Telomere-to-Telomere Genome Assembly of Tibetan Medicinal Mushroom Ganoderma leucocontextum and the First Copia Centromeric Retrotransposon in Macro-Fungi Genome.

A complete telomere-to-telomere (T2T) genome has been a longstanding goal in the field of genomic research. By integrating high-coverage and precise long-read sequencing data using multiple assembly strategies, we present here the first T2T gap-free genome assembly of Ganoderma leucocontextum strain GL72, a Tibetan medicinal mushroom. The T2T genome, with a size of 46.69 Mb, consists 13 complete nuclear chromosomes and typical telomeric repeats (CCCTAA)n were detected at both ends of 13 chromosomes. The high mapping rate, uniform genome coverage, a complete BUSCOs of 99.7%, and base accuracy exceeding 99.999% indicate that this assembly represents the highest level of completeness and quality. Regions characterized by distinct structural attributes, including highest Hi-C interaction intensity, high repeat content, decreased gene density, low GC content, and minimal or no transcription levels across all chromosomes may represent potential centromeres. Sequence analysis revealed the first Copia centromeric retrotransposon in macro-fungi genome. Phylogenomic analysis identified that G. leucocontextum and G. tsugae diverged from the other Ganoderma species approximately 9.8-17.9 MYA. The prediction of secondary metabolic clusters confirmed the capability of this fungus to produce a substantial quantity of metabolites. This T2T gap-free genome will contribute to the genomic 'dark matter' elucidation and server as a great reference for genetics, genomics, and evolutionary studies of G. leucocontextum.

Shengmai san-derived compound prescriptions: A review on chemical constituents, pharmacokinetic studies, quality control, and pharmacological properties.

BACKGROUND: Shengmai San Formula (SMS), composed of Ginseng Radix et Rhizoma, Ophiopogon Radix and Schisandra chinensis Fructus, was a famous formula in Tradition Chinese Medicine (TCM). With the expansion of clinical applications, SMS was developed to different dosage forms, including Shengmai Yin Oral liquid (SMY), Shengmai Capsule (SMC), Shengmai Granule (SMG), Shengmai Injection (SMI) and Dengzhan Shengmai Capsule (DZSMC). These above SMS-derived compound prescriptions (SSCPs) play an important role in the clinical treatment. This review is aimed to providing a comprehensive perspective of SSCP. METHODS: The relevant literatures were collected from classical TCM books and a variety of databases, including PubMed, Google Scholar, Science Direct, Springer Link, Web of Science, China National Knowledge Infrastructure, and Wanfang Data. RESULTS: The chemical constituents of SSCPs, arrived from the individual medicinal materials including Ginseng Radix et Rhizoma, Ophiopogon Radix, Schisandra chinensis Fructus, Erigerontis Herba, were firstly summarized respectively. Then the pharmacokinetics studies, quality control, and pharmacological properties of SSCPs were all reviewed. The active compounds, pharmacokinetics characterizes, quality control markers, the effects and mechanisms of pharmacology of the different dosage forms of SSCPs were summarized. Furthermore, the research deficiencies of SSCPs and an innovative research paradigm for Chinese materia medica (CMM) formula were proposed. CONCLUSIONS: SMS, as a famous CMM formula, has great values in drug research and in clinical treatment especially for cardiocerebrovascular diseases. This article firstly make a comprehensive and systematic review on SMS.

Engineering Electronic Band Structure of Binary Thermoelectric Nanocatalysts for Augmented Pyrocatalytic Tumor Nanotherapy.

Photothermal therapy (PTT) has emerged as a distinct therapeutic modality owing to its noninvasiveness and spatiotemporal selectivity. However, heat-shock proteins (HSPs) endow tumor cells with resistance to heat-induced apoptosis, severely lowering the therapeutic efficacy of PTT. Here, a high-performance pyroelectric nanocatalyst, Bi13 S18 I2 nanorods (NRs), with prominent pyroelectric conversion and photothermal conversion performance for augmented pyrocatalytic tumor nanotherapy, is developed. Canonical binary compounds are reconstructed by inserting a third biocompatible agent, thus facilitating the formation of Bi13 S18 I2 NRs with enhanced pyrocatalytic conversion efficiency. Under 808 nm laser irradiation, Bi13 S18 I2 NRs induce a conspicuous temperature elevation for photonic hyperthermia. In particular, Bi13 S18 I2 NRs harvest pyrocatalytic energy from the heating and cooling alterations to produce abundant reactive oxygen species, which results in the depletion of HSPs and hence the reduction of thermoresistance of tumor cells, thereby significantly augmenting the therapeutic efficacy of photothermal tumor hyperthermia. By synergizing the pyroelectric dynamic therapy with PTT, tumor suppression with a significant tumor inhibition rate of 97.2% is achieved after intravenous administration of Bi13 S18 I2 NRs and subsequent exposure to an 808 nm laser. This work opens an avenue for the design of high-performance pyroelectric nanocatalysts by reconstructing canonical binary compounds for therapeutic applications in biocatalytic nanomedicine.

Engineering Oxygen-Irrelevant Radical Nanogenerator for Hypoxia-Independent Magnetothermodynamic Tumor Nanotherapy.

Tumor hypoxia substantially lowers the treatment efficacy of oxygen-relevant therapeutic modalities because the production of reactive oxygen species in oxygen-relevant anticancer modalities is highly dependent on oxygen level in tumor tissues. Here a distinctive magnetothermodynamic anticancer strategy is developed that takes the advantage of oxygen-irrelevant free radicals produced from magnetothermal decomposable initiators for inducing cancer-cell apoptosis in vitro and tumor suppression in vivo. Free-radical nanogenerator is constructed through in situ engineering of a mesoporous silica coating on the surface of superparamagnetic Mn and Co-doped nanoparticles (MnFe2 O4 @CoFe2 O4 , denoted as Mag) toward multifunctionality, where mesoporous structure provides reservoirs for efficient loading of initiators and the Mag core serves as in situ heat source under alternating magnetic field (AMF) actuation. Upon exposure to an exogenous AMF, the magnetic hyperthermia effect of superparamagnetic core lead to the rapid decomposition of the loaded/delivered initiators (AIPH) to produce oxygen-irrelevant free radicals. Both the magnetothermal effect and generation of toxic free radicals under AMF actuation are synergistically effective in promoting cancer-cell death and tumor suppression in the hypoxic tumor microenvironment. The prominent therapeutic efficacy of this radical nanogenerator represents an intriguing paradigm of oxygen-irrelevant nanoplatform for AMF-initiated synergistic cancer treatment.

Biodegradable and Excretable 2D W1.33 C i-MXene with Vacancy Ordering for Theory-Oriented Cancer Nanotheranostics in Near-Infrared Biowindow.

MXenes, a new class of two-dimensional (2D) nanomaterials, have shown enormous potential for biological applications. Notably, the development of 2D MXenes in nanomedicine is still in its infancy. Herein, a distinct W1.33 C i-MXene with multiple theranostic functionalities, fast biodegradation, and satisfactory biocompatibility is explored. By designing a parent bulk laminate in-plane ordered (W2/3 Y1/3 )2 AlC ceramic and optionally etching aluminum (Al) and yttrium (Y) elements, 2D W1.33 C i-MXene nanosheets with ordered divacancies are efficiently fabricated. Especially, theoretical simulations reveal that W1.33 C i-MXene possesses a strong predominance of near-infrared (NIR) absorbance. The constructed ultrathin W1.33 C nanosheets feature excellent photothermal-conversion effectiveness (32.5% at NIR I and 49.3% at NIR II) with desirable biocompatibility and fast degradation in normal tissue rather than in tumor tissue. Importantly, the multimodal-imaging properties and photothermal-ablation performance of W1.33 C-BSA nanosheets are systematically revealed and demonstrated both in vitro and in vivo. The underlying mechanism and regulation factors for the W1.33 C-BSA nanosheets-induced hyperthermia ablation are also revealed by transcriptome and proteome sequencing. This work offers a paradigm that i-MXenes achieve the tailoring biomedical applications through composition and structure design on the atomic scale.

Co-delivery of nanoparticle and molecular drug by hollow mesoporous organosilica for tumor-activated and photothermal-augmented chemotherapy of breast cancer.

BACKGROUND: In comparison with traditional therapeutics, it is highly preferable to develop a combinatorial therapeutic modality for nanomedicine and photothermal hyperthermia to achieve safe, efficient, and localized delivery of chemotherapeutic drugs into tumor tissues and exert tumor-activated nanotherapy. Biocompatible organic-inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) have shown high performance in molecular imaging and drug delivery as compared to other inorganic nanosystems. Disulfiram (DSF), an alcohol-abuse drug, can act as a chemotherapeutic agent according to its recently reported effectiveness for cancer chemotherapy, whose activity strongly depends on copper ions. RESULTS: In this work, a therapeutic construction with high biosafety and efficiency was proposed and developed for synergistic tumor-activated and photothermal-augmented chemotherapy in breast tumor eradication both in vitro and in vivo. The proposed strategy is based on the employment of HMONs to integrate ultrasmall photothermal CuS particles onto the surface of the organosilica and the molecular drug DSF inside the mesopores and hollow interior. The ultrasmall CuS acted as both photothermal agent under near-infrared (NIR) irradiation for photonic tumor hyperthermia and Cu2+ self-supplier in an acidic tumor microenvironment to activate the nontoxic DSF drug into a highly toxic diethyldithiocarbamate (DTC)-copper complex for enhanced DSF chemotherapy, which effectively achieved a remarkable synergistic in-situ anticancer outcome with minimal side effects. CONCLUSION: This work provides a representative paradigm on the engineering of combinatorial therapeutic nanomedicine with both exogenous response for photonic tumor ablation and endogenous tumor microenvironment-responsive in-situ toxicity activation of a molecular drug (DSF) for augmented tumor chemotherapy.

Ultrathin 2D Inorganic Ancient Pigment Decorated 3D-Printing Scaffold Enables Photonic Hyperthermia of Osteosarcoma in NIR-II Biowindow and Concurrently Augments Bone Regeneration.

Osteosarcoma (OS) is the primary malignant bone tumor. Despite therapeutic strategies including surgery, chemotherapy, and radiotherapy have been introduced into the war of fighting OS, the 5-year survival rate for patients still remains unchangeable for decades. Besides, the critical bone defects after surgery, drug-resistance and side effects also attenuate the therapeutic effects and predict poor prognosis. Recently, photothermal therapy (PTT) has attracted extensive attention featuring minimal invasiveness and high spatial-temporal precision characteristics. Herein, an ultrathin 2D inorganic ancient pigment Egyptian blue decorated 3D-printing scaffold (CaPCu) with profound PTT efficacy at the second near-infrared (NIR-II) biowindow against OS and enhanced osteogenesis performance is successfully constructed. Importantly, this work uncovers the underlying biological mechanisms that genes associated with cell death, proliferation, and bone development are regulated by CaPCu-scaffold-based therapy. This work not only elucidates the fascinating clinical translation prospects of CaPCu-scaffold-based PTT against OS in NIR-II biowindow, but also demonstrates the potential mechanisms and offers a novel strategy to develop the next-generation, multifunctional tissue-engineering biomaterials.

The Genus Pachyma (Syn. Wolfiporia) Reinstated and Species Clarification of the Cultivated Medicinal Mushroom "Fuling" in China.

The fungus "Fuling" has been used in Chinese traditional medicine for more than 2000 years, and its sclerotia have a wide range of biological activities including antitumour, immunomodulation, anti-inflammation, antioxidation, anti-aging etc. This prized medicinal mushroom also known as "Hoelen" is resurrected from a piece of pre-Linnean scientific literature. Fries treated it as Pachyma hoelen Fr. and mentioned that it was cultivated on pine trees in China. However, this name had been almost forgotten, and Poria cocos (syn. Wolfiporia cocos), originally described from North America, and known as "Tuckahoe" has been applied to "Fuling" in most publications. Although Merrill mentioned a 100 years ago that Asian Pachyma hoelen and North American P. cocos are similar but different, no comprehensive taxonomical studies have been carried out on the East Asian Pachyma hoelen and its related species. Based on phylogenetic analyses and morphological examination on both the sclerotia and the basidiocarps which are very seldomly developed, the East Asian samples of Pachyma hoelen including sclerotia, commercial strains for cultivation and fruiting bodies, nested in a strongly supported, homogeneous lineage which clearly separated from the lineages of North American Wolfiporia cocos and other species. So we confirm that the widely cultivated "Fuling" Pachyma hoelen in East Asia is not conspecific with the North American Wolfiporia cocos. Based on the changes in Art. 59 of the International Code of Nomenclature for algae, fungi, and plants, the generic name Pachyma, which was sanctioned by Fries, has nomenclatural priority (ICN, Art. F.3.1), and this name well represents the economically important stage of the generic type. So we propose to use Pachyma rather than Wolfiporia, and subsequently Pachyma hoelen and Pachyma cocos are the valid names for "Fuling" in East Asia and "Tuckahoe" in North America, respectively. In addition, a new combination, Pachyma pseudococos, is proposed. Furthermore, it seems that Pachyma cocos is a species complex, and that three species exist in North America.

Distinguishing Homokaryons and Heterokaryons in Medicinal Polypore Mushroom Wolfiporia cocos (Agaricomycetes) Based on Cultural and Genetic Characteristics.

The sclerotia of Wolfiporia cocos are a kind of traditional medicine and food with excellent benefits and are widely used in China, Japan, and other Asian countries. The mating system of fungi is not only of practical importance for breeding but also has profound effects on genetic variability and molecular evolution. However, the lack of clamp connections in W. cocos increases the difficulty of research on mating systems. In this study, homokaryons and heterokaryons were distinguished by comparing the characteristics of culture, fruiting tests, and molecular markers, which was further demonstrated by k-mer analysis based on Illumina sequencing. Uninucleate, binucleate, and nuclei-free condition basidiospores of W. cocos were observed, and binucleate basidiospores were the most predominant. Brown-type colonies, slow growth rates in both PDA medium and sawdust substrate, and neutral pH after the growth of mycelia and unfruiting were found to be the morphological and growth characteristics of homokaryotic strains. Primers SSR37 and 38 were screened to identify homokaryons. K-mer analysis based on Illumina sequencing exhibited different heterozygous ratios for homokaryons and heterokaryons. The results revealed that pseudo-homothallism was the predominant mode of reproduction in the Chinese population of W. cocos, and heterothallism also existed in all probability. This study will be helpful for the cross-breeding of this precious medicinal mushroom and for understanding its evolution and population structure.

Carotenoid Production by Caterpillar Medicinal Mushrooms, Cordyceps militaris (Ascomycetes), under Different Culture Conditions.

Cordyceps militaris, a well-known edible and medicinal species, is a potential source of natural carotenoids. The optimized conditions for carotenoid production are important for high-quality cultivation since carotenoid contents are the key factors for the appearance of fruiting bodies. In this study, carotenoid production by C. militaris under different culture conditions was compared. It was found that two-stage culture and fruiting body cultivation were suitable for the carotenoid production. Light is one of the important factors for carotenoid accumulation in this fungus and carotenoid can be produced by continuous shaking under light irradiation. Blue light with intensity of 17.3-64.3 lux can promote carotenoid production under the three tested culture methods. The carotenoid content was 4410.42 ± 30.83 and 3747.92 ± 178.13 µg g-1 under blue light intensity of 64.3 lux for the velum under two-stage culture and fruiting body cultivation, respectively. Oat medium may be suitable for the cultivation of fruiting bodies due to its high carotenoid production compared with other grains such as rice, wheat, and millet. Oxygen vector and oxidative stress induced by hydrogen peroxide can promote carotenoid production significantly under the two-stage culture. The carotenoid extracted from C. militaris showed strong antioxidant activity with IC50 value of 0.219 ± 0.01 mg ml-1, even higher than that of BHT, a positive control. This study will benefit the high-quality cultivation of this fungus and confirm that the carotenoid from C. militaris has the potential to be developed as a health food.

Classification, Biological Characteristics and Cultivations of Ganoderma.

Species of Ganoderma (Ling-zhi) have been widely researched and cultivated due to their highly prized medicinal value, which is famous as a traditional Chinese medicine. The aims of this chapter are to (1) review the historical taxonomy of the family Ganodermataceae, (2) provide an account of the genera and species of Ganoderma together with the distributions and habitats, (3) evaluate morphological features and phylogenetic methods to define the genera and species and (4) present two commonly used cultivated methods (wood-log cultivation and substitute cultivation) for Ganoderma.

Effect of Environmental Conditions on Synnema Formation and Nucleoside Production in Cicada Flower, Isaria cicadae (Ascomycetes).

Isaria cicadae (syn. Cordyceps cicadae) is one of the most valued edible and medicinal fungi and has been used in Asia as a substitute for Ophiocordyceps sinensis. Wild I. cicadae is limited and seasonal, and its cultivation is deserved. In this investigation we studied synnema formation by and nucleoside production in cicada flower under different environmental conditions. I. cicadae produced an asexual structure and mitospores instead of meiotic ascospores; this indicates that the term "synnema" is more suitable than "fruiting body" for this species. The optimal temperature was 25°C for growth of I. cicadae mycelia on potato dextrose agar plates but was 20°C for synnema formation on wheat medium. Synnemata can grow well under blue, green, and white light, and the dry weight of samples grown under these 3 light wavelengths is not significantly different. However, neither primordia nor synnemata formed under red light. Blue light promotes conidia production and white light promotes N6-(2-hydroxyethyl)-adenosine (HEA) production. Weak white light at 50 and 150 lux was more suitable for synnema production than strong-intensity light at 850 lux. The growth curve showed that HEA content has the same trend as synnema production over the entire cultivation period. The optimal harvesting time for I. cicadae cultivated on wheat medium is 35 days after inoculation. HEA content in the synnemata cultivated on wheat medium under the optimal conditions was significantly higher than that of the wild species and of synnemata cultivated on pupae, suggesting that synnemata cultivated on wheat medium may have potential as a substitute for wild resources. The results presented herein provide a new strategy for producing superior-quality synnemata of I. cicadae and further elucidate the effects of environmental conditions on metabolite accumulation in fungi.

A breakthrough in the artificial cultivation of Chinese cordyceps on a large-scale and its impact on science, the economy, and industry.

Chinese cordyceps, an entity of the Chinese caterpillar fungus (Ophiocordyceps sinensis, syn. Cordyceps sinensis) that parasitizes ghost moth larvae, is one of the best known traditional Chinese medicines and is found exclusively on the Tibetan Plateau with limited natural resources. Although the fungus O. sinensis can grow on artificial substrates and the ghost moth has been successfully reared, the large-scale artificial cultivation of Chinese cordyceps has only recently been accomplished after several decades of efforts and attempts. In this article, research progress related to this breakthrough from living habitats, the life history of the fungus, its host insect, fungal isolation and culture, host larvae rearing, infection cycle of the fungus to the host, primordium induction, and fruiting body development have been reviewed. An understanding of the basic biology of O. sinensis, its host insect and the simulation of the Tibetan alpine environment resulted in the success of artificial cultivation on a large scale. Practical workshop production has reached annual yields of 2.5, 5, and 10 tons in 2014, 2015, and 2016, respectively. There was no difference in the chemical components detected between the cultivated and natural Chinese cordyceps. However, the artificial cultivation system can be controlled to avoid heavy metal contamination and results in high-quality products. Although omics studies, including genomic, transcriptomic, proteomic, and metabolomic studies, have helped to understand the biology of the fungus, the success of the artificial cultivation of the Chinese cordyceps is clearly a milestone and provides the possibility for research on the in-depth mechanisms of the interaction between the fungus and host insects and their adaptation to the harsh habitats. This cultivation will not only result in a large industry to alleviate the pressure of human demand but also protect the limited natural resources for sustainable utilization.

Influence of Strain Preservation Methods on Fruiting Body Growth and Metabolite Production by the Medicinal Mushroom Cordyceps militaris (Ascomycetes).

Cordyceps militaris is a highly valued edible and medicinal fungus because of its production of various metabolites including adenosine, cordycepin, and N6-(2-hydroxyethyl)-adenosine. Fruiting bodies of this fungus have been used successfully in industrial production and widely as a substitute for Ophiocordyceps sinensis (syn. C. sinensis) in traditional Chinese medicine and health supplements. Strain degeneration occurs with high frequency during the subculturing and preservation of C. militaris strains, which leads to significant losses during industrial production. In this study, we evaluated the effects of different strain preservation methods on fruiting body growth and metabolite production. We found that strain degeneration affects not only fruiting body differentiation but also metabolite production, and suitable preservation methods can avoid degeneration. Preservation in sterile water has a similar effect as cryopreservation in liquid nitrogen at -196°C with regard to maintaining the characteristics of C. militaris strains for at least 1 year, and it is a practical and satisfactory method for preserving C. militaris strains that can be used in factories. Ultracold freezing at -80°C is not suitable for this fungus. Lyophilization, which causes C. militaris strains to retain their inherent characteristics and avoid degeneration, is suitable for long-term preservation (at least 4 years). This study provides practical preservation methods for C. militaris strains over the short and long term and will be helpful to achieve stable and superior-quality production of C. militaris fruiting bodies.

Nutritional Requirements for Mycelial Growth of Milk-White Toothed Mushroom, Irpex lacteus (Agaricomycetes), in Submerged Culture.

Irpex lacteus, a medicinal fungus, is used in traditional Chinese medicine to treat chronic glomerulonephritis. In this work, a strain of I. lacteus was isolated from the fruiting body of a wild specimen and identified by ITS-5.8S ribosomal DNA sequencing analysis. Then the nutritional requirements and culture conditions for mycelial growth of I. lacteus in semisynthetic liquid media were investigated using the one-factor-at-a-time and orthogonal matrix methods. Optimum growth occurred at 30°C and 35°C. I. lacteus mycelia grew well at pH values between 3 and 9, suggesting that this strain is not sensitive to pH. The nutritional components, including 9 carbohydrates, 9 nitrogen compounds, 11 vitamins, and 10 mineral elements, were studied for their effects on mycelial growth in submerged cultures of I. lacteus. Among these variables, soluble starch, peptone, yeast extract, and calcium chloride were identified as required for optimum mycelial growth. The concentrations of each component were optimized using an orthogonal design, and the effects of medium composition on mycelial growth were found in the order soluble starch > yeast extract > peptone > calcium chloride. The optimal concentrations of these components for mycelial growth were determined to be 60 g/L soluble starch, 35 g/L peptone, 15 g/L yeast extract, and 0.6 g/L calcium chloride. Under the optimum medium and culture conditions, the maximum biomass reached 13.73 g/L after 3 days in submerged culture, a value over twice that reached using the basal medium. These results provide a basis for further physiological study and industrial fermentation of I. lacteus.

Photoperiodic Responses and Characterization of the Cmvvd Gene Encoding a Blue Light Photoreceptor from the Medicinal Caterpillar Fungus Cordyceps militaris (Ascomycetes).

Light is a necessary environmental factor for production of conidia and pigment, formation of stroma, and development of Cordyceps militaris, a well-known edible and medicinal mushroom. In this study, an obvious rhythm loop was observed in certain strains of C. militaris under conditions of alternating 12-hour intervals of dark and light. A possibly related gene, Cmvvd, the homologue of the blue-light photoreceptor of Neurospora crassa, was cloned from the genome of C. militaris. The protein CmVVD is predicted to be 203 amino acids in length and is characterized by the presence of a light, oxygen, or voltage domain. Analysis of the CmVVD sensor domain (light, oxygen, or voltage) suggested that it is a blue-light receptor. Cysteine 108 is essential for the in vivo function of VIVID (VVD) in N. crassa photoadaptation. However, proline is in this position instead in all of the tested CmVVD proteins, suggesting that CmVVD may have a different function or may function in ways different from VVD in N. crassa. Genetic variation analysis of CmVVD in 6 representative strains indicated that 3 informative sites exist. Cmvvd messenger RNA was able to be induced by light, and the expression level increased over 10 times after irradiation and was maintained at high levels in the nascent fruiting body. The light-induced expression of Cmvvd was abolished in Cmwc-1 mutants, suggesting that the expression of Cmvvd is dependent on the photoreceptor CmWC-1 or on a functional CmWC-1/WC-2 complex. This article will help to open the still-unexplored field of circadian rhythms for this fungus.

Comparison of Major Bioactive Compounds of the Caterpillar Medicinal Mushroom, Cordyceps militaris (Ascomycetes), Fruiting Bodies Cultured on Wheat Substrate and Pupae.

In this study, the main bioactive compounds of the fruit bodies of Cordyceps militaris-such as adenosine, cordycepin, polysaccharides, mannitol, superoxide dismutase (SOD), and carotenoids-were cultivated on wheat and pupae, as well as sclerotium (the pupae portion) and sclerotium with fruiting bodies. The amounts of adenosine and polysaccharide in all the tested samples (except for the polysaccharides of sclerotium) are higher than the quality standards (adenosine ≥0.055% and polysaccharide ≥2.5%) determined by the Ministry of Health of the People's Republic of China. As the most important bioactive compound in C. militaris, cordycepin is the highest in the fruiting bodies on pupae than in other samples, whereas it is the lowest in the sclerotium. The amounts of cordycepin, carotenoids, and SOD were higher in the fruiting bodies on pupae than that in the fruiting bodies on wheat, whereas the amounts of adenosine, polysaccharides, and mannitol were higher in the fruiting bodies on wheat than in the fruiting bodies on pupae. There was no significant difference in the amounts of cordycepin, carotenoids, and SOD in the sclerotium with fruiting bodies and the fruiting bodies on wheat. The adenosine, polysaccharide, and mannitol contents in the sclerotium with fruiting bodies were significantly lower than those of the fruiting bodies on wheat. Overall, the results of this evaluation could not distinguish which is better: the fruiting bodies on pupae or those on wheat; each has its own merits. The fruiting bodies of C. militaris cultivated on both wheat and pupae are important candidates for medicinal and tonic use for the welfare of humankind.

Development of Ling-zhi industry in China - emanated from the artificial cultivation in the Institute of Microbiology, Chinese Academy of Sciences (IMCAS).

Ling-zhi is a medicinal herb that generally refers to a fungus in the genus Ganoderma. It has been used as a medicinal mushroom in traditional Chinese medicine for more than 2000 years. Mycologists at the Institute of Microbiology, Chinese Academy of Sciences (IMCAS) first artificially cultivated the Ling-zhi fruiting body in the late 1960s (X.J. Liu's team). In IMCAS, different research teams have extensively studied Ling-zhi in the aspects of national resource surveys, systematic taxonomy, chemical analysis, and processing for medicinal and health applications. The research results from IMCAS have provided essential support and prompted the development of the Ling-zhi industry in China to some extent. This review aims to summarize the history of research on Ling-zhi in IMCAS and its role in the development of the Ling-zhi economy.

Cordyceps industry in China.

Cordyceps, as a general term, describes a group of ascomycetous fungi growing on arthropods and other related fungi. Some cordyceps have been used in traditional Chinese medicine for centuries and cordyceps-derived products are currently a big industry in China. A number of medicinal and health products have been developed and extensively commercialized from natural Chinese cordyceps, its anamorphic fungus (Hirsutella sinensis), and other fungi known as Chinese cordyceps. The lack of a defined classification system for medicinal cordyceps fungi is a source of confusion in the industry and the public, and even among pharmaceutical scientists. This review summarizes the cordyceps fungi currently used in the industry in China with a special reference to clarify Chinese cordyceps and associated fungi. Cordyceps militaris, Cordyceps guangdongensis and Isaria cicadae are well recognized and commercialized cordyceps fungi in China. Except the natural Chinese cordyceps and its anamorphic fungus, Paecilomyces hepiali, Mortierella hepiali, Cephalosporium sinensis and Clonostachys rosea isolated from natural Chinese cordyceps are classified as Chinese cordyceps-associated fungi. P. hepiali is a cordyceps fungus based on current phylogenetic analysis of Hypocreales, while M. hepiali is a fungus in the Zygomycetes and should only be treated as associated fungus of Chinese cordyceps. C. sinensis and C. rosea belong to the Hypocreales and their relationship to cordyceps fungi should be further studied. The exploitation of the resources of cordyceps fungi and their quality control in the industry should be major topics for future studies. Cooperation between the industry and the research community will enhance the whole cordyceps industry.