Fungi are bound up with human life. Although some species are pathogens threaten to human and plants, most of them are beneficial to human, which have been used in food (such as making of cheeses and bread), drinks (such as making of beer and wine), and medicines (e.g. Ganoderma Lucidum) for thousands of years. They have played a key role in satisfying people’s demand for healthy.

In this issue of Chinese Journal of Natural Medicines (CJNM), we are pleased to organize several foundation research papers on SMs from various fungi, including marine fungi, plant endophytic fungi, and mushrooms. QI Shu-Hua et al. reported an unprecedented Fe (III) chelator of copro-gen-type siderophore (mycosphazine A) composed of L-or-nithine and D-ornithine units from the fermentation broth of the deep-sea-derived fungus Mycosphaerella sp. SCSIO z059 collected at a depth of 1330 m from Okinawa Trough sediment, and mycosphazine A showed promoting the biofilm formation of bacterium Bacillus amyloliquefaciens with the rate of about 249% at 100 μg·mL −1 . Four new 16-methyl steroids (penicildiones A−D) were isolated from a marine soft coral-derived fungus Penicillium sp. SCSIO41201 collected from the soft coral Sinularia sp. by LIU Yong-Hong et al. along with a known 16-methyl steroid and two knownphenylspirodrimanes (stachybotrylactone B and stachybotrin), and it was the first report for stachybotrylactone B showing significant cytotoxic activities against HL-60, K562, MOLT-4, ACHN, 786-O, and OS-RC-2 cell lines with IC 50 values of 5.23, 4.12, 4.31, 23.55, 7.65, and 10.81 μmol·L −1, respectively. SHE Zhi-Gang et al. isolated three new isocoumarin derivatives ((S)-6,8-dihydroxy-5-(methoxymethyl)-3,7-dimethylisochroman-1-one,(S)-6,8-dihydroxy-3,5,7-tri-methylisochroman-1-one, and (R)-2-chloro-3-(8-hydroxy-6-methoxy-1-oxo-1H-isochromen-3-yl)propyl acetate) from a mangrove endophytic fungus Penicillium sp. YYSJ-3 collected from the stem of the mangrove plant Heritiera littoralis, and (R)-2-chloro-3-(8-hydroxy-6-methoxy-1-oxo-1H-isochro-men-3-yl) propyl acetate showed obvious anti-α -glucosidase activity with IC 50 of 100.6 μmol·L −1, which was more potent than that of the positive control 1-deoxynojirimycin (IC50 141.2 μmol·L −1). Two new caryophyllene-type sesquit-erpenoids (pestathenols A and B) with a 4/6/5 tricyclic ring system and one new α-furanone (pestatheranone A) were isolated from a plant endophytic fungus Pestalotiopsis theae from Camellia sinensis (Theaceae) by LIU Ling et al. And pestathenols A and B showed cytotoxicity against HeLa cell line with IC 50 values of 78.2 and 88.4 μmol·L −1 , respectively. LIU Hong-Wei et al. carried out a chemical investigation on a solid culture of mushroom Panus lecomtei, which led to the isolation of two new meroterpenoids (5-methoxy-3 ′,3′-di-methyl-3H-spiro[benzofuran-2, 2 ′-oxiran]-3-one and 2-((2-carboxypropan-2-yl)oxy)-5-methoxybenzioc acid) and five known meroterpenoids. In addition, 5-methoxy-3′,3′-di-methyl-3H-spiro[benzofuran-2,2′-oxiran]-3-one was the first benzofuran-3(2H)-one meroterpenoid with spiroketal characteristic, and its plausible biosynthetic pathway was proposed based on the isolated compounds.

In the atmosphere of the earth, many gases including nitrogen (N2), oxygen (O2), and carbon dioxide (CO2) naturally exist to support universal lives. Interestingly, in mammals and plants, some gases are produced endogenously and are known to play essential roles in sustaining life’s processes. Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) are such molecules. The trinity of such gaseous molecules is sometimes referred to as gasotransmitters, with some debate. In this issue of Chinese Journal of Natural Medicines (CJNM), we are pleased to publish three comprehensive review articles describing the state of the art of the field and challenges ahead in developing therapies based on these gaseous molecules. In the first paper, MAO YJ et al. discuss NO donating anti-glaucoma drugs. They firstly summarize the therapeutic effects of NO against glaucoma, including reduction of intraocular pressure via both increasing aqueous humor outflow facility and inhibiting aqueous humor production, as well as regulation of eye blood flow and protection for the optic nerve. Then some NO donating molecules, including latanoprostene bunod, which was approved by the US FDA for the treatment of glaucoma in 2017, and other candidate compounds are discussed. They also point out that administration of eye drops of NO-donating drugs limits NO locally in the eyes and avoids systemic side effects, thus enhancing developability of this class of NO donating agents. In the second paper, YANG XX et al.  introduced CO’s evolution from a well-known toxic gas to its establishment as an endogenous signaling molecule and efforts to develop different delivery forms of CO for therapeutic application. As a matter of fact, under normal situations, CO exists in the blood in the hemoglobin bound form (called carboxy hemoglobin (COHb), and the estimated concentration of COHb is about 150 μmol·L −1 , which is far higher than many hormones and nutrients such as epinephrine, insulin, vitamin D and E. In recent clinical trials in kidney delayed graft function, the US FDA approved 14% of COHb as an allowable threshold . All indications are that CO has a high enough safety margin for its development as a therapeutic agent. Several forms of CO delivery including CO gas, metal-based CO-releasing molecules (CO-RMs), organic CO prodrugs, and CO in a solution, among others, are reviewed in detail. In the third paper, ZHENG YQ et al.  focus on prodrug approaches to deliver H 2 S for various applications and mechanistic studies. Many H2S prodrugs triggered by different stimuli including light, pH, esterases, biorthogonal reactions and thiols are discussed. Since carbonyl sulfide (COS) can be hydrolyzed to H2S by carbonic anhydrase (CA) present in mammalian cells, it has been proven to be an important precursor of H2S. Given that S-persulfidation is an important form of sulfur-mediated post-translational modification of protein, the authors also briefly discuss persulfidation chemistry and donors capable of releasing sulfur species for direct persulfidation.

The public health and economic impacts of fatty liver disease have emerged globally and provoked intense interest among patients, regulators and the biotechnology and pharmaceutical industries. In this issue of Chinese Journal of Natural Medicines (CJNM), we are pleased to organize several foundational research papers and one comprehensive review about lipid metabolism.

LIU Hai-Liang et al. reported that the effect of Berbamine (BM) on ethanol-induced hepatic injury in mice and its underlying mechanism. Results were shown that BM significantly inhibited lipopolysaccharide (LPS) or acetate-induced IL-1 and IL-6 mRNA expression in RAW264.7 cells. Hepatic histopathology analysis showed that inflammatory cells infiltration and lipid accumulation were suppressed by 25 and 50 mg·kg−1 BM administration in ethanol-induced hepatic injury mouse model. Meanwhile, BM treatment significantly inhibited serum ALT and AST levels, hepatic triglyceride (TG) and total cholesterol (TC) contents and hepatic lipid accumulation in ethanol-fed mice. Remarkably, the mechanism of action of BM was related to the reduction of ethanol-induced NF-κB and STAT3 and ERK pathway in liver. Thus, this study reports a natural compound BM, which can be applied for the treatment of alcoholic liver diseases. As a potential candidate therapeutic drug, it can inhibit inflammation effectively while exist low toxicity.

Intestinal microbiome is also important in maintaining physiological and metabolic homeostasis [20]. Many kinds of probiotics are related to fatty liver and insulin resistance. YI Hong-Wei and his colleagues reported the protective effects of Bifidobacterium longu (BL) and Selenium-enriched Bifidobacterium longum (SeBL) on alcohol plus high fat diet (HFD) induced mice hepatic injury. They found that SeBL inhibited lipid accumulation in hepatocytes; reduced serum AST and ALT levels; improved dyslipidemia; decreased serum FFAs, TC, TG and LDL-C levels. In addition, SeBL inhibited alcohol plus HFD-induced hepatocyte oxidative stress through decrease in hepatic MDA levels and increase in SOD activity. SeBL also regulated lipid metabolism related genes such as AMPK, PPAR-α and SREBP1. Although BL showed similar protective effect, SeBL was more effective than BL. In summary, SeBL protected mice from alcohol plus HFD-induced hepatic injury in mice because of its inhibitory effect on hepatocellular oxidative stress, lipogenesis and inflammation. Selenium enhanced the protective effect of BL. This research demonstrates that SeBL represents a promising nutritional supplement for alcohol or HFD-induced hepatic injury.

More and more evidences show that metabolism disorder is also an important factor of tumor development. Enhanced glucose metabolism is one of the hallmarks of pancreatic cancer . FU Xiao et al. reported that MUC1, a transmembrane protein, is a global regulator of glucose metabolism and essential for progression of pancreatic cancer. They found that MUC1 knockout (KO) cells uptook less glucose and secreted less lactate with a much lower proliferating rate compared with wild type. As the elevated glucose metabolism is known to facilitate cancer cells to gain chemoresistance, they treated wild type and MUC1 KO cells with gemcitabine and FOLFIRINOX in vitro and in vivo. Their results showed that MUC1 KO significantly sensitized pancreatic cancer cells to chemotherapy. This article suggests that it is effective to increase the chemosensitivity of tumor cells by changing the metabolic status.

Metabolism plays a pivotal role in many processes of biological process. Therefore, in-depth understanding of the metabolic mechanism can help us to control developments of various disease, and find potential drugs.