Ependymal polarity defects coupled with disorganized ciliary beating drive abnormal cerebrospinal fluid flow and spine curvature in zebrafish.

Idiopathic scoliosis (IS) is the most common spinal deformity diagnosed in childhood or early adolescence, while the underlying pathogenesis of this serious condition remains largely unknown. Here, we report zebrafish ccdc57 mutants exhibiting scoliosis during late development, similar to that observed in human adolescent idiopathic scoliosis (AIS). Zebrafish ccdc57 mutants developed hydrocephalus due to cerebrospinal fluid (CSF) flow defects caused by uncoordinated cilia beating in ependymal cells. Mechanistically, Ccdc57 localizes to ciliary basal bodies and controls the planar polarity of ependymal cells through regulating the organization of microtubule networks and proper positioning of basal bodies. Interestingly, ependymal cell polarity defects were first observed in ccdc57 mutants at approximately 17 days postfertilization, the same time when scoliosis became apparent and prior to multiciliated ependymal cell maturation. We further showed that mutant spinal cord exhibited altered expression pattern of the Urotensin neuropeptides, in consistent with the curvature of the spine. Strikingly, human IS patients also displayed abnormal Urotensin signaling in paraspinal muscles. Altogether, our data suggest that ependymal polarity defects are one of the earliest sign of scoliosis in zebrafish and disclose the essential and conserved roles of Urotensin signaling during scoliosis progression.

Polyketides with Anti-Inflammatory Activity from Trichoderma koningiopsis, a Rhizosphere Fungus from the Medicinal Plant Polygonum paleaceum.

Twelve new fungal polyketides, koningiopisins I-P (1-8) and trichoketides C-F (9-12), together with six known congeners (13-18), were isolated from Trichoderma koningiopsis, a rhizosphere fungus obtained from the medicinal plant Polygonum paleaceum. Their structures and absolute configurations were established by spectroscopic analysis, single-crystal X-ray diffraction, the modified Mosher's method, chemical derivatization, the octant rule, and 13C NMR and ECD calculations. Compounds 1-5 are tricyclic polyketides possessing an octahydrochromene framework with a 6,8-dioxabicyclo[3.2.1]octane core. Compounds 7 and 8 contain a unique ketone carbonyl group at C-7 and differ from other members of this group of compounds with the ketone carbonyl group at C-1. Compounds 1, 2, and 13 showed inhibitory activity on LPS-induced BV-2 cells on NO production with IC50 values of 14 ± 1, 3.0 ± 0.5, and 8.9 ± 2.7 µM, respectively.

Libertellenone C attenuates oxidative stress and neuroinflammation with the capacity of NLRP3 inhibition.

Neurodegenerative diseases (NDs) are common chronic diseases arising from progressive damage to the nervous system. Here, in-house natural product database screening revealed that libertellenone C (LC) obtained from the fermentation products of Arthrinium arundinis separated from the gut of a centipede collected in our Tongji campus, showed a remarkable neuroprotective effect. Further investigation was conducted to clarify the specific mechanism. LC dose-dependently reversed glutamate-induced decreased viability, accumulated reactive oxygen species, mitochondrial membrane potential loss, and apoptosis in SH-SY5Y cells. Network pharmacology analysis predicted that the targets of LC were most likely directly related to oxidative stress and the regulation of inflammatory factor-associated signaling pathways. Further study demonstrated that LC attenuated nitrite, TNF-α, and IL-1ß production and decreased inducible nitric oxide synthase and cyclooxygenase expression in lipopolysaccharide-induced BV-2 cells. LC could directly inhibit NLRP3 inflammasome activation by decreasing the expression levels of NLRP3, ASC, cleaved Caspase-1, and NF-κB p65. Our results provide a new understanding of how LC inhibits the NLRP3 inflammasome in microglia, providing neuroprotection. These findings might guide the development of effective LC-based therapeutic strategies for NDs.

Spirohypertones A and B as potent antipsoriatics: Tumor necrosis factor-α inhibitors with unprecedented chemical architectures.

Tumor necrosis factor-α (TNF-α) is a promising target for inflammatory and autoimmune diseases. Spirohypertones A (1) and B (2), two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons, were isolated from Hypericum patulum. The structures of 1 and 2 were confirmed through comprehensive spectroscopic analysis, single-crystal X-ray diffraction and electronic circular dichroism calculations. Importantly, 2 showed remarkable TNF-α inhibitory activity, which could protect L929 cells from death induced by co-incubation with TNF-α and actinomycin D. It also demonstrated the ability to suppress the inflammatory response in HaCaT cells stimulated with TNF-α. Notably, in an imiquimod-induced psoriasis murine model, 2 restrained symptoms of epidermal hyperplasia associated with psoriasis, presenting anti-inflammatory and antiproliferative effects. This discovery positions 2 as a potent TNF-α inhibitor, providing a promising lead compound for developing an antipsoriatic agent.

Ten ring-B aromatized ergosterols from Aspergillus spectabilis.

Spectasterols F-O (1-10), ten interesting ergosterols with an aromatized B ring, were obtained from Aspergillus spectabilis. Their structures and absolute configurations were determined using a combination of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), nuclear magnetic resonance (NMR) spectroscopy, single-crystal X-ray diffraction analyses, and electronic circular dichroism (ECD) calculations. Structurally, these aromatic ergosterols feature versatile side chains. Notably, compound aromatic ergosterols featured versatile side chains, and compound 4 is an unusual C23 ergosterol characterized by a shorter side chain due to oxidative cleavage between C-23 and C-24. All compounds were evaluated for their neuroprotective activities, with compound 8 showing a dose-dependent ability to reduce apoptosis and protect mitochondrial function in glutamate-induced SH-SY5Y cells.

Morphology and ultrastructure of antennal sensilla of the parasitic wasp Baryscapus dioryctriae (Hymenoptera: Eulophidae).

Baryscapus dioryctriae is an endoparasitic wasp in the pupae of many Pyralidae pests, such as Dioryctria mendacella, Ostrinia furnacalis, and Chilo suppressalis. To provide requisite background for our ongoing research on the mechanisms of host location in B. dioryctriae, the morphology, abundance, distribution, and ultrastructure of the antennal sensilla were investigated using scanning and transmission electron microscopy. The geniculate antennae of B. dioryctriae are composed of scape, pedicel, and flagellum. Eight types of sensilla including Böhm sensilla, chaetica, trichodea, basiconic capitate peg, campaniformia, placodea, coeloconica, and sensilla styloconicum with a long hair were identified on both sexes. Sexual dimorphism exists in the antennae of B. dioryctriae. The number of flagellomere in males is over females, and the subtypes and abundance of sensilla are also different between the sexes. Additionally, the possible functions of distinct sensilla were discussed, which varies from olfaction, contact chemoreceptive, mechanoreception to hygro-/thermoreception, especially, the sensilla trichodea and placodea might be involved in olfactory perception in B. dioryctriae. These results provide an essential basis for further study on chemical communication between B. dioryctriae and their hosts, and contribute to the development of B. dioryctriae becoming an effective biocontrol agent against the pests of agriculture and forestry.

Cilia regulate meiotic recombination in zebrafish.

Meiosis is essential for evolution and genetic diversity in almost all sexual eukaryotic organisms. The mechanisms of meiotic recombination, such as synapsis, have been extensively investigated. However, it is still unclear whether signals from the cytoplasm or even from outside of the cell can regulate the meiosis process. Cilia are microtubule-based structures that protrude from the cell surface and function as signaling hubs to sense extracellular signals. Here, we reported an unexpected and critical role of cilia during meiotic recombination. During gametogenesis of zebrafish, cilia were specifically present in the prophase stages of both primary spermatocytes and primary oocytes. By developing a germ cell-specific CRISPR/Cas9 system, we demonstrated that germ cell-specific depletion of ciliary genes resulted in compromised double-strand break repair, reduced crossover formation, and increased germ cell apoptosis. Our study reveals a previously undiscovered role for cilia during meiosis and suggests that extracellular signals may regulate meiotic recombination via this particular organelle.

Four undescribed ergostane-type steroids from Lasiodiplodia pseudotheobromae and their neuroprotective activity.

Four undescribed ergostane-type steroids, (22E,24R)-4α,5α-epoxyergosta-9α,14ß-dihydroxy-7,22-diene-3,6-dione, (22E,24R)-4α,5α-epoxyergosta-9α,14α-dihydroxy-7,22-diene-3,6-dione, 12α-hydroxyergosta-7,22,24(28)-triene-3-one, and 3ß,12α-dihydroxyergosta-7,24(28)-diene, along with a known congener (22E,24R)-9α,14ß-dihydroxyergosta-4,7,22-triene-3,6-dione, were isolated from the fungus Lasiodiplodia pseudotheobromae. Their structures were elucidated using NMR, HRESIMS, ECD calculation, and X-ray diffraction analyses. (22E,24R)-4α,5α-epoxyergosta-9α,14ß-dihydroxy-7,22-diene-3,6-dione and (22E,24R)-4α,5α-epoxyergosta-9α,14α-dihydroxy-7,22-diene-3,6-dione are a pair of C-14 epimers possessing an unusual epoxy group between C-4 and C-5, which was demonstrated using single-crystal X-ray diffraction analyses. The absolute configurations of 12α-hydroxyergosta-7,22,24(28)-triene-3-one and 3ß,12α-dihydroxyergosta-7,24(28)-diene were determined by ECD calculations. Moreover, 3ß,12α-dihydroxyergosta-7,24(28)-diene exhibited neuroprotective activity in vitro in glutamate-treated SH-SY5Y cell lines.