Morphology and multigene phylogeny reveal four new Xylaria (Xylariales, Xylariaceae) species from karst region in China.

This study presents the identification of four novel Xylaria species, discovered in the karst region of China. The discovery was facilitated by a rigorous analysis that encompassed both morpho-anatomical features and multi-locus phylogenetics utilizing sequences from the ITS, rpb2, and TUB2 loci. The newly identified species are designated as Xylariajichuanii sp. nov., X.nanningensis sp. nov., X.orientalis sp. nov., and X.taiyangheensis sp. nov. The distinction of these species from their known counterparts was verified through comparison of morphological features and phylogenetic analysis. The study further provides detailed morphological descriptions, illustrative representations, and a phylogenetic tree, all of which contribute to the taxonomic positioning of these novel species.

 Stromatolinea, a new diatrypaceous fungal genus (Ascomycota, Sordariomycetes, Xylariales, Diatrypaceae) from China.

Molecular phylogeny and morphological characteristics of collections of diatrypaceous fungi from Guizhou Province, China, lead to the establishment of a new genus, Stromatolinea, and the identification of four new species and two new combinations. The taxa were found growing on the dead culms of Phyllostachys bamboo. The new genus is distinguished by its well-developed, discrete linear stromata with yellow interior tissue and allantoid subhyaline ascospores. The newly described species are Stromatolineagrisea, S.guizhouensis, S.hydei, and S.xishuiensis. Additionally, two new combinations, Stromatolinealinearis and S.phaselina, are proposed based on comparative analysis and morphology. Phylogenetic analyses were conducted using ITS and TUB2 sequences. The study includes comprehensive morphological descriptions, illustrations, and a phylogenetic tree depicting the placement of the new taxa.

Development and validation of PAMPA-BBB QSAR model to predict brain penetration potential of novel drug candidates.

Efficiently circumventing the blood-brain barrier (BBB) poses a major hurdle in the development of drugs that target the central nervous system. Although there are several methods to determine BBB permeability of small molecules, the Parallel Artificial Membrane Permeability Assay (PAMPA) is one of the most common assays in drug discovery due to its robust and high-throughput nature. Drug discovery is a long and costly venture, thus, any advances to streamline this process are beneficial. In this study, ∼2,000 compounds from over 60 NCATS projects were screened in the PAMPA-BBB assay to develop a quantitative structure-activity relationship model to predict BBB permeability of small molecules. After analyzing both state-of-the-art and latest machine learning methods, we found that random forest based on RDKit descriptors as additional features provided the best training balanced accuracy (0.70 ± 0.015) and a message-passing variant of graph convolutional neural network that uses RDKit descriptors provided the highest balanced accuracy (0.72) on a prospective validation set. Finally, we correlated in vitro PAMPA-BBB data with in vivo brain permeation data in rodents to observe a categorical correlation of 77%, suggesting that models developed using data from PAMPA-BBB can forecast in vivo brain permeability. Given that majority of prior research has relied on in vitro or in vivo data for assessing BBB permeability, our model, developed using the largest PAMPA-BBB dataset to date, offers an orthogonal means to estimate BBB permeability of small molecules. We deposited a subset of our data into PubChem bioassay database (AID: 1845228) and deployed the best performing model on the NCATS Open Data ADME portal (https://opendata.ncats.nih.gov/adme/). These initiatives were undertaken with the aim of providing valuable resources for the drug discovery community.

[miR-99b-5p inhibits the activation of NLRP3 inflammasome to alleviate the neurotoxicity induced by paclitaxel chemotherapy].

OBJECTIVE: To study the effects of miR-99b-5p (non-coding RNA) in alleviating pathological neuropathic pain after paclitaxel chemotherapy by inhibiting NLRP3 inflammatory vesicle activation and the effects on neuronal cells pyrosis and apoptosis. METHODS: SD rats were randomly divided into blank group, model group, agomiR-99b-5P treatment group, and agomiR-NC group, 6 rats in each group. The blank group received saline treatment as a control, the model group established a pain model induced by paclitaxel, and the rats in agomiR-99b-5p treatment group and agomiR-NC group were treated with agomiR-99b-5p and agomiR-NC injections, respectively. The expressions of miR-99b-5p in the blank group, model group, and treatment group were detected by RT-qPCR. The mechanical foot retraction threshold (MWT) of the blank group, model group, and treatment group were detected. TUNEL was used to detect the apoptosis of spinal dorsal horn cells. The levels of ROS, MDA, and SOD were detected by ELISA kits. The protein expressions of NLRP3, caspase-1, and IL-1ß were detected by immunofluorescence staining. RESULTS: Compared with the model group, the expression level of miR-99b-5p and the MWT were increased significantly in agomiR-99b-5p treatment group (P＜0.05), the apoptosis of dorsal horn cells was inhibited (P＜0.05), the level of antioxidant stress was increased in rats, the levels of ROS and MDA were decreased (P＜0.05), while the level of SOD was increased (P＜0.05). Immunofluorescence showed that the expressions of NLRP3, caspase-1, and IL-1ß were inhibited by miR-99b-5p. CONCLUSION: miR-99b-5p can alleviate the apoptosis and pyroptosis of neurons after paclitaxel chemotherapy by inhibiting the activation of NLRP3 and improving oxidative stress in vivo.

Trigonelline Extends the Lifespan of C. Elegans and Delays the Progression of Age-Related Diseases by Activating AMPK, DAF-16, and HSF-1.

Trigonelline is the main alkaloid with bioactivity presented in fenugreek, which was used in traditional medicine in Asian countries for centuries. It is reported that trigonelline has anti-inflammatory, anti-oxidant, and anti-pathogenic effects. We are wondering whether trigonelline have anti-aging effect. We found that 50 µM of trigonelline had the best anti-aging activity and could prolong the lifespan of Caenorhabditis elegans (C. elegans) by about 17.9%. Trigonelline can enhance the oxidative, heat, and pathogenic stress resistance of C. elegans. Trigonelline could also delay the development of neurodegenerative diseases, such as AD, PD, and HD, in models of C. elegans. Trigonelline could not prolong the lifespan of long-lived worms with loss-of-function mutations in genes regulating energy and nutrition, such as clk-1, isp-1, eat-2, and rsks-1. Trigonelline requires daf-16, hsf-1, and aak-2 to extend the lifespan of C. elegans. Trigonelline can also up-regulate the expression of daf-16 and hsf-1 targeted downstream genes, such as sod-3, gst-4, hsp-16.1, and hsp-12.6. Our results can be the basis for developing trigonelline-rich products with health benefits, as well as for further research on the pharmacological usage of trigonelline.