Perturbed microbial ecology in neuromyelitis optica spectrum disorder: Evidence from the gut microbiome and fecal metabolome.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating immune-mediated ailment, which is influenced by genetic, epigenetic, and environmental elements. The escalating incidence of NMOSD in recent years implies alterations in environmental risk factors. Recent research has established a correlation between gut microbiomes and the development of NMOSD. METHODS: Metagenomic shotgun sequencing and gas chromatography-mass spectrometry (GC-MS) were employed to assess alterations of the structure and function in the fecal microbiome, as well as levels of short-chain fatty acids (SCFAs) in fecal and blood samples, among individuals with neuromyelitis optica spectrum disorder (NMOSD) during the acute phase (n = 25), the remission phase (n = 11), and a group of healthy controls (HCs) (n = 24). We further explored the correlation between gut microbiota and the pathogenesis of NMOSD through fecal microbiota transplantation (FMT). The gut microbiome from human donors diagnosed with NMOSD or HCs was transplanted into germ-free mice, followed by an analysis of the alterations in the structure and functionality of the transplanted mice's gut microbiome. Additionally, the impact of microbiome transfer on the immunity and spinal cord of germ-free mice was assessed through various techniques, including ELISA, flow cytometry, western blot, histopathology, and transcriptome sequencing. RESULTS: (1) At the taxonomic levels of genus and species, there were significant differences in the α-diversity of the microbiome between HCs and NMOSD patients in the acute phase, with NMOSD patients having higher species diversity. (2) In the acute phase, the gut microbiota of NMOSD patients was characterized by Ruminococcaceae_unclassified, Campylobacter, Parabacteroides, Lactobacillus, Akkermansia, Streptococcus oralis, Clostridium leptum, Clostridium asparagiforme, Firmicutes bacterium CAG 238, and Lactobacillus fermentum. (3) The relative abundances of Coprobacter, Turicimonas, Gemmiger, Enterobacter, Roseburia sp.CAG 471, Veillonella tobetsuensis, Proteobacteria bacterium CAG 139, Ruminococcus bicirculans, Lactococcus lactis, Flavonifractor plautii, and Streptococcus cristatus were notably lower in patients experiencing remission compared to NMOSD patients in the acute phase, On the other hand, the relative abundances of Flavonifractor (P = 0.049) and Clostridium aldenense (P = 0.049) were significantly higher. Following medication, the gut microbiome distribution in NMOSD patients during remission closely resembled that of healthy controls (HCs). (4) Compared with HCs, acetate levels in the feces of patients with NMOSD in the acute phase were significantly lower. (5) In addition, we transplanted feces from NMOSD patients into germ-free mice and revealed a significant increase in the levels of IL-6, IL-17A, and IL-23 in the blood of mice belonging to the NMOSD fecal transplantation (NFMT) group. Additionally, the IL-10 level exhibited a significant reduction. Moreover, the proportion of Th17 cells displayed a significant increase, while the proportion of Treg cells exhibited a significant decrease in the spleens of NFMT mice. CONCLUSION: Patients in the acute phase of neuromyelitis optica spectrum disorder (NMOSD) exhibited imbalances in their gut microbiota and a deficiency in short-chain fatty acids (SCFAs). Following drug treatment, the composition of intestinal microbes in NMOSD patients during the remission phase closely resembled that of the healthy control population. The FMT experiment provided evidence of the significant association between intestinal flora and the pathogenesis of NMOSD. Consequently, investigating gut microbiota and identifying novel microbial markers hold promise for the diagnosis and treatment of NMOSD patients.

Comparative Analysis of the Potential Adaptability of Tibetan Dzo and Yellow Cattle Based on Blood Indices, Metabolites, and Fecal Microbiota.

This study aimed to investigate the differences in environmental adaptability between dzo and Tibetan yellow cattle by using corresponding assay kits to analyze blood indices, utilizing mass spectrometry for blood metabolite profiling, and performing 16S rDNA sequencing of fecal microbiota. Forty female cattle were randomly divided into a dzomo (female dzo) group (MG, n = 20) and a Tibetan-yellow-cattle group (HG, n = 20). After 150 days of uniform feeding, six cattle from each group were randomly picked for jugular blood sampling and collection of fecal microorganisms. The results showed that the serum albumin, creatinine, total protein, superoxide dismutase, IgG, and IgM concentrations in the MG group were higher (p < 0.05), whereas the serum triglyceride concentration was lower, compared to the HG group (p < 0.05). The higher level of phospholipids containing long-chain polyunsaturated fatty acids (PUFAs) (PC (18:5e/2:0), PC (20:5e/2:0), LPC 18:2, LPC 20:5) observed in the serum of the dzo suggests that they have an advantage in adapting to the challenging conditions of the plateau environment. The fecal microbiota analysis showed that Akkermansia was significantly enriched in the MG group; this might be the key bacterial genus leading to the strong adaptability of dzo. Our findings indicated the dzo's superior adaptation to the Tibetan Plateau's harsh environment.

Electrolyte Composition-Dependent Product Selectivity in CO2 Reduction with a Porphyrinic Metal-Organic Framework Catalyst.

A copper porphyrin-derived metal-organic framework electrocatalyst, FICN-8, was synthesized and its catalytic activity for CO2 reduction reaction (CO2RR) was investigated. FICN-8 selectively catalyzed electrochemical reduction of CO2 to CO in anhydrous acetonitrile electrolyte. However, formic acid became the dominant CO2RR product with the addition of a proton source to the system. Mechanistic studies revealed the change of major reduction pathway upon proton source addition, while catalyst-bound hydride (*H) species was proposed as the key intermediate for formic acid production. This work highlights the importance of electrolyte composition on CO2RR product selectivity.

The Potential of the lncRNAs ADAMTSL4-AS1, AC067931 and SOCS2-AS1 in Peripheral Blood Mononuclear Cells as Novel Diagnostic Biomarkers for Hepatitis B Virus-Associated Hepatocellular Carcinoma.

Purpose: Long noncoding RNAs (lncRNAs) might be closely associated with hepatocellular carcinoma (HCC) progression and could serve as diagnostic and prognostic markers. This study aimed to investigate lncRNA-based diagnostic biomarkers for hepatitis B virus (HBV)-associated HCC. Materials and Methods: High-throughput transcriptome sequencing was conducted on the liver tissues of 15 patients with HBV-associated liver diseases (5 with chronic hepatitis B [CHB], 5 with liver cirrhosis [LC], and 5 with HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze lncRNA expressions. Potential diagnostic performance for HBV-associated HCC screening was evaluated. Results: Through trend analysis and functional analysis, we found that 8 lncRNAs were gradually upregulated and 1 lncRNA was progressively downregulated by regulation of target mRNAs and downstream HCC-associated signaling pathways. The validation of dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) and HCC tissues by qRT-PCR revealed that ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were significantly increased in HCC compared with CHB and cirrhosis. Moreover, differentially expressed lncRNAs were aberrantly elevated in Huh7, Hep3B, HepG2, and HepG2.215 cells compared with LX2 cells. Furthermore, ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were identified as novel biomarkers for HBV-associated HCC. For distinguishing HCC from CHB, ADAMTSL4-AS1, AC067931, and SOCS2-AS1 combined with alpha-fetoprotein (AFP) had an area under the curve (AUC) of 0.945 (sensitivity, 83.9%; specificity, 89.8%). Similarly, for distinguishing HCC from LC, this combination had an AUC of 0.871 (sensitivity, 91.1%; specificity, 68.2%). Furthermore, this combination showed the highest diagnostic ability to distinguish HCC from CHB and LC (AUC, 0.905; sensitivity, 91.1%; specificity, 75.3%). In particular, this combination identified AFP-negative (AFP < 20 ng/mL) (AUC = 0.814), small (AUC = 0.909), and early stage (AUC = 0.863) tumors. Conclusion: ADAMTSL4-AS1, SOCS2-AS1, and AC067931 combined with AFP in PBMCs may serve as a noninvasive diagnostic biomarker for HBV-associated HCC, especially AFP-negative, small, and early stage HCC.

Poor outcome in congenital mesoblastic nephroma with TPM3::NTRK1 fusion: a case report from multi-disciplinary treatment to molecular tumor board.

Background: Congenital mesoblastic nephroma (CMN) is a rare renal tumor with good prognosis in children; however, cellular CMN is a special subtype with poor prognosis. The ETV6 fusion gene has been found in some cellular CMNs, whereas CMNs with TPM3::NTRK1 fusion gene have not been reported. This study aims to share the progression and treatment of a case of CMNs with TPM3::NTRK1 fusion gene, in order to provide experience for the diagnosis and treatment of such specific diseases. Case Description: We report a case of CMN with TPM3::NTRK1 fusion gene and a 3-year course of disease that originated during the fetal period. The child experienced rapid tumor progression 22 months after birth, followed by tumor recurrence 3 months after complete resection of CMN. Although traditional chemotherapy could not prevent the tumor progression. The tropomyosin receptor kinase (TRK) inhibitor larotrectinib resulted in significant inhibitory effects on metastatic lesions in the lungs, liver, and peritoneum. However, the patient ultimately died as the tumor became resistant to larotrectinib. Conclusions: CMN, is a rare pediatric renal tumor that warrant prompt surgical management. A watchful waiting approach may allow for aggressive growth of metastatic disease, as seen in this case of cellular CMN with TPM3::NTRK1 fusion gene, TRK inhibitors can play significant roles in the treatment of CMN with TPM3::NTRK1 fusion gene, but we still need to pay attention to the phenomenon of drug resistance to larotrectinib caused by site mutations of TRKA.

Research trends and hotspots of ferroptosis in neurodegenerative diseases from 2013 to 2023: A bibliometrics study.

Background: With the aging population, the incidence of neurodegenerative diseases increases yearly, seriously impacting human health. Various journals have published studies on the pathogenesis of ferroptosis in neurodegenerative diseases. However, bibliometric analysis in this field is still lacking. The study aims to visually analyze global research trends in this field over the past decade. Methods: The articles and reviews regarding ferroptosis in neurodegenerative diseases were retrieved from the Web of Science on September 1, 2023. Citespace [version 6.2. R4 (64-bit)] and VOSviewer (version 1.6.18) were used to conduct the bibliometric and knowledge-map analysis. Results: In total, 370 studies were included in the paper and ranked by their citation frequency. Many articles on ferroptosis in neurodegenerative diseases have been published in the past decade. The country, institution, author, and journal with the highest publications were China, Guangzhou Medical University, Maher, Pamela, and Free Radical Biology And Medicine, respectively. The analysis of keyword co-occurrence indicated that research frontiers were molecular mechanisms of ferroptosis in neurodegenerative diseases, especially a few key pathways that triggered ferroptosis in these diseases, including lipid peroxidation signaling, iron metabolism, and GSH/GPX4 signaling. In addition, ferroptosis inhibitors such as liproxstatins and ferrostatins had protective effects in animal models of neurodegenerative diseases. Therefore, future attention should also be focused on therapeutic drugs that target ferroptosis. Conclusion: This study comprehensively analyzed the publications on ferroptosis in neurodegenerative diseases from a bibliometric perspective. Research on this topic is currently expanding at a rapid pace, and the China holds a leading position in this field by its scientific achievements and productivity. Moreover, the research frontiers were molecular mechanisms of ferroptosis in neurodegenerative diseases and developing targeted therapeutic drugs. In summary, our results showed an all-sided overview of the knowledge atlas and a valuable reference for the future research in this field.

Dabrafenib mitigates the neuroinflammation caused by ferroptosis in experimental autoimmune encephalomyelitis by up regulating Axl receptor.

Multiple sclerosis is an autoimmune disease that causes inflammatory damage to the central nervous system. At present, the pathogenesis of the disease is unknown. There is a lack of few effective therapy medications available. Therefore, it is necessary to further explore the pathogenesis of this illness and develop potential therapeutic drugs. Dabrafenib is potential therapeutic medicine for nervous system disease. In this study, we preliminarily studied the possible mechanism of dabrafenib in the treatment of multiple sclerosis from the perspective of ferroptosis. First, we observed that dabrafenib significantly improved symptoms of gait abnormalities, limb weakness or paralysis, and down-regulated levels of spinal cord inflammation in an experimental autoimmune encephalitis (EAE) model. Meanwhile, we also observed that dabrafenib could inhibit the proteins of ferroptosis in spinal cord tissue of EAE mice by Western blot. The results of immunohistochemical analysis showed that the effect of dabrafenib on ferroptosis mainly occurred in microglia. Second, dabrafenib was demonstrated to be able to inhibit the S phase of the cell cycle, reduce ROS levels, and reinstate mitochondrial activity in the LPS-induced BV2 inflammatory cell model. Futhermore, we found that dabrafenib inhibits P-JAK2 and P-STAT3 activation by acting Axl receptor, which in turn prevents neurogenic inflammation in microglia. The co-stimulated BV2 cell model with LPS and Erastin also verified these findings. Ultimately, the Axl knockout mice used to construct the EAE model allowed for the confirmation that dabrafenib prevented ferroptosis in microglia by up-regulating Axl receptor, which reduced the inflammatory demyelination associated with EAE. In summary, our research demonstrates the advantages of dabrafenib in multiple sclerosis treatment, which can prevent ferroptosis in microglia in multiple sclerosis through up-regulating Axl receptor, thus halting the progression of multiple sclerosis.

High-entropy engineering with regulated defect structure and electron interaction tuning active sites for trifunctional electrocatalysis.

High-entropy alloy nanoparticles (HEANs) possessing regulated defect structure and electron interaction exhibit a guideline for constructing multifunctional catalysts. However, the microstructure-activity relationship between active sites of HEANs for multifunctional electrocatalysts is rarely reported. In this work, HEANs distributed on multi-walled carbon nanotubes (HEAN/CNT) are prepared by Joule heating as an example to explain the mechanism of trifunctional electrocatalysis for oxygen reduction, oxygen evolution, and hydrogen evolution reaction. HEAN/CNT excels with unmatched stability, maintaining a 0.8V voltage window for 220 h in zinc-air batteries. Even after 20 h of water electrolysis, its performance remains undiminished, highlighting exceptional endurance and reliability. Moreover, the intrinsic characteristics of the defect structure and electron interaction for HEAN/CNT are investigated in detail. The electrocatalytic mechanism of trifunctional electrocatalysis of HEAN/CNT under different conditions is identified by in situ monitoring and theoretical calculation. Meanwhile, the electron interaction and adaptive regulation of active sites in the trifunctional electrocatalysis of HEANs were further verified by density functional theory. These findings could provide unique ideas for designing inexpensive multifunctional high-entropy electrocatalysts.

Curcumin protects mice with myasthenia gravis by regulating the gut microbiota, short-chain fatty acids, and the Th17/Treg balance.

Curcumin is widely used as a traditional drug in Asia. Interestingly, curcumin and its metabolites have been demonstrated to influence the microbiota. However, the effect of curcumin on the gut microbiota in patients with myasthenia gravis (MG) remains unclear. This study aimed to investigate the effects of curcumin on the gut microbiota community, short-chain fatty acids (SCFAs) levels, intestinal permeability, and Th17/Treg balance in a Torpedo acetylcholine receptor (T-AChR)-induced MG mouse model. The results showed that curcumin significantly alleviated the clinical symptoms of MG mice induced by T-AChR. Curcumin modified the gut microbiota composition, increased microbial diversity, and, in particular, reduced endotoxin-producing Proteobacteria and Desulfovibrio levels in T-AChR-induced gut dysbiosis. Moreover, we found that curcumin significantly increased fecal butyrate levels in mice with T-AChR-induced gut dysbiosis. Butyrate levels increased in conjunction with the increase in butyrate-producing species such as Oscillospira, Akkermansia, and Allobaculum in the curcumin-treated group. In addition, curcumin repressed the increased levels of lipopolysaccharide (LPS), zonulin, and FD4 in plasma. It enhanced Occludin expression in the colons of MG mice induced with T-AChR, indicating dramatically alleviated gut permeability. Furthermore, curcumin treatment corrected T-AChR-induced imbalances in Th17/Treg cells. In summary, curcumin may protect mice against myasthenia gravis by modulating both the gut microbiota and SCFAs, improving gut permeability, and regulating the Th17/Treg balance. This study provides novel insights into curcumin's clinical value in MG therapy.

MicroRNA­155­5p affects regulatory T cell activation and immunosuppressive function by targeting BCL10 in myasthenia gravis.

The imbalance in immune homeostasis plays a crucial role in the pathogenesis of myasthenia gravis (MG). MicroRNAs (miRs) have been identified as key regulators of immune homeostasis. B-cell lymphoma/leukemia 10 (BCL10) has been implicated in the activation and suppressive function of regulatory T cells (Tregs). This study aimed to investigate the potential role of miR-155-5p in modulating the activation and function of Tregs in MG. To achieve this objective, blood samples were collected from MG patients to assess the expression levels of miR-155-5p and BCL10, as well as the proportion of circulating Tregs, in comparison to healthy controls. The correlation between miR-155-5p and BCL10 levels was evaluated in human samples. The expression levels of miR-155-5p and the numbers of circulating Tregs were also examined in an animal model of experimental autoimmune MG (EAMG). A dual-luciferase reporter assay was used to verify whether miR-155-5p can target BCL10. To determine the regulatory function of BCL10 in Tregs, CD4+ CD25+ Tregs were transfected with either small interfering-BCL10 or miR-155-5p inhibitor, and the expression levels of the anti-inflammatory cytokine IL-10 and transcription factors Foxp3, TGF-ß1, CTLA4, and ICOS were measured. The results demonstrated that the expression level of miR-155-5p was significantly higher in patients with MG compared with that in healthy controls, whereas the expression level of BCL10 was significantly decreased in patients with MG. Furthermore, there was a significant negative correlation between the expression levels of miR-155-5p and BCL10. The number of circulating Tregs was significantly reduced in patients with MG and in the spleen of rats with EAMG compared with that in the corresponding control groups. The dual-luciferase reporter assay demonstrated that miR-155-5p could target BCL10. The Tregs transfected with si-BCL10 demonstrated significant decreases in the protein levels of TGF-ß1 and IL-10, as well as in the mRNA expression levels of Foxp3, TGF-ß1, CTLA-4 and ICOS. Conversely, the Tregs transfected with the miR-155-5p inhibitor exhibited a substantial increase in these protein and mRNA expression levels compared with their respective control groups. Furthermore, the knockdown of BCL10 exhibited a decline in the suppressive efficacy of Tregs on the proliferation of CD4+ T cells. Conversely, the suppression of miR-155-5p expression attenuated the inhibition of the BCL10 gene, potentially causing an indirect influence on the suppressive capability of Tregs on the proliferation of CD4+ T cells. BCL10 was thus found to contribute to the activation and immunosuppressive function of Tregs. In summary, the present study demonstrated that miR-155-5p inhibited the activation and immunosuppressive function of Tregs by targeting BCL10, which may be used as a future potential target for the treatment of MG.

Exogenous priming of chitosan induces resistance in Chinese prickly ash against stem canker caused by Fusarium zanthoxyli.

Stem canker is a highly destructive disease that threatens prickly ash plantations in China. This study demonstrated the effective control of stem canker in prickly ash using chitosan priming, reducing lesion areas by 46.77 % to 75.13 % across all chitosan treatments. The mechanisms underlying chitosan-induced systemic acquired resistance (SAR) in prickly ash were further investigated. Chitosan increased H2O2 levels and enhanced peroxidase and catalase enzyme activities. A well-constructed regulatory network depicting the genes involved in the SAR and their corresponding expression levels in prickly ash plants primed with chitosan was established based on transcriptomic analysis. Additionally, 224 ZbWRKYs were identified based on the whole genome of prickly ash, and their phylogenetic evolution, conserved motifs, domains and expression patterns of ZbWRKYs were comprehensively illustrated. The expression of 12 key genes related to the SAR was significantly increased by chitosan, as determined using reverse transcription-quantitative polymerase chain reaction. Furthermore, the activities of defensive enzymes and the accumulation of lignin and flavonoids in prickly ash were significantly enhanced by chitosan treatment. Taken together, this study provides valuable insights into the chitosan-mediated activation of the immune system in prickly ash, offering a promising eco-friendly approach for forest stem canker control.

Candidate molecules as alternative nitric oxide donors with better antibacterial property against Escherichia coli and Staphylococcus aureus.

AIMS: Four nitric oxide (NO) donors, S-nitrosoglutathione (GSNO), S-nitrosocysteine (CySNO), S-nitroso-N-acetylcysteine (SNAC), and 2-(2-S-nitroso propionamide) acetic acid (GAS) were prepared and their physicochemical characteristics were analyzed. Besides, the antibacterial properties of NO donors were investigated against Escherichia coli and Staphylococcus aureus. METHODS AND RESULTS: UV-visible absorption spectrum and Fourier transform infrared spectrum verified the successful preparation of RSNOs. All NO donors (10 mmol l-1) could release NO continuously, and the amount of NO release was from 80.22 µmol l-1 to 706.63 µmol l-1, in which the release of NO from SNAC was the highest, and the release of NO from NaNO2 was the least. The inhibition zone indicated that all NO donors showed stronger antibacterial activity against E. coli and S. aureus, and the antibacterial ability was in the order of SNAC > GSNO > CySNO > GAS > NaNO2 for both E. coli and S. aureus (P < 0.05). Scanning electron microscopy(SEM) showed that all NO donors could result in varying degrees of damage to cell wall and membrane of both E. coli and S. aureus and the damage of E. coli was more severe. CONCLUSION: Four alternative NO donors were successfully synthesized. All alternative NO donors showed better antibacterial properties against E. coli and S. aureus than NaNO2.

Sodium butyrate alleviates R97-116 peptide-induced myasthenia gravis in mice by improving the gut microbiota and modulating immune response.

Fermented butyrate exhibits an anti-inflammatory response to maintain immune homeostasis within the gut. However, the effect and underlying mechanism of butyrate on myasthenia gravis (MG) remain unclear. The changes in the gut microbiota and fecal contents of SCFAs in MG patients were examined. R97-116 peptide was used to induce the experimental autoimmune myasthenia gravis (EAMG) mice and sodium butyrate (NaB) was gavaged to the EAMG mice. Gut microbiota, the frequency of Th1, Th17, Treg, Tfh, and B cells, the levels of IFN-γ, IL-17 A, IL-10, IL-21, and anti-R97-116 IgG, RNA-seq of total B cells in the spleen were explored by metagenomics, flow cytometry, ELISA, and transcriptomics. A significant reduction in SCFA-producing bacteria including Butyricimonas synergistica and functional modules including butyrate synthesis/production II was observed in MG patients and fecal SCFAs detection confirmed the increase. The EAMG mice were successfully constructed and NaB supplementation has changed the composition and function of the gut microbiota. The numbers of Th1, Th17, Tfh, and B cells were significantly increased while that of Treg cells was obviously decreased in EAMG mice compared with controls. Interestingly, NaB treatment has reduced the amounts of Th17, Tfh, and B cells but increased that of Treg cells. Accordingly, the levels of IL-17 A, IL-21, and IgG were increased while IL-10 was decreased in EAMG mice. However, NaB treatment reduced IL-17 A and IL-21 but increased that of IL-10. RNA-seq of B cells has revealed 4577 deferentially expressed genes (DEGs), in which 1218 DEGs were up-regulated while 3359 DEGs were down-regulated in NaB-treated EAMG mice. GO enrichment and KEGG pathway analysis unveiled that the function of these DEGs was mainly focused on immunoglobulin production, mitochondrial respiratory chain complex, ribosome, oxidative phosphorylation, and CNS diseases including amyotrophic lateral sclerosis. We have found that butyrate was significantly reduced in MG patients and NaB gavage could evidently improve MG symptoms in EAMG mice by changing the gut microbiota, regulating the immune response, and altering the gene expression and function of B cells, suggesting NaB might be a potential immunomodulatory supplement for MG drugs.

AXL-Induced Autophagy mitigates experimental autoimmune encephalomyelitis by suppressing microglial inflammation via the PI3K/AKT/mTOR signaling pathway.

Microglia, being the primary immune cells of the central nervous system (CNS), are responsible for pathological inflammatory demyelination in multiple sclerosis (MS). It has been demonstrated that AXL, one of the receptor tyrosine kinases, could alleviate the inflammatory response of microglia. However, the specific mechanism remains unclear. Herein, we explored the role of AXL in the autophagy of microglia and its effect on the experimental autoimmune encephalomyelitis (EAE) model. We revealed that knockout of AXL in BV2 microglia significantly promoted the expression of phosphorylated-PI3K/p-AKT/p-mTOR while significantly inhibiting LC3-Ⅱ/Beclin1. Similarly, autophagy was significantly inhibited in the AXL-/- mice. Knockout of AXL induced serious symptoms, infiltration of inflammatory cells, and demyelination changes, manifesting as the upregulation of pro-inflammatory factors TNF-α and IL-6 and downregulation of anti-inflammatory factors TGF-ß and IL-10. In conclusion, this study substantiated that autophagy induced by AXL inhibited the inflammatory response of microglia and alleviated symptoms of EAE. Autophagy activation was mediated by the PI3K/AKT/mTOR signaling pathway.

Multimodal imaging of primary cardiac angiosarcoma with brain metastasis.

Angiosarcoma is an extremely rare primary cardiac malignant tumor, with characteristics of early blood metastasis and radiochemotherapy resistance. Early diagnosis and timely treatment are of great significance to the prognosis of patients. Hereinafter, we report a case of angiosarcoma in the left atrium of a 61-year-old woman who underwent multimodality imaging and successful resection of the angiosarcoma. Results of the present case suggest that multimodal imaging plays an important role in detecting angiosarcoma and determining the treatment plan and prognosis for patients after treatment.

Lead-Free Zero-Dimensional Zn-Based Metal Halides of Highly Efficient Blue Luminescence from Self-Trapping Exciton.

Recently, hybrid metal halides have received great attention in the field of solid-state lighting because of their diverse structures and excellent photoluminescence properties. In this work, we first reported two hybrid zinc-based metal halides with zero-dimensional structures, (BMPP)2ZnBr4 and (TBA)2ZnBr4, which exhibited broadband emission with large Stokes shifts. Notably, the highest photoluminescence quantum yield of 59.76% was observed. Additionally, the luminescence mechanism of metal halides was investigated by using time-resolved femtosecond transient absorption experiments. A broad excited-state absorption platform with the tendency of slowly decaying was shown in the detection range, demonstrating that after the electrons were excited to the excited state, the free excitons underwent a nonadiabatic transition to self-trapped excitons and went through a radiation recombination process to the ground state. A blue-light-emitting diode could be easily obtained by coating (BMPP)2ZnBr4 on a GaN chip, which indicated that it has good competitiveness in the application of solid-state lighting devices.

Insight into efficient photoluminescence regulation mechanism by lattice distortion and Mn2+ doping in organic-inorganic hybrid perovskites.

The space configurations of organic ammonium cations play a vital role in indirectly revealing the relationship between the structures and photoluminescence properties. Structural transformation induced tunability of the photophysical properties has rarely been reported. In this work, two organic-inorganic halide perovskites with different octahedral distortions were synthesized to explore the relationships between "steric effect" of organic cations and photoluminescence properties. The broadband emission of (DETA)PbBr5·H2O with high octahedral distortion is attributed to self-trapped excitons and trap states, whereas smaller steric hindrance ammonium cation 1,4-butanediamine form a 2D layered perovskite with narrowband emission due to free excitons. More importantly, the photoactive metal ions Mn2+ doping strategy gives rise to tunable broadband light emission from weak to strong orange emission with higher PLQY up to 20.96 % and 12.90% in 0D (DETA)Pb0.2Mn0.8Br5·H2O and 2D (BDA)Pb0.8Mn0.2Br4 respectively. Combined with time-correlated single photon counting and photoluminescence spectra, Mn-doped perovskites reveal energy transfer from host to Mn2+ characteristic energy level (4T1-6A1). Importantly, defect states are reduced by doping manganese ions in (DETA)PbBr5·H2O to enhance photoluminescence intensity. This work sheds light on the mechanism of defect-related emission and provides a successful strategy for designing novel and adjustable materials.

Construction of a novel anoikis-related prognostic model and analysis of its correlation with infiltration of immune cells in neuroblastoma.

Background: Anoikis resistance (AR) plays an important role in the process of metastasis, which is an important factor affecting the risk stage of neuroblastoma (NB). This study aims to construct an anoikis-related prognostic model and analyze the characteristics of hub genes, important pathways and tumor microenvironment of anoikis-related subtypes of NB, so as to provide help for the clinical diagnosis, treatment and research of NB. Methods: We combined transcriptome data of GSE49710 and E-MTAB-8248, screened anoikis-related genes (Args) closely related to the prognosis of NB by univariate cox regression analysis, and divided the samples into anoikis-related subtypes by consistent cluster analysis. WGCNA was used to screen hub genes, GSVA and GSEA were used to analyze the differentially enriched pathways between anoikis-related subtypes. We analyzed the infiltration levels of immune cells between different groups by SsGSEA and CIBERSORT. Lasso and multivariate regression analyses were used to construct a prognostic model. Finally, we analyzed drug sensitivity through the GDSC database. Results: 721 cases and 283 Args were included in this study. All samples were grouped into two subtypes with different prognoses. The analyses of WGCNA, GSVA and GSEA suggested the existence of differentially expressed hub genes and important pathways in the two subtypes. We further constructed an anoikis-related prognostic model, in which 15 Args participated. This model had more advantages in evaluating the prognoses of NB than other commonly used clinical indicators. The infiltration levels of 9 immune cells were significantly different between different risk groups, and 13 Args involved in the model construction were correlated with the infiltration levels of immune cells. There was a relationship between the infiltration levels of 6 immune cells and riskscores. Finally, we screened 15 drugs with more obvious effects on NB in high-risk group. Conclusion: There are two anoikis-related subtypes with different prognoses in the population of NB. The anoikis-related prognostic model constructed in this study can accurately predict the prognoses of children with NB, and has a good guiding significance for clinical diagnosis, treatment and research of NB.

Evaluation of Left Ventricular Systolic Function Using Layer-Specific Strain in Rats Performing Endurance Exercise: A Pilot Study.

OBJECTIVE: The functional characteristics of exercise-induced myocardial hypertrophy were studied in a rat model in conjunction with ultrasound layered strain technique to investigate the hidden changes in the heart brought about by exercise. METHODS: Forty specific pathogen free (SPF) adult Sprague-Dawley rats were selected and randomly divided into two groups of 20 exercise and 20 control rats. The longitudinal and circumferential strain parameters were measured using the ultrasonic stratified strain technique. The differences between the two groups and the predictive effect of stratified strain parameters on left ventricular systolic function were analyzed. RESULTS: The exercise group had significantly higher global endocardial myocardial longitudinal strain (GLSendo), global mid-myocardial global longitudinal strain (GLSmid) and global endocardial myocardial global longitudinal strain (GCSendo) values than the control group (p < 0.05). Even though global mid-myocardial circumferential strain (GCSmid) and global epicardial myocardial circumferential strain (GCSepi) were higher in the exercise group than in the control group, statistical significance was not reached (p > 0.05). Conventional echocardiography parameters were well correlated with GLSendo, GLSmid, and GCSendo (p < 0.05). GLSendo was the best predictor of left ventricular myocardial contractile performance in athletes determined using the receiver operating characteristic curve, with an area under the curve of 0.97, sensitivity of 95% and specificity of 90%. CONCLUSION: Rats performing endurance exercise exhibited subclinical changes in the heart after prolonged high-intensity exercise. A stratified strain parameter, GLSendo, played an important role in the evaluation of LV systolic performance in exercising rats.