Phylogeny of genera in Maleae (Rosaceae) based on chloroplast genome analysis.

In Rosaceae, the replacement of the traditional four-subfamily division (Amygdaloideae or Prunoideae, Maloideae, Rosoideae, and Spiraeoideae) by the three-subfamily division (Dryadoideae, Rosoideae, and Amygdaloideae), the circumscription, systematic position, and phylogeny of genera in Maleae need to be reconsidered. The study aimed to circumscribe Maleae, pinpoint its systematic position, and evaluate the status of all generally accepted genera in the tribe using complete chloroplast genome data. Results indicated that Maleae consisted of pome-bearing genera that belonged to Maloideae as well as four genera (Gillenia, Kageneckia, Lindleya, and Vauquelinia) that were formerly considered to be outside Maloideae. The tribe could be subdivided into four subtribes: Gilleniinae (Gillenia), Lindleyinae (Kageneckia and Lindleya), Vaugueliniinae (Vauquelinia), and Malinae (all other genera; the core Maleae). Among the 36 recognized genera, Aria, Docyniopsis, Chamaemespilus, and Mespilus were not considered distinct and more research is needed to determine the taxonomic status of Rhaphiolepis from Eriobotrya. Within the core Maleae, five groups were revealed, whereas Sorbus L. was split as its members belonged to different groups.

[Resources and utilization of medicinal plants in countries and regions involved in "the Belt and Road" Initiative].

The protection, development, and utilization of medicinal plant resources are important cornerstones of maintaining human health. However, due to factors such as the reduction of high-quality land resources, deterioration of ecological environments, and excessive and disorderly resource development, medicinal plant resources are becoming scarce, and some of them are insufficiently supplied. With the proposal of "the Belt and Road" Initiative, the cooperation between China and "the Belt and Road" partners(the countries and regions involved in "the Belt and Road" Initiative)is increasingly close, which provides a new opportunity for carrying out trade of medicinal plant resources and alleviating the problem of imbalance and relative inadequacy of medicinal plant resources in countries. This study first determined the distribution and species information of plant resources in countries and regions involved in "the Belt and Road" Initiative by investigating the database of plant distribution and that of medicinal plant resources. Then, according to the published data from the International Union for Conservation of Nature(IUCN) and the Convention on International Trade in Endangered Species of Wild Fauna and Flora(CITES), this study identified the rare and endangered medicinal plants and the medicinal plants under trade control in countries and regions involved in "the Belt and Road" Initiative and finally sorted out the list of potential medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative that can be used by China. This data resource can not only be used for the overall protection of important endangered species but also scientifically guide the development and utilization of medicinal resources, providing guidance and a theoretical basis for the sustainable development of medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative.

Oral-gut microbial transmission promotes diabetic coronary heart disease.

BACKGROUND: Diabetes is a predominant driver of coronary artery disease worldwide. This study aims to unravel the distinct characteristics of oral and gut microbiota in diabetic coronary heart disease (DCHD). Simultaneously, we aim to establish a causal link between the diabetes-driven oral-gut microbiota axis and increased susceptibility to diabetic myocardial ischemia-reperfusion injury (MIRI). METHODS: We comprehensively investigated the microbial landscape in the oral and gut microbiota in DCHD using a discovery cohort (n = 183) and a validation chohort (n = 68). Systematically obtained oral (tongue-coating) and fecal specimens were subjected to metagenomic sequencing and qPCR analysis, respectively, to holistically characterize the microbial consortia. Next, we induced diabetic MIRI by administering streptozotocin to C57BL/6 mice and subsequently investigated the potential mechanisms of the oral-gut microbiota axis through antibiotic pre-treatment followed by gavage with specific bacterial strains (Fusobacterium nucleatum or fecal microbiota from DCHD patients) to C57BL/6 mice. RESULTS: Specific microbial signatures such as oral Fusobacterium nucleatum and gut Lactobacillus, Eubacterium, and Roseburia faecis, were identified as potential microbial biomarkers in DCHD. We further validated that oral Fusobacterium nucleatum and gut Lactobacillus are increased in DCHD patients, with a positive correlation between the two. Experimental evidence revealed that in hyperglycemic mice, augmented Fusobacterium nucleatum levels in the oral cavity were accompanied by an imbalance in the oral-gut axis, characterized by an increased coexistence of Fusobacterium nucleatum and Lactobacillus, along with elevated cardiac miRNA-21 and a greater extent of myocardial damage indicated by TTC, HE, TUNEL staining, all of which contributed to exacerbated MIRI. CONCLUSION: Our findings not only uncover dysregulation of the oral-gut microbiota axis in diabetes patients but also highlight the pivotal intermediary role of the increased abundance of oral F. nucleatum and gut Lactobacillus in exacerbating MIRI. Targeting the oral-gut microbiota axis emerges as a potent strategy for preventing and treating DCHD. Oral-gut microbial transmission constitutes an intermediate mechanism by which diabetes influences myocardial injury, offering new insights into preventing acute events in diabetic patients with coronary heart disease.

Estimating the Amount of the Wild Artemisia annua in China Based on the MaxEnt Model and Spatio-Temporal Kriging Interpolation.

In order to determine the distribution area and amount of Artemisia annua Linn. (A. annua) in China, this study estimated the current amount of A. annua specimens based on the field survey sample data obtained from the Fourth National Census of Chinese Medicinal Resources. The amount was calculated using the maximum entropy model (MaxEnt model) and spatio-temporal kriging interpolation. The influencing factors affecting spatial variations in the amount were studied using geographic probes. The results indicated that the amount of A. annua in China was about 700 billion in 2019. A. annua was mainly distributed in the circular coastal belt of Shandong Peninsula, central Hebei, Tianjin, western Liaoning, and along the Yangtze River and in the middle and lower reaches of Jiangsu, Anhui, and the northern Chongqing provinces. The main factors affecting the amount are the precipitation in the wettest and the warmest seasons, the average annual precipitation, and the average temperature in the coldest and the driest seasons. The results show that the amount of A. annua is strongly influenced by precipitation and temperature.

Unveiling the regulatory mechanisms of nodules development and quality formation in Panax notoginseng using multi-omics and MALDI-MSI.

INTRODUCTION: Renowned for its role in traditional Chinese medicine, Panax notoginseng exhibits healing properties including bidirectional regulatory effects on hematological system diseases. However, the presence of nodular structures near the top of the main root, known as nail heads, may impact the quality of the plant's valuable roots. OBJECTIVES: In this paper, we aim to systematically analyze nail heads to identify their potential correlation with P. notoginseng quality. Additionally, we will investigate the molecular mechanisms behind nail head development. METHODS: Morphological characteristics and anatomical features were analyzed to determine the biological properties of nail heads. Active component analysis and MALDI mass spectrometry imaging (MALDI-MSI) were performed to determine the correlation between nail heads and P. notoginseng quality. Phytohormone quantitation, MALDI-MSI, RNA-seq, and Arabidopsis transformation were conducted to elucidate the mechanisms of nail head formation. Finally, protein-nucleic acid and protein-protein interactions were investigated to construct a transcriptional regulatory network of nodule development and quality formation. RESULTS: Our analyses have revealed that nail heads originate from an undeveloped lateral root. The content of ginsenosides was found to be positively associated with the amount of nail heads. Ginsenoside Rb1 specifically accumulated in the cortex of nail heads, while IAA, tZR and JAs also showed highest accumulation in the nodule. RNA-seq analysis identified PnIAA14 and PnCYP735A1 as inhibitors of lateral root development. PnMYB31 and PnMYB78 were found to form binary complexes with PnbHLH31 to synergistically regulate the expression of PnIAA14, PnCYP735A1, PnSS, and PnFPS. CONCLUSION: Our study details the major biological properties of nodular structures in P. notoginseng and outlines their impact on the quality of the herb. It was also determined that PnMYB31- and PnMYB78-PnbHLH31 regulate phytohormones and ginsenosides accumulation, further affecting plant development and quality. This research provides insights for quality evaluation and clinical applications of P. notoginseng.

A Highly Sensitive and Rapid Colloidal Gold Immunoassay for Puerarin Detection.

Radix Puerariae is a traditional Chinese medicinal material with a rich history of use in East and Southeast Asia. Puerarin, a unique component of the Pueraria genus, serves as a quality control marker for herbal medicines like Pueraria lobata and Pueraria thomsonii in China, displaying diverse pharmacological properties. This study developed puerarin colloidal gold immunoassay dipsticks utilizing an anti-puerarin monoclonal antibody, resulting in a fast and sensitive detection method with a limit of 500-1000 ng·mL-1. Evaluation using tap water-extracted P. lobata and P. thomsonii samples showed consistent results compared to LC-MS analysis. Cross-reactivity assessments of puerarin analogs revealed minimal interference, affirming the dipstick's reliability for distinguishing between the two species.

Supplementation of Crataegi fructus alleviates functional dyspepsia and restores gut microbiota in mice.

Introduction: Functional dyspepsia (FD), also known as non-ulcerative dyspepsia, is a common digestive system disorder. Methods: In this study, an FD model was established using hunger and satiety disorders combined with an intraperitoneal injection of L-arginine. Indices used to evaluate the efficacy of hawthorn in FD mice include small intestinal propulsion rate, gastric residual rate, general condition, food intake, amount of drinking water, gastric histopathological examination, and serum nitric oxide (NO) and gastrin levels. Based on the intestinal flora and their metabolites, short-chain fatty acids (SCFAs), the mechanism of action of Crataegi Fructus (hawthorn) on FD was studied. The fecal microbiota transplantation test was used to verify whether hawthorn altered the structure of the intestinal flora. Results: The results showed that hawthorn improved FD by significantly reducing the gastric residual rate, increasing the intestinal propulsion rate, the intake of food and drinking water, and the levels of gastrointestinal hormones. Simultaneously, hawthorn elevated substance P and 5-hydroxytryptamine expression in the duodenum, reduced serum NO levels, and increased vasoactive intestinal peptide expression in the duodenum. Notably, hawthorn increased the abundance of beneficial bacteria and SCFA-producing bacteria in the intestines of FD mice, decreased the abundance of conditional pathogenic bacteria, and significantly increased the SCFA content in feces. Discussion: The mechanism by which hawthorn improves FD may be related to the regulation of intestinal flora structure and the production of SCFAs.

Extraction and analysis of high-quality chloroplast DNA with reduced nuclear DNA for medicinal plants.

BACKGROUND: Obtaining high-quality chloroplast genome sequences requires chloroplast DNA (cpDNA) samples that meet the sequencing requirements. The quality of extracted cpDNA directly impacts the efficiency and accuracy of sequencing analysis. Currently, there are no reported methods for extracting cpDNA from Erigeron breviscapus. Therefore, we developed a suitable method for extracting cpDNA from E. breviscapus and further verified its applicability to other medicinal plants. RESULTS: We conducted a comparative analysis of chloroplast isolation and cpDNA extraction using modified high-salt low-pH method, the high-salt method, and the NaOH low-salt method, respectively. Subsequently, the number of cpDNA copies relative to the nuclear DNA (nDNA ) was quantified via qPCR. As anticipated, chloroplasts isolated from E. breviscapus using the modified high-salt low-pH method exhibited intact structures with minimal cell debris. Moreover, the concentration, purity, and quality of E. breviscapus cpDNA extracted through this method surpassed those obtained from the other two methods. Furthermore, qPCR analysis confirmed that the modified high-salt low-pH method effectively minimized nDNA contamination in the extracted cpDNA. We then applied the developed modified high-salt low-pH method to other medicinal plant species, including Mentha haplocalyx, Taraxacum mongolicum, and Portulaca oleracea. The resultant effect on chloroplast isolation and cpDNA extraction further validated the generalizability and efficacy of this method across different plant species. CONCLUSIONS: The modified high-salt low-pH method represents a reliable approach for obtaining high-quality cpDNA from E. breviscapus. Its universal applicability establishes a solid foundation for chloroplast genome sequencing and analysis of this species. Moreover, it serves as a benchmark for developing similar methods to extract chloroplast genomes from other medicinal plants.

Contribution of Phenolamides to the Quality Evaluation in Lycium spp.

ETHNOPHARMACOLOGICAL RELEVANCE: Goji berry is a general term for various plant species in the genus Lycium. Goji has long been historically used in traditional Chinese medicines. Goji is a representative tonic medicine that has the effects of nourishing the liver and kidney and benefiting the essence and eyesight. It has been widely used in the treatment of various diseases, including tinnitus, impotence, spermatorrhea and blood deficiency, since ancient times. AIM OF THE REVIEW: This study aims to comprehensively summarize the quality evaluation methods of the main compounds in goji, as well as the current research status of the phenolamides in goji and their pharmacological effects, to explore the feasibility of using phenolamides as quality control markers and thus improve the quality and efficacy in goji. MATERIALS AND METHODS: Relevant literature from PubMed, Web of Science, Science Direct, CNKI and other databases was comprehensively collected, screened and summarized. RESULTS: According to the collected literature, the quality evaluation markers of goji in the Pharmacopoeia of the People's Republic of China are Lycium barbarum polysaccharide (LBP) and betaine. As a result of its structure complexity, only the total level of LBP can be determined, while betaine is not prominent in the pharmacological action of goji and lacks species distinctiveness. Neither of them can well explain the quality of goji. KuA and KuB are commonly used as quality evaluation markers of the Lycii cortex because of their high levels and suitable pharmacological activity. Goji is rich in polyphenols, carotenoids and alkaloids. Many studies have used the above compounds to establish quality evaluation methods but the results have not been satisfactory. Phenolamides have often been neglected in previous studies because of their low single compound levels and high separation difficulty. However, in recent years, the favourable pharmacological activities of phenolamides have been gradually recognized, and studies on goji phenolamides are greatly increasing. In addition, phenolamides have higher species distinctiveness than other compounds and can be combined with other compounds to better evaluate the quality of goji to improve its average quality. CONCLUSIONS: The phenolamides in the goji are rich and play a key role in antioxidation, anti-inflammation, neuroprotection and immunomodulation. As a result of their characteristics, it is suitable to evaluate the quality by quantitative analysis of multi-components by single-marker and fingerprint. This method can be combined with other techniques to improve the quality evaluation system of goji, which lays a foundation for their effectiveness and provides a reference for new quality evaluation methods of similar herbal medicines.

A Prenyltransferase Participates in the Biosynthesis of Anthraquinones in Rubia cordifolia.

Anthraquinones constitute the largest group of natural quinones, which are used as safe natural dyes and have many pharmaceutical applications. In plants, anthraquinones are biosynthesized through two main routes: the polyketide pathway and the shikimate pathway. The latter primarily forms alizarin-type anthraquinones, and the prenylation of 1,4-dihydroxy-2-naphthoic acid is the first pathway-specific step. However, the prenyltransferase responsible for this key step remains uncharacterized. In this study, the cell suspension culture of Madder (Rubia cordifolia), a plant rich in alizarin-type anthraquinones, was discovered to be capable of prenylating 1,4-dihydroxy-2-naphthoic acid to form 2-carboxyl-3-prenyl-1,4-naphthoquinone and 3-prenyl-1,4-naphthoquinone. Then, a candidate gene belonging to the UbiA superfamily, R. cordifolia  dimethylallyltransferase 1 (RcDT1), was shown to account for the prenylation activity. Substrate specificity studies revealed that the recombinant RcDT1 recognized naphthoic acids primarily, followed by 4-hydroxyl benzoic acids. The prenylation activity was strongly inhibited by 1,2- and 1,4-dihydroxynaphthalene. RcDT1 RNA interference significantly reduced the anthraquinones content in R. cordifolia callus cultures, demonstrating that RcDT1 is required for alizarin-type anthraquinones biosynthesis. The plastid localization and root-specific expression further confirmed the participation of RcDT1 in anthraquinone biosynthesis. The phylogenetic analyses of RcDT1 and functional validation of its rubiaceous homologs indicated that DHNA-prenylation activity evolved convergently in Rubiaceae via recruitment from the ubiquinone biosynthetic pathway. Our results demonstrate that RcDT1 catalyzes the first pathway-specific step of alizarin-type anthraquinones biosynthesis in R. cordifolia. These findings will have profound implications for understanding the biosynthetic process of the anthraquinone ring derived from the shikimate pathway.

An evaluation of Astragali Radix with different growth patterns and years, based on a new multidimensional comparison method.

Introduction: With the depletion of wild Astragali Radix (WA) resources, imitated-wild Astragali Radix (IWA) and cultivated Astragali Radix (CA) have become the main products of Astragali Radix. However, the quality differences of three growth patterns (WA, IWA, CA) and different growth years of Astragali Radix have not been fully characterized, leading to a lack of necessary scientific evidence for their use as substitutes for WA. Methods: We innovatively proposed a multidimensional evaluation method that encompassed traits, microstructure, cell wall components, saccharides, and pharmacodynamic compounds, to comprehensively explain the quality variances among different growth patterns and years of Astragali Radix. Results and discussion: Our study showed that the quality of IWA and WA was comparatively similar, including evaluation indicators such as apparent color, sectional structure and odor, thickness of phellem, diameter and number of vessels, morphology of phloem and xylem, and the levels and ratios of cellulose, hemicellulose, lignin, sucrose, starch, water-soluble polysaccharides, total-saponins. However, the content of sucrose, starch and sorbose in CA was significantly higher than WA, and the diameter and number of vessels, total-flavonoids content were lower than WA, indicating significant quality differences between CA and WA. Hence, we suggest that IWA should be used as a substitute for WA instead of CA. As for the planting years of IWA, our results indicated that IWA aged 1-32 years could be divided into three stages according to their quality change: rapid growth period (1-5 years), stable growth period (6-20 years), and elderly growth period (25-32 years). Among these, 6-20 years old IWA exhibited consistent multidimensional comparative results, showcasing elevated levels of key active components such as water-soluble polysaccharides, flavonoids, and saponins. Considering both the quality and cultivation expenses of IWA, we recommend a cultivation duration of 6-8 years for growers. In conclusion, we established a novel multidimensional evaluation method to systematically characterize the quality of Astragali Radix, and provided a new scientific perspective for the artificial cultivation and quality assurance of Astragali Radix.

Characterization of CYP82 genes involved in the biosynthesis of structurally diverse benzylisoquinoline alkaloids in Corydalis yanhusuo.

Benzylisoquinoline alkaloids (BIAs) represent a significant class of secondary metabolites with crucial roles in plant physiology and substantial potential for clinical applications. CYP82 genes are involved in the formation and modification of various BIA skeletons, contributing to the structural diversity of compounds. In this study, Corydalis yanhusuo, a traditional Chinese medicine rich in BIAs, was investigated to identify the catalytic function of CYP82s during BIA formation. Specifically, 20 CyCYP82-encoding genes were cloned, and their functions were identified in vitro. Ten of these CyCYP82s were observed to catalyze hydroxylation, leading to the formation of protopine and benzophenanthridine scaffolds. Furthermore, the correlation between BIA accumulation and the expression of CyCYP82s in different tissues of C. yanhusuo was assessed their. The identification and characterization of CyCYP82s provide novel genetic elements that can advance the synthetic biology of BIA compounds such as protopine and benzophenanthridine, and offer insights into the biosynthesis of BIAs with diverse structures in C. yanhusuo.

Comparative Analysis of Metabolome and Transcriptome in Different Tissue Sites of Aquilaria sinensis (Lour.) Gilg.

The resinous stem of Aquilaria sinensis (Lour.) Gilg is the sole legally authorized source of agarwood in China. However, whether other tissue parts can be potential substitutes for agarwood requires further investigation. In this study, we conducted metabolic analysis and transcriptome sequencing of six distinct tissues (root, stem, leaf, seed, husk, and callus) of A. sinensis to investigate the variations in metabolite distribution characteristics and transcriptome data across different tissues. A total of 331 differential metabolites were identified by chromatography-mass spectrometry (GC-MS), of which 22.96% were terpenoids. The differentially expressed genes (DEGs) in RNA sequencing were enriched in sesquiterpene synthesis via the mevalonate pathway. The present study establishes a solid foundation for exploring potential alternatives to agarwood.

[Cloning and functional analysis of 3ß-hydroxysteroid dehydrogenase gene involved in biosynthesis of digitoxin].

Digitoxin, an important secondary metabolite of Digitalis purpurea, is a commonly used cardiotonic in clinical practice. 3ß-Hydroxysteroid dehydrogenase(3ßHSD) is a key enzyme involved in the biosynthesis of digitoxin. It belongs to the short-chain dehydrogenase/reductase(SDR) family, playing a role in the biosynthesis of cardiac glycosides by oxidizing and isomerizing the precursor sterol. In this study, two 3ßHSD genes were cloned from D. purpurea. The results showed that the open reading frame(ORF) of Dp3ßHSD1 was 780 bp, encoding 259 amino acid residues. The ORF of Dp3ßHSD2 was 774 bp and encoded 257 residues. Dp3ßHSD1/2 had the cofactor binding site TGxxxA/GxG and the catalytic site YxxxK. In vitro experiments confirmed that Dp3ßHSD1/2 catalyzed the generation of progesterone from pregnenolone, and Dp3ßHSD1 had stronger catalytic capacity than Dp3ßHSD2. The expression level of Dp3ßHSD1 was much higher than that of Dp3ßHSD2 in leaves, and digitoxin was only accumulated in leaves. The results implied that Dp3ßHSD1 played a role in the dehydrogenation of pregnenolone to produce progesterone in the biosynthesis of digitoxin. This study provides a reference for further exploring the biosynthetic pathway of cardiac glycosides in D. purpurea.

Highly Promiscuous Flavonoid Di-O-glycosyltransferases from Carthamus tinctorius L.

Safflower (Carthamus tinctorius L.) has been recognized for its medicinal value, but there have been limited studies on the glycosyltransferases involved in the biosynthesis of flavonoid glycosides from safflower. In this research, we identified two highly efficient flavonoid O-glycosyltransferases, CtOGT1 and CtOGT2, from safflower performing local BLAST alignment. By constructing a prokaryotic expression vector, we conducted in vitro enzymatic reactions and discovered that these enzymes were capable of catalyzing two-step O-glycosylation using substrates such as kaempferol, quercetin, and eriodictyol. Moreover, they exhibited efficient catalytic activity towards various compounds, including flavones (apigenin, scutellarein), dihydrochalcone (phloretin), isoflavones (genistein, daidzein), flavanones (naringenin, glycyrrhizin), and flavanonols (dihydrokaempferol), leading to the formation of O-glycosides. The broad substrate specificity of these enzymes is noteworthy. This study provides valuable insights into the biosynthetic pathways of flavonoid glycosides in safflower. The discovery of CtOGT1 and CtOGT2 enhances our understanding of the enzymatic processes involved in synthesizing flavonoid glycosides in safflower, contributing to the overall comprehension of secondary metabolite biosynthesis in this plant species.

Fuling production areas in China: climate and distribution changes (A.D. 618-2100).

Through a meticulous analysis of ancient Chinese literature, this study comprehensively documents the geographical distribution of Fuling, a traditional Chinese medicinal material, during the Tang, Song, Ming, and Qing dynasties spanning from the seventh to the twentieth century in China. Based on the contemporary distribution information of Fuling, we utilized the maximum entropy (MaxEnt) model to simulate the suitable distribution areas of Fuling under both present-day conditions and in the future (2081~2100). The findings reveal that climate change has influenced the distribution of Fuling production areas. The shifts in Fuling's origin during different periods in ancient and modern times align with climate fluctuations and concurrent societal development. During the Tang and Song dynasties, Fuling primarily originated in northern China. However, it migrated southward during the Little Ice Age (LIA) and has recently shown a slight northward shift, in line with the climate fluctuations of the LIA and contemporary global warming trends. This study offers a comprehensive analysis of the changes in the distribution and production areas of Fuling over a 1500-year period, encompassing ancient, modern, and future periods. The results provide critical insights for adjusting Fuling cultivation areas in response to climate change and for further exploration of the mechanisms through which climate impacts the growth of Fuling.

The lipid droplet in cancer: From being a tumor-supporting hallmark to clinical therapy.

INTRODUCTION: Abnormal lipid metabolism, one of the hallmarks in cancer, has gradually emerged as a novel target for cancer treatment. As organelles that store and release excess lipids, lipid droplets (LDs) resemble "gears" and facilitate cancer development in the body. AIM: This review discusses the life cycle of LDs, the relationship between abnormal LDs and cancer hallmarks, and the application of LDs in theragnostic and clinical contexts to provide a contemporary understanding of the role of LDs in cancer. METHODS: A systematic literature search was conducted in PubMed and SPORTDiscus. Retrieve and summarize clinical trials of drugs that target proteins associated with LD formation using the Clinical Trials website. Create a schematic diagram of lipid droplets in the tumor microenvironment using Adobe Illustrator. CONCLUSION: As one of the top ten hallmarks of cancer, abnormal lipid metabolism caused by excessive generation of LDs interrelates with other hallmarks. The crosstalk between excessive LDs and intracellular free fatty acids (FFAs) promotes an inflammatory environment that supports tumor growth. Moreover, LDs contribute to cancer metastasis and cell death resistance in vivo. Statins, as HMGCR inhibitors, are promising to be the pioneering commercially available anti-cancer drugs that target LD formation.

Characterization of the Cytochrome P450 CYP716C52 in Celastrol Biosynthesis and Its Applications in Engineered Saccharomyces cerevisiae.

Celastrol is a bioactive pentacyclic triterpenoid with promising therapeutic effects that is mainly distributed in Celastraceae plants. Although some enzymes involved in the celastrol biosynthesis pathway have been reported, many biosynthetic steps remain unknown. Herein, transcriptomics and metabolic profiles of multiple species in Celastraceae were integrated to screen for cytochrome P450s (CYPs) that are closely related to celastrol biosynthesis. The CYP716 enzyme, TwCYP716C52, was found to be able to oxidize the C-2 position of polpunonic acid, a precursor of celastrol, to form the wilforic acid C. RNAi-mediated repression of TwCYP716C52 in Tripterygium wilfordii suspension cells further confirmed its involvement in celastrol biosynthesis. The C-2 catalytic mechanisms of TwCYP716C52 were further explored by using molecular docking and site-directed mutagenesis experiments. Moreover, a modular optimization strategy was used to construct an engineered yeast to produce wilforic acid C at a titer of 5.8 mg·L-1. This study elucidates the celastrol biosynthetic pathway and provides important functional genes and sufficient precursors for further enzyme discovery.

IMP: bridging the gap for medicinal plant genomics.

Medicinal plants have garnered significant attention in ethnomedicine and traditional medicine due to their potential antitumor, anti-inflammatory and antioxidant properties. Recent advancements in genome sequencing and synthetic biology have revitalized interest in natural products. Despite the availability of sequenced genomes and transcriptomes of these plants, the absence of publicly accessible gene annotations and tabular formatted gene expression data has hindered their effective utilization. To address this pressing issue, we have developed IMP (Integrated Medicinal Plantomics), a freely accessible platform at https://www.bic.ac.cn/IMP. IMP curated a total of 8 565 672 genes for 84 high-quality genome assemblies, and 2156 transcriptome sequencing samples encompassing various organs, tissues, developmental stages and stimulations. With the integrated 10 analysis modules, users could simply examine gene annotations, sequences, functions, distributions and expressions in IMP in a one-stop mode. We firmly believe that IMP will play a vital role in enhancing the understanding of molecular metabolic pathways in medicinal plants or plants with medicinal benefits, thereby driving advancements in synthetic biology, and facilitating the exploration of natural sources for valuable chemical constituents like drug discovery and drug production.