High-altitude hypoxia exposure inhibits erythrophagocytosis by inducing macrophage ferroptosis in the spleen.

High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic conditions. The exact mechanisms behind HAPC are not fully understood. We utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O2 to investigate these mechanisms. Our findings indicate that HH significantly boosts erythropoiesis, leading to erythrocytosis and splenic changes, including initial contraction to splenomegaly over 14 days. A notable decrease in red pulp macrophages (RPMs) in the spleen, essential for RBCs processing, was observed, correlating with increased iron release and signs of ferroptosis. Prolonged exposure to hypoxia further exacerbated these effects, mirrored in human peripheral blood mononuclear cells. Single-cell sequencing showed a marked reduction in macrophage populations, affecting the spleen's ability to clear RBCs and contributing to splenomegaly. Our findings suggest splenic ferroptosis contributes to decreased RPMs, affecting erythrophagocytosis and potentially fostering continuous RBCs production in HAPC. These insights could guide the development of targeted therapies for HAPC, emphasizing the importance of splenic macrophages in disease pathology.

The effect of magnetic coupling along the magnetic axis on slow magnetic relaxation in DyIII complexes with D5h configuration based on an aggregation-induced-emission-active ligand.

The adjustment of crystal symmetry and intramolecular magnetic coupling is of great importance for the construction of high-performance single-molecule magnets. By using an aggregation-induced-emission-active pyridine-carbohydrazone-based Schiff base ligand and phosphine oxides, four dinuclear and one one-dimensional DyIII-based complexes, [Dy2(TPE-pc)2(Bu3PO)2Cl2]·2CH3CN·2H2O (1), [Dy2(TPE-pc)2(Cy3PO)2Cl2] (2), [Dy2(TPE-pc)2(MePA)2Cl2]·2CH3OH (3), [Dy2(TPE-pc)2(Ph3PO)2Cl2]2 (4) and [Dy2(TPE-pc)2(DPPO)Cl2]n (5) (H2TPE-pc = (E)-N'-(2-hydroxy-5-(1,2,2-triphenylvinyl)benzylidene)picolinohydrazide, MePA = N-phenyl-N',N''-bis(morpholinyl) phosphoric triamide, DPPO = piperazine-1,4-diylbis(diphenyl phosphine oxide)), were isolated. All complexes are made up of an enol oxygen-bridged Dy2 unit, where DyIII ions possess a pentagonal bipyramidal geometry with pseudo D5h symmetry. Magnetic measurements reveal that intramolecular DyIII-DyIII couplings are ferromagnetic and all complexes display a significant slow magnetic relaxation phenomenon below 30 K under a zero dc field. Ab initio calculations indicate that the anisotropic magnetic axes of all DyIII ions are approximately perpendicular to the higher-order symmetric axes in all complexes, and that DyIII-DyIII magnetic couplings along the magnetic axes effectively suppress the ground state quantum tunneling effect of magnetization and promote the occurrence of slow magnetic relaxation. Raman relaxation prevails in all complexes. In addition, the H2TPE-pc ligand shows an aggregation-induced emission (AIE) effect; however, all complexes exhibit an aggregation-caused quenching (ACQ) phenomenon.

Phytoecdysteroids from Dianthus superbus L.: Structures and anti-neuroinflammatory evaluation.

Six undescribed C27-phytoecdysteroid derivatives, named superecdysones A-F, and ten known analogs were extracted from the whole plant of Dianthus superbus L. Their structures were identified by extensive spectroscopy, mass spectrometric methods, chemical transformations, chiral HPLC analysis, and the single-crystal X-ray diffraction analysis. Superecdysones A and B possess a tetrahydrofuran ring in the side chain and superecdysones C-E are rare phytoecdysones containing a (R)-lactic acid moiety, whereas superecdysone F is an uncommon B-ring-modified ecdysone. Notably, based on the variable temperature (from 333 K to 253 K) NMR experiments of superecdysone C, the missing carbon signals were visible at 253 K and assigned. The neuroinflammatory bioassay of all compounds were evaluated, and 22-acetyl-2-deoxyecdysone, 2-deoxy-20-hydroxyecdysone, 20-hydroxyecdysone, ecdysterone-22-O-benzoate, 20-hydroxyecdysone-20,22-O-R-ethylidene, and acetonide derivative 20-hydroxyecdysterone-20, 22-acetonide significantly suppressed the LPS-induced nitric oxide generation in microglia cells (BV-2), with IC50 values ranging from 6.9 to 23.0 µM. Structure-activity relationships were also discussed. Molecular docking simulations of the active compounds confirmed the possible mechanism of action against neuroinflammations. Furthermore, none compounds showed cytotoxicity against HepG2 and MCF-7. It is the first report about the occurrence and anti-neuroinflammatory activity of the phytoecdysteroids in the genus Dianthus. Our findings demonstrated that ecdysteroids may be used as potential anti-inflammatory drugs.

Secondary Metabolites of Bird's Nest Fungi: Chemical Structures and Biological Activities.

Bird's nest fungi, a general term for species in the family Nidulariaceae, are named for their fruiting bodies that resemble bird's nests. Two of their members, Cyathus stercoreus (Schw.) de Toni. and Cyathus striatus Will. ex Pers., are known as medicinal fungi in Chinese medicine. Bird's nest fungi produce a variety of secondary metabolites that provide natural materials for screening and developing medicinal compounds. This review presents a systematic summary of the literature on the secondary metabolites of bird's nest fungi up to January 2023, including 185 compounds, mainly cyathane diterpenoids, with prominently characterized antimicrobial and antineurodegenerative activities. Our work aims to advance our understanding of bird's nest fungi and support studies on their natural product chemistry, pharmacology, and biosynthesis of secondary metabolites.

The optimal timing of frozen-thawed embryo transfer: delayed or not delayed? A systematic review and meta-analysis.

Background: The use of frozen embryo transfer (FET) has grown exponentially over the past few years. However, in clinical practice, there are no specific criteria as to whether a delay of at least one menstrual cycle is required for an FET after a failed fresh ET or a freeze-all cycle. Objective: Through the effects on live birth rate (LBR), clinical pregnancy rate (CPR) and pregnancy loss rate (PLR), to determine whether FET requires a delay of at least one menstrual cycle after fresh ET failure or a freeze-all cycle. Methods: The search was conducted through PubMed, Web of Science, CNKI, and Wanfang databases for terms related to FET timing as of April 2023. There are no restrictions on the year of publication or follow-up time. Women aged 20 to 46 with any indication for in vitro fertilization and embryo transfer (IVF-ET) treatment are eligible for inclusion. Oocyte donation studies are excluded. Except for the case report, study protocol, and abstract, all original studies are included. Results: In 4,124 search results, 19 studies were included in the review. The meta-analysis includes studies on the adjusted odds ratio (OR) and 95% confidence interval (CI) of reported live birth rate (LBR), clinical pregnancy rate (CPR), and pregnancy loss rate (PLR), 17 studies were retrospective cohort study, and 2 studies were randomized controlled trial, a total of 6,917 immediate FET cycles and 16,105 delayed FET cycles were involved. In this meta-analysis, the combined OR of LBR was [OR = 1.09, 95% CI (0.93­1.28)], the combined OR of CPR was [OR = 1.05, 95% CI (0.92­1.20)], and the combined OR of PLR was (OR = 0.96, 95% CI 0.75­1.22). There was no statistical significance between the two groups. Conclusion: Overall, delaying FET by at least one menstrual cycle has no advantage in LBR, CPR, or PLR. So, flexible scheduling of FETs is available to both doctors and patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020161648.

Neuroprotective effects of a new triterpenoid from edible mushroom on oxidative stress and apoptosis through the BDNF/TrkB/ERK/CREB and Nrf2 signaling pathway in vitro and in vivo.

Inonotus obliquus (Fr.) Pilat is an edible mushroom which is used to produce tea and syrup due to its medicinal properties. In this study, 10 secondary metabolites (1-10), including a new lanostane triterpenoid named 2α-hydroxy-inotodiol (2α-HI, 1), were identified from the edible mushroom I. obliquus through high-resolution electrospray ionization mass spectrometry (HRESIMS) and nuclear magnetic resonance spectroscopy (NMR) data analysis. The neuroprotective function of all steroidal metabolites in H2O2-induced SH-SY5Y cells was investigated. The results showed that 2α-HI exhibited the most remarkable neuroprotective activity. In the meantime, 2α-HI significantly ameliorated oxidative stress damage, reactive oxygen species (ROS) accumulation and mitochondrial damage induced by H2O2 in SH-SY5Y cells. The Nrf2 siRNA and inhibitors transfected the SH-SY5Y cells, indicating the Nrf2 and BDNF/TrkB/ERK/CREB pathway mediated the neuroprotective effects of 2α-HI against the H2O2-stimulated oxidative stress and apoptosis. Moreover, the neuroprotection of 2α-HI was preliminarily verified in zebrafish. In conclusion, this research was the first to confirm that 2α-HI could effectively protect SH-SY5Y cells against H2O2-induced oxidative stress and apoptosis via the Nrf2 and BDNF/TrkB/ERK/CREB signaling pathway. Hence, this mushroom could be a potential dietary supplement to ameliorate neurodegenerative diseases.

Impact of intracytoplasmic sperm injection in women with non-male factor infertility: A systematic review and meta-analysis.

Objective: The purpose of this study is to determine whether intracytoplasmic sperm injection (ICSI) is beneficial in patients with non-male factor infertility. Methods: This systematic review and meta-analysis included articles from inception to May 2022. Published studies of non-male factor infertile women undergoing ICSI or in vitro fertilization (IVF) included in PubMed, Embase, web of science, Wanfang Database, and CNKI were searched by computer, without language restrictions. A random-effect model was applied to calculate the risk ratios (RRs) and their 95% confidence intervals (CIs). Letters, case reports, and review articles including meta-analyses and expert opinions were excluded. The primary endpoints were laboratory outcomes and pregnancy outcomes. The Secondary endpoints were neonatal outcomes. Results: Six randomized controlled studies and 20 retrospective cohort studies met the inclusion criteria. In meta-analytic forest plots, compared with IVF, those who received ICSI treatment were not different in fertilization rate (RR = 0.99, 95% CI [0.90-1.09], P = 0.88), total fertilization failure rate (RR = 1.30, 95% CI [1.17-1.45], P < 0.00001), and good quality embryo rate (RR = 0.94, 95% CI [ 0.86-1.02], P = 0.15), clinical pregnancy rate (RR = 0.84, 95% CI [0.70-1.01], P = 0.06), live birth rate (RR = 0.89, 95% CI [0.77-1.03], P = 0.13), miscarriage rate (RR = 1.06, 95% CI [0.78-1.43], P = 0.71), preterm neonatal delivery rate (RR = 0.92, 95% CI [0.67-1.26], P = 0.61), and low neonatal weight rate (RR = 1.13, 95% CI [0.80-1.61], P = 0.48). However, the implantation rate of IVF was better than ICSI (RR = 0.77, 95% CI [0.64-0.93], P = 0.005). In the subgroup analysis of the live birth rate of fresh embryo transfer, IVF performed in those ≥35 years had a higher live birth rate (RR = 0.82, 95% CI [0.78-0.83], P < 0.001). Conclusion: The findings of this study indicate that ICSI is not superior to IVF in the treatment of infertility related to non-male factors. In order to confirm this result, more high-quality clinical studies are needed.

Triterpenoids and meroterpenoids from the edible Ganoderma resinaceum and their potential anti-inflammatory, antioxidant and anti-apoptosis activities.

Ganoderma resinaceum, as a traditional edible mushroom, has been widely reported to improve neurodegenerative diseases characterized by oxidative stress and inflammation. In this study, five new terpenoids, including four lanostane triterpenoids, named ganoresinoid A-D (1-4) and one meroterpenoid, named ganoresinoid E (5), along with 27 known compounds (6-32), were isolated from the fruiting bodies of edible mushroom G. resinaceum. These structures were identified by NMR, HRESIMS data analysis. All metabolites were evaluated for anti-inflammatory, antioxidative and anti-apoptosis activities. Among them, ganoresinoid A showed notably restrained nitric oxide (NO), IL-1ß, IL-6 and TNF-α levels in LPS-activated BV-2 microglial cells via suppressing TLR-4/ NF-κB and MAPK signaling pathway. Simultaneously, ganoresinoid A remarkably alleviated LPS-induced apoptosis by means of the decrease of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). In addition, ganoresinoid A demonstrated antioxidant effects in H2O2-induced SH-SY5Y cells by activating the Akt/GSK-3ß/Nrf2 signaling pathway. Taken together, these results may provide a stronger theoretical basis for ganoresinoid A from G. resinaceum as nutrition intervention to alleviate neurodegenerative diseases.

Structures of ganorbifates C-I, seven previously undescribed lanostanoids from the mushroom Ganoderma orbiforme, and insights of computed biosynthesis with DFT.

Ganorbifates C-I, seven undescribed biosynthetically related polyoxygenated 3,4-seco-27-norlanostanoid congeners, were isolated from the edible mushroom, Ganoderma orbiforme. Ganorbifate C features a unique cyclobutene ring constructed at C19/C11, and both D and E incorporate an unusual cyclopropane ring formed by C-19/C-9 linkage. Their structures, including the absolute configurations, were determined by spectroscopic methods and ECD calculations. The proposed Norrish-Yang cyclization-based key biosynthetic pathway for ganorbifates C-E is revealed by density functional theory (DFT) calculations. The computational studies uncover the formation of both cyclobutene and cyclopropane rings in the isolates and the stereoselectivity centers of these steps are consistent with those in the natural products. All compounds exhibited NO generation inhibition in LPS-induced BV-2 microglial cells, among them ganorbifate C was the most promising one with the IC50 values of 4.37 µM.

Ganoderterpene A, a New Triterpenoid from Ganoderma lucidum, Attenuates LPS-Induced Inflammation and Apoptosis via Suppressing MAPK and TLR-4/NF-κB Pathways in BV-2 Cells.

An investigation of the fruiting bodies of edible mushroom Ganoderma lucidum produced 13 steroids, containing one new lanostane-type triterpene compound, named ganoderterpene A (1). Nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data were used to deduce these structures. All the isolates were evaluated for their ability to suppress NO generation in BV-2 microglial cells treated with lipopolysaccharide (LPS) and exhibited moderate to strong inhibition effects, with IC50 values in the range 7.15-36.88 µM. Among the tested compounds, compound 1 exhibited the most marked activity with an IC50 value of 7.15 µM, and the structure-activity relationships were studied. This study showed that compound 1 significantly suppressed the activation of MAPK and TLR-4/NF-κB signaling pathways, as evidenced by an immunofluorescence assay and a molecular docking experiment. Furthermore, compound 1 effectively improved the LPS-induced mitochondrial membrane potential and apoptosis. These findings suggest that ganoderterpene A could exert protective effects in microglial cells from apoptosis by restraining the inflammatory response. Hence, G. lucidum could be used as a novel preventative agent for neurodegenerative disorders.

Alkylated Salicylaldehydes and Prenylated Indole Alkaloids from the Endolichenic Fungus Aspergillus chevalieri and Their Bioactivities.

Sixteen metabolites, including seven C7-alkylated salicylaldehyde derivatives (1-7) and nine prenylated indole alkaloids (8-16), three of which are new, namely, asperglaucins A and B (1 and 2) and neoechinulin F (8), were separated from the endolichenic fungus Aspergillus chevalieri SQ-8. Asperglaucin A (1) represents an unusual phthalide-like derivative with a benzo[c]thiophen-1(3H)-one scaffold. All compounds were assessed in vitro for antibacterial, antineuroinflammatory, and antioxidant activities. Notably, asperglaucins A and B exhibited potent antibacterial activities against two plant pathogens Pseudomonas syringae pv actinidae (Psa) and Bacillus cereus, with an MIC value of 6.25 µM; further SEM analyses illustrated that the possible bacteriostatic mechanisms for compounds 1 and 2 were to alter the external structure of B. cereus and Psa, and to cause the rupture or deformation of the cell membranes, respectively, and the results suggest that compounds 1 and 2 may serve as potential promising candidates for lead compounds of agrochemical bactericides. Furthermore, compounds 6 and 10 significantly inhibited nitric oxide production with an IC50 value of ca. 12 µM, and the possible anti-inflammatory mechanisms involved were also studied by molecular docking. Finally, the tested phenolics 3-5 showed significant antioxidative effects. Thus, strain SQ-8 represents a novel resource of these bioactive metabolites to be utilized.

Structurally Diverse Sesquiterpenoids with Anti-neuroinflammatory Activity from the Endolichenic Fungus Cryptomarasmius aucubae.

Two new sterpurane sesquiterpenoids named sterpurol D (1) and sterpurol E (2), and one skeletally new sesquiterpene, cryptomaraone (3), bearing a 5,6-fused bicyclic ring system, along with five known ones, sterpurol A (4), sterpurol B (5), paneolilludinic Acid (6), murolane-2α, 9ß-diol-3-ene (7) and (-)-10,11-dihydroxyfarnesol (8) were isolated from an endolichenic fungus Cryptomarasmius aucubae. The structures of the new compounds were elucidated by analysis of NMR spectroscopic spectra and HRESIMS data. The absolute configurations of 1 and 2 were established by spectroscopic data analysis and comparison of specific optical rotation, as well as the biosynthetic consideration. Additionally, compounds 1, 2, 4-6, and 8 showed significant nitric oxide (NO) production inhibition in Lipopolysaccharide (LPS)-induced BV-2 microglial cells with the IC50 values ranging from 9.06 to 14.81 µM.

DL-3-n-butylphthalide improved physical and learning and memory performance of rodents exposed to acute and chronic hypobaric hypoxia.

BACKGROUND: Studies have revealed the protective effect of DL-3-n-butylphthalide (NBP) against diseases associated with ischemic hypoxia. However, the role of NBP in animals with hypobaric hypoxia has not been elucidated. This study investigated the effects of NBP on rodents with acute and chronic hypobaric hypoxia. METHODS: Sprague-Dwaley rats and Kunming mice administered with NBP (0, 60, 120, and 240 mg/kg for rats and 0, 90, 180, and 360 mg/kg for mice) were placed in a hypobaric hypoxia chamber at 10,000 m and the survival percentages at 30 min were determined. Then, the time and distance to exhaustion of drug-treated rodents were evaluated during treadmill running and motor-driven wheel-track treadmill experiments, conducted at 5800 m for 3 days or 20 days, to evaluate changes in physical functions. The frequency of active escapes and duration of active escapes were also determined for rats in a shuttle-box experiment, conducted at 5800 m for 6 days or 27 days, to evaluate changes in learning and memory function. ATP levels were measured in the gastrocnemius muscle and malonaldehyde (MDA), superoxide dismutase (SOD), hydrogen peroxide (H2O2), glutathione peroxidase (GSH-Px), and lactate were detected in sera of rats, and routine blood tests were also performed. RESULTS: Survival analysis at 10,000 m indicated NBP could improve hypoxia tolerance ability. The time and distance to exhaustion for mice (NBP, 90 mg/kg) and time to exhaustion for rats (NBP, 120 and 240 mg/kg) significantly increased under conditions of acute hypoxia compared with control group. NBP treatment also significantly increased the time to exhaustion for rats when exposed to chronic hypoxia. Moreover, 240 mg/kg NBP significantly increased the frequency of active escapes under conditions of acute hypoxia. Furthermore, the levels of MDA and H2O2 decreased but those of SOD and GSH-Px in the sera of rats increased under conditions of acute and chronic hypoxia. Additionally, ATP levels in the gastrocnemius muscle significantly increased, while lactate levels in sera significantly decreased. CONCLUSION: NBP improved physical and learning and memory functions in rodents exposed to acute or chronic hypobaric hypoxia by increasing their anti-oxidative capacity and energy supply.

Author Correction: Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys.

Following the publication of our paper (Zhang et al., 2020), it has come to our attention that we erroneously listed two funding sources unrelated to this study in the "ACKNOWLEDGEMENTS" section. Hereby, we wish to update the "ACKNOWLEDGEMENTS" section as a correction.

Anti-neuroinflammatory polyoxygenated lanostanoids from Chaga mushroom Inonotus obliquus.

Chaga mushroom, Inonotus obliquus, was used as food and nutrient food and traditional herbs in Russia, China and Japan, with anti-inflammatory and anticancer activities. Chemical investigations of the fruiting bodies of Chaga were carried to uncover the bioactive metabolites. As a result, seven undescribed lanostane-type triterpenoids, namely inonotusols H-N, were isolated, and all lanostanoids remarkably inhibited NO production in lipopolysaccharide-stimulated BV-2 microglial cells. Of these, inonotusols I and L presented the most potent inhibitory effects on inducible nitric oxide synthase (iNOS) and NO production without any significant cytotoxicity. Molecular docking studies confirmed the capacity of inonotusols I and L to interact with iNOS protein. Structure-activity relationships were also discussed. These results indicated that the potential anti-inflammatory effects of inonotusols I and L in microglial BV-2 cells may be imparted through suppression of iNOS. These results may support the use of I. obliquus for food and medicinal application.

Trinor- and tetranor-eremophilane sesquiterpenoids with anti-neuroinflammatory activity from cultures of the fungus Septoria rudbeckiae.

Fifteen eremophilane sesquiterpenoids, including nine undescribed congeners, septeremophilane A-H, and chaetopenoid G, together with four conjugated unsaturated polyketide fatty acids, including an undescribed derivative, were isolated from cultures of the fungus Septoria rudbeckiae, a plant pathogenic fungus isolated from the halophyte Karelinia caspia. Septeremophilane A represents an unprecedented tetranor-eremophilane sesquiterpenoid with an α,ß-unsaturated δ-lactone unit bearing a hemiacetal group, while septeremophilane B-H possesses a trinor-eremophilane skeleton. Their structures and absolute configurations were established based on spectroscopic data (NMR and HRESIMS), quantum chemical calculations and electronic circular dichroism (ECD) experiments. All metabolites were tested for nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-activated BV-2 microglial cells, while dendryphiellin D, septeremophilane D, and septeremophilane E were found to display significant inhibition, with IC50 values of 11.9 ± 1.0, 8.5 ± 0.1, and 6.0 ± 0.2 µM, respectively.

Asymmetric synthesis of 9-alkyl tetrahydroxanthenones via tandem asymmetric Michael/cyclization promoted by chiral phosphoric acid.

A tandem asymmetric Michael-addition/cyclization of cyclic 1,3-dicarbonyl compounds to ß,γ-unsaturated α-ketoesters catalyzed by chiral phosphoric acid is presented. This protocol provides a facile approach for the construction of enantioenriched 9-alkyl tetrahydroxanthenones, an ubiquitous framework found in a number of natural products and pharmaceutical molecules, in high yields with good to high enantioselectivities.

Highly enantioselective addition of aliphatic aldehydes to 2-hydroxychalcone enabled by cooperative organocatalysts.

Herein, we developed an enantioselective addition of aliphatic aldehydes to 2-hydroxychalcone promoted by cooperative organocatalysts, giving access to hybrid flavonoids in excellent enantioselectivities. This reaction took advantage of cycloisomerization of 2-hydroxychalcone to form a transient flavylium under the irradiation of 24 W CFL, which was trapped by the in situ generated chiral enamine intermediate. The synergistic action of chiral phosphoric acid secured the excellent outcome of this reaction by ion-pairing with the transient flavylium.

Visible-light driven synthesis of polycyclic benzo[d][1,3]oxazocine from 2-aminochalcone.

Herein, we report a tandem cycloisomerization/nucleophilic addition/cyclization of 2-amino chalcone with bifunctional nucleophiles driven by visible light. This cascade process is realized by the irradiation of a blue LED at room temperature, which provides a concise route to structurally diverse benzo[d][1,3]oxazocine scaffolds. Mechanistic studies show that the reaction is initiated with the E to Z isomerization of a C-C double bond upon the irradiation of visible light, followed by cyclization/rearomatization to generate a transient quinolinium intermediate, which is trapped by the nucleophile and cyclized to produce the polycyclic benzo[d][1,3]oxazocine.

Microbial Transformations of Two Beyerane-Type Diterpenes by Cunninghamella echinulata.

Microbial transformations of two tetracyclic beyerane-type diterpenes, ent-16ß-oxobeyeran-19-oic acid (1) and its chemical reduction product, ent-16ß-hydroxybeyeran-19-oic acid (2), by the filamentous fungus Cunninghamella echinulata ATCC 8688a yielded eight metabolites (3-10). Incubation of the substrate 2 with C. echinulata afforded three new hydroxylated ones (3-5) along with two known ones (6-7), while incubation of 1 gave three known ones (8-10). The new compounds were characterized by 1D and 2D NMR as well as HRESIMS analysis, and the stereostructures of 3 and 4 were confirmed by X-ray crystallography. The bioreactions were involved not only in stereoselective incorporation of hydroxyl groups at inert positions C-7, -9, -12, and -14 of the two beyerane diterpenes but also in glucosidation at C-19 of 2. This is the first report on the biotransformation of the diterpenes by using C. echinulata. All compounds were assayed for their α-glucosidase inhibitory, neurotrophic, anti-inflammatory, and phytotoxic activity, and only in neurotrophic assay compounds, 2 and 9 were found to display nerve growth factor-mediated neurite-outgrowth promoting effects in PC12 cells; the others were inactive.