TIMP1 protects against blood-brain barrier disruption after subarachnoid haemorrhage by inhibiting ubiquitination of astrocytic ß1-integrin.

BACKGROUND: Astrocytes regulate blood-brain barrier (BBB) integrity, whereas subarachnoid haemorrhage (SAH) results in astrocyte dysregulation and BBB disruption. Here, we explored the involvement of tissue inhibitor of matrix metalloprotease-1 (TIMP1) in astrocyte-mediated BBB protection during SAH, along with its underlying mechanisms. METHODS: C57BL/6J mice were used to establish a model of SAH. The effects of TIMP1 on SAH outcomes were analysed by intraperitoneal injection of recombinant mouse TIMP1 protein (rm-TIMP1; 250 µg/kg). The roles of TIMP1 and its effector ß1-integrin on astrocytes were observed by in vivo transduction with astrocyte-targeted adeno-associated virus carrying TIMP1 overexpression plasmid or ß1-integrin RNAi. The molecular mechanisms underlying TIMP1 and ß1-integrin interactions were explored in primary cultured astrocytes stimulated with red blood cells (RBCs). RESULTS: TIMP1 was upregulated after SAH. Administration of rm-TIMP1 mitigated SAH-induced early brain injury (EBI) in male and female mice. TIMP1 was primarily expressed in astrocytes; its overexpression in astrocytes led to increased ß1-integrin expression in astrocytes, along with the preservation of astrocytic endfoot attachment to the endothelium and subsequent recovery of endothelial tight junctions. All of these effects were reversed by the knockdown of ß1-integrin in astrocytes. Molecular analysis showed that TIMP1 overexpression decreased the RBC-induced ubiquitination of ß1-integrin; this effect was partially achieved by inhibiting the interaction between ß1-integrin and the E3 ubiquitin ligase Trim21. CONCLUSION: TIMP1 inhibits the interaction between ß1-integrin and Trim21 in astrocytes, thereby rescuing the ubiquitination of astrocytic ß1-integrin. It subsequently restores interactions between astrocytic endfeet and the endothelium, as well as BBB integrity, eventually mitigating SAH-induced EBI.

RBBP6 maintains glioblastoma stem cells through CPSF3-dependent alternative polyadenylation.

Glioblastoma is one of the most lethal malignant cancers, displaying striking intratumor heterogeneity, with glioblastoma stem cells (GSCs) contributing to tumorigenesis and therapeutic resistance. Pharmacologic modulators of ubiquitin ligases and deubiquitinases are under development for cancer and other diseases. Here, we performed parallel in vitro and in vivo CRISPR/Cas9 knockout screens targeting human ubiquitin E3 ligases and deubiquitinases, revealing the E3 ligase RBBP6 as an essential factor for GSC maintenance. Targeting RBBP6 inhibited GSC proliferation and tumor initiation. Mechanistically, RBBP6 mediated K63-linked ubiquitination of Cleavage and Polyadenylation Specific Factor 3 (CPSF3), which stabilized CPSF3 to regulate alternative polyadenylation events. RBBP6 depletion induced shortening of the 3'UTRs of MYC competing-endogenous RNAs to release miR-590-3p from shortened UTRs, thereby decreasing MYC expression. Targeting CPSF3 with a small molecular inhibitor (JTE-607) reduces GSC viability and inhibits in vivo tumor growth. Collectively, RBBP6 maintains high MYC expression in GSCs through regulation of CPSF3-dependent alternative polyadenylation, providing a potential therapeutic paradigm for glioblastoma.

Radiotherapy-Induced Astrocyte Senescence Promotes an Immunosuppressive Microenvironment in Glioblastoma to Facilitate Tumor Regrowth.

Accumulating evidence suggests that changes in the tumor microenvironment caused by radiotherapy are closely related to the recurrence of glioma. However, the mechanisms by which such radiation-induced changes are involved in tumor regrowth have not yet been fully investigated. In the present study, how cranial irradiation-induced senescence in non-neoplastic brain cells contributes to glioma progression is explored. It is observed that senescent brain cells facilitated tumor regrowth by enhancing the peripheral recruitment of myeloid inflammatory cells in glioblastoma. Further, it is identified that astrocytes are one of the most susceptible senescent populations and that they promoted chemokine secretion in glioma cells via the senescence-associated secretory phenotype. By using senolytic agents after radiotherapy to eliminate these senescent cells substantially prolonged survival time in preclinical models. The findings suggest the tumor-promoting role of senescent astrocytes in the irradiated glioma microenvironment and emphasize the translational relevance of senolytic agents for enhancing the efficacy of radiotherapy in gliomas.

Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma.

The mesenchymal (MES) phenotype of glioblastoma (GBM) is the most aggressive and therapy-resistant subtype of GBM. The MES phenotype transition during tumor progression results from both tumor-intrinsic genetic alterations and tumor-extrinsic microenvironmental factors. In this study, we sought to identify genes that can modulate the MES phenotype via both mechanisms. By integrating weighted gene co-expression network analysis (WGCNA) and the differential expression analysis of hypoxia-immunosuppression-related genes, we identified the plasminogen activator, urokinase receptor (PLAUR) as the hub gene. Functional enrichment analysis and GSVA analysis demonstrated that PLAUR was associated with the MES phenotype of glioma and the hypoxia-immunosuppression-related microenvironmental components. Single-cell sequencing analysis revealed that PLAUR mediated the ligand-receptor interaction between tumor-associated macrophages (TAMs) and glioma cells. Functional experiments in vitro with cell lines or primary glioma cells and xenograft models using BALB/c nude mice confirmed the role of PLAUR in promoting the MES phenotype of GBM. Our findings indicate that PLAUR regulates both glioma cells and tumor cell-extrinsic factors that favor the MES phenotype and suggest that PLAUR might be a potential target for GBM therapy.

Single-Cell Transcriptomics Reveals the Heterogeneity of the Immune Landscape of IDH-Wild-Type High-Grade Gliomas.

Isocitrate dehydrogenase (IDH)-wild-type (WT) high-grade gliomas, especially glioblastomas, are highly aggressive and have an immunosuppressive tumor microenvironment. Although tumor-infiltrating immune cells are known to play a critical role in glioma genesis, their heterogeneity and intercellular interactions remain poorly understood. In this study, we constructed a single-cell transcriptome landscape of immune cells from tumor tissue and matching peripheral blood mononuclear cells (PBMC) from IDH-WT high-grade glioma patients. Our analysis identified two subsets of tumor-associated macrophages (TAM) in tumors with the highest protumorigenesis signatures, highlighting their potential role in glioma progression. We also investigated the T-cell trajectory and identified the aryl hydrocarbon receptor (AHR) as a regulator of T-cell dysfunction, providing a potential target for glioma immunotherapy. We further demonstrated that knockout of AHR decreased chimeric antigen receptor (CAR) T-cell exhaustion and improved CAR T-cell antitumor efficacy both in vitro and in vivo. Finally, we explored intercellular communication mediated by ligand-receptor interactions within the tumor microenvironment and PBMCs and revealed the unique cellular interactions present in the tumor microenvironment. Taken together, our study provides a comprehensive immune landscape of IDH-WT high-grade gliomas and offers potential drug targets for glioma immunotherapy.

Development of microRNA-based therapeutics for central nervous system diseases.

MicroRNA (miRNA)-mediated gene silencing is a method of RNA interference in which a miRNA binds to messenger RNA sequences and regulates target gene expression. MiRNA-based therapeutics have shown promise in treating a variety of central nervous system diseases, as verified by results from diverse preclinical model organisms. Over the last decade, several miRNA-based therapeutics have entered clinical trials for various kinds of diseases, such as tumors, infections, and inherited diseases. However, such clinical trials for central nervous system diseases are scarce, and many central nervous system diseases, including hemorrhagic stroke, ischemic stroke, traumatic brain injury, intractable epilepsy, and Alzheimer's disease, lack effective treatment. Considering its effectiveness for central nervous system diseases in preclinical experiments, microRNA-based intervention may serve as a promising treatment for these kinds of diseases. This paper reviews basic principles and recent progress of miRNA-based therapeutics and summarizes general procedures to develop such therapeutics for treating central nervous system diseases. Then, the current obstacles in drug development are discussed. This review also provides a new perspective on possible solutions to these obstacles in the future.

Experimental and theoretical study on the photoionization of styrene.

This study employed a vacuum ultraviolet synchrotron radiation source and reflectron time-of-flight mass spectrometry (TOF-MS) to investigate the photoionization and dissociation of styrene. By analyzing the photoionization mass spectrum and efficiency curve alongside G3B3 theoretical calculations, we determined the ionization energy of the molecular ion, appearance energy of fragment ions, and relevant dissociation pathways. The major ion peaks observed in the photoionization mass spectra of styrene correspond to C8 H8 + , C8 H7 + and C6 H6 + . The ionization energy of styrene is measured as 8.46 ± 0.03 eV, whereas the appearance energies of C8 H7 + and C6 H6 + are found to be 12.42 ± 0.03 and 12.22 ± 0.03 eV, respectively, in agreement with theoretical values. The main channel for the photodissociation of styrene molecular ions is the formation of benzene ions, whereas the dissociation channel that loses hydrogen atoms is the secondary channel. Based on the experimental results and empirical formulas, the required dissociation energies (Ed ) of C8 H7 + , C8 H6 + and C6 H6 + are calculated to be (3.96 ± 0.06), (4.00 ± 0.06) and (3.76 ± 0.06) eV, respectively. Combined with related thermochemical parameters, the standard enthalpies of formations of C8 H8 + , C8 H7 + , C8 H6 + and C6 H6 + are determined to be 964.2, 1346.3, 1350.2 and 1327.0 kJ/mol, respectively. Based on the theoretical study, the kinetic factors controlling the styrene dissociation reaction process are determined by using the Rice-Ramsperger-Kassel-Marcus (RRKM) theory. This provides a reference for further research on the atmospheric photooxidation reaction mechanism of styrene in atmospheric and interstellar environments.

Role of complement C1q/C3-CR3 signaling in brain injury after experimental intracerebral hemorrhage and the effect of minocycline treatment.

Aim: The complement cascade is activated and may play an important pathophysiologic role in brain injury after experimental intracerebral hemorrhage (ICH). However, the exact mechanism of specific complement components has not been well studied. This study determined the role of complement C1q/C3-CR3 signaling in brain injury after ICH in mice. The effect of minocycline on C1q/C3-CR3 signaling-induced brain damage was also examined. Methods: There were three parts to the study. First, the natural time course of C1q and CR3 expression was determined within 7 days after ICH. Second, mice had an ICH with CR3 agonists, LA-1 or vehicle. Behavioral score, neuronal cell death, hematoma volume, and oxidative stress response were assessed at 7 days after ICH. Third, the effect of minocycline on C1q/C3-CR3 signaling and brain damage was examined. Results: There were increased numbers of C1q-positive and CR3-positive cells after ICH. Almost all perihematomal C1q-positive and CR3-positive cells were microglia/macrophages. CR3 agonist LA-1 aggravated neurological dysfunction, neuronal cell death, and oxidative stress response on day 7 after ICH, as well as enhancing the expression of the CD163/HO-1 pathway and accelerating hematoma resolution. Minocycline treatment exerted neuroprotective effects on brain injury following ICH, partly due to the inhibition of C1q/C3-CR3 signaling, and that could be reversed by LA-1. Conclusions: The complement C1q/C3-CR3 signaling is upregulated after ICH. The activation of C1q/C3-CR3 signaling by LA-1 aggravates brain injury following ICH. The neuroprotection of minocycline, at least partly, is involved with the repression of the C1q/C3-CR3 signaling pathway.

Unusual Diradical Intermediates in Ozonolysis of Alkenes: A Combined Theoretical and Synchrotron Radiation Photoionization Mass Spectrometric Study on Ozonolysis of Alkyl Vinyl Ethers.

Calculations and experiments were conducted on ozonolysis of ethyl vinyl ether (EVE) and butyl vinyl ether to identify an unconventional diradical intermediate generated from the O-O bond cleavage of primary ozonide. The diradical can undergo a H atom shifting process that yields keto-hydroperoxide (KHP), the characteristic product that identifies the existence of a diradical intermediate. RRKM-ME calculation, based on the PES at the CCSD(T)/VTZ//M06-2X/6-311++G(2df,2p) level, disclosed branching ratios of ∼0.65% for KHP formation. Using synchrotron-generated vacuum-ultraviolet photoionization mass spectrometry measurements, the formation of KHPs (C4H8O4) in ozonolysis of EVE was confirmed by ion signals of C4H8O4+ (ionization of KHP) and C4H7O2+ (ion fragment from the loss of HO2 from KHP) by comparing their photoionization efficiency spectra with the calculated adiabatic ionization energies and appearance energies.

Matricellular protein tenascin C: Implications in glioma progression, gliomagenesis, and treatment.

Matricellular proteins are nonstructural extracellular matrix components that are expressed at low levels in normal adult tissues and are upregulated during development or under pathological conditions. Tenascin C (TNC), a matricellular protein, is a hexameric and multimodular glycoprotein with different molecular forms that is produced by alternative splicing and post-translational modifications. Malignant gliomas are the most common and aggressive primary brain cancer of the central nervous system. Despite continued advances in multimodal therapy, the prognosis of gliomas remains poor. The main reasons for such poor outcomes are the heterogeneity and adaptability caused by the tumor microenvironment and glioma stem cells. It has been shown that TNC is present in the glioma microenvironment and glioma stem cell niches, and that it promotes malignant properties, such as neovascularization, proliferation, invasiveness, and immunomodulation. TNC is abundantly expressed in neural stem cell niches and plays a role in neurogenesis. Notably, there is increasing evidence showing that neural stem cells in the subventricular zone may be the cells of origin of gliomas. Here, we review the evidence regarding the role of TNC in glioma progression, propose a potential association between TNC and gliomagenesis, and summarize its clinical applications. Collectively, TNC is an appealing focus for advancing our understanding of gliomas.

Global Trends and Hotspots in Trigeminal Neuralgia Research From 2001 to 2021: A Bibliometric Analysis.

Background: In recent years, there have been an increasing number of studies on trigeminal neuralgia (TN). However, a scientific and comprehensive study of the current situation and trends in the field of TN research is lacking. The purpose of this study is to summarize and visualize the development, research hotspots, and future trends in TN based on a bibliometric approach. Methods: Studies on TN published from 2001 to 2021 were obtained from the Web of Science Core Collection (WoSCC). Bibliometrics, CiteSpace, and VOSviewer tools were used for bibliometric analysis and visualization. Results: In total, 4,112 documents were searched. The number of research articles in the field is generally on an upward trend, with the fastest growth in the number of articles from 2017 to 2020. Shanghai Jiao Tong University, Pittsburgh University, and Mayo Clinic are the three institutions with the most publications. Shiting Li and Zakrzewska JM are the most prolific author and top co-cited authors, respectively. The Journal of Neurosurgery is the most influential journal. The top 5 keywords in that time frame are TN, microvascular decompression, facial pain, stereotactic radiosurgery, and neuropathic pain. Conclusion: This is the first comprehensive scientific bibliometric analysis of the global research field on TN over the past 21 years, providing a meaningful reference for further exploration of topical issues and research trends in the field.

The Novel Nrf2 Activator Omaveloxolone Regulates Microglia Phenotype and Ameliorates Secondary Brain Injury after Intracerebral Hemorrhage in Mice.

The polarization of microglia is recognized as a crucial factor in reducing neuroinflammation and promoting hematoma clearance after intracerebral hemorrhage (ICH). Previous studies have revealed that redox components participate in the regulation of microglial polarization. Recently, the novel Nrf2 activator omaveloxolone (Omav) has been validated to improve neurological function in patients with neurodegenerative disorders by regulating antioxidant responses. In this study, we examined the efficacy of Omav in ICH. Omav significantly promoted Nrf2 nuclear accumulation and the expression of HO-1 and NQO1 in BV2 cells. In addition, both in vitro and in vivo experiments showed that Omav treatment inhibited M1-like activation and promoted the activation of the M2-like microglial phenotype. Omav inhibited OxyHb-induced ROS generation and preserved the function of mitochondria in BV2 cells. Intraperitoneal administration of Omav improved sensorimotor function in the ICH mouse model. Importantly, these effects were blocked by pretreatment with ML385, a selective inhibitor of Nrf2. Collectively, Omav modulated microglial polarization by activating Nrf2 and inhibiting ROS generation in ICH models, suggesting that it might be a promising drug candidate for the treatment of ICH.

Case Report: A Pregnant Woman Diagnosed as ALK-Rearrangement Lung Large Cell Neuroendocrine Cancer With Brain Metastasis.

Concomitant malignant tumors and pregnancy present many difficult questions to both clinicians and patients. Due to no specific guidelines, each aspect of clinical management requires special considerations. This current report presents a rare case of a 38-year-old pregnant woman at gestational age 33 weeks with complaints of weakness of her right limbs for 2 weeks. After successive cesarean section and craniotomy, a diagnosis of lung large cell neuroendocrine carcinoma (LCNEC) metastatic to the brain was eventually made. Next generation sequencing (NGS) showed ALK-EML4 gene fusion. Immediately afterwards she was started on the targeted therapy with the ALK inhibitor alectinib. Ten months later, all known lesions exhibited a rapid regression, and no new brain metastases were found. Consequently, the therapeutic effect was considered as a partial response. Then, we review the previous literature using PubMed on maternal malignant brain tumors diagnosed during pregnancy, or lung LCNEC associated with ALK fusion, or ALK inhibitors treatment among the pregnant women, eventually, and discuss the concerns of dealing with these patients.

CircSCAP Aggravates Oxidized Low-density Lipoprotein-induced Macrophage Injury by Upregulating PDE3B by miR-221-5p in Atherosclerosis.

ABSTRACT: Atherosclerosis (AS) is a major risk factor for cardiovascular disease, in which circular RNAs play important regulatory roles. This research aimed to explore the biological role of circular RNA Sterol Regulatory Element Binding Transcription Factor Chaperone (circSCAP) (hsa_circ_0001292) in AS development. Real-time PCR or Western blot assay was conducted to analyze RNA or protein expression. Cell proliferation and apoptosis were analyzed by CCK-8 assay and flow cytometry. The levels of lipid accumulation-associated indicators and oxidative stress factors were detected using commercial kits. The levels of inflammatory cytokines were examined using enzyme-linked immunosorbent assay. Intermolecular interaction was verified by dual-luciferase reporter analysis or RNA pull-down analysis. CircSCAP and phosphodiesterase 3B (PDE3B) levels were elevated, whereas the miR-221-5p level was decreased in patients with AS and oxidized low-density lipoprotein (ox-LDL)-induced THP-1 cells. CircSCAP absence suppressed lipid deposition, inflammation, and oxidative stress in ox-LDL-induced THP-1 cells. MiR-221-5p was a target of circSCAP, and anti-miR-221-5p largely reversed si-circSCAP-induced effects in ox-LDL-induced THP-1 cells. PDE3B was a target of miR-221-5p, and PDE3B overexpression largely counteracted miR-221-5p accumulation-mediated effects in ox-LDL-induced THP-1 cells. NF-κB signaling pathway was regulated by circSCAP/miR-221-5p/PDE3B axis in ox-LDL-induced THP-1 cells. In conclusion, circSCAP facilitated lipid accumulation, inflammation, and oxidative stress in ox-LDL-induced THP-1 macrophages by regulating miR-221-5p/PDE3B axis.

Epitranscriptomic editing of the RNA N6-methyladenosine modification by dCasRx conjugated methyltransferase and demethylase.

N6-methyladenosine (m6A) is a common modification on endogenous RNA transcripts in mammalian cells. Technologies to precisely modify the RNA m6A levels at specific transcriptomic loci empower interrogation of biological functions of epitranscriptomic modifications. Here, we developed a bidirectional dCasRx epitranscriptome editing platform composed of a nuclear-localized dCasRx conjugated with either a methyltransferase, METTL3, or a demethylase, ALKBH5, to manipulate methylation events at targeted m6A sites. Leveraging this platform, we specifically and efficiently edited m6A modifications at targeted sites, reflected in gene expression and cell proliferation. We employed the dCasRx epitranscriptomic editor system to elucidate the molecular function of m6A-binding proteins YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3), revealing that YTHDFs promote m6A-mediated mRNA degradation. Collectively, our dCasRx epitranscriptome perturbation platform permits site-specific m6A editing for delineating of functional roles of individual m6A modifications in the mammalian epitranscriptome.

Ro-vibrational Distribution of NO+ Dissociated from NO2+ Ions in the a3B2 and b3A2 States: A Slow "Impulsive" Dissociation Example Revealed from Threshold Photoelectron-Photoion Coincidence Imaging.

To clarify the contentions about dissociative photoionization mechanism of nitrogen dioxide via the a3B2 and b3A2 ionic states, a new threshold photoelectron-photoion coincidence (TPEPICO) velocity imaging has been conducted in the 12.8-14.0 eV energy range at the Hefei Light Source. The fine vibrational-resolved threshold photoelectron spectrum agrees well with the previous measurements. The ro-vibrational distributions of NO+, as the unique fragment ion in the dissociation of NO2+ in specific vibronic levels of a3B2 and b3A2 states, are derived from the recorded TPEPICO velocity images. A "cold" vibrational (v+ = 0) and "hot" rotational population is observed at the a3B2(0,3,0) and (0,4,0) vibronic levels, while the dissociation of NO2+ in b3A2(0,0,0) leads to the NO+ fragment with both hot vibrational and rotational populations. With the aid of the quantum chemical calculations at the time-dependent B3LYP level, minimum energy paths on the potential energy surfaces of the a3B2 and b3A2 states clarify their adiabatic dissociation mechanisms near the thresholds, and this study proposes reliable explanations for the observed internal energy distributions of fragment ions. Additionally, this study provides valuable insights into the application of the classical "impulsive" model on an overall slow dissociation process.

Intramolecular CH3-migration-controlled cation reactions in the VUV photochemistry of 2-methyl-3-buten-2-ol investigated by synchrotron photoionization mass spectrometry and theoretical calculations.

2-Methyl-3-buten-2-ol (MBO232) is a biogenic volatile organic compound (BVOC), and has a large percentage of emission into the atmosphere. The vacuum ultraviolet (VUV) photochemistry of BVOCs is of great importance for atmospheric chemistry. Studies have been carried out on several BVOCs but have not extended to MBO232. In the present report, the photoionization and dissociation processes of MBO232 in the energy range of 8.0-15.0 eV have been studied by tunable VUV synchrotron radiation coupled with a time-of-flight mass spectrometer. By measuring the photoionization spectra, the adiabatic ionization energy (AIE) of MBO232 and the appearance energies (AEs) of the eight identified fragment ions (i.e., C4H7O+, C3H7O+, C5H9+, C3H6O+, CH3CO+, CH3O+, C4H5+, and C3H5+) were determined. High-level quantum chemistry calculations suggest that there are 3 direct channels and 5 indirect channels via transition states and intermediates accountable for these fragments. Among the reaction channels, the direct elimination of CH3 is the most dominant channel and produces the resonance-stabilized radical cation. Most interestingly, our results show that the CH3 selectively migrates towards the cation, which leads to the different indirect channels. The CH3 migration is a rare process in the dissociative photoionization of metal-free organic molecules. We explain the process by molecular orbital calculations and electron localization function analysis and explore the non-conventional dissociation channels via the CH3 roaming mechanism. We further perform kinetics analysis using RRKM theory for the channels of interest. The activation barrier, and rate constants are analyzed for the branching fractions of the products. These results provide important implications for the VUV photochemistry of BVOCs in the atmosphere.

Metformin Alleviates Neuroinflammation Following Intracerebral Hemorrhage in Mice by Regulating Microglia/Macrophage Phenotype in a Gut Microbiota-Dependent Manner.

The gut microbiota plays a key role in regulating intracerebral hemorrhage (ICH)-induced neuroinflammation. The anti-neuroinflammatory effects of metformin (Met) have been reported in many central nervous system (CNS) diseases. However, whether Met regulates neuroinflammation through the gut microbiota in ICH-induced brain injury remains unknown. We found that Met treatment substantially alleviated neurological dysfunction and reduced neuroinflammation by inhibiting pro-inflammatory polarization of microglia/macrophages in mice with ICH. Moreover, Met treatment altered the microbiota composition and improved intestinal barrier function. The expression of lipopolysaccharide-binding protein (LBP), a biomarker of intestinal barrier damage, was also significantly reduced by Met treatment. Neuroinflammation was also potently ameliorated after the transplantation of fecal microbiota from Met-treated ICH mice. The neuroprotective effects of fecal microbiota transplantation (FMT) were similar to those of oral Met treatment. However, suppression of the gut microbiota negated the neuroprotective effects of Met in ICH mice. Therefore, Met is a promising therapeutic agent for neuroinflammation owing to ICH-induced imbalance of the gut microbiota.

C-F and C-H bond cleavage mechanisms of trifluoromethane ions in low-lying electronic states: threshold photoelectron-photoion coincidence imaging and theoretical investigations.

Dissociative ionization of trifluoromethane (CHF3) is investigated in the 13.9-18.0 eV energy range using the threshold photoelectron-photoion coincidence (TPEPICO) technique coupled to a vacuum ultraviolet synchrotron radiation source. Four electronic states of CHF3+, i.e., the X2A1, A2A2, B2E, and C2E states, are populated upon ionization. In this energy range, the parent CHF3+ ions fully dissociate. For the CHF3+ ions in the ground state, the analysis of the time-of-flight profile of the unique CF3+ fragment ions suggests statistical dissociation. For the electronically excited CHF3+ ions, the C-F bond cleavage preferentially occurs to predominantly produce CHF2+ + F. Moreover, all TPEPICO images of the CHF2+ ions exhibit identical patterns, with a weak central spot revealing a previously unobserved statistical decomposition pathway, and the predominant ring in the images documents a fast nonstatistical dissociation channel. The unimolecular decomposition mechanisms of the CHF3+ ions are illuminated with the aid of the one-dimensional potential energy curves along the C-H and C-F coordinates calculated using the time-dependent density-functional theory. Moreover, a comparison of the dissociation dynamics of CHF3+ in these low-lying states with those of CF3Cl+ strongly suggests a substituent effect of chlorine atoms on the binding structure.

Solitary fibrous tumor of the pineal region with delayed ectopic intracranial metastasis: A case report and review of the literature.

RATIONALE: Solitary fibrous tumors of central nervous system are rare spindle-cell mesenchymal tumors. Although most are benign in nature, malignant transformation and extracranial metastasis have been reported. Up to now, only one case of CSF dissemination was described. Here we described an extremely rare case of intracranial Solitary fibrous tumors arising from the pineal region with a delayed ectopic metastasis. PATIENT CONCERNS: A 35-year-old female presented with double vision, memory disturbance and unsteady gait was referred to our center. MRI showed an irregular mass in the pineal region. DIAGNOSES: The patient was diagnosed as pineal tumor, with unknown pathology. INTERVENTIONS: Gross total resection was achieved and the pathologic studies confirmed a solitary fibrous tumor. Thirty-nine months later local recurrence occurred and gamma-knife radiotherapy was offered. Seven months later, MRI found a metastasis in the left temporal lobe. Surgical resection was conducted and pathological analysis revealed changes in cell morphology, counts and Ki-67 level, confirmed the diagnosis of solitary fibrous tumor/hemangiopericytoma (WHO Grade III). The patient received post-operational radiotherapy. OUTCOMES: The patient was followed up for 7 months with no signs of recurrence. LESSONS: Here, we report an extremely rare case of primary solitary fibrous tumor of pineal region with delayed intracranial ectopic metastasis, together with literature review of metastatic solitary fibrous tumors. Strict surveillance is strongly recommended, considering the malignant potential of this seemingly benign disease entity. Complete resection of the tumor is the treatment of first choice and radiotherapy might be an effective adjuvant therapy for high grade SFT/HPCs.