人工智能加速GPCR配体的发现

G protein-coupled receptors(GPCRs)are crucial players in various physiological processes,making them attractive candidates for drug discovery.However,traditional approaches to GPCR ligand discovery are time-consuming and resource-intensive.The emergence of artificial intelligence(AI)methods has revolutionized the field of GPCR ligand discovery and has provided valuable tools for accelerating the identification and optimization of GPCR ligands.In this study,we provide guidelines for effectively utilizing AI methods for GPCR ligand discovery,including data collation and representation,model selection,and specific applications.First,the online resources that are instrumental in GPCR ligand discovery were summarized,including databases and repositories that contain valuable GPCR-related information and ligand data.Next,GPCR and ligand representation schemes that can convert data into computer-readable formats were introduced.Subsequently,the key applications of AI methods in the different stages of GPCR drug discovery were discussed,ranging from GPCR function prediction to ligand design and agonist identification.Furthermore,an AI-driven multi-omics integration strategy for GPCR ligand discovery that combines information from various omics disciplines was proposed.Finally,the challenges and future directions of the application of AI in GPCR research were deliberated.In conclusion,continued advancements in AI techniques coupled with interdisciplina ry collaborations will offer great potential for improving the efficiency of GPCR ligand discovery.

Minimizing interfacial energy losses in inverted perovskite solar cells by a dipolar stereochemical 2D perovskite interface

Inverted perovskite solar cells(PSCs) have attracted broad research and industrial interest owing to their suppressed hysteresis,cost-effectiveness,and easy-fabrication.However,the issue of non-radiative recombination losses at the n-type interface between the perovskite and fullerene has impeded further improvement of photovoltaic performance.Here,we modify the n-type interface of FAPbI_(3) perovskite films by constructing a stereochemical two-dimensional(2D) perovskite interlayer,in which the organic cations comprise both pyridine and ammonium groups.The pyridine N donor can create stable bonding with the surface-uncoordinated Pb on the perovskite,thereby passivating the shallow-level defects and enhancing the air stability of the film.Furthermore,the pyridine N donor also offers a positive polar interface to decrease the surface work function of the perovskite film,enabling n-type modification.Ultimately,we employ a p-i-n photovoltaic(PV) device with the positive dipole interlayer at perovskite/fullerene contact and achieve remarkable photoelectric conversion efficiency(PCE) of 22.0%.

热消融治疗肺部亚实性结节专家共识(2021年版)

局部热消融技术在肺部结节治疗领域正处在起步与发展阶段,为了肺结节热消融治疗的临床实践和规范发展,由"中国医师协会肿瘤消融治疗技术专家组""中国医师协会介入医师分会肿瘤消融专业委员会""中国抗癌协会肿瘤消融治疗专业委员会""中国临床肿瘤学会消融专家委员会"组织多学科国内有关专家,讨论制定了"热消融治疗肺部亚实性结节专家共识(2021年版)"。主要内容包括:(1)肺部亚实性结节的临床评估;(2)热消融治疗肺部亚实性结节技术操作规程、适应证、禁忌证、疗效评价和相关并发症;(3)存在的问题和未来发展方向。

DNA barcoding in herbal medicine: Retrospective and prospective

DNA barcoding has been widely used for herb identification in recent decades,enabling safety and innovation in the field of herbal medicine.In this article,we summarize recent progress in DNA bar-coding for herbal medicine to provide ideas for the further development and application of this tech-nology.Most importantly,the standard DNA barcode has been extended in two ways.First,while conventional DNA barcodes have been widely promoted for their versatility in the identification of fresh or well-preserved samples,super-barcodes based on plastid genomes have rapidly developed and have shown advantages in species identification at low taxonomic levels.Second,mini-barcodes are attractive because they perform better in cases of degraded DNA from herbal materials.In addition,some mo-lecular techniques,such as high-throughput sequencing and isothermal amplification,are combined with DNA barcodes for species identification,which has expanded the applications of herb identification based on DNA barcoding and brought about the post-DNA-barcoding era.Furthermore,standard and high-species coverage DNA barcode reference libraries have been constructed to provide reference se-quences for species identification,which increases the accuracy and credibility of species discrimination based on DNA barcodes.In summary,DNA barcoding should play a key role in the quality control of traditional herbal medicine and in the international herb trade.

A Comparative Analysis of the Chloroplast Genomes of Four Salvia Medicinal Plants

Herbgenomics is an emerging field of traditional Chinese medicine(TCM)research and development.By combining TCM research with genomics,herbgenomics can help to establish the scientific validity of TCM and bring it into wider usage within the field of medicine.Salvia Linn.(S.Linn.)is a large genus of Labiatae that includes important medicinal plants.In this herbgenomics study,the complete chloroplast(cp)genomes of two Salvia spp.—namely,S.przewalskii and S.bulleyana,which are used as a surrogate for S.miltiorrhiza—were sequenced and compared with those of two other reported Salvia spp.—namely,S.miltiorrhiza and S.japonica.The genome organization,gene number,type,and repeat sequences were compared.The annotation results showed that both Salvia plants contain 114 unique genes,including 80 protein-coding,30 transfer RNA(tRNA),and four ribosomal RNA(rRNA)genes.Repeat sequence analysis revealed 21 forward and 22 palindromic sequences in both Salvia cp genomes,and 17 and 21 tandem repeats in S.przewalskii and S.bulleyana,respectively.A synteny comparison of the Salvia spp.cp genomes showed a high degree of sequence similarity in the coding regions and a relatively high divergence of the intergenic spacers.Pairwise alignment and single-nucleotide polymorphism(SNP)analyses found some candidate fragments to identify Salvia spp.,such as the intergenic region of the trnV–ndhC,trnQ–rps16,atpI–atpH,psbA–ycf3,ycf1,rpoC2,ndhF,matK,rpoB,rpoA,and accD genes.All of the results—including the repeat sequences and SNP sites,the inverted repeat(IR)region border,and the phylogenetic analysis—showed that S.przewalskii and S.bulleyana are extremely similar from a genetic standpoint.The cp genome sequences of the two Salvia spp.reported here will pave the way for breeding,species identification,phylogenetic evolution,and cp genetic engineering studies of Salvia medicinal plants.

Cannabis sativa: origin and history, glandular trichome development, and cannabinoid biosynthesis

Is Cannabis a boon or bane?Cannabis sativa has long been a versatile crop for fiber extraction(industrial hemp),traditional Chinese medicine(hemp seeds),and recreational drugs(marijuana).Cannabis faced global prohibition in the twentieth century because of the psychoactive properties of △^(9)-tetrahydrocannabinol;however,recently,the perspective has changed with the recognition of additional therapeutic values,particularly the pharmacological potential of cannabidiol.A comprehensive understanding of the underlying mechanism of cannabinoid biosynthesis is necessary to cultivate and promote globally the medicinal application of Cannabis resources.Here,we comprehensively review the historical usage of Cannabis,biosynthesis of trichome-specific cannabinoids,regulatory network of trichome development,and synthetic biology of cannabinoids.This review provides valuable insights into the efficient biosynthesis and green production of cannabinoids,and the development and utilization of novel Cannabis varieties.

Rapid Authentication of the Poisonous Plant Gelsemium elegans by Combining Filter-Paper-Based DNA Extraction and RPA–LFD Detection

Numerous plants and animals are edible and officinal,but some can be poisonous.There is sometimes confusion between poisonous and non-poisonous materials because of similarities in their morphologies.Consequently,the unwitting intake of poisonous plant or animal material has resulted in poisoning cases and sometimes in death,especially for situation in the wild.Rapid and accurate authentication of toxic species is essential for establishing and adopting optimal and urgent treatment for patients in such cases,and can be life-saving or can at least minimize the damage to health.Unfortunately,most of the current species authentication methods,including DNA barcoding,loop-mediated isothermal amplification(LAMP),chromatography technologies,and other methods,depend on professional equipment and a specialist laboratory,which are impracticable for real-time application in the field.It is therefore crucial to develop a rapid,accurate,and specific authentication method for poisonous species that does not require any equipment.

Can statins reduce risk of lung cancer,especially among elderly people? A meta-analysis

Objective： As the most common cause of cancer mortality throughout the world, lung cancer has drawn people＇s attention on how to reduce the risk with chemopreventive ways. Many epidemiological studies have shown inconsistent effects of statins on lung cancer, but some observational studies have showed that statins had protective effect on lung cancer among elderly people. So we preformed this meta-analysis to find whether statins were chemopreventive. Methods： We searched MEDLINE, EMBASE and Web of Science databases from inception to September, 2013. A total of 23 studies were selected, including 15 observational studies and 8 randomized controlled trials （RCTs）. Both fixed and random-effects models were used to calculate pooled estimates in primary and sensitivity analyses. We used Q and 12 statistics to assess statistical heterogeneity, and evaluated publication bias by Begg＇s test and Egger＇s test. Results： No association between statins and lung cancer risk was identified either in the meta-analysis among RCTs [relative risk （RR）： 0.95, 95% confidence interval （95% CI）： 0.85-1.06] or observational studies （RR： 0.89, 95% CI： 0.77-1.04）. We also selected 6 observational studies that all researched on elderly people. The result of meta-analysis showed that there was still no protective effect between statins and lung cancer among elderly people （RR： 1.03, 95% CI： 0.96-1.11）. Conclusions： Our results did not support a protective effect of statins on the overall lung cancer risk and the lung cancer risk among elderly people. More well-designed RCTs are needed to enhance our understanding of the chemopreventive effect of statins on lung cancer.

Progress and prediction of multicomponent quantification in complex systems with practical LC-UV methods

Complex systems exist widely,including medicines from natural products,functional foods,and biological samples.The biological activity of complex systems is often the result of the synergistic effect of multiple components.In the quality evaluation of complex samples,multicomponent quantitative analysis(MCQA)is usually needed.To overcome the difficulty in obtaining standard products,scholars have proposed achieving MCQA through the“single standard to determine multiple components(SSDMC)”approach.This method has been used in the determination of multicomponent content in natural source drugs and the analysis of impurities in chemical drugs and has been included in the Chinese Pharmacopoeia.Depending on a convenient(ultra)high-performance liquid chromatography method,how can the repeatability and robustness of the MCQA method be improved?How can the chromatography conditions be optimized to improve the number of quantitative components?How can computer software technology be introduced to improve the efficiency of multicomponent analysis(MCA)?These are the key problems that remain to be solved in practical MCQA.First,this review article summarizes the calculation methods of relative correction factors in the SSDMC approach in the past five years,as well as the method robustness and accuracy evaluation.Second,it also summarizes methods to improve peak capacity and quantitative accuracy in MCA,including column selection and twodimensional chromatographic analysis technology.Finally,computer software technologies for predicting chromatographic conditions and analytical parameters are introduced,which provides an idea for intelligent method development in MCA.This paper aims to provide methodological ideas for the improvement of complex system analysis,especially MCQA.

N-glucosyltransferase GbNGT1 from ginkgo complements the auxin metabolic pathway

As auxins are among the most important phytohormones,the regulation of auxin homeostasis is complex.Generally,auxin conjugates,especially IAA glucosides,are predominant at high auxin levels.Previous research on terminal glucosylation focused mainly on the O-position,while IAA-N-glucoside and IAA-Asp-N-glucoside have been neglected since their discovery in 2001.In our study,IAA-Asp-N-glucoside was found to be specifically abundant(as high as 4.13 mg/g)in the seeds of 58 ginkgo cultivars.Furthermore,a novel N-glucosyltransferase,termed GbNGT1,was identified via differential transcriptome analysis and in vitro enzymatic testing.It was found that GbNGT1 could catalyze IAA-Asp and IAA to form their corresponding N-glucosides.The enzyme was demonstrated to possess a specific catalytic capacity toward the N-position of the IAA-amino acid or IAA from 52 substrates.Docking and site-directed mutagenesis of this enzyme confirmed that the E15G mutant could almost completely abolish its N-glucosylation ability toward IAA-Asp and IAA in vitro and in vivo.The IAA modification of GbNGT1 and GbGH3.5 was verified by transient expression assay in Nicotiana benthamiana.The effect of GbNGT1 on IAA distribution promotes root growth in Arabidopsis thaliana.

Whole-genome and genome-wide association studies improve key agricultural traits of safflower for industrial and medicinal use

Safflower(Carthamus tinctorius)is widely cultivated around the world for its seeds and flowers.The presence of linoleic acid(LA)in its seeds and hydroxysafflor yellow A(HSYA)in its flowers are the crucial traits that enable safflower to be used for industrial and medicinal purposes.Understanding the genetic control of these traits is essential for optimizing the quality of safflower and its breeding.To further this research,we present a chromosome-scale assembly of the genome of the safflower variety‘Chuanhonghua 1’,which was achieved using an integrated strategy combining Illumina,Oxford Nanopore,and Hi-C sequencing.We obtained a 1.17-Gb assembly with a contig N50 of 1.08 Mb,and all assembled sequences were assigned to 12 pseudochromosomes.Safflower’s evolution involved the core eudicotγ-triplication event and a whole-genome duplication event,which led to large-scale genomic rearrangements.Extensive genomic shuffling has occurred since the divergence of the ancestor of dicotyledons.We conducted metabolite and transcriptome profiles with time-and part-dependent changes and screened candidate genes that significantly contribute to seed lipid biosynthesis.We also analyzed key gene families that participate in LA and HSYA biosynthesis.Additionally,we re-sequenced 220 safflower lines and carried out a genome-wide association study using high-quality SNP data for eight agronomic traits.We identified SNPs related to important traits in safflower.Besides,the candidate gene HH_034464(CtCGT1)was shown to be involved in the biosynthesis of HSYA.Overall,we provide a high-quality reference genome and elucidate the genetic basis of LA and HSYA biosynthesis in safflower.This vast amount of data will benefit further research for functional gene mining and breeding in safflower.

Promoter variations in DBR2-like affect artemisinin production in different chemotypes of Artemisia annua

Artemisia annua is the only known plant source of the potent antimalarial artemisinin,which occurs as the low-and high-artemisinin producing(LAP and HAP)chemotypes.Nevertheless,the different mechanisms of artemisinin producing between these two chemotypes were still not fully understood.Here,we performed a comprehensive analysis of genome resequencing,metabolome,and transcriptome data to systematically compare the difference in the LAP chemotype JL and HAP chemotype HAN.Metabolites analysis revealed that 72.18%of sesquiterpenes was highly accumulated in HAN compared to JL.Integrated omics analysis found a DBR2-Like(DBR2L)gene may be involved in artemisinin biosynthesis.DBR2L was highly homologous with DBR2,belonged to ORR3 family,and had the DBR2 activity of catalyzing artemisinic aldehyde to dihydroartemisinic aldehyde.Genome resequencing and promoter cloning revealed that complicated variations existed in DBR2L promoters among different varieties of A.annua and were clustered into three variation types.The promoter activity of diverse variant types showed obvious differences.Furthermore,the core region(-625 to 0)of the DBR2L promoter was identified and candidate transcription factors involved in DBR2L regulation were screened.Thus,the result indicates that DBR2L is another key enzyme involved in artemisinin biosynthesis.The promoter variation in DBR2L affects its expression level,and thereby may result in the different yield of artemisinin in varieties of A.annua.It provides a novel insight into the mechanism of artemisinin-producing difference in LAP and HAP chemotypes of A.annua,and will assist in a high yield of artemisinin in A.annua.

Genome sequencing provides potential strategies for drug discovery and synthesis

Medicinal plants are renowned for their abundant production of secondary metabolites,which exhibit notable pharmacological activities and great potential for drug development.The biosynthesis of secondary metabolites is highly intricate and influenced by various intrinsic and extrinsic factors,resulting in substantial species diversity and content variation.Consequently,precise regulation of secondary metabolite synthesis is of utmost importance.In recent years,genome sequencing has emerged as a valuable tool for investigating the synthesis and regulation of secondary metabolites in medicinal plants,facilitated by the widespread use of high-throughput sequencing technologies.This review highlights the latest advancements in genome sequencing within this field and presents several strategies for studying secondary metabolites.Specifically,the article elucidates how genome sequencing can unravel the pathways for secondary metabolite synthesis in medicinal plants,offering insights into the functions and regulatory mechanisms of participating enzymes.Comparative analyses of plant genomes allow identification of shared pathways of metabolite synthesis among species,thereby providing novel avenues for obtaining cost-effective biosynthetic intermediates.By examining individual genomic variations,genes or gene clusters associated with the synthesis of specific compounds can be discovered,indicating potential targets and directions for drug development and the exploration of alternative compound sources.Moreover,the advent of gene-editing technology has enabled the precise modifications of medicinal plant genomes.Optimization of specific secondary metabolite synthesis pathways becomes thus feasible,enabling the precise editing of target genes to regulate secondary metabolite production within cells.These findings serve as valuable references and lessons for future drug development endeavors,conservation of rare resources,and the exploration of new resources.

Whole-genome sequencing in medicinal plants:current progress and prospect

Advancements in genomics have dramatically accelerated the research on medicinal plants,and the development of herbgenomics has promoted the“Project of 1K Medicinal Plant Genome”to decipher their genetic code.However,it is difficult to obtain their high-quality whole genomes because of the prevalence of polyploidy and/or high genomic heterozygosity.Whole genomes of 123 medicinal plants were published until September 2022.These published genome sequences were investigated in this review,covering their classification,research teams,ploidy,medicinal functions,and sequencing strategies.More than 1,000 institutes or universities around the world and 50 countries are conducting research on medicinal plant genomes.Diploid species account for a majority of sequenced medicinal plants.The whole genomes of plants in the Poaceae family are the most studied.Almost 40%of the published papers studied species with tonifying,replenishing,and heat-cleaning medicinal effects.Medicinal plants are still in the process of domestication as compared with crops,thereby resulting in unclear genetic backgrounds and the lack of pure lines,thus making their genomes more difficult to complete.In addition,there is still no clear routine framework for a medicinal plant to obtain a high-quality whole genome.Herein,a clear and complete strategy has been originally proposed for creating a high-quality whole genome of medicinal plants.Moreover,whole genome-based biological studies of medicinal plants,including breeding and biosynthesis,were reviewed.We also advocate that a research platform of model medicinal plants should be established to promote the genomics research of medicinal plants.

Strategies on biosynthesis and production of bioactive compounds in medicinal plants

Medicinal plants are a valuable source of essential medicines and herbal products for healthcare and disease therapy.Compared with chemical synthesis and extraction,the biosynthesis of natural products is a very promising alternative for the successful conservation of medicinal plants,and its rapid development will greatly facilitate the conservation and sustainable utilization of medicinal plants.Here,we summarize the advances in strategies and methods concerning the biosynthesis and production of natural products of medicinal plants.The strategies and methods mainly include genetic engineering,plant cell culture engineering,metabolic engineering,and synthetic biology based on multiple“OMICS”technologies,with paradigms for the biosynthesis of terpenoids and alkaloids.We also highlight the biosynthetic approaches and discuss progress in the production of some valuable natural products,exemplifying compounds such as vindoline(alkaloid),artemisinin and paclitaxel(terpenoids),to illustrate the power of biotechnology in medicinal plants.

Decoding the chromatin accessibility in Andrographis paniculata genome,a case study of genome-wide investigation of the cis-regulatory elements in medicinal plants

To the Editor:Medicinal plants have the ability to synthesize a large number of pharmaceutical metabolites,the production and regulation of which are influenced by both intrinsic signals(e.g.,the spatial and temporal stage)and extrinsic environmental conditions(e.g.,temperature,light availability,and water availability)^(1).According to the Encyclopedia of DNA Elements(ENCODE)project^(2),accessible chromatin regions(ACRs)served essential roles in maintaining the genome architecture and gene regulation in both mammals and plants.Nowadays,identifying ACRs within medicinal plant genomes remains a challenge,as genomic sequences have been determined for numerous species yet the characterization of such functional elements lags.In this study,we selected Andrographis paniculata(APA)^(3) as a model system to map ACRs genome-wide by the assay for transposase-accessible chromatin with sequencing(ATAC-seq)method.We aimed to uncover the genomic features of ACRs as well as their association with the expression of genes involved in secondary metabolite biosynthesis(e.g.,andrographolide)within medicinal plants(Supporting Information Fig.S1).

Genome-wide pan-GPCR cell libraries accelerate drug discovery

G protein-coupled receptors(GPCRs)are pivotal in mediating diverse physiological and pathological processes,rendering them promising targets for drug discovery.GPCRs account for about 40%of FDA-approved drugs,representing the most successful drug targets.However,only approximately 15%of the 800 human GPCRs are targeted by market drugs,leaving numerous opportunities for drug discovery among the remaining receptors.Cell expression systems play crucial roles in the GPCR drug discovery field,including novel target identification,structural and functional characterization,potential ligand screening,signal pathway elucidation,and drug safety evaluation.Here,we discuss the principles,applications,and limitations of widely used cell expression systems in GPCR-targeted drug discovery,GPCR function investigation,signal pathway characterization,and pharmacological property studies.We also propose three strategies for constructing genome-wide pan-GPCR cell libraries,which will provide a powerful platform for GPCR ligand screening,and facilitate the study of GPCR mechanisms and drug safety evaluation,ultimately accelerating the process of GPCR-targeted drug discovery.

Biosynthesis of natural products from medicinal plants:Challenges,progress and prospects

Medicinal plants play a crucial role in traditional Chinese medicine and modern pharmaceuticals,serving as valuable resources for natural products used for plant-based medicines and new drugs.Nevertheless,the conventional techniques for acquiring natural products have been unable to meet the increasing requirements of drug research and development.Chemical synthesis of natural products are usually complex process and might bring the risk of causing environmental problems.The extraction of natural products from medicinal plants are difficult and impractical,resulting in inefficient outputs.The creative methods and strategies are imperative to be developed to enhance the production of natural product from medicinal plants.Therefore,focusing on the biosynthetic pathways,metabolic engineering,and synthetic biology of natural products provides the avenues for obtaining abundant natural product resources.

The Chrysanthemum nankingense Genome Provides Insights into the Evolution and Diversification of Chrysanthemum Flowers and Medicinal Traits

The Asteraceae (Compositae),a large plant family of approximately 24 000-35 000 species,accounts for^10% of all angiosperm species and contributes a lot to plant diversity.The most representative members of the Asteraceae are the economically important chrysanthemums (Chrysanthemum L.)that diversified through reticulate evolution.Biodiversity is typically created by multiple evolutionary mechanisms such as wholegenome duplication 0NGD)or polyploidization and locally repetitive genome expansion.However,the lack of genomic data from chrysanthemum species has prevented an in-depth analysis of the evolutionary mechanisms involved in their diversification.Here,we used Oxford Nanopore long-read technologyto sequence the diploid Chrysanthemum nankingense genome,which represents one of the progenitor genomes of domesticated chrysanthemums.Our analysis revealed that the evolution of the C.nankingense genome was driven by bursts of repetitive element expansion and WGD events including a recentWGD that distinguishes chrysanthemum from sunflower,which diverged from chrysanthemum approximately 38.8 million years ago.Variations of ornamental and medicinal traits in chrysanthemums are linked to the expansion of candidate gene families by duplication events including paralogous gene duplication.Collectively,our study of the assembled reference genome offers new knowledge and resources to dissect the history and pattern of evolution and diversification of chrysanthemum plants,and also to accelerate their breeding and improvement.

Evidence chain-based causality identification in herb-induced liver injury： exemplification of a well-known liver-restorative herb Polygonum multiflorum

Herbal medicines have recently been recognized as the second most common cause of drug-induced liver injury （DILI） in the United States. However, reliable methods to identify the DILl causality of some herbs, such as Heshouwu （dried root ofPolygonum multiflorum）, remain lacking. In this study, a total of 12 307 inpatients with liver dysfunction and 147 literature-reported cases of Heshouwu DILI were screened. A general algorithm indicated that only 22.5% （9/40） and 30.6% （45/147） of all hospitalization and literature case reports, respectively, demonstrate the high probability of DILI causality of Heshouwu. By contrast, 95% （19/20） of all cases prospectively investigated by pharmacognosy, phytochemistry, and metabolomic tests exhibited highly probable causality, including a patient who was previously incorrectly attributed and a case that was excluded from Heshouwu causality by pharmacognostic evidence. Toxin （heavy metals, pesticides, and mycotoxins） contamination was also excluded from Heshouwu DILI causality. The objectivity of these screening methods for Heshouwu DILI diagnosis addresses safety concerns regarding stilbene-containing herbal medicines and dietary supplements.