in 2020.This multipurpose beamline was designed to provide X-ray scattering techniques such as ultra-small-angle X-ray scattering(USAXS),small-angle X-ray scattering(SAXS),wide-angle X-ray scattering,and microfocus SAXS(μSAXS)for a broad user community.To realize fast time-resolved USAXS experiments,the beamline adopted an in-vacuum undulator with a total length of 1.6 m as the photon source.An in-house cryogenic-cooled double multilayer monochromator was installed to deliver a photon flux of approximately 10^(13) photons/s at a photon energy of 10 keV.The three-year successful operation of this beamline demonstrated that the monochromator operated smoothly,as expected.BL10U1 has three end stations in succession:USAXS end station,μSAXS end station,and end station for industrial applications.The minimum scattering vector q~0.0042 nm^(-1) at 10 keV can be achieved at the USAXS end station equipped with a 28 m-long and 1.8 m-diameter vacuum flight tube.At theμSAXS end station,a beam spot of less than 10×8μm was achieved for micro-SAXS experiments.In contrast,in situ experimental instruments up to 5 m high and 8 m wide can be mounted at the industrial application end station,which offers industrial scientists the opportunity to use their large industrial equipment.BL10U1 opens up a new capability to investigate phenomena such as non-equilibrium and dynamic processes of materials with a wide length scale from angstroms to micrometers with millisecond time resolution.In this paper,we also report beamline design considerations and commissioning results.

Parallelization strategies for resolved simulations of fluid-structure-particle interactions

Fluid-structure-particle interactions in three spatial dimensions happen in many environmental and engineering flows.This paper presents the parallel algorithms for the hybrid diffuse and sharp interface immersed boundary(IB)method developed in our previous work.For the moving structure modeled using the sharp interface IB method,a recursive box method is developed for efficiently classifying the background grid nodes.For the particles modeled using the diffuse interface IB method,a‘master-slave’approach is adopted.For the particle-particle interaction(PPI)and particle-structure interaction(PSI),a fast algorithm for classifying the active and inactive Lagrangian points,which discretize the particle surface,is developed for the‘dry’contact approach.The results show that the proposed recursive box method can reduce the classifying time from 52seconds to 0.3 seconds.Acceptable parallel efficiency is obtained for cases with different particle concentrations.Furthermore,the lubrication model is utilized when a particle approaches a wall,enabling an accurate simulation of the rebounding phenomena in the benchmark particle-wall collision problem.At last,the capability of the proposed computational framework is demonstrated by simulating particle-laden turbulent channel flows with rough walls.

理想的“数字面孔”——Davinci Resolve与肤色调整(上)

肤色处理是调色中最为复杂、最为棘手的难题,至今业界仍缺乏通用的规范供调色师参考。以达芬奇为首的一批数字调色软件的出现虽然突破了传统胶片配光自身的技术局限,但是带来巨大创作空间的同时,这种技术却以惊人的规模被滥用。对"电影感"的片面认识和追求,导致银屏上充斥着相当数量的不符合艺术真实的作品。艺术创造一定是以真实生活为依据,那么皮肤色调的标准又何在?本文借鉴DSC实验室的标准测试图和人类学等学科对肤色标准的贡献,结合达芬奇调色软件,总结了影视创作中肤色处理的几种色彩倾向和规律,并通过几个案例展示了在肤色修饰方面的基本技巧,希望能帮助调色师厘清思路,创造理想的"数字面孔"。

两类图的Resolvent Estrada指标的研究

图G的Resolvent Estrada指标是近年来引入的图的不变量,记作EE_r(G)=∑i=1n(1-λ_i/n-1)^(-1).该文得出图C_n和P_n的Resolvent Estrada指标更为精确的上下界,利用Matlab软件得到当n较小时的EE_r(C_n)和EE_r(P_n)的准确值.

理想的“数字面孔”——Davinci Resolve与肤色调整(下)

肤色处理是调色中最为复杂、最为棘手的难题,至今业界仍缺乏通用的规范供调色师参考。以达芬奇为首的一批数字调色软件的出现虽然突破了传统胶片配光自身的技术局限,但是带来巨大创作空间的同时,这种技术却以惊人的规模被滥用。对"电影感"的片面认识和追求,导致银屏上充斥着相当数量的不符合艺术真实的作品。艺术创造一定是以真实生活为依据,那么皮肤色调的标准又何在?本文借鉴DSC实验室的标准测试图和人类学等学科对肤色标准的贡献,结合达芬奇调色软件,总结了影视创作中肤色处理的几种色彩倾向和规律,并通过几个案例展示了在肤色修饰方面的基本技巧,希望能帮助调色师厘清思路,创造理想的"数字面孔"。

一些特殊超立方体的Resolvent Estrada指标的研究

图G的Resolvent Estrada指标是E.Estrada和D.J.Higham 2010年引入的图的不变量,记作EE r G=(∑n i=11-λi n-1)-1=∑n i=1 n-1 n-1-λi.研究超立方体B n、折叠超立方体F n和增广超立方体D n的Resolvent Estrada指标的界.

Photodissociation Dynamics of 2-1odotoluene Investigated by Femtosecond Time-Resolved Mass Spectrometry

The photodissociation dynamics of 2-iodotoluene following excitation at 266 nm have been investigated employing femtosecond time-resolved mass spectrometry. The photofragments are detected by multiphoton ionization using an intense laser field centered at 800 nm. A dissociation time of 3804-50 fs was measured from the rising time of the co-fragments of toluene radical （C7H7） and iodine atom （I）, which is attributed to the averaged time needed for the C-I bond breaking for the simultaneously excited nσ and ππ＊ states by 266 nm pump light. In addition, a probe light centered at 298.23 nm corresponding to resonance wavelength of ground-state iodine atom is used to selectively ionize ground-state iodine atoms generated from the dissociation of initially populated hσ＊ and ππ＊ states. And a rise time of 4004-50 fs is extracted from the fitting of time-dependent I＋ transient, which is in agreement with the dissociation time obtained by multiphoton ionization with 800 nm, suggesting that the main dissociative products are ground-state iodine atoms.

高清弥散Resolve序列与常规弥散序列在头颅检查中的价值比较

目的:探讨高清弥散Resolve序列与常规弥散序列在头颅检查中的价值。方法:选取2019年5月-2020年4月在本院行头颅磁共振成像(MRI)检查的34例患者为研究对象,均行单次激发平面回波(SS-EPI)及读出方向分段采样(Resolve)序列扫描,比较SS-EPI及Resolve序列的图像质量、信噪比(SNR)、表观弥散系数(ADC)、相对分辨率(RR)及对比分辨率(CR)。结果:Resolve DWI图像伪影、图像变形程度、病灶清晰度、周围结构清晰度及总体评价得分均高于SS-EPI,差异均有统计学意义(P<0.01)。Resolve DWI的SNR检测值低于SS-EPI,差异有统计学意义(P<0.01);Resolve DWI的病灶区域RR及CR检测值均高于SS-EPI,差异均有统计学意义(P<0.01)。结论:Resolve DWI 图像伪影少、图像变形率低、病灶及周围组织结构清晰、图像分辨率高,在头颅检查中应用价值更高。

Probable benign paroxysmal positional vertigo, spontaneously resolved:Incidence in medical practice, patients’ characteristics and the natural course

Background: Probable benign paroxysmal positional vertigo, spontaneously resolved (pBPPVsr), is a variant of benign paroxysmal positional vertigo (BPPV) in which there is no observable nystagmus and no vertigo with any positional maneuver. Objectives: To calculate the incidence pBPPVsr, compare the characteristics of the patients with pBPPVsr and BPPV not spontaneously resolved and describe the spontaneous resolution in the natural course of BPPV. Methods: Multicenter prospective descriptive study. During a one-year period, all patients with suspected BPPV that presented to the Neurotology Units of five participating centers were recruited. The incidence of pBPPVsr was calculated as a percentage of the total number of patients with BPPV. The prevalence of several variables was compared between pBPPVsr and BPPV not spontaneously resolved. The timing of spontaneous resolution was estimated using Kaplan-Meier curves. Results: 457 patients met the inclusion criteria. The incidence of pBPPVsr was 33.5%. It was significantly higher in males, in patients with normal bone mass and in patients who were not taking sulpiride. A rate of 18% of spontaneous resolution after the first month and 51% after the first year was found. This percentage did not change in a significant way after this moment. The curves for males, patients under 50 and patients with normal blood pressure decreased significantly faster. Conclusions: In our serie, BPPV spontaneously resolved in half of the patients with BPPV during the first year. This seemed to occur more commonly in males and could have been hindered by sulpiride intake, osteoporosis, advanced age and high blood pressure.

A gap-free and haplotype-resolved lemon genome provides insights into flavor synthesis and huanglongbing (HLB) tolerance

The lemon(Citrus limon;family Rutaceae)is one of the most important and popular fruits worldwide.Lemon also tolerates huan-glongbing(HLB)disease,which is a devastating citrus disease.Here we produced a gap-free and haplotype-resolved chromosome-scale genome assembly of the lemon by combining Pacific Biosciences circular consensus sequencing,Oxford Nanopore 50-kb ultra-long,and high-throughput chromatin conformation capture technologies.The assembly contained nine-pair chromosomes with a contig N50 of 35.6 Mb and zero gaps,while a total of 633.0 Mb genomic sequences were generated.The origination analysis identified 338.5Mb genomic sequences originating from citron(53.5%),147.4Mb frommandarin(23.3%),and 147.1Mb frompummelo(23.2%).The genome included 30528 protein-coding genes,and most of the assembled sequences were found to be repetitive sequences.Several significantly expanded gene families were associated with plant-pathogen interactions,plant hormone signal transduction,and the biosynthesis of major active components,such as terpenoids and f lavor compounds.Most HLB-tolerant genes were expanded in the lemon genome,such as 2-oxoglutarate(2OG)/Fe(II)-dependent oxygenase and constitutive disease resistance 1,cell wall-related genes,and lignin synthesis genes.Comparative transcriptomic analysis showed that phloem regeneration and lower levels of phloem plugging are the elements that contribute to HLB tolerance in lemon.Our results provide insight into lemon genome evolution,active component biosynthesis,and genes associated with HLB tolerance.

Haplotype-resolved genome assembly and allele- specific gene expression in cultivated ginger

Ginger(Zingiber officinale)is one of the most valued spice plants worldwide;it is prized for its culinary and folk medicinal applications and is therefore of high economic and cultural importance.Here,we present a haplotype-resolved,chromosome-scale assembly for diploid ginger anchored to 11 pseudochromosome pairs with a total length of 3.1 Gb.Remarkable structural variation was identified between haplotypes,and two inversions larger than 15Mb on chromosome 4 may be associated with ginger infertility.We performed a comprehensive,spatiotemporal,genome-wide analysis of allelic expression patterns,revealing that most alleles are coordinately expressed.The alleles that exhibited the largest differences in expression showed closer proximity to transposable elements,greater coding sequence divergence,more relaxed selection pressure,and more transcription factor binding site differences.We also predicted the transcription factors potentially regulating 6-gingerol biosynthesis.Our allele-aware assembly provides a powerful platform for future functional genomics,molecular breeding,and genome editing in ginger.

High-quality haplotype-resolved genome assembly of cultivated octoploid strawberry

Cultivated strawberry(Fragaria×ananassa),a perennial herb belonging to the family Rosaceae,is a complex octoploid with high heterozygosity at most loci.However,there is no research on the haplotype of the octoploid strawberry genome.Here we aimed to obtain a high-quality genome of the cultivated strawberry cultivar,“Yanli”,using single molecule real-time sequencing and high-throughput chromosome conformation capture technology.The“Yanli”genome was 823 Mb in size,with a long terminal repeat assembly index of 14.99.The genome was phased into two haplotypes,Hap1(825 Mb with contig N50 of 26.70 Mb)and Hap2(808 Mb with contig N50 of 27.51 Mb).Using the combination of Hap1 and Hap2,we obtained for the first time a haplotype-resolved genome with 56 chromosomes for the cultivated octoploid strawberry.We identified a∼10 Mb inversion and translocation on chromosome 2-1.104957 and 102356 protein-coding genes were annotated in Hap1 and Hap2,respectively.Analysis of the genes related to the anthocyanin biosynthesis pathway revealed the structural diversity and complexity in the expression of the alleles in the octoploid F.×ananassa genome.In summary,we obtained a high-quality haplotype-resolved genome assembly of F.×ananassa,which will provide the foundation for investigating gene function and evolution of the genome of cultivated octoploid strawberry.

Correction:Haplotype-resolved genome of diploid ginger (Zingiber officinale)and its unique gingerol biosynthetic pathway

After online publication of the article 1,the authors noticed the affiliation“College of Landscape Architecture and Life Science/Institute of Special Plants,Chongqing University of Arts and Sciences,Yongchuan,Chongqing,China”for author Yiqing Liu was missing.

Space-time Resolved Spectroscopic System Based on a Rotating Hexahedral Mirror for Measurement of Visible and Ultraviolet Spectral Line Emissions

By using a rotating hexahedral mirror placed in front of the objective lens and two sets of visible and ultraviolet monochromators coupled with a branchy quartz fiber bundle, a space-time resolved spectroscopic system has been developed on the HT-7 superconducting tokamak. A center monitoring system has been used including a Helium-Neon laser and a photodiode detector to indicate the absolute position of the measurement in order to reduce the error caused by the uncertain emissive position of the plasma. By using the asymmetric Abel inversion, the space-time resolved local emission coefficients of the spectroscopic line emissions have been obtained. Presented in this article are simultaneous measurements of two spectral line emissions such as CV-227.1 nm and OV-278.1 nm during a single plasma discharge on the HT-7. Experimental results indicate that the time resolution is better than 3 ms, the space resolution is better than 1.5cm, the ratio of signal to background is better than 10：1, and the relative error of chord-integrated emission profile is less than 10%. Compared to traditional multichannel detecting systems, this system has considerably improved measurement efficiency, reduced uncertainty, and is therefore suitable for transport studies of global particles and impurities.

Disappearance of Superconductivity and a Concomitant Lifshitz Transition in Heavily Overdoped Bi_2Sr_2CuO_6 Superconductor Revealed by Angle-Resolved Photoemission Spectroscopy

By partially doping Pb to effectively suppress the superstructure in single-layered cuprate Bi_2Sr_2CuO_(6+δ)(Pb-Bi2201) and annealing them in vacuum or in high pressure oxygen atmosphere, a series of high quality Pb-Bi2201 single crystals are obtained with T_c covering from 17 K to non-superconducting in the overdoped region. High resolution angle resolved photoemission spectroscopy measurements are carried out on these samples to investigate the evolution of the Fermi surface topology with doping in the normal state. Clear and complete Fermi surfaces are observed and quantitatively analyzed in all of these overdoped Pb-Bi2201 samples. A Lifshitz transition from holelike Fermi surface to electron-like Fermi surface with increasing doping is observed at a doping level of ~0.35. This transition coincides with the change that the sample undergoes superconducting-to-non-superconducting states.Our results reveal the emergence of an electron-like Fermi surface and the existence of a Lifshitz transition in heavily overdoped Bi2201 samples. This provides important information in understanding the connection between the disappearance of superconductivity and the Lifshitz transition in the overdoped region.

Promise of spatially resolved omics for tumor research

Tumors are spatially heterogeneous tissues that comprise numerous cell types with intricate structures.By interacting with the microenvironment,tumor cells undergo dynamic changes in gene expression and metabolism,resulting in spatiotemporal variations in their capacity for proliferation and metastasis.In recent years,the rapid development of histological techniques has enabled efficient and high-throughput biomolecule analysis.By preserving location information while obtaining a large number of gene and molecular data,spatially resolved metabolomics(SRM)and spatially resolved transcriptomics(SRT)approaches can offer new ideas and reliable tools for the in-depth study of tumors.This review provides a comprehensive introduction and summary of the fundamental principles and research methods used for SRM and SRT techniques,as well as a review of their applications in cancer-related fields.

Computer Assisted Assignments of Rotationally Resolved Molecular Spectra

A graphically oriented interactive program for assignments of rotationally resolved molecular spectra has been devised. The program functions by grouping spectral lines in term of the second difference principle. and graphing spectral intensity versus frequency in a bar graph of the selected groups, distinguished by color and/or line-type. This allows for easy detection of regular patterns buried in the observed spectrum. Furthermore, it includes a Loomis-Wood view for assisting in spectral assignments. As an example, the program was applied in assigning the molecular spectrum of the production in the discharge of PCl3 buffered by helium gas, which may belong to several species. The results suggest that the program is highly efficient and quite useful in the assignment and the analysis of molecular spectra, especially those of symmetric top, slightly asymmetric top and linear molecules. The accuracy and efficiency of this program will likely ensure its wide application in the processing of molecular spectra.

RESOLVE研究对我国胃癌新辅助化疗的临床意义及展望

RESOLVE研究为一项3期开放、多中心、随机、对照临床研究,旨在为中国人群提供进展期胃癌围手术期治疗方案。研究纳入cT;期患者,比较了SOX(奥沙利铂+替吉奥)辅助化疗和CapOx(奥沙利铂+卡培他滨)辅助化疗以及SOX新辅助化疗与CapOx辅助化疗的疗效,证实SOX新辅助化疗对于中国人群进展期胃癌的优效性。RESOLVE研究为针对中国进展期胃癌患者围手术期治疗方案研究的良好开端,然而,该研究及国际上其他大型研究(MAGIC、FLOT4)均非相同化疗药物新辅助治疗与辅助治疗的直接比较,期待后续进行完善,并结合组织学分类、基因分型,进行更精准的治疗方案研究。