山茱萸炮制的历史沿革及探讨

山茱萸为山茱萸科植物山茱萸(Cornus officinalis Sieb.et Zuce)的干燥成熟果肉。中医临床常用以补肝益肾,涩精固脱,并多要求炮制后入药。其炮制历史久远,本文拟就其炮制历史沿革、传统炮制理论及现代研究结果作一概述。1山茱萸炮制历史沿革山茱萸炮制历史悠久。汉代《金匮玉函     

不寐方组方配伍历史沿革

系统分析历代不寐方发展演变及组方选药的特点。汉唐时期组方以清热泻火药和滋阴养血药为主,宋金元时期以清心安神、补气养心、养血安神药为主,又出现气血双补、交通心肾、滋阴潜阳、补益肝肾类方剂,在治法上取得了突破性进展;明清时期以养血安神方、重镇安神方、祛痰化饮方、交通心肾方为主,和胃消食方、理气解郁方、活血化瘀方的出现进一步完善了不寐证的治疗思路。     

基于肺络理论论治肺结节病

随着肺结节病发病率及检出率的逐年上升,肺结节病逐渐引起各界的关注及重视,对肺结节病CT随访期进行有效的干预治疗,延缓进展,控制生长,以致消除结节,是现代医学面临的关键问题。从肺络论治肺结节病,着手于肺络之内涵、结构、生理特点等,进而探究肺络虚损是肺结节病的病理基础、肺络-气机失调是肺结节病发生的病理环节、肺络-气郁痰瘀停聚是肺结节病的重要病理演变、肺络郁闭是肺结节病的基本病机。最终,立足于中医络病理论的优势,提出通络法论治肺结节病,以期为临床论治肺结节打开新的诊疗思路,提供新的理论认识。     

Accumulation and maintenance of information in evolution

Selection accumulates information in the genome—it guides stochastically evolving populations toward states (genotype frequencies) that would be unlikely under neutrality. This can be quantified as the Kullback–Leibler (KL) divergence between the actual distribution of genotype frequencies and the corresponding neutral distribution. First, we show that this population-level information sets an upper bound on the information at the level of genotype and phenotype, limiting how precisely they can be specified by selection. Next, we study how the accumulation and maintenance of information is limited by the cost of selection, measured as the genetic load or the relative fitness variance, both of which we connect to the control-theoretic KL cost of control. The information accumulation rate is upper bounded by the population size times the cost of selection. This bound is very general, and applies across models (Wright–Fisher, Moran, diffusion) and to arbitrary forms of selection, mutation, and recombination. Finally, the cost of maintaining information depends on how it is encoded: Specifying a single allele out of two is expensive, but one bit encoded among many weakly specified loci (as in a polygenic trait) is cheap.

Throughout evolution, selection accumulates information in the genome. It guides evolving populations toward fitter phenotypes, genotypes, and genotype frequencies, which would be highly unlikely to arise by chance. This information—the degree to which selection can control the stochastic process of evolution—has been a long-standing subject of research (1–7), and relates to basic questions in evolutionary biology and genetics.     

Comparing the development of cortex-wide gene expression patterns between two species in a common reference frame

Advances in sequencing techniques have made comparative studies of gene expression a current focus for understanding evolutionary and developmental processes. However, insights into the spatial expression of genes have been limited by a lack of robust methodology. To overcome this obstacle, we developed methods and software tools for quantifying and comparing tissue-wide spatial patterns of gene expression within and between species. Here, we compare cortex-wide expression of RZRβ and Id2 mRNA across early postnatal development in mice and voles. We show that patterns of RZRβ expression in neocortical layer 4 are highly conserved between species but develop rapidly in voles and much more gradually in mice, who show a marked expansion in the relative size of the putative primary visual area across the first postnatal week. Patterns of Id2 expression, by contrast, emerge in a dynamic and layer-specific sequence that is consistent between the two species. We suggest that these differences in the development of neocortical patterning reflect the independent evolution of brains, bodies, and sensory systems in the 35 million years since their last common ancestor.

Almost everything we know about the human brain comes from comparative studies of other animals: from genes involved in cortical development to system-level networks that generate complex behaviors. Comparative studies of living species provide a robust means by which to understand unknown forms, like humans, and even extinct forms like our early mammalian ancestors. Importantly, these types of studies are critical for identifying features of brain organization that are conserved between species and those that may have been derived in different lineages. They also allow us to determine how developmental programs and timing schedules may vary across species, and to better understand how phenotypic diversity can be generated over shorter and longer timescales. Finally, by making valid comparisons across species, we can begin to understand how complexity emerges in different nervous systems, the rules of brain construction, and the constraints imposed on developing and evolving nervous systems.Despite the importance of comparative studies in biology, most comparisons of anatomically reconstructed data are subjective, and most gene sequencing studies neglect the actual spatial patterns of gene expression across a structure, focusing instead on cell-type expression (1–3). Moreover, many current methods for making comparisons fail to capture the three-dimensional nature of the brain, which is composed of asymmetrical structures that can vary markedly in relative shape, size, and location across species and between developmental time-points. Despite the three-dimensional (3D) nature of the brain, most studies collapse data into two dimensions driven largely by the plane of section at which the brain is cut.As such, neurobiologists are faced with two challenges. First, attempting to understand 3D structures by analyzing two-dimensional (2D) images is inherently problematic because the loss of spatial information is unavoidable, especially in curved structures (4). 2D analysis often involves prespecifying regions of interest (ROIs) to quantify the presence of labeled cells or mRNA expression after in-situ hybridization (ISH), narrowing the focus and potentially missing overall differences across a structure, such as the neocortex. A second challenge, which arises when making comparisons between structures in different species and/or at different developmental time-points, or between different experimental conditions, is determining the extent to which 2D spatial patterning might be invariant to basic transformations in the size and shape of the 3D structure. To this end, it is important for comparisons to be made with respect to a common anatomical reference frame.In the current study, we overcame these challenges by developing a set of algorithms for brain slice registration in 3D, and for incorporating ISH data into a common reference frame to enable point-by-point comparisons between species or experimental conditions (see Materials and Methods). These tools, which we refer to collectively as Stalefish, the Spatial Analysis of Fluorescent (and nonfluorescent) In-Situ Hybridization, allowed for the laminar and spatial patterns of expression of genes involved in cortical development to be quantified and compared in two species of age matched rodents across early postnatal development. Our analysis of Id2 and RZRβ cortical expression patterns in mouse and vole brains reveals both a strong layer-specific conservation of the patterning of these genes, as well as area-specific differences in development that shed new light on the ontogeny and phylogeny of neocortical arealization.     

Interlaminar Microstructure and Mechanical Properties of Narrow Gap Laser Welding of 40-mm-Thick Ti-6Al-4V Alloy

Narrow gap laser welding (NGLW) is a common solution for the welding of thick structures. NGLW was carried out on narrow-gap butt joints of 40 mm-thick Ti-6Al-4V alloy plates with a U-shaped groove. The distribution characteristics of the interlaminar microstructure in different height ranges of the joint were investigated, and the evolution behavior and formation mechanism of the interlaminar microstructure of the joint were also revealed. This showed that a large amount of short needle martensite nucleated and grew up near the fusion line and the upper boundary of the remelting zone. The “softening” phenomenon occurred in all welds except the cover layer weld. The microstructure evolution and defect migration, induced by multiple welding thermal cycles in the upper weld forming process, were the main reasons for the “softening” of the lower weld. The tensile strength of each sample changed in the range of 920~990 MPa; the fracture mode of the sample belongs to a transgranular ductile fracture. In addition, compared with the upper part of the joint, the plasticity and toughness of the weld area in the lower part of the joint was improved.     

Apprehending the NAD+–ADPr-Dependent Systems in the Virus World

NAD⁺ and ADP-ribose (ADPr)-containing molecules are at the interface of virus–host conflicts across life encompassing RNA processing, restriction, lysogeny/dormancy and functional hijacking. We objectively defined the central components of the NAD⁺–ADPr networks involved in these conflicts and systematically surveyed 21,191 completely sequenced viral proteomes representative of all publicly available branches of the viral world to reconstruct a comprehensive picture of the viral NAD⁺–ADPr systems. These systems have been widely and repeatedly exploited by positive-strand RNA and DNA viruses, especially those with larger genomes and more intricate life-history strategies. We present evidence that ADP-ribosyltransferases (ARTs), ADPr-targeting Macro, NADAR and Nudix proteins are frequently packaged into virions, particularly in phages with contractile tails (Myoviruses), and deployed during infection to modify host macromolecules and counter NAD⁺-derived signals involved in viral restriction. Genes encoding NAD⁺–ADPr-utilizing domains were repeatedly exchanged between distantly related viruses, hosts and endo-parasites/symbionts, suggesting selection for them across the virus world. Contextual analysis indicates that the bacteriophage versions of ADPr-targeting domains are more likely to counter soluble ADPr derivatives, while the eukaryotic RNA viral versions might prefer macromolecular ADPr adducts. Finally, we also use comparative genomics to predict host systems involved in countering viral ADP ribosylation of host molecules.     

Evolution of Swine Influenza Virus H3N2 in Vaccinated and Nonvaccinated Pigs after Previous Natural H1N1 Infection

Swine influenza viruses (SIV) produce a highly contagious and worldwide distributed disease that can cause important economic losses to the pig industry. Currently, this virus is endemic in farms and, although used limitedly, trivalent vaccine application is the most extended strategy to control SIV. The presence of pre-existing immunity against SIV may modulate the evolutionary dynamic of this virus. To better understand these dynamics, the viral variants generated in vaccinated and nonvaccinated H3N2 challenged pigs after recovery from a natural A(H1N1) pdm09 infection were determined and analyzed. In total, seventeen whole SIV genomes were determined, 6 from vaccinated, and 10 from nonvaccinated animals and their inoculum, by NGS. Herein, 214 de novo substitutions were found along all SIV segments, 44 of them being nonsynonymous ones with an allele frequency greater than 5%. Nonsynonymous substitutions were not found in NP; meanwhile, many of these were allocated in PB2, PB1, and NS1 proteins. Regarding HA and NA proteins, higher nucleotide diversity, proportionally more nonsynonymous substitutions with an allele frequency greater than 5%, and different domain allocations of mutants, were observed in vaccinated animals, indicating different evolutionary dynamics. This study highlights the rapid adaptability of SIV in different environments.     

Origin of New Lineages by Recombination and Mutation in Avian Infectious Bronchitis Virus from South America

The gammacoronavirus avian infectious bronchitis virus (IBV) is a highly contagious respiratory pathogen of primary economic importance to the global poultry industry. Two IBV lineages (GI-11 and GI-16) have been widely circulating for decades in South America. GI-11 is endemic to South America, and the GI-16 is globally distributed. We obtained full-length IBV genomes from Argentine and Uruguayan farms using Illumina sequencing. Genomes of the GI-11 and GI-16 lineages from Argentina and Uruguay differ in part of the spike coding region. The remaining genome regions are similar to the Chinese and Italian strains of the GI-16 lineage that emerged in Asia or Europe in the 1970s. Our findings support that the indigenous GI-11 strains recombine extensively with the invasive GI-16 strains. During the recombination process, GI-11 acquired most of the sequences of the GI-16, retaining the original S1 sequence. GI-11 strains with recombinant genomes are circulating forms that underwent further local evolution. The current IBV scenario in South America includes the GI-16 lineage, recombinant GI-11 strains sharing high similarity with GI-16 outside S1, and Brazilian GI-11 strains with a divergent genomic background. There is also sporadic recombinant in the GI-11 and GI-16 lineages among vaccine and field strains. Our findings exemplified the ability of IBV to generate emergent lineage by using the S gene in different genomic backgrounds. This unique example of recombinational microevolution underscores the genomic plasticity of IBV in South America.     

Evolution of Animal South American RVA Told by the NSP4 Gene E12 Genotype

Rotavirus A (RVA) possesses a genome of 11 double-stranded (ds) RNA segments, and each segment encodes one protein, with the exception of segment 11. NSP4 is a non-structural multifunctional protein encoded by segment 10 that defines the E-genotype. From the 31 E-genotypes described, genotype E12 has been described in Argentina, Uruguay, Paraguay, and Brazil in RVA strains infecting different animal species and humans. In this work, we studied the evolutionary relationships of RVA strains carrying the E12 genotype in South America using phylogenetic and phylodynamic approaches. We found that the E12 genotype has a South American origin, with a guanaco (Lama guanicoe) strain as natural host. Interestingly, all the other reported RVA strains carrying the E12 genotype in equine, bovine, caprine, and human strains are related to RVA strains of camelid origin. The evolutionary path and genetic footprint of the E12 genotype were reconstructed starting with the introduction of non-native livestock species into the American continent with the Spanish conquest in the 16th century. The imported animal species were in close contact with South American camelids, and the offspring were exposed to the native RVA strains brought from Europe and the new RVA circulating in guanacos, resulting in the emergence of new RVA strains in the current lineages’ strongly species-specific adaption. In conclusion, we proposed the NSP4 E12 genotype as a genetic geographic marker in the RVA strains circulating in different animal species in South America.