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Abstract Sterile alpha and Toll/interleukin-1 receptor motif containing 1 (SARM1), a nicotinamide adenine dinucleotide (NAD)-utilizing enzyme, mediates axon degeneration (AxD) in various neurodegenerative diseases. It is activated by nicotinamide mononucleotide (NMN) to produce a calcium messenger, cyclic ADP-ribose (cADPR). This activity is blocked by elevated NAD level. Here, we verified this metabolic regulation in somatic HEK-293T cells by overexpressing NMN-adenyltransferase to elevate cellular NAD, which resulted not only in inhibition of their own SARM1 from producing cADPR but, surprisingly, also in the 5–10 neighboring wildtype cells in mixed cultures via connexin (Cx)-43. Direct visualization of gap junction intercellular communication (GJIC) was achieved by incubating cells with a permeant probe, PC11, which is converted by SARM1 into PAD11, a fluorescent NAD analog capable of traversing GJs. Extending the findings to dorsal root ganglion neurons, we further showed that CZ-48, a permeant NMN analog, or axotomy, activated SARM1 and the produced PAD11 was transferred to contacting axons via GJIC. The gap junction involved was identified as Cx36 instead. This neuronal GJIC was demonstrated to be functional, enabling healthy neurons to protect adjacent axotomized axons from degeneration. Inhibition of GJIC in mice by AAV-PHP.eB-mediated knockdown of Cx36 in brain induced neuroinflammation, which in turn activated SARM1 and resulted in axon degeneration as well as behavioral deficits. Our results demonstrate a novel intercellular regulation mechanism of SARM1 and reveal a protective role of healthy tissue against AxD induced by injury or neuroinflammation.

Glioblastoma, a formidable brain tumor characterized by dysregulated NAD metabolism, poses a significant therapeutic challenge. The NAMPT inhibitor FK866, which induces NAD depletion, has shown promise in controlling tumor proliferation and modifying the tumor microenvironment. However, the clinical efficacy of FK866 as a single drug therapy for glioma is limited. In this study, we aim to disrupt NAD metabolism using fluorinated NAD precursors and explore their synergistic effect with FK866 in inducing cytotoxicity in glioblastoma cells. The synthesized analogue of nicotinamide riboside (NR), ara-F nicotinamide riboside (F-NR), inhibits nicotinamide ribose kinase (NRK) activity in vitro, reduces cellular NAD levels, and enhances FK866’s cytotoxicity in U251 glioblastoma cells, indicating a collaborative impact on cell death. Metabolic analyses reveal that F-NR undergoes conversion to fluorinated nicotinamide mononucleotide (F-NMN) and other metabolites, highlighting the intact NAD metabolic pathway in glioma cells. The activation of SARM1 by F-NMN, a potent NAD-consuming enzyme, is supported by the synergistic effect of CZ-48, a cell-permeable SARM1 activator. Temporal analysis underscores the sequential nature of events, establishing NAD depletion as a precursor to ATP depletion and eventual massive cell death. This study not only elucidates the molecular intricacies of glioblastoma cell death but also proposes a promising strategy to enhance FK866 efficacy through fluorinated NAD precursors, offering potential avenues for innovative therapeutic interventions in the challenging landscape of glioblastoma treatment.

Medium- and long-chain triacylglycerols (MLCTs) with high 1,3-oleic-2-medium chain (OMO) triacylglycerols content were synthesized by the acidolysis reaction between Cinnamomum camphora seed oil (CCSO) and oleic acid, catalyzed by lipozyme RM IM. In addition, the simultaneous rate of acyl migration (RAM) was investigated during the esterification process. The maximal yield of OMO-structured triacylglycerols (YST) was up to 64.45% under the optimum condition: the molar ratio of CCSO to oleic acid, 1:4; enzyme dosage, 10 wt%; temperature, 60°C; and reaction time, 24 h. RAM was 28.66% at same time. It is shown that YST positively related to RAM at single experiments of the molar ratio (r2 = 0.999, P .05) or a reaction time longer than 24 h (r2 = −0.594, P> .05). The effect of temperature on the reaction could be verified by molecular dynamics simulation, opened enzyme lids were increased with temperature elevated, and helped substrates invade into catalytic triad. When temperature rose to higher than 333 K (60°C), rearrangement of the catalytic triad was promoted, which resulted in both decreasing enzyme catalytic activity and irritating acyl migration. This study could help understand the trigger cause of acyl migration at high temperature, and conclusively reaction temperature was a vital factor to balance YST and RAM in a solvent-free system. OMO-structured triacylglycerols might possess a potential application as a new type of nutritional lipids for daily diet.

A novel actinobacterium, designated strain JXJ CY 19T, was isolated from a culture mat of Microcystis aeruginosa FACHB-905 collected from Dianchi Lake, South-west China. 16S rRNA gene sequences comparison of strain JXJ CY 19T and the available sequences in the GenBank database showed that the strain was closely related to Modestobacter marinus 42H12-1T (99.1% similarity) and Modestobacter roseus KLBMP 1279T (99.0%). The isolate had meso-diaminopimelic in the cell wall with whole-cell sugars of mannose, rhamnose, ribose, glucose, galactose, and arabinose. The menaquinone detected was MK-9(H4), while the major cellular fatty acids include C17:1 ω8c, C15:0 iso, C15:1 iso G and C16:0 iso. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside and an unidentified phospholipid. The DNA-DNA hybridization values between strains JXJ CY 19T and the closely related type strains Modestobacter marinus CGMCC 4.5581T and Modestobacter roseus NBRC 108673T were determined to be 50.8 ± 0.8% and 44.1 ± 1.7%, respectively. The DNA G+C content was 71.9 mol%. On the basis of the above taxonomic data and differences in physiological characters from the closely related type strains, strain JXJ CY 19T was recognized as a novel species of the genus Modestobacter, for which the name Modestobacter lacusdianchii sp. nov. (JXJ CY 19T = KCTC 39600T = CPCC 204352T) is proposed. The type strain JXJ CY 19T can solubilize calcium phosphate tribasic (Ca3(PO4)2), phytin and L-α-phosphatidylcholine. The phosphate-solubilizing property of the novel actinobacterium could be a possible factor for the increase in growth of Microcystis aeruginosa FACHB-905 in ecosystem where the amount of available soluble phosphate is limited such as Dianchi Lake.

Abstract Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed ‘subgenome dominance’ remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.

The aim of this study was to investigate the cellular uptake and antitumor activity of 2 different structural flaxseed orbitides ([1–9-NαC]-linusorb B2 containing methionine residue and [1–9-NαC]-linusorb B3 containing isoleucine residue) in SGC-7901 cells as well as its underlying molecule mechanism. Results showed that the absorption efficiency of [1–9-NαC]-linusorb B3 was higher than that of [1–9-NαC]-linusorb B2. Besides, through the evaluation of mitochondrial membrane potential (Δφm), cytochrome c (Cyt C) release, caspase, death receptor activation and cleavage of PARP, we found that [1–9-NαC]-linusorb B3 exhibited more obvious apoptosis induction on SGC-7901 cells than [1–9-NαC]-linusorb B2. Interestingly, [1–9-NαC]-linusorb B3-induced cell apoptosis might involve a mitochondrial- and death receptor-mediated intrinsic and extrinsic pathway; however, [1–9-NαC]-linusorb B2 induced cell apoptosis by the activation of Fas, FasL, caspase 8 as well as caspase 3 instead of Bax, Cyt C, tBid and caspase 9, suggesting that extrinsic pathway might be involved in the apoptotic process.

Excavation of resistance genes is one of the most effective and environment-friendly measures to control the devastating rice disease caused by Magnaporthe oryzae. Many resistance genes have been mapped and characterized in the last century. Nevertheless, only a few of the total resistance genes could be really applied in the rice breeding program. Huazhan (HZ) is a new native rice restorer line developed in China and widely used in hybrid rice in recent years. HZ and its crossed combinations usually show a broad spectrum of resistance against rice blast in different rice ecosystems in China. Dissection of the genetic background of HZ is very useful for its further application. In this study, a combined method based on bulked segregation analysis (BSA) and specific length amplified fragment sequencing (SLAF-seq) was used to identify blast resistance gene(s) in HZ. A total of 56,187 SLAFs labels were captured and 9051 polymorphic SLAFs markers were analysed and procured in this study. One trait associated with candidate resistance genes region on chromosome 12 overlapping 10.2–17.6 Mb has been identified, in which 10 NBS-LRR (nucleotide-binding site-leucine-rich repeat) coding genes were used as resistance gene candidates. Our result indicated that SLAF-seq with BSA is a rapid and effective method for initial identification of blast resistance genes. The identification of resistance gene in HZ will improve its molecular breeding and resistance variety application.

Copper sulfate (CuSO4) has been widely used as an algicide to control harmful cyanobacterial blooms (CyanoHABs) in freshwater lakes. However, there are increasing concerns about this application, due mainly to the general toxicity of CuSO4 to other aquatic species and its long-term persistence in the environment. This study reported the isolation and characterization of two natural algicidal compounds, i.e., tryptamine and tryptoline, from Streptomyces eurocidicus JXJ-0089. At a concentration of 5 μg/ml, both compounds showed higher algicidal efficiencies than CuSO4 on Microcystis sp. FACHB-905 and some other harmful cyanobacterial strains. Tryptamine and tryptoline treatments induced a degradation of chlorophyll and cell walls of cyanobacteria. These two compounds also significantly increased the intracellular oxidant content, i.e., superoxide anion radical (O2-) and malondialdehyde (MDA), but reduced the activity of intracellular reductants, i.e., superoxide dismutase (SOD), of cyanobacteria. Moreover, tryptamine and tryptoline treatments significantly altered the internal and external contents of microcystin-LR (MC-LR), a common cyanotoxin. Like CuSO4, tryptamine and tryptoline led to releases of intracellular MC-LR from Microcystis, but with lower rates than CuSO4. Tryptamine and tryptoline (5 μg/ml) in cyanobacterial cultures were completely degraded within 8 days, while CuSO4 persisted for months. Overall, our results suggest that tryptamine and tryptoline could potentially serve as more efficient and environmentally friendly alternative algicides than CuSO4 in controlling harmful cyanobacterial blooms. [ABSTRACT FROM AUTHOR]