Effect of an Intermittent Calorie-restricted Diet on Type 2 Diabetes Remission: A Randomized Controlled Trial.

CONTEXT: The 2021 consensus report on the definition and interpretation of remission of type 2 diabetes (T2D) has been released. Although intermittent fasting diets (IF) are becoming very popular, no studies have investigated their benefit in diabetes remission. OBJECTIVE: The present study examined the effectiveness of IF in diabetes remission and potential remission durability. METHODS: Participants between ages 38 and 72 years with a duration of T2D of 1 to 11 years, a body mass index (BMI) of 19.1 to 30.4, 66.7% male, and antidiabetic agent use and/or insulin injection were randomly allocated at a ratio of 1:1 to the Chinese Medical Nutrition Therapy (CMNT) or control group. The primary outcome was diabetes remission, defined as a stable glycated hemoglobin A1c (HbA1c) level of less than 48 mmol/mol (< 6.5%) for at least 3 months after discontinuing all antidiabetic medications. The secondary outcomes included HbA1c level, fasting blood glucose level, blood pressure, weight, quality of life, and medication costs. We conducted a 12-month follow-up to assess the continuation of remission. RESULTS: On completing the 3-month intervention plus 3-month follow-up, 47.2% (17/36) of participants achieved diabetes remission in the CMNT group, whereas only 2.8% (1/36) of individuals achieved remission in the control group (odds ratio 31.32; 95% CI, 2.39-121.07; P < 0.0001). The mean body weight of participants in the CMNT group was reduced by 5.93 kg (SD 2.47) compared to 0.27 kg (1.43) in the control group. After the 12-month follow-up, 44.4% (16/36) of the participants achieved sustained remission, with an HbA1c level of 6.33% (SD 0.87). The medication costs of the CMNT group were 77.22% lower than those of the control group (60.4/month vs 265.1/month). CONCLUSION: This study demonstrated the clinical efficacy of CMNT in achieving diabetes remission for at least 1 year.

The glucotoxicity protecting effect of honokiol in human hepatocytes via directly activating AMPK.

Introduction: Sustained hyperglycemia causes glucotoxicity, which has been regarded as a contributor to hepatocyte damage in type 2 diabetes (T2D) and its metabolic comorbidities. Honokiol is a natural biphenolic component derived from the dietary supplement Magnolia officinalis extract. This study aimed to investigate the effects of honokiol on glucose metabolism disorders and oxidative stress in hepatocytes and the underlying mechanisms. Methods: HepG2 cells were treated with glucosamines (18 mM) to induce glucotoxicity as a diabetic complication model in vitro. Results and discussion: Honokiol significantly increased glucose consumption, elevated 2-NBDG uptake, and promoted GLUT2 translocation to the plasma membrane in glucosamine-treated HepG2 cells, indicating that honokiol ameliorates glucose metabolism disorders. Furthermore, glucosamine-induced ROS accumulation and loss of mitochondrial membrane potential were markedly reduced by honokiol, suggesting that honokiol alleviated glucotoxicity-induced oxidative stress. These effects were largely abolished by compound C, an AMPK inhibitor, suggesting an AMPK activation-dependent manner of honokiol function in promoting glucose metabolism and mitigating oxidative stress. Molecular docking results revealed that honokiol could interact with the amino acid residues (His151, Arg152, Lys243, Arg70, Lys170, and His298) in the active site of AMPK. These findings provide new insights into the antidiabetic effect of honokiol, which may be a promising agent for the prevention and treatment of T2D and associated metabolic comorbidities.

A Chinese medical nutrition therapy diet accompanied by intermittent energy restriction alleviates type 2 diabetes by enhancing pancreatic islet function and regulating gut microbiota composition.

Medicine food homologous (MFH) plants and wholegrains have gained increasing attention for prevention and treatment of type 2 diabetes (T2D). Substantial evidence supports the effectiveness of intermittent energy restriction (IER) in T2D management. However, there are few studies that report intermittent use of a low-calorie pre-prepared food including MFH plants and wholegrains in T2D. The aim of this study was to investigate the effects of Chinese Medical Nutrition Therapy (CMNT), a MFH plants and wholegrains diet accompanied by IER, on glycemic control and potential mechanism. Ten-week-old diabetic db/db mice were randomly divided into CMNT group (feeding low-calorie mouse CMNT diet in day 1-4 and ad libitum regular chow for up to 7 days per cycle) and control group (ad libitum access to regular chow). The results showed that CMNT reduced fasting blood glucose, improved glucose tolerance with higher insulin secretion, attenuated macrophage infiltration, promoted ß-cell proliferation of pancreatic islets, and increased diabetes-improving microbiota (Bacteroides, Rikenellaceae_RC9_gut_group and Coprococcus_1) in db/db mice. Additionally, we performed a pilot study evaluating CMNT in thirty-nine T2D patients without obesity. Participants with T2D randomly assigned to two groups: CMNT group (receiving a consecutive 5-day low-calorie human CMNT diet with 10 days of habitual eating per cycle for 90 days) and control group (continuing on a normal diet). We observed an improvement in glycemic control in CMNT group with significant reduction in HbA1c, fasting glucose, 2 h postprandial blood glucose but control group were not affected. After CMNT intervention, the abundance of the phylum Bacteroidetes, and genus Bacteroides, Parabacteroides and Roseburia were significantly higher than baseline in T2D patient, which were closely associated with glycemic control. These findings suggested that CMNT is a promising nutritional intervention approach in diabetes management.

The root extract of Scutellaria baicalensis Georgi promotes ß cell function and protects from apoptosis by inducing autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi (SBG) is a traditional Chinese medicine with a remarkable remedial effect on diabetes mellitus. However, the precise mechanism involved has not been fully elucidated yet. Here, we aimed to explore the anti-diabetes effects of its traditional decoction in vitro and elucidate the autophagy-related mechanism. AIM OF THE STUDY: This study was designed to investigate the effects of the water extract of SBG (WSB) on the ß cell viability, insulin secretion and the mechanism related to autophagy. MATERIALS AND METHODS: Detection of insulin secretion using an enzyme immunoassay method, and analysis of apoptosis rate in MIN-6 cells by the flow cytometry with PI and Annexin V-FITC staining. In addition, the autophagy levels and pathways were evaluated from the number of autophagosomes and the expression of autophagy-related proteins. 3-Methyladenine (3-MA) was used as the autophagy inhibitor. Autophagosomes were observed using a confocal microscopy, and autophagy-related proteins (LC3-II/I, p62, S6k, p-AMPK/AMPK, p-mTOR/mTOR) were measured by Western blot. RESULTS: Here we detected a significant increase in insulin release from MIN-6 cells after treated with WSB. It is about 1.6 times as much as that of the control group with 2.8 mM glucose and 2.2 times more than the 16.8 mM glucose group. At the same time, WSB increased the number of autophagosomes and the ratio of LC3 Ⅱ/LC3 Ⅰ, indicating that autophagy were activated in MIN-6 cells. When inhibiting autophagy, there was no significant difference in insulin release between the two groups. The apoptotic rate of the high glucose group was as high as 33.23%. After pretreatment with WSB, the apoptotic rate decreased to 14.95%, and increased to 22.57% when treated with 3-MA and WSB. At the same time, WSB treatment enhanced the phosphorylation of AMPK, but had no significant effect on the expression of mTOR and S6K. CONCLUSION: Our data suggested that WSB increased insulin secretion and reduced apoptosis under high glucose by inducing autophagy through the AMPK pathway, which elucidated the mechanism of WSB in the treatment of diabetes.

Phytosterols in hull-less pumpkin seed oil, rich in ∆7-phytosterols, ameliorate benign prostatic hyperplasia by lowing 5α-reductase and regulating balance between cell proliferation and apoptosis in rats.

BACKGROUND: Pumpkin seed oil is widely used to treat benign prostatic hyperplasia (BPH), a common disease in elder men. However, its active components and mechanism have remained to be elucidated. OBJECTIVE: The objective of the present study was to investigate the active components of pumpkin seed oil and its mechanism against BPH. DESIGN: Total phytosterol (TPS) was isolated from hull-less pumpkin (Cucurbita pepo L. var. Styriaca) seed oil and analyzed by gas chromatography/mass spectrometry (GC/MS). Three phytosterols were purified by preparative HPLC (high performance liquid chromatography) and confirmed by NMR (nuclear magnetic resonance). TPS (3.3 mg/kg body weight, 1 mL/day/rat) was administered intragastrically to the testosterone propionate-induced BPH rats for 4 weeks. The structure changes of prostate tissues were assessed by hematoxylin & eosin (H&E) staining. The expression of androgen receptor (AR) and steroid receptor coactivator 1 (SRC-1) was analyzed by immunohistochemistry, while that of 5α-reductase (5AR), apoptosis, or proliferation-related growth factors/proteins was detected by real-time quantitative polymerase chain reaction or western blotting. RESULTS: The ∆7-phytosterols in TPS reached up to 87.64%. Among them, 24ß-ethylcholesta-7,22,25-trienol, 24ß-ethylcholesta-7,25(27)-dien-3-ol, and ∆7-avenasterol were confirmed by NMR. TPS treatment significantly ameliorated the pathological prostate enlargement and restored histopathological alterations of prostate in BPH rats. It effectively suppressed the expressions of 5AR, AR, and coactivator SRC-1. TPS inhibited the expression of proliferation-related growth factor epidermal growth factor, whereas it increased the expressions of apoptosis-related growth factor/gene transforming growth factor-ß1. The proliferation-inhibiting effect was achieved by decreasing the ERK (extracellular signal-regulated kinase) phosphorylation, while apoptosis was induced by Caspase 3 activation through JNK (c-Jun N-terminal kinase) and p38 phosphorylation. CONCLUSION: TPS from hull-less pumpkin seed oil, with ∆7-phytosterols as its main ingredients, is a potential nutraceutical for BPH prevention.

Glibenclamide-Induced Autophagy Inhibits Its Insulin Secretion-Improving Function in ß Cells.

Diabetes is a metabolic disease, partly due to hypoinsulinism, which affects ∼8% of the world's adult population. Glibenclamide is known to promote insulin secretion by targeting ß cells. Autophagy as a self-protective mechanism of cells has been widely studied and has particular physiological effects in different tissues or cells. However, the interaction between autophagy and glibenclamide is unclear. In this study, we investigated the role of autophagy in glibenclamide-induced insulin secretion in pancreatic ß cells. Herein, we showed that glibenclamide promoted insulin release and further activated autophagy through the adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) pathway in MIN-6 cells. Inhibition of autophagy with autophagy inhibitor 3-methyladenine (3-MA) potentiated the secretory function of glibenclamide further. These results suggest that glibenclamide-induced autophagy plays an inhibitory role in promoting insulin secretion by activating the AMPK pathway instead of altering the mammalian target of rapamycin (mTOR).

[Detection of Huperzine A and Huperzine B in fermentation broth of endophytic fungus Colletotrichum gloesporioides from Huperzia serrate by HPLC].

In this study, we established a rapid and efficient HPLC method to determine the accumulation of Huperzine A and Huperzine B in the fermentation broth of endophytic fungus Colletotrichum gloesporioides from Huperzia serrate. The chloroform extracts of fermentation broth were dissolved in methanol and filtered before injection for HPLC analysis. The analysis was performed on an Agilent Eclipse plus-C18 column (250 mm×4.6 mm, 5 µm) by isocratic elution. The mobile phase was 0.015 mol/L ammonium acetate-methanol (70:30, V/V), the flow rate was 1 mL/min and the detection wavelength was set at 308 nm. Huperzine A and Huperzine B could be well separated within 25 min. Good linearity of Huperzine A was found in the range of 1.50-48.00 µg/mL (r=0.999 5), and that of huperzine B was in 0.25-7.50 µg/mL (r=0.999 7). The average recoveries of Huperzine A and Huperzine B were 106.83% and 108.06%, respectively (RSD=3.34%, 3.60%). The results demonstrate that this method can detect the content of huperzine A and huperzine B in fermentation broth simply, rapidly, accurately and in good reproducibility. Under the optimized conditions, the accumulated content of huperzine A and huperzine B were measured from the sixth to the fifteenth day. Huperzine A and Huperzine B reached the highest (12.417 0 µg/mL and 4.660 3 µg/mL, respectively) at the fourteenth and eighth days. The analysis methodology could contribute to the future study of huperzine A and huperzine B biosynthesis in C. gloeosporioides, consequently facilitate the development of new drug resources.

A Meloidogyne incognita effector MiISE5 suppresses programmed cell death to promote parasitism in host plant.

Root-knot nematodes (RKNs) are highly specialized parasites that interact with their host plants using a range of strategies. The esophageal glands are the main places where nematodes synthesize effector proteins, which play central roles in successful invasion. The Meloidogyne incognita effector MiISE5 is exclusively expressed within the subventral esophageal cells and is upregulated during early parasitic stages. In this study, we show that MiISE5 can be secreted to barley cells through infectious hyphae of Magnaporthe oryzae. Transgenic Arabidopsis plants expressing MiISE5 became significantly more susceptible to M. incognita. Inversely, the tobacco rattle virus (TRV)-mediated silence of MiISE5 decreased nematode parasitism. Moreover, transient expression of MiISE5 suppressed cell death caused by Burkholderia glumae in Nicotiana benthamiana. Based on transcriptome analysis of MiISE5 transgenic sample and the wild-type (WT) sample, we obtained 261 DEGs, and the results of GO and KEGG enrichment analysis indicate that MiISE5 can interfere with various metabolic and signaling pathways, especially the JA signaling pathway, to facilitate nematode parasitism. Results from the present study suggest that MiISE5 plays an important role during the early stages of parasitism and provides evidence to decipher the molecular mechanisms underlying the manipulation of host immune defense responses by M. incognita.

Genomic Characterization Provides New Insights Into the Biosynthesis of the Secondary Metabolite Huperzine a in the Endophyte Colletotrichum gloeosporioides Cg01.

A reliable source of Huperzine A (HupA) meets an urgent need due to its wide use in Alzheimer's disease treatment. In this study, we sequenced and characterized the whole genomes of two HupA-producing endophytes, Penicillium polonicum hy4 and Colletotrichum gloeosporioides Cg01, to clarify the mechanism of HupA biosynthesis. The whole genomes of hy4 and Cg01 were 33.92 and 55.77 Mb, respectively. We compared the differentially expressed genes (DEGs) between the induced group (with added extracts of Huperzia serrata) and a control group. We focused on DEGs with similar expression patterns in hy4 and Cg01. The DEGs identified in GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were primarily located in carbon and nitrogen metabolism and nucleolus, ribosome, and rRNA processing. Furthermore, we analyzed the gene expression for HupA biosynthesis genes proposed in plants, which include lysine decarboxylase (LDC), copper amine oxidase (CAO), polyketides synthases (PKS), etc. Two LDCs, one CAO, and three PKSs in Cg01 were selected as prime candidates for further validation. We found that single candidate biosynthesis-gene knock-out did not influence the HupA production, while both LDC gene knock-out led to increased HupA production. These results reveal that HupA biosynthesis in endophytes might differ from that proposed in plants, and imply that the HupA-biosynthesis genes in endophytic fungi might co-evolve with the plant machinery rather than being acquired through horizontal gene transfer (HGT). Moreover, we analyzed the function of the differentially expressed epigenetic modification genes. HupA production of the histone acetyltransferase (HAT) deletion mutant ΔCgSAS-2 was not changed, while that of the histone methyltransferase (HMT) and histone deacetylase (HDAC) deletion mutants ΔCgClr4, ΔCgClr3, and ΔCgSir2-6 was reduced. Recovery of HupA-biosynthetic ability can be achieved by retro-complementation, demonstrating that HMT and HDACs associated with histone modification are involved in the regulation of HupA biosynthesis in endophytic fungi. This is the first report on epigenetic modification in high value secondary metabolite- producing endophytes. These findings shed new light on HupA biosynthesis and regulation in HupA-producing endophytes and are crucial for industrial production of HupA from fungi.

SMRT Sequencing Revealed Mitogenome Characteristics and Mitogenome-Wide DNA Modification Pattern in Ophiocordyceps sinensis.

Single molecule, real-time (SMRT) sequencing was used to characterize mitochondrial (mt) genome of Ophiocordyceps sinensis and to analyze the mt genome-wide pattern of epigenetic DNA modification. The complete mt genome of O. sinensis, with a size of 157,539 bp, is the fourth largest Ascomycota mt genome sequenced to date. It contained 14 conserved protein-coding genes (PCGs), 1 intronic protein rps3, 27 tRNAs and 2 rRNA subunits, which are common characteristics of the known mt genomes in Hypocreales. A phylogenetic tree inferred from 14 PCGs in Pezizomycotina fungi supports O. sinensis as most closely related to Hirsutella rhossiliensis in Ophiocordycipitaceae. A total of 36 sequence sites in rps3 were under positive selection, with dN/dS >1 in the 20 compared fungi. Among them, 16 sites were statistically significant. In addition, the mt genome-wide base modification pattern of O. sinensis was determined in this study, especially DNA methylation. The methylations were located in coding and uncoding regions of mt PCGs in O. sinensis, and might be closely related to the expression of PCGs or the binding affinity of transcription factor A to mtDNA. Consequently, these methylations may affect the enzymatic activity of oxidative phosphorylation and then the mt respiratory rate; or they may influence mt biogenesis. Therefore, methylations in the mitogenome of O. sinensis might be a genetic feature to adapt to the cold and low PO2 environment at high altitude, where O. sinensis is endemic. This is the first report on epigenetic modifications in a fungal mt genome.

Complete mitogenome of the high ethanol production fungus Fusarium oxysporum Mh2-2.

Fusarium spp. are significantly important plant pathogens, and some of them are ethanol-producing strains. During infection and/or ethanol production, Fusarium requires a plenty of energy that is mainly provided by mitochondria. Here we report the first mitogenome from a selected Fusarium oxysporum strain mh2-2 that produces ethanol from glucose and xylose. The size of this mitogenome, 46 kb, is different from the size of any reported Fusarium mitogenome. Our results provide insight into the functions and evolution of mitochondrial genes and genomes.

The mitochondrial genome of the lepidopteran host cadaver (Thitarodes sp.) of Ophiocordyceps sinensis and related phylogenetic analysis.

To understand the phylogeny of the host insect (Thitarodes sp.) of the fungus Ophiocordyceps sinensis, we sequenced, annotated and characterized the complete mitochondrial (mt) genome of the host cadaver of a natural O. sinensis. Further, we compared the Thitarodes sp. mt genome with those of the other 7 sequenced Hepialidae and examined the phylogenetic relationships using a constructed Maximum Likelihood (ML) phylogenetic tree and mt genomic features (genetic distances and intergenic spacers). The mt genome is a circular molecule of 16,280bp in length with a high A+T content (81.20%) and contains 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes and an AT-rich region. The gene arrangement is identical to the ancestral arrangement but differs from those of other lepidopteran mt genomes because of the arrangement of tRNA genes. The tRNA region, which is located between the AT-rich region and nad2, is trnI/trnQ/trnM (IQM) in Thitarodes sp., rather than the trnM/trnI/trnQ (MIQ) of the Lepidoptera-specific rearrangement. All PCGs begin with the canonical start codons ATN or NTG, except for cox1, which starts with CGA. Most PCGs terminate with the typical stop codon TAA, although some have an incomplete stop codon (T). The 1473bp AT-rich region is located between the rrnS (12S rRNA) and trnI, which is the longest sequenced in a Thitarodes mt genome to date, containing nine 112bp copies and one partial copy of a 55bp sequence. The results derived from the phylogenetic tree, the genetic distances and the intergenic spacers of the mt genome show that the host insect of O. sinensis belongs to the Thitarodes, while Endoclita signifer and Napialus hunanensis form a relatively distinct lineage from Thitarodes. The sequence and full annotation of this moth mt genome will provide more molecular information about the Exoporia within the Lepidoptera, and the clarification of its phylogeny will improve the management of this insect resource and the conservation and sustainable use of this endangered medicinal species in China.

The complete mitochondrial genome of huperzine A-producing endophytic fungus Penicillium polonicum.

Huperzine A-producing fungus Penicillium polonicum Hy4 (CCTCC No.M2010086) was isolated from Huperzia serrata (Thunb) Trev. The complete mitochondrial genome of P. polonicum is 28 192 bp in length, containing 15 protein-encoding genes, 27 tRNA genes and two rRNA genes. The whole mitogenome is high in AT content (74.40%) and low in GC content (25.60%). The mitochondrial gene order and arrangement of P. polonicum are identical to those of other Penicillium. Phylogenetic analysis based on 14 concatenated protein-encoding genes showed that P. polonicum was close to P. solitum. This study reports the complete mitogenome of P. polonicum for the first time and provides valuable information for further exploration of mitochondrial evolution.

The protective effects and genetic pathways of thorn grape seeds oil against high glucose-induced apoptosis in pancreatic ß-cells.

BACKGROUND: Excessive apoptosis of ß-cell is closely related to diabetes mellitus. Chronic exposure to high glucose causes ß-cell dysfunction and apoptosis in diabetes. Thorn grape (Vitis davidii Foex.) has been used to treat diabetes in Traditional Chinese medicine for many years. In our previous research, thorn grape seeds oil (TGSO) showed promising anti-diabetic effects in animal models. However, it is unknown whether TGSO played an anti-apoptotic role in the anti-diabetic effects and the mechanism regarding signal transduction pathway is unclear either. METHODS: The rattus pancreatic ß-cell line RIN-m5F was treated with/without TGSO which was extracted by supercritical carbon dioxide (CO2) fluid extraction and analyzed by Gas Chromatography/Mass Spectrometry (GC/MS). Cell apoptosis was detected by fluorescence activated cell sorting (FACS), insulin secretion was assayed by Enzyme-Linked Immunosorbent Assay (ELISA), and the apoptosis-related genes expressions were evaluated by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR). RESULTS: TGSO, containing 87.02% unsaturated fatty acids (UFAs), significantly reduced pancreatic ß-cell apoptosis and protected the insulin secretion impaired by high glucose. The expressions of pro-apoptotic genes such as iNOS, Caspase-3, ATF-3, JNK, p38 and Fas were down-regulated while the anti-apoptotic genes Akt and Bcl-2/Bax were up-regulated. CONCLUSIONS: The results indicated that TGSO protected ß-cells from high glucose-induced apoptosis and its protective activity may be linked to mitochondrial pathway, endoplasmic reticulum (ER) stress pathway and Fas signal pathway, which implied that TGSO might be an effective complementary or alternative medicine to reduce ß-cell apoptosis and dysfunction.

Anti-apoptotic function and mechanism of ginseng saponins in Rattus pancreatic ß-cells.

Apoptosis is the main form of ß-cell death in diabetes. Ginseng has been used as an anti-diabetic herb for several thousand years in Asia with ginsenoside Rg1 and ginsenoside Rb1 as important active ingredients. In this study, we demonstrated ginsenoside Rg1 and Rb1 protect ß-cells from high glucose/cytokine-induced pancreatic ß-cell apoptosis via inhibiting nitric oxide (NO) production and regulating apoptosis-related genes. Among these genes, Bax, Fas and Caspase-3 gene expressions were up-regulated by high glucose, whereas only Bax and Caspase-3 gene expression were elevated by cytokines. In these two stimuli-induced apoptotic cells, Rg1 down-regulated Fas gene expression, while Rb1 decreased Caspase-3 gene expression. As a conclusion, Fas signal pathway and mitochondria stress is mostly related to anti-diabetes function of ginsenoside Rg1, while Caspase-3 pathway is essential when Rb1 is present.

The genome of Ganoderma lucidum provides insights into triterpenes biosynthesis and wood degradation [corrected].

BACKGROUND: Ganoderma lucidum (Reishi or Ling Zhi) is one of the most famous Traditional Chinese Medicines and has been widely used in the treatment of various human diseases in Asia countries. It is also a fungus with strong wood degradation ability with potential in bioenergy production. However, genes, pathways and mechanisms of these functions are still unknown. METHODOLOGY/PRINCIPAL FINDINGS: The genome of G. lucidum was sequenced and assembled into a 39.9 megabases (Mb) draft genome, which encoded 12,080 protein-coding genes and ∼83% of them were similar to public sequences. We performed comprehensive annotation for G. lucidum genes and made comparisons with genes in other fungi genomes. Genes in the biosynthesis of the main G. lucidum active ingredients, ganoderic acids (GAs), were characterized. Among the GAs synthases, we identified a fusion gene, the N and C terminal of which are homologous to two different enzymes. Moreover, the fusion gene was only found in basidiomycetes. As a white rot fungus with wood degradation ability, abundant carbohydrate-active enzymes and ligninolytic enzymes were identified in the G. lucidum genome and were compared with other fungi. CONCLUSIONS/SIGNIFICANCE: The genome sequence and well annotation of G. lucidum will provide new insights in function analyses including its medicinal mechanism. The characterization of genes in the triterpene biosynthesis and wood degradation will facilitate bio-engineering research in the production of its active ingredients and bioenergy.