Design, synthesis and activity evaluation of novel quinazolinone compounds as TRPC5 inhibitors.

The TRPC5 channel plays an important role in regulating various physiological processes, which is related to various human diseases, especially psychiatric and kidney diseases. Although the TRPC5 channel is one of the essential potential target, no drugs against TRPC5 channels have been granted in the market to date. In this study, based on the structure of hit compound ph1, we further synthesied 49 compounds of novel quinazolinone and heterocyclic fusion pyrimidinone derivatives, and their activities were evaluated by electrophysiological assays.

Ellagitannins from Pomegranate Flower with Whitening and Anti-skin Photoaging Effect.

A new depside glucoside rosarugoside E (1), together with four known compounds punicalagin (2), corilagin (3), granatin B (4) and ellagic acid (5) were isolated from the ethanol extract of pomegranate (Punica granatum L.) flower. Their structures were identified based on careful analysis of various spectral data including UV, IR, HR-ESI-MS, 1D and 2D NMR.

Design, synthesis and biological evaluation of Alisol B derivatives for potential treatment of non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD), also known as metabolic dysfunction- associated with fatty liver disease (MAFLD), is one of the most prevalent chronic liver diseases globally. NAFLD is characterized by the accumulation of liver fat unrelated to excessive alcohol consumption. Non-alcoholic steatohepatitis (NASH) is the disease progression of NAFLD and could develop into cirrhosis and hepatocellular carcinoma.

Widely targeted metabolomics analysis reveals dynamic changes in metabolites of 'Hass' avocado during postharvest ripening period.

Avocado (Persea americana Mill) is a climacteric fruit harvested at the green stage that ripens postharvest to become edible. The 'Hass' cultivar, known for its rich, buttery flavor and pear-shaped appearance, was studied for metabolite changes during postharvest ripening using UPLC-MS/MS approach. The 16-day ripening period could be divided into three stages: evolution (days 1-9), edible ripe (days 10-15) and overripe (day 16).

Environment and management jointly shape the spatial patterns of plant species diversity of moist grasslands in the mountains of northeastern Yunnan.

Grasslands account for about a quarter of the Earth's land area and are one of the major terrestrial ecosystems, with significant ecological and economic values. The influence of environmental factors and management types on grassland biodiversity has garnered considerable attention. This study investigated how patterns of species richness are influenced by geographical distance, environmental gradients, and management type in the moist mountain grasslands of northeastern Yunnan, China.

Leaf nitrogen and phosphorus are more sensitive to environmental factors in dicots than in monocots, globally.

Leaf nitrogen (N) and phosphorus (P) levels provide critical strategies for plant adaptions to changing environments. However, it is unclear whether leaf N and P levels of different plant functional groups (e.g.

Skmer approach improves species discrimination in taxonomically problematic genus (Theaceae).

Genome skimming has dramatically extended DNA barcoding from short DNA fragments to next generation barcodes in plants. However, conserved DNA barcoding markers, including complete plastid genome and nuclear ribosomal DNA (nrDNA) sequences, are inadequate for accurate species identification. Skmer, a recently proposed approach that estimates genetic distances among species based on unassembled genome skims, has been proposed to effectively improve species discrimination rate.

The Indo-Burma biodiversity hotspot for ferns: Updated phylogeny, hidden diversity, and biogeography of the java fern genus (Polypodiaceae).

The Indo-Burma Biodiversity Hotspot is renowned for its rich biodiversity, including that of vascular plants. However, the fern diversity and its endemism in this hotspot have not been well understood and so far, the diversity of very few groups of ferns in this region has been explored using combined molecular and morphological approaches. Here, we updated the plastid phylogeny of the Java fern genus with 226 (115% increase of the latest sampling) samples across the distribution range, specifically those of three phylogenetically significant species, , .

Phylogenomics, reticulation, and biogeographical history of Elaeagnaceae.

The angiosperm family Elaeagnaceae comprises three genera and . 100 species distributed mainly in Eurasia and North America. Little family-wide phylogenetic and biogeographic research on Elaeagnaceae has been conducted, limiting the application and preservation of natural genetic resources.

Transferrin Disassociates TCR from CD3 Signaling Apparatus to Promote Metastasis.

Immune recognition and activation by the peptide-laden major histocompatibility complex-T cell receptor (TCR)-CD3 complex is essential for anti-tumor immunity. Tumors may escape immune surveillance by dissembling the complex. Here, we report that transferrin, which is overexpressed in patients with liver metastasis, disassociates TCR from the CD3 signaling apparatus by targeting the constant domain (CD) of T cell receptor α (TCRα), consequently suppresses T cell activation, and inhibits anti-metastatic and anti-tumor immunity.

[Cloning and application in synthetic biology of chalcone synthase gene from Lithocarpus litseifolius].

Lithocarpus litseifolius is rich in the chalcones phloridzin and trilobatin, the biosynthesis pathways of which have not been fully demonstrated. Chalcone synthase(CHS) is the first key rate-limiting enzyme in the biosynthesis of flavonoids in plants. To explore the functions of CHS gene family in chalcone synthesis of L.

Discovery and Total Synthesis of a New Class of Minor Immunosuppressive Plant Sesterterpenoids.

Plant sesterterpenoids are an extremely rare family of natural products that generally possess novel chemical structures and diverse biological activities. Here, we report the discovery of an unprecedented group of minor plant sesterterpenoids, gracilisoids B-E (2-5), which feature two types of highly functionalized bicyclo[3.2.

Tumor cell-derived N-acetyl-aspartyl-glutamate reshapes the tumor microenvironment to facilitate breast cancer metastasis.

Neurotransmitters are increasingly recognized to play important roles in limiting anti-tumor immunity. N-acetyl-aspartyl-glutamate (NAAG) has been extensively studied in neurological disorders; however, its potential role in restricting anti-tumor immunity has not been investigated. Here, we demonstrated that NAAG or its synthetase RimK-like family member B (RIMKLB) significantly disrupted anti-tumor immunity by rewiring the myeloid progenitor differentiation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), which in turn promoted breast cancer growth and metastasis.

Elevated MRPS23 expression facilitates aggressive phenotypes in breast cancer cells.

Mitochondrial ribosomal protein S23 (MRPS23), encoded by a nuclear gene, is a well-known driver of proliferation in cancer. It participates in mitochondrial protein translation, and its expression association has been explored in many types of cancer. However, MRPS23 expression associations are rarely reported in breast cancer (BC).

The Potential Mechanism of Fructus Against Hyperuricemia: An Integration of Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Experiments.

: Fructus (AOF) is a medicinal and edible resource that holds potential to ameliorate hyperuricemia (HUA), yet its mechanism of action warrants further investigation. : We performed network pharmacology, molecular docking, molecular dynamics simulation, and in vitro experiments to investigate the potential action and mechanism of AOF against HUA. : The results indicate that 48 potential anti-HUA targets for 4 components derived from AOF were excavated and predicted through public databases.

Preharvest Treatment with Melatonin Improves Antioxidant and Phenylpropanoid Pathways During Postharvest Storage.

is known for its popularity and robust nutritional value. While fresh fruit is a perishable commodity, it has a short post-harvest life and is susceptible to fungal decay after harvest. Melatonin has been reported to delay the aging and quality decline of various fruits and vegetables after harvest.

Cooperative and Independent Functionality of tmRNA and SmpB in : A Multifunctional Exploration Beyond Ribosome Rescue.

The trans-translation system, mediated by transfer-messenger RNA (tmRNA, encoded by the gene) and its partner protein SmpB, helps to release ribosomes stalled on defective mRNA and targets incomplete protein products for hydrolysis. Knocking out the and genes in various pathogens leads to different phenotypic changes, indicating that they have both cooperative and independent functionalities. This study aimed to clarify the functional relationships between tmRNA and SmpB in a pathogen that poses threats in aquaculture and human health.

Advances in Whole Genome Sequencing: Methods, Tools, and Applications in Population Genomics.

With the rapid advancement of high-throughput sequencing technologies, whole genome sequencing (WGS) has emerged as a crucial tool for studying genetic variation and population structure. Utilizing population genomics tools to analyze resequencing data allows for the effective integration of selection signals with population history, precise estimation of effective population size, historical population trends, and structural insights, along with the identification of specific genetic loci and variations. This paper reviews current whole genome sequencing technologies, detailing primary research methods, relevant software, and their advantages and limitations within population genomics.

Macrocyclic Diterpenoids from Possessing Activity Towards Autophagic Flux.

Euphjatrophanes H-L (-), four new jatrophane-type and one new lathyrane-type diterpenoid, were isolated from , along with eight known diterpenoids (-). Their structures were established on the basis of extensive spectroscopic analysis and X-ray crystallographic experiments. All compounds were subjected to bioactivity evaluation using flow cytometry in autophagic flux assays with HM mCherry-GFP-LC3 cells, the human microglia cells which stably expressed the tandem monomeric mCherry-GFP-tagged LC3.

Elucidating the Underlying Allelopathy Effects of on Using Metabolomics Profiling.

dominates the subalpine meadows in Shangri-La (Southwest China) owing to its potent allelopathic effects. However, the effects underlying its allelopathy require further characterization at the physiological and molecular levels. In this study, the physiological, biochemical, and metabolic mechanisms underlying allelopathy were investigated using as a receptor plant.

A New '-morphotype' Species of Tube-Nosed Bat (Chiroptera: Vespertilionidae: ) from China.

During an examination of various specimens previously collected from different locations at different times, we discovered four specimens that had been collected in October and December 2023 from the Huanglianshan National Nature Reserve, Lvchun, Yunnan, China. Morphologically, these specimens can be distinguished from and other congeneric species based on a combination of body size, hair distribution, fur colour, and skull and teeth characteristics; molecularly, an analysis of Cyt and COI gene sequences showed that these specimens form a monophyletic group with with high posterior probability and bootstrap support values. Furthermore, the genetic distance between our specimens and was greater than the minimum threshold for interspecific differentiation, indicating that they are phylogenetically close but have diverged.

Using Recombinase-Aid Amplification Combined with Argonaute for Rapid Sex Identification in Flamingo ().

Flamingos () are among the oldest birds worldwide and are loved by people for their bright red feathers. In addition, flamingos are sexually monomorphic birds, and distinguishing between males and females is difficult. The polymerase chain reaction (PCR) is widely used for sex identification.

Characterization and comparative transcriptomic analysis of high-altitude adaptation in Tibetan chicken using RNA-sequencing.

Tibetan chicken, an indigenous breed, inhabit highland regions and are crucial livestock for local Tibetans. Compared with other chicken breeds that have migrated from lowlands to highlands, Tibetan chicken exhibits superior physiological adaptations to high-altitude environments. However, the genetic mechanisms underlying these adaptations remain unclear.

From Monocyclization to Pentacyclization: A Versatile Plant Cyclase Produces Diverse Sesterterpenes with Anti-Liver Fibrosis Potential.

A prolific multi-product sesterterpene synthase CbTPS1 is characterized from the medicinal Brassicaceae plant Capsella bursa-pastoris. Twenty different sesterterpenes including 16 undescribed compounds, possessing 10 different mono-/di-/tri-/tetra-/penta-carbocyclic skeletons, including the unique 15-membered macrocyclic and 24(15→14)-abeo-capbuane scaffolds, are isolated and structurally elucidated from engineered Escherichia coli strains expressing CbTPS1. Site-directed mutagenesis assisted by molecular dynamics simulations resulted in the variant L354M with up to 13.

Four Alkaloids from with Antitumor Activity via Disturbing Glutathione Homeostasis.

Alstoschoquinolines A-D (-) representing three unprecedented scaffolds were isolated from the leaves of through direct separation by LC/MS detection. and consisted of a 5/6/5-coupled quinoline architecture containing six consecutive chiral carbons, while and possessed a bridged ring featuring 6/6/6/6 and 6/6/8/6 skeletons, respectively. They might be derived from the corynantheine-type indole alkaloid via sequential oxidation and rearrangement.