Investigation of Lithium-Ion Battery Performance Utilizing Magnetic Controllable Superionic Conductor Li3(V1-x Fe x )2(PO4)3/C (x = 0.05 and 0.10).

Lithium-ion batteries with Li3V2(PO4)3/C as the cathode have been a popular research topic in recent years; however, studies of the effects of external magnetic fields on them are less common. This study investigates the effects of an external magnetic field applied parallel to the direction of the anode and cathode on the ion transport through iron-doped Li3(V1-x Fe x )2(PO4)3, the outer carbon coating, the film/electrolyte/separator, and up to the lithium metal electrode on a microscopic level. The results reveal that for the x = 0.05 sample with lower doping, the magnetostriction expansion of Li3(V1-x Fe x )2(PO4)3 and the magnetostrictive contraction effect of the outer ordered carbon layer cancel each other out, resulting in no significant enhancement of the battery's energy and power density due to the external magnetic field. In contrast, the x = 0.1 sample, lacking magnetostrictive contraction in the outer ordered carbon layer, shows that its energy and power density can be influenced by the magnetic field. Under zero magnetic field, the cyclic performance exhibits superior average capacity performance in the x = 0.05 sample, while the x = 0.1 sample shows a lower decay rate. Both samples are affected by the magnetic field; however, the x = 0.1 sample performs better under magnetic conditions. In particular, in the C-rate tests under a magnetic field, the sample with x = 0.1 showed a significant relative reduction in capacity decay rate by 20.18% compared to the sample with x = 0.05.

Vitamin D is involved in the regulation of Cl- uptake in zebrafish (Danio rerio).

Cl- is a major anion in the bodily fluids of vertebrates, and maintaining its homeostasis is essential for normal physiological functions. Fishes inhabiting freshwater (FW) passively lose body fluid ions, including Cl-, to the external environment because of the electrochemical gradient of ions across the body surface. Therefore, FW fishes have to actively absorb Cl- from the surroundings to maintain ion homeostasis in their bodily fluids. Hormonal control is vital for modulating ion uptake in fish. Vitamin D is involved in the regulation of Ca2+ uptake and acid secretion in fish. In the present study, we found that the levels of bioactive vitamin D, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), significantly increased in zebrafish embryos and adults after exposure to water containing low levels of Cl-. Moreover, the administration of 1α,25(OH)2D3 treatment (20 µg/L) in zebrafish embryos, and intraperitoneal (i.p.) injection of 1α,25(OH)2D3 (5 µg/kg body mass) in zebrafish adults, resulting the increased Cl- content in bodily fluid in zebrafish. Na+-Cl- cotransporter 2b (NCC2b) and Cl- channel 2c (CLC2c) are specifically expressed during Cl- uptake by ionocytes in zebrafish. Our results indicated that the mRNA and protein expression of NCC2b and CLC2c considerably increased in the zebrafish with exogenous 1α,25(OH)2D3 treatment. Additionally, exogenous 1α,25(OH)2D3 administration increased the number of NCC2b- and CLC2c-expressing cells in yolk skins of zebrafish embryos and the gill filaments of zebrafish adults. Transcript signals of vitamin D receptors (VDRs) were identified in NCC2b-expressing cells. Knockdown of VDRa and VDRb significantly reduced the expression of NCC2b and CLC2c and the number of NCC2b- and CLC2c-expressing cells. These results indicate that vitamin D can affect Cl- uptake in zebrafish and extend our knowledge of the role of vitamin D in fish physiology.

Insights into dynamic evolution of glucuronofucogalactoglucan from water extract of Agrocybe cylindracea during maturation.

This study explored the physicochemical properties and structural characteristics of Agrocybe cylindracea polysaccharides at four developmental stages, as well as their dynamic evolution during maturation. Results showed that the polysaccharides from A. cylindracea water extract exhibited similar structural characteristics across all four maturity stages, despite a significant reduction in yields. Four water-soluble heteroglycans, including one high molecular weight (ACPM-Et50-I) and three low molecular weight (ACPM-Et50-II, ACPM-Et60, ACPM-Et80), were isolated from A. cylindracea at each maturity stage. ACPM-Et50-I was identified as branched heterogalactans, while ACPM-Et60 and ACPM-Et80 were branched heteroglucans. However, ACPM-Et50-II was characterized as a branched glucuronofucogalactoglucan at the tide-turning stage but a glucuronofucoglucogalactan at the pileus expansion stage due to the increase of its α-(1 â†’ 6)-D-Galp. In general, although the structural skeletons of most A. cylindracea heteroglycans were similar during maturation as shown by their highly consistent glycosyl linkages, there were still differences in the distribution of some heteroglucans. This work has for the first time reported a glucuronofucogalactoglucan in A. cylindracea and its dynamic evolution during maturation, which may facilitate the potential application of A. cylindracea in food and biomedicine industries.

Biomarkers Screening and Mechanisms Analysis of the Restraint Stress-Induced Myocardial Injury in Hyperlipidemia ApoE-/- Mice.

OBJECTIVES: To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/- mice. METHODS: The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/- mice. Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers. RESULTS: Proteomic analysis showed that there were 43 significantly up-regulated and 58 significantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group. Among them, GBP2, TAOK3, TFR1 and UCP1 were biomarkers with great diagnostic potential. KEGG pathway enrichment analysis indicated that ferroptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model. The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model. CONCLUSIONS: Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferroptosis. Four potential biomarkers are selected for myocardial injury diagnosis, providing a new direction for sudden cardiac death (SCD) caused by hyperlipidemia combined with the restraint stress.

Johnson-noise-limited cancellation-free microwave impedance microscopy with monolithic silicon cantilever probes.

Microwave impedance microscopy (MIM) is an emerging scanning probe technique for nanoscale complex permittivity mapping and has made significant impacts in diverse fields. To date, the most significant hurdles that limit its widespread use are the requirements of specialized microwave probes and high-precision cancellation circuits. Here, we show that forgoing both elements not only is feasible but also enhances performance. Using monolithic silicon cantilever probes and a cancellation-free architecture, we demonstrate Johnson-noise-limited, drift-free MIM operation with 15 nm spatial resolution, minimal topography crosstalk, and an unprecedented sensitivity of 0.26 zF/√Hz. We accomplish this by taking advantage of the high mechanical resonant frequency and spatial resolution of silicon probes, the inherent common-mode phase noise rejection of self-referenced homodyne detection, and the exceptional stability of the streamlined architecture. Our approach makes MIM drastically more accessible and paves the way for advanced operation modes as well as integration with complementary techniques.

Multiplexing intensity and frequency sensations for artificial touch by modulating temporal features of electrical pulse trains.

In neural prostheses, intensity modulation of a single channel (i.e., through a single stimulating electrode) has been achieved by increasing the magnitude or width of each stimulation pulse, which risks eliciting pain or paraesthesia; and by changing the stimulation rate, which leads to concurrent changes in perceived frequency. In this study, we sought to render a perception of tactile intensity and frequency independently, by means of temporal pulse train patterns of fixed magnitude, delivered non-invasively. Our psychophysical study exploits a previously discovered frequency coding mechanism, where the perceived frequency of stimulus pulses grouped into periodic bursts depends on the duration of the inter-burst interval, rather than the mean pulse rate or periodicity. When electrical stimulus pulses were organised into bursts, perceived intensity was influenced by the number of pulses within a burst, while perceived frequency was determined by the time between the end of one burst envelope and the start of the next. The perceived amplitude was modulated by 1.6× while perceived frequency was varied independently by 2× within the tested range (20-40 Hz). Thus, the sensation of intensity might be controlled independently from frequency through a single stimulation channel without having to vary the injected electrical current. This can form the basis for improving strategies in delivering more complex and natural sensations for prosthetic hand users.

Circulating Small Extracellular Vesicles Involved in Systemic Regulation Respond to RGC Degeneration in Glaucoma.

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma-derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV-miR-29s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR-29s in RGC pathophysiology. It is showed that the overexpression of miR-29b-3p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR-29b-3p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV-miR-29s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV-based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases.

State Estimation for Markovian Jump Neural Networks Under Probabilistic Bit Flips: Allocating Constrained Bit Rates.

In this article, the state estimation problem is studied for Markovian jump neural networks (MJNNs) within a digital network framework. The wireless communication channel with limited bandwidth is characterized by a constrained bit rate, and the occurrence of bit flips during wireless transmission is mathematically modeled. A transmission mechanism, which includes coding-decoding under bit-rate constraints and considers probabilistic bit flips, is introduced, providing a thorough characterization of the digital transmission process. A mode-dependent remote estimator is designed, which is capable of effectively capturing the internal state of the neural network. Furthermore, a sufficient condition is proposed to ensure the estimation error to remain bounded under challenging network conditions. Within this theoretical framework, the relationship between the neural network's estimation performance and the bit rate is explored. Finally, a simulation example is provided to validate the theoretical findings.

Polyhedral {Ag12} and {Ag16} Clusters: Synthesis, Structural Characterization and Third-Order Nonlinear Optical Properties.

Two polyhedral silver-thiolate clusters, [S@Ag16(Tab)10(MeCN)8](PF6)14 (Ag16) and [Ag12(Tab)6(DMF)12](PF6)12 (Ag12), were synthesized by using electroneutral Tab species as protective ligands (Tab=4-(trimethylammonio)benzenethiolate, DMF=N,N-dimethylformamide, MeCN=acetonitrile). Ag16 has a decahedral shape composed of eight pentagon {Ag5} units and two square {Ag4} units. The structure of Ag12 is a cuboctahedron, a classical Archimedean structure composed of six triangular faces and eight square faces. The former configuration is discovered in silver-thiolate cluster for the first time, possibly benefited from the more flexible coordination between the Tab ligand and Ag+ facilitated by the electropositive -N(CH3)3 + substituent group. Third-order nonlinear optical studies show that both clusters in DMF exhibit reverse saturate absorption response under the irradiation of 532 nm laser.

Hippocampal proteome comparison of infant and adult Fmr1 deficiency mice reveals adult-related changes associated with postsynaptic density.

Deficiency in fragile X mental retardation 1 (Fmr1) leads to loss of its encoded protein FMRP and causes fragile X syndrome (FXS) by dysregulating its target gene expression in an age-related fashion. Using comparative proteomic analysis, this study identified 105 differentially expressed proteins (DEPs) in the hippocampus of postnatal day 7 (P7) Fmr1-/y mice and 306 DEPs of P90 Fmr1-/y mice. We found that most DEPs in P90 hippocampus were not changed in P7 hippocampus upon FMRP absence, and some P90 DEPs exhibited diverse proteophenotypes with abnormal expression of protein isoform or allele variants. Bioinformatic analyses showed that the P7 DEPs were mainly enriched in fatty acid metabolism and oxidoreductase activity and nutrient responses; whereas the P90 PEPs (especially down-regulated DEPs) were primarily enriched in postsynaptic density (PSD), neuronal projection development and synaptic plasticity. Interestingly, 25 of 30 down-regulated PSD proteins present in the most enriched protein to protein interaction network, and 6 of them (ANK3, ATP2B2, DST, GRIN1, SHANK2 and SYNGAP1) are both FMRP targets and autism candidates. Therefore, this study suggests age-dependent alterations in hippocampal proteomes upon loss of FMRP that may be associated with the pathogenesis of FXS and its related disorders. SIGNIFICANCE: It is well known that loss of FMRP resulted from Fmr1 deficiency leads to fragile X syndrome (FXS), a common neurodevelopmental disorder accompanied by intellectual disability and autism spectrum disorder (ASD). FMRP exhibits distinctly spatiotemporal patterns in the hippocampus between early development and adulthood, which lead to distinct dysregulations of gene expression upon loss of FMRP at the two age stages potentially linked to age-related phenotypes. Therefore, comparison of hippocampal proteomes between infancy and adulthood is valuable to provide insights into the early causations and adult-dependent consequences for FXS and ASD. Using a comparative proteomic analysis, this study identified 105 and 306 differentially expressed proteins (DEPs) in the hippocampi of postnatal day 7 (P7) and P90 Fmr1-/y mice, respectively. Few overlapping DEPs were identified between P7 and P90 stages, and the P7 DEPs were mainly enriched in the regulation of fatty acid metabolism and oxidoreduction, whereas the P90 DEPs were preferentially enriched in the regulation of synaptic formation and plasticity. Particularly, the up-regulated P90 proteins are primarily involved in immune responses and neurodegeneration, and the down-regulated P90 proteins are associated with postsynaptic density, neuron projection and synaptic plasticity. Our findings suggest that distinctly changed proteins in FMRP-absence hippocampus between infancy and adulthood may contribute to age-dependent pathogenesis of FXS and ASD.

Enlarged perivascular spaces and their association with motor, cognition, MRI markers and cerebrovascular risk factors in male fragile X premutation carriers.

FMR1 premutation carriers (55-200 CGG repeats) are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder associated with motor and cognitive impairment. Bilateral hyperintensities of the middle cerebellar peduncles (MCP sign) are the major radiological hallmarks of FXTAS. In the general population, enlarged perivascular spaces (PVS) are biomarkers of small vessel disease and glymphatic dysfunction and are associated with cognitive decline. Our aim was to determine if premutation carriers show higher ratings of PVS than controls and whether enlarged PVS are associated with motor and cognitive impairment, MRI features of neurodegeneration, cerebrovascular risk factors and CGG repeat length. We evaluated 655 MRIs (1-10 visits/participant) from 229 carriers (164 with FXTAS and 65 without FXTAS) and 133 controls. PVS in the basal ganglia (BG-EPVS), centrum semiovale, and midbrain were evaluated with a semiquantitative scale. Mixed-effects models were used for statistical analysis adjusting for age. In carriers with FXTAS, we revealed that (1) BG-PVS ratings were higher than those of controls and carriers without FXTAS; (2) BG-PVS severity was associated with brain atrophy, white matter hyperintensities, enlarged ventricles, FXTAS stage and abnormal gait; (3) age-related increase in BG-PVS was associated with cognitive dysfunction; and (4) PVS ratings of all three regions showed robust associations with CGG repeat length and were higher in carriers with the MCP sign than carriers without the sign. This study demonstrates clinical relevance of PVS in FXTAS especially in the basal ganglia region and suggests microangiopathy and dysfunctional cerebrospinal fluid circulation in FXTAS physiopathology.

Ascorbic acid-mediated reduction of arabinoxylan viscosity through free radical reactions.

Arabinoxylan (AX) is a potential natural food additive that can enhance the textural properties of food. However, the addition of ascorbic acid (AA) can easily lead to a decrease in the viscosity of AX, which poses a challenge in the development of AX-rich foods. Therefore, the purpose of this study is to elucidate the mechanisms behind the reduction in AX viscosity in the presence of AA. The results indicated that AA could reduce the apparent viscosity and molecular weight of AX without significantly affecting the monosaccharide composition, suggesting a potential mechanism related to the cleavage of AX glycosidic bonds. Interestingly, free radicals were present in the reaction system, and the generation of free radicals under different conditions was consistent with the reduction in apparent viscosity of AX. Furthermore, the reduction in AX apparent viscosity by AA was influenced by various factors including AA concentration, reaction time, temperature, pH, and metal ions. These findings suggested that the mechanism of AX degradation may be due to AA-induced free radical generation, leading to non-selective attacks on glycosidic bonds. Therefore, this study revealed that the potential mechanism behind the reduction in AX viscosity induced by AA involved the generation of ascorbic acid radicals.

Changes of the Physicochemical Properties and Structural Characteristics of Alkali-Extracted Polysaccharides from Agrocybe cylindracea Across the Growth Process.

Polysaccharides derived from Agrocybe cylindracea have been demonstrated to exhibit various bioactivities. However, studies on their structural characteristics during the growth process are limited. This study aimed to compare the physicochemical properties and structural characteristics of alkali-extracted polysaccharides from A. cylindracea fruiting bodies (JACP) across four growth stages. Results showed that the extraction yields and protein levels of JACP declined along with the growth of A. cylindracea, while the contents of neutral sugar and glucose increased significantly. However, JACP exhibited structural characteristics similar to those across the four stages. Four polysaccharide subfractions were isolated from each growth stage, including JACP-Et30, JACP-Et50, JACP-Et60, and JACP-Et70. JACP-Et30 from the four stages and JACP-Et50 from the initial three stages were identified as heteroglucans with ß-1,3-d-Glcp and ß-1,6-d-Glcp residues as main chains, respectively. However, other subfractions were considered as ß-1,6-d-glucans containing minor glucuronic acid. These subfractions were predominantly replaced by Glcp residues at the O-3 and O-6 positions. Overall, while JACP exhibited variable physicochemical properties, its structural characteristics remained stable during the growth process, offering new insights into its potential applications in the food and medicinal industries.

Development of soy protein isolate gels added with Tremella polysaccharides and psyllium husk powder as 3D printing inks for people with dysphagia.

The aim of this study was to investigate the feasibility of soy protein isolate (SPI) gels added with Tremella polysaccharides (TPs) and psyllium husk powder (PHP) as 3D printing inks for developing dysphagia-friendly food and elucidate the potential mechanism of TPs and PHP in enhancing the printing and swallowing performance of SPI gels. The results indicated that the SPI gels with a TP : PHP ratio of 3 : 7 could be effectively used as printing inks to manufacture dysphagia-friendly food. The addition of TPs increased the free water content, resulting in a decrease in the viscosity of the SPI gels, which, in turn, reduced the line width of the 3D-printed product and structural strength of the gel system. The addition of PHP increased disulfide bond interactions and excluded volume interactions, which determined the mechanical strength of SPI gels and increased the line width of the printed product. The synergistic effects between TPs and PHP improved the printing precision and structural stability. This study presents meaningful insights for the utilization of 3D printing in the creation of dysphagia-friendly food using protein-polysaccharide complexes.

The Intersection of cerebral cholesterol metabolism and Alzheimer's disease: Mechanisms and therapeutic prospects.

Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly, the exact pathogenesis of which remains incompletely understood, and effective preventive and therapeutic drugs are currently lacking. Cholesterol plays a vital role in cell membrane formation and neurotransmitter synthesis, and its abnormal metabolism is associated with the onset of AD. With the continuous advancement of imaging techniques and molecular biology methods, researchers can more accurately explore the relationship between cholesterol metabolism and AD. Elevated cholesterol levels may lead to vascular dysfunction, thereby affecting neuronal function. Additionally, abnormal cholesterol metabolism may affect the metabolism of ß-amyloid protein, thereby promoting the onset of AD. Brain cholesterol levels are regulated by multiple factors. This review aims to deepen the understanding of the subtle relationship between cholesterol homeostasis and AD, and to introduce the latest advances in cholesterol-regulating AD treatment strategies, thereby inspiring readers to contemplate deeply on this complex relationship. Although there are still many unresolved important issues regarding the risk of brain cholesterol and AD, and some studies may have opposite conclusions, further research is needed to enrich our understanding. However, these findings are expected to deepen our understanding of the pathogenesis of AD and provide important insights for the future development of AD treatment strategies targeting brain cholesterol homeostasis.

The truncated AXIN1 isoform promotes hepatocellular carcinoma metastasis through SRSF9-mediated exon 9 skipping.

Axis inhibitor protein 1 (AXIN1) is a protein recognized for inhibiting tumor growth and is commonly involved in cancer development. In this study, we explored the potential molecular mechanisms that connect alternative splicing of AXIN1 to the metastasis of hepatocellular carcinoma (HCC). Transcriptome sequencing, RT‒PCR, qPCR and Western blotting were utilized to determine the expression levels of AXIN1 in human HCC tissues and HCC cells. The effects of the AXIN1 exon 9 alternative splice isoform and SRSF9 on the migration and invasion of HCC cells were assessed through wound healing and Transwell assays, respectively. The interaction between SRSF9 and AXIN1 was investigated using UV crosslink RNA immunoprecipitation, RNA pulldown, and RNA immunoprecipitation assays. Furthermore, the involvement of the AXIN1 isoform and SRSF9 in HCC metastasis was validated in a nude mouse model. AXIN1-L (exon 9 including) expression was downregulated, while AXIN1-S (exon 9 skipping) was upregulated in HCC. SRSF9 promotes the production of AXIN1-S by interacting with the sequence of exons 8 and 10 of AXIN1. AXIN1-S significantly promoted HCC cells migration and invasion by activating the Wnt pathway, while the opposite effects were observed for AXIN1-L. In vivo experiments demonstrated that AXIN1-L inhibited HCC metastasis, whereas SRSF9 promoted HCC metastasis in part by regulating the level of AXIN1-S. AXIN1, a tumor suppressor protein that targets the AXIN1/Wnt/ß-catenin signaling axis, may be a promising prognostic factor and a valuable therapeutic target for HCC.

Histone deacetylase Hos2 regulates protein expression noise by potentially modulating the protein translation machinery.

Non-genetic variations derived from expression noise at transcript or protein levels can result in cell-to-cell heterogeneity within an isogenic population. Although cells have developed strategies to reduce noise in some cellular functions, this heterogeneity can also facilitate varying levels of regulation and provide evolutionary benefits in specific environments. Despite several general characteristics of cellular noise having been revealed, the detailed molecular pathways underlying noise regulation remain elusive. Here, we established a dual-fluorescent reporter system in Saccharomyces cerevisiae and performed experimental evolution to search for mutations that increase expression noise. By analyzing evolved cells using bulk segregant analysis coupled with whole-genome sequencing, we identified the histone deacetylase Hos2 as a negative noise regulator. A hos2 mutant down-regulated multiple ribosomal protein genes and exhibited partially compromised protein translation, indicating that Hos2 may regulate protein expression noise by modulating the translation machinery. Treating cells with translation inhibitors or introducing mutations into several Hos2-regulated ribosomal protein genes-RPS9A, RPS28B and RPL42A-enhanced protein expression noise. Our study provides an effective strategy for identifying noise regulators and also sheds light on how cells regulate non-genetic variation through protein translation.

A Comprehensive Flap Classification: Beyond the Reconstructive Ladder.

ABSTRACT: Perforator flaps have progressed massively in the last years. The improved vascular imaging techniques and the use of supermicrosurgery have shifted the practice from the traditional predefined angiosomal flaps to the endless variations of custom-made flaps. In this article, we propose a broadened classification of free-style flaps in 3 categories, the angiosomal, including all traditional perforator flaps and their variations, the extra-angiosomal, including flaps that are manufactured to include tissue from a different angiosome, such as turbocharging or supercharging a flap, and neoangiosomal flaps, which are based on the process of neoangiogenesis on autologous or allogenous tissue, such as the venous flow-through flap and integra flap. With this classification, we hope to help unify the classifications and, by doing so, facilitate the exchange of ideas, techniques and knowledge.MeSH terms: surgical flap / classification, terminology as topic.

Ent-eudesmane sesquiterpenoids with anti-neuroinflammatory activity from the marine-derived fungus Eutypella sp. F0219.

In this study, twenty-three ent-eudesmane sesquiterpenoids (1-23) including fifteen previously undescribed ones, named eutypelides A-O (1-15) were isolated from the marine-derived fungus Eutypella sp. F0219. Their planar structures and relative configurations were established by HR-ESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of the previously undescribed compounds were determined by single-crystal X-ray diffraction analyses, modified Mosher's method, and ECD calculations. Structurally, eutypelide A (1) is a rare 1,10-seco-ent-eudesmane, whereas 2-15 are typically ent-eudesmanes with 6/6/-fused bicyclic carbon nucleus. The anti-neuroinflammatory activity of all isolated compounds (1-23) was accessed based on their ability to NO production in LPS-stimulated BV2 microglia cells. Compound 16 emerged as the most potent inhibitor. Further mechanistic investigation revealed that compound 16 modulated the inflammatory response by decreasing the protein levels of iNOS and increasing ARG 1 levels, thereby altering the iNOS/ARG 1 ratio and inhibiting macrophage polarization. qRT-PCR analysis showed that compound 16 reversed the LPS-induced upregulation of pro-inflammatory cytokines, including iNOS, TNF-α, IL-6, and IL-1ß, at both the transcriptional and translational levels. These effects were linked to the inhibition of the NF-κB pathway, a key regulator of inflammation. Our findings suggest that compound 16 may be a potential structure basis for developing neuroinflammation-related disease therapeutic agents.