Porcine epidemic diarrhea virus E protein induces formation of stress granules and attenuates protein translation through activation of the PERK/eIF2α signaling pathway.

Porcine epidemic diarrhea virus (PEDV) envelope protein (E) has been characterized as an important structural protein that plays critical roles in the interplay with its host to affect the virus life cycle. Stress granules (SGs) are host translationally silent ribonucleoproteins, which are mainly induced by the phosphorylation of eIF2α in the PERK/eIF2α signaling pathway. Our previous study found that PEDV E protein caused endoplasmic reticulum stress response (ERS)-mediated suppression of antiviral proteins' translation. However, the link and the underlying mechanism by which PEDV induces SGs formation and suppresses host translation remain elusive. In this study, our results showed that PEDV E protein significantly elevated the expression of GRP78, CANX, and phosphorylation of PERK and eIF2α, indicating that the PERK/eIF2α branch of ERS was activated. PEDV E protein localized to the ER and aggregated into puncta to reconstruct ER structure, and further induced SGs formation, which has been caused through upregulating the G3BP1 expression level. In addition, a significant global translational stall and endogenous protein translation attenuation were detected in the presence of E protein overexpression, but the global mRNA transcriptional level remained unchanged, suggesting that the shutoff of protein translation was associated with the translation, not with the transcription process. Collectively, this study demonstrates that PERK/eIF2α activation is required for SGs formation and protein translation stall. This study is beneficial for us to better understand the mechanism by which PEDV E suppresses host protein synthesis, and provides us a new insight into the host translation regulation during virus infection.

A lysosome-targeted fluorescent probe for fluorescence imaging of hypochlorous acid in living cells and in vivo.

Lysosomes, as crucial acidic organelles in cells, play a significant role in cellular functions. The levels and distribution of hypochlorous acid (HOCl) within lysosomes can profoundly impact their biological functionality. Hence, real-time monitoring of the concentration of HOCl in lysosomes holds paramount importance for further understanding various physiological and pathological processes associated with lysosomes. In this study, we developed a bodipy-based fluorescent probe derived from pyridine and phenyl selenide for the specific detection of HOCl in aqueous solutions. Leveraging the probe's sensitive photoinduced electron transfer effect from phenyl selenide to the fluorophore, the probe exhibited satisfactory high sensitivity (with a limit of detection of 5.2 nM and a response time of 15 s) to hypochlorous acid. Further biological experiments confirmed that the introduction of the pyridine moiety enabled the probe molecule to selectively target lysosomes. Moreover, the probe successfully facilitated real-time monitoring of HOCl in cell models stimulated by N-acetylcysteine (NAC) and lipopolysaccharide (LPS), as well as in a normal zebrafish model. This provides a universal method for dynamically sensing HOCl in lysosomes.

Spin-degree manipulation for one-dimensional room-temperature ferromagnetism in a haldane system.

The intricate correlation between lattice geometry, topological behavior and charge degrees of freedom plays a key role in determining the physical and chemical properties of a quantum-magnetic system. Herein, we investigate the introduction of the unusual oxidation state as an alternative pathway to modulate the magnetic ground state in the well-known S = 1 Haldane system nickelate Y2BaNiO5 (YBNO). YBNO is topologically reduced to incorporate d9-Ni+ (S = 1/2) in the one-dimensional Haldane chain system. The random distribution of Ni+ for the first time results in the emergence of a one-dimensional ferromagnetic phase with a transition temperature far above room temperature. Theoretical calculations reveal that the antiferromagnetic interplay can evolve into ferromagnetic interactions with the presence of oxygen vacancies, which promotes the formation of ferromagnetic order within one-dimensional nickel chains. The unusual electronic instabilities in the nickel-based Haldane system may offer new possibilities towards unconventional physical and chemical properties from quantum interactions.

Thermodynamic properties and enhancement of diamagnetism in nitrogen doped lutetium hydride synthesized at high pressure.

Nitrogen doped lutetium hydride has drawn global attention in the pursuit of room-temperature superconductivity near ambient pressure and temperature. However, variable synthesis techniques and uncertainty surrounding nitrogen concentration have contributed to extensive debate within the scientific community about this material and its properties. We used a solid-state approach to synthesize nitrogen doped lutetium hydride at high pressure and temperature (HPT) and analyzed the residual starting materials to determine its nitrogen content. High temperature oxide melt solution calorimetry determined the formation enthalpy of LuH1.96N0.02 (LHN) from LuH2 and LuN to be -28.4 ± 11.4 kJ/mol. Magnetic measurements indicated diamagnetism which increased with nitrogen content. Ambient pressure conductivity measurements observed metallic behavior from 5 to 350 K, and the constant and parabolic magnetoresistance changed with increasing temperature. High pressure conductivity measurements revealed that LHN does not exhibit superconductivity up to 26.6 GPa. We compressed LHN in a diamond anvil cell to 13.7 GPa and measured the Raman signal at each step, with no evidence of any phase transition. Despite the absence of superconductivity, a color change from blue to purple to red was observed with increasing pressure. Thus, our findings confirm the thermodynamic stability of LHN, do not support superconductivity, and provide insights into the origins of its diamagnetism.

A new highly sensitive fluorescent probe for visualization of phosgene in liquid and gas phases.

Phosgene is an important and widely used highly toxic chemical that poses a serious potential threat to public health and property if leaked or abused. Therefore, developing an efficient and convenient detection method for phosgene is of great significance. In this work, we synthesized a novel fluorescent probe, BCyP, based on benzohemicyanine for highly selective and sensitive detection of phosgene in both liquid and gas phases. The probe uses amino alcohol as a specific recognition group for phosgene and does not fluoresce due to the strong intramolecular charge transfer effect (ICT). However, in the presence of phosgene, the amino alcohol part in the probe can form oxazolidinone in situ with phosgene, reducing the ICT effect in the probe molecule and lighting fluorescence, thus realizing the selective phosgene detection. The probe exhibits good specificity towards phosgene, with significant fluorescence enhancement (approximately 400-fold), a remarkable Stokes shift (139 nm), a fast response speed (less than 17 s), and a low detection limit (0.12 ppm). Additionally, we prepared a phosgene detection paper strip loaded with the probe on filter paper and combined it with color recognition software on a smartphone to achieve visual detection of phosgene in the gas phase.

Signatures of superconductivity near 80 K in a nickelate under high pressure.

Although high-transition-temperature (high-Tc) superconductivity in cuprates has been known for more than three decades, the underlying mechanism remains unknown1-4. Cuprates are the only unconventional superconductors that exhibit bulk superconductivity with Tc above the liquid-nitrogen boiling temperature of 77 K. Here we observe that high-pressure resistance and mutual inductive magnetic susceptibility measurements showed signatures of superconductivity in single crystals of La3Ni2O7 with maximum Tc of 80 K at pressures between 14.0 GPa and 43.5 GPa. The superconducting phase under high pressure has an orthorhombic structure of Fmmm space group with the [Formula: see text] and [Formula: see text] orbitals of Ni cations strongly mixing with oxygen 2p orbitals. Our density functional theory calculations indicate that the superconductivity emerges coincidently with the metallization of the σ-bonding bands under the Fermi level, consisting of the [Formula: see text] orbitals with the apical oxygen ions connecting the Ni-O bilayers. Thus, our discoveries provide not only important clues for the high-Tc superconductivity in this Ruddlesden-Popper double-layered perovskite nickelates but also a previously unknown family of compounds to investigate the high-Tc superconductivity mechanism.

A novel benzo hemicyanine-based fluorescent probe for susceptible visualizing detection of phosgene.

Leakage and misuse of phosgene, a common and highly hazardous industrial chemical, have always constituted a safety risk. Therefore, it is crucial to develop sensitive detection methods for gaseous phosgene. This work describes the design and development of a new fluorescent dye based on benzohemicyanine, as well as the synthesis of fluorescent probes for the sensitive detection of gaseous phosgene. Due to the excellent intramolecular charge transfer (ICT) effect from the strong electron-donating impact of the o-aminophenol group on benzo hemicyanine, the probe does not emit fluorescence. When the probe reacts with phosgene, the ICT effect is inhibited, and the result exhibits observable green fluorescence, thereby visualizing the response to phosgene. The probe offers exceptional sensitivity, a rapid response, and a low phosgene detection limit. In addition, we developed probe-loaded, portable test strips for the quick and sensitive detection of phosgene in the gas phase. Finally, the constructed probe-loaded test strips were utilized effectively to monitor the simulated phosgene leakage.

A benzo BODIPY based fluorescent probe for selective visualization of hypochlorous acid in living cells and zebrafish.

Hypochlorous acid (HOCl) is an essential endogenous reactive oxygen species in biological systems, playing a critical role in various physiological processes. Real-time monitoring of HOCl concentration in living organisms is essential for understanding its biological functions and pathological roles. In this study, we developed a novel fluorescent probe based on benzobodipy, BBDP, for rapid and sensitive detection of HOCl in aqueous solutions. The probe exhibited a significant fluorescence turn-on response to HOCl based on its specific oxidation reaction towards diphenylphosphine, with high selectivity, instantaneous response (less than 10 s), and low detection limit (21.6 nM). Furthermore, bioimaging results illustrated that the probe could be applied for real-time fluorescence imaging of HOCl in live cells and zebrafish. The development of BBDP may provide a new tool for exploring the biological functions of HOCl and its pathological roles in diseases.

A new benzo-bodipy based fluorescent probe for the highly sensitive detection of hypochlorous acid and its application in the living cells and zebrafish imaging.

Due to the highly significant biological activity of hypochlorous acid, the monitoring of its concentration in vivo has received extensive attention. In this work, a photoinduced electron transfer (PeT) based benzo-bodipy fluorescent probe BBy-T has been developed for the rapid, sensitive, and selective detection of HClO in an aqueous solution. Based on the HClO-specific oxidation reaction, BBy-T exhibited a distinct fluorescence turn-on response to HClO with a remarkable Stokes shift (84 nm), immediate response (less than 20 s), and low detection limit (13.7 nM). In addition, the bioimaging results indicated that the probe BBy-T could be applied to real-time fluorescence imaging of living HeLa cells as well as living zebrafish.

Inhibition of angiotensin II type 1 receptor partially prevents acute elevation of pulmonary arterial pressure induced by endovascular ethanol injection.

This study aimed to examine whether the administration of losartan can prevent acute elevation of pulmonary arterial pressure (AEPAP) induced by endovascular ethanol injection and to assess its related mechanisms. Male swine were selected and performed with absolute ethanol endovascular injection. Saline was used as the negative control. Losartan was administered preoperatively. Pulmonary arterial pressure (PAP), femoral arterial pressure (FAP) and heart rate (HR) were monitored during operations. Venous plasma and pulmonary artery (PA) tissue were harvested for analyses. Protein level was detected by Western blotting and ELISA, whereas qRT-PCR was used in mRNA detection. H & E staining and immunohistochemistry were conducted to evaluate histopathology. Ethanol injection elevated PAP in swine. The concentration of RAS ligands was elevated in plasma (all P < 0.0001) but not in PA. The level of oxidative stress increased in both plasma and PA. MRNA level of AT1R (P < 0.01, 95% CI: 0.251-1.006), not AT2R increased in PA. Losartan failed to inhibit AEPAP after all sessions of ethanol injection, and partially reversed the ethanol-induced PA remodeling. The P38 MAPK was activated after ethanol injection and could be inhibited by losartan (P < 0.01, 95% CI: -0.391 to -0.164). Ethanol also promoted the translocation of the P40-PHOX/P47-PHOX/P67-PHOX complex and the activation of NOX, which was independent from RAS. Endovascular ethanol injection can induce AEPAP mainly by activating RAS and P38 MAPK signaling. Losartan can partially prevent AEPAP and vascular remodeling owing to the promotion of NOX activity by ethanol. Mechanism diagram of endovascular ethanol injection-induced acute elevation of pulmonary arterial pressure (AEPAP) partially prevented by losartan. RAS: Renin-angiotensin system; AGT: angiotensinogen; Ang I: angiotensin I; ACE: angiotensin I converting enzyme; Ang II: angiotensin II. AT1R: angiotensin II type 1 receptor. NOX2: NADPH oxidase 2. PA: pulmonary artery.

Novel classification for simple peripheral arteriovenous malformations based on anatomic localization: Prevalence data from the tertiary referral center in China.

Background: In absence of the large-sample study of simple peripheral arteriovenous malfomations (pAVM), we aimed to perform the epidemiological analysis of over 1,000 simple pAVM patients from our center in the past 5 years, and establish a novel classification based on the anatomical localization of the primary lesion. Results: Between March 27, 2016, and March 31, 2021, Chinese patients who were diagnosed with simple pAVM were taken into account. Those who suffered from simple arteriovenous malformations of the central nervous system (cnsAVM), combined types of AVM, and syndromes, such as CLOVES syndrome, etc. were all excluded from this study. A total of 1,070 simple pAVM patients were screened out. All of the simple pAVM patients were diagnosed by clinical manifestations and imaging examinations. Demographic data were obtained from the National Bureau of Statistics of China. The 5-year prevalence of simple pAVM was about (2.15-6.60) /1,000,000 population. The male-female ratio was approximately 1.22:1. The pAVM inpatients that were included in the age group of 21~30 years old had the highest constituent ratio (P = 0.01). The classification included four groups: Type I (primarily occurring in soft tissue); Type II (primarily occurring in bone); Type III (primarily occurring in the viscus) and Type IV (simple pAVM coexisting with CNS lesions). There were two subtypes of Type I: the A subtype (involving one major anatomical region) and the B subtype (involving two or more major anatomical regions); two subtypes of Type II: the A subtype (the cortex was intact) and the B subtype (the lesion had broken through the cortex). Generally, 657 patients were classified as Type IA (61.4%), 232 patients were Type IB (21.7%), 82 patients were Type IIA (7.7%) and 79 were categorized as Type IIB (7.4%); the number of patients who had Type III and Type IV pAVM were 9 (0.8%) and 11 (1.0%), respectively. The clinical manifestations and diagnostic standards for each type were also systematically summarized. Conclusions: Prevalence data for simple pAVM were analyzed, and a novel classification was proposed based on the anatomy of the lesions. The present work was expected to facilitate the diagnosis of simple pAVM in clinical works.

Thermochemical Mechanism of Optimized Lanthanum Chromite Heaters for High-Pressure and High-Temperature Experiments.

High-pressure heaters in large volume presses must reconcile potentially contradictory properties, and the whole high-pressure and high-temperature (HPHT) community has been engaged for years to seek a better heater. LaCrO3 (LCO)-based ceramic heaters have been widely applied in multianvil apparatus; however, their performance is far from satisfactory, motivating further research on the chemical optimization strategy and corresponding thermochemical mechanism. Here, we adopted a chemical-screening strategy and manufactured tubular heaters using the electrically, chemically, and mechanically optimized Sr-Cu codoped La0.9Sr0.1Cr0.8Cu0.2O3-δ (LSCCuO-9182). HPHT examinations of cylindrical LSCCuO-9182 heaters on Walker-type multianvil apparatuses demonstrated a small temperature gradient, robust thermochemical stability, and excellent compatibility with high-pressure assemblies below 2273 K and 10 GPa. Thermochemical mechanism analysis revealed that the temperature limitation of the LSCCuO-9182 heater was related to the autoredox process of the Cu dopant and Cr and the exchanging ionic migration of Cu and Mg between the LSCCuO-9182 heater and the MgO sleeve. Our combinatorial strategy coupled with thermochemical mechanism analysis makes the prioritization of contradictory objectives more rational, yields reliable LCO heaters, and sheds light on further improvement of the temperature limitation and thermochemical stability.

In Situ Imaging of Formaldehyde in Live Mice with High Spatiotemporal Resolution Reveals Aldehyde Dehydrogenase-2 as a Potential Target for Alzheimer's Disease Treatment.

Alterations in formaldehyde (FA) homeostasis are associated with the pathology of Alzheimer's disease (AD). In vivo tracking of FA flux is important for understanding the underlying molecular mechanisms, but is challenging due to the lack of sensitive probes favoring a selective, rapid, and reversible response toward FA. In this study, we re-engineered the promiscuous and irreversible phenylhydrazines to make them selective and reversible toward FA by tuning their nucleophilicity. This effort resulted in PFM309, a selective (selectivity coefficient KFA,methylglyoxal = 0.06), rapid (t1/2 = 32 s at [FA] = 200 µM), and reversible fluorogenic probe (K = 6.24 mM-1) that tracks the FA flux in both live cells and live mice. In vivo tracking of the FA flux was realized by PFM309 imaging, which revealed the gradual accumulation of FA in the live mice brain during normal aging and its further increase in AD mice. We further identified the age-dependent loss of catabolism enzymes ALDH2 and ADH5 as the primary mechanism responsible for formaldehyde excess. Activating ALDH2 with the small molecular activator Alda1 significantly protected neurovascular cells from formaldehyde overload and consequently from impairment during AD progress both in vitro and in vivo. These findings revealed PFM309 as a robust tool to study AD pathology and highlight ALDH2 as a potential target for AD drug development.

MiR-18a-5p acts as a novel serum biomarker for venous malformation and promotes angiogenesis by regulating the thrombospondin-1/P53 signaling axis.

Venous malformation (VM) is a kind of congenital vascular anomaly with high recurrence, and screening for VM lacks an efficient, inexpensive and noninvasive approach now. Serum miRNAs with stable structures are expected to become new postoperative and postablative monitoring biomarkers. Thus, we identified a prognostic serum miR-18a-5p and validated its function in VM. Notably, higher expression level of miR-18a-5p was detected in VM patients than in healthy individuals. We found that miR-18a-5p plays a promotive role in human umbilical vein endothelial cells in vitro. In addition, immunohistochemistry (IHC) results showed a distinct increase of vessels in miR-18a-5p mimics group and a decrease of vessels in inhibitors group compared to the control group in a murine VM model. Furthermore, thrombospondin-1 (TSP1), a potential miR-18a-5p-binding protein, was identified via RNA-seq, luciferase reporter and RNA immunoprecipitation (RIP) assays. Moreover, miR-18a-5p regulated the activation of P53 signaling pathway constituents and consequently led to the regulation of proliferation, migration, invasion and angiogenesis. These results provide a strong theoretical basis for further investigations into pathological mechanism of VM and may provide novel and noninvasive biomarker for VM diagnosis and monitoring.

Strategy of De Novo Design toward First-In-Class Imaging Agents for Simultaneously Differentiating Glioma Boundary and Grades.

The extent of resection and tumor grade are two predominant prognostic factors for glioma. Fluorescent imaging is promising to facilitate accurate resection and simultaneous tumor grading. However, no probe fulfilling this task has been reported. Herein, we proposed a strategy of de novo design toward first-in-class fluorescent probes for simultaneously differentiating glioma boundary and grades. By bioinformatics analysis in combination with experimental validation, platelet-derived growth factor receptor ß (PDGFRß) was revealed as a promising biomarker for glioma imaging and grading. Then, fluorogenic probe PDGFP 1 was designed, guided by the structure-activity relationship study. Finally, the probe was demonstrated to stain glioma cells and tissues in the mice orthotopic glioma model with high selectivity over normal brain cells or tissues. Meanwhile, ex vivo experiments using patient-derived samples indicated that the fluorescence was significantly positively correlated with the tumor grades. This result highlighted the feasibility of the three-step de novo probe design strategy and suggested PDGFP 1 as a promising probe for simultaneously differentiating glioma boundary and grades, showing prospects of clinical translation.

Robust Yellow-Violet Pigments Tuned by Site-Selective Manganese Chromophores.

The rational design of multifunctional inorganic pigments relies on the manipulation of ionic valence and local surroundings of a chromophore in structurally and chemically habitable hosts. To date, the development of environmentally benign and intense violet/purple pigments is still a challenge. Here we report a family of A3-xMnxTeO6 and A3-2xMnxLixTeO6 (A = Zn, Mg; x = 0.01-0.15) pigments colored by site-selective Mn2+O4 yellow and Mn3+O5-6 violet chromophores. Zn2.9Mn0.1TeO6 is intense bright yellow, comparable with commercial BiVO4, and has better near-infrared reflectivity (∼89%) in comparison to commercial TiO2. The codoped Li+ "activator" generates holes and charge-balanced Mn3+ (Mn3+O5-6), realizing a color transformation from yellow to the bright violet pigments of A3-2xMnxLixTeO6. The most vivid Mg2.8Mn0.1Li0.1TeO6 is probably the best violet pigment known to date, exhibits excellent chemical and thermodynamic stability, and demonstrates pressure-dependent stability up to 5-7 GPa, before a (reversible) phase transition to pink. Theoretical calculations revealed the correlation between site-preference occupancy and chromophore motifs and predicted a wide color gamut of pigments in Zn3TeO6-hosted 3d transition-metal ions other than manganese.

Clinical and imaging features of intraosseous arteriovenous malformations in jaws: a 15-year experience of single centre.

Intraosseous arteriovenous malformations in jaws (j-AVMs) are rare congenital high-flow vascular anomalies with a high tendency of life-threatening haemorrhage and are regarded as one of the most dangerous haemorrhagic diseases in maxillofacial region. Pre-treatment clinical and imaging evaluations serve as the most important diagnostic modalities. A retrospective study involved 211 patients with j-AVMs from November 2003 to November 2017 was performed. The male-to-female ratio of j-AVMs was approximately 4:3. The mean age of the patients with j-AVMs is 21.86. Bleeding was the main complaint associated with j-AVMs. J-AVMs occurred in the mandible more often than in the maxilla (64.93% and 32.23%, respectively). Most j-AVMs (95.26%) occurred in the posterior teeth region. Classical imaging features of j-AVMs included: an unclear maxillary sinus with a mild ground-glass appearance (maxillary j-AVMs) and a clear oval or irregular lucency that is mostly centred on the root of the first molar (mandibular j-AVMs) on OPGs, enhancement in the cancellous bone on contrast-enhanced CTs. Other atypical features of j-AVMs were also concluded. A comprehensive diagnose system based on clinical and imaging features of j-AVMs could provide valuable reference data for clinical management of j-AVMs and help avoid improper iatrogenic trauma or delayed treatment.

Universal A-Cation Splitting in LiNbO3-Type Structure Driven by Intrapositional Multivalent Coupling.

Understanding the electric dipole switching in multiferroic materials requires deep insight of the atomic-scale local structure evolution to reveal the ferroelectric mechanism, which remains unclear and lacks a solid experimental indicator in high-pressure prepared LiNbO3-type polar magnets. Here, we report the discovery of Zn-ion splitting in LiNbO3-type Zn2FeNbO6 established by multiple diffraction techniques. The coexistence of a high-temperature paraelectric-like phase in the polar Zn2FeNbO6 lattice motivated us to revisit other high-pressure prepared LiNbO3-type A2BB'O6 compounds. The A-site atomic splitting (∼1.0-1.2 Šbetween the split-atom pair) in B/B'-mixed Zn2FeTaO6 and O/N-mixed ZnTaO2N is verified by both powder X-ray diffraction structural refinements and high angle annular dark field scanning transmission electron microscopy images, but is absent in single-B-site ZnSnO3. Theoretical calculations are in good agreement with experimental results and suggest that this kind of A-site splitting also exists in the B-site mixed Mn-analogues, Mn2FeMO6 (M = Nb, Ta) and anion-mixed MnTaO2N, where the smaller A-site splitting (∼0.2 Šatomic displacement) is attributed to magnetic interactions and bonding between A and B cations. These findings reveal universal A-site splitting in LiNbO3-type structures with mixed multivalent B/B', or anionic sites, and the splitting-atomic displacement can be strongly suppressed by magnetic interactions and/or hybridization of valence bands between d electrons of the A- and B-site cations.

Comprehensive analysis of dysregulated exosomal long non-coding RNA networks associated with arteriovenous malformations.

Arteriovenous malformations (AVMs) are congenital vascular lesions with a high tendency for aggravation and recurrence after treatment, and their genesis remains enigmatic. In this study, we investigated exosomal long non-coding RNA (lncRNA) and mRNA expression and constructed a competitive endogenous RNA regulatory network in AVMs. Ethics approval was provided, and informed written consent was given prior to the inclusion of all participants. Blood samples were obtained from patients with AVMs and healthy controls at Shanghai Ninth People's Hospital, China, from May to November 2018, and total exosomes were isolated and validated. Differentially expressed exosomal lncRNAs and mRNAs were detected by RNA-seq, analysed by bioinformatic methods and validated by qRT-PCR. A competitive endogenous RNA regulatory network was constructed. The characteristics of the captured extracellular vesicles conformed to the features of exosomes. A total of 117 dysregulated exosomal lncRNAs and 1159 dysregulated exosomal mRNAs were identified in AVMs. qRT-PCR demonstrated that the exosomal lncRNAs MIR4435-1HG, LINC00657, LOC101927854 and SEPT5-GP1BB were upregulated in AVM exosomes. The Gene Ontology (GO) terms haemopoiesis and negative regulation of neuron projection development were significantly enriched in relation to dysregulated exosomal cis lncRNAs. A total of 199 GO terms and 80 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched for the dysregulated exosomal mRNAs. In the exosomal lncRNA-miRNA-mRNA-related ceRNA regulatory network, the top 3 significant modules involved 31 dysregulated exosomal lncRNAs and 114 dysregulated exosomal mRNAs, which were enriched in the Rap 1, Ras, MAPK signalling pathways and platelet activation KEGG pathway. This study comprehensively identified dysregulated exosomal lncRNAs and mRNAs in AVMs, demonstrated the involvement of dysregulated lncRNA and mRNA patterns in AVMs and constructed an exosomal competitive endogenous RNA regulatory network.

Ethanol embolization of lingual arteriovenous malformations: Positive experience in 52 patients during 11 years.

OBJECTIVE: Lingual arteriovenous malformations (AVMs) are extremely rare in clinical practice, which has limited comprehensive research to find standard treatment protocols. This study summarizes the clinical features of lingual AVMs and assesses the safety and efficacy of ethanol embolotherapy in the management of these lesions. METHODS: Our study group was composed of 52 patients with lingual AVMs treated by ethanol embolization, all of whom received general anesthesia. The optimal access to the nidus of the AVM was by direct puncture, transarterial catheterization, transvenous catheterization, and a combination of these routes. Pure ethanol was manually injected into the nidus of the AVMs. The observed major or minor complications related to ethanol embolization were analyzed, and periodic follow-up of the patients was performed. The devascularization of the lingual AVMs between baseline and final angiography and the clinical outcomes of symptoms and signs after ethanol embolization were evaluated. RESULTS: There were 171 embolization procedures (mean, 3.3; range, 1-20) including 166 ethanol embolizations performed; the average volume of ethanol injected in a single ethanol embolization session was 29.8 mL (range, 1-65 mL). Therapeutic outcomes were complete response in 17 patients (33%), partial response in 33 patients (63%), and no response in 2 patients (4%). The effective therapeutic outcomes were gained in 96% of the patients with lingual AVMs treated with ethanol embolization; 25 (48%) of the patients had 83 complications, which were necrosis, infection, hemorrhage of the puncture point, transient hemoglobinuria, postoperative irritability, airway constriction, and coil migration, occurring in 78 procedures (46%). Regular follow-up of all the patients was performed, with the average follow-up period of 37.9 months (range, 1-125 months) after the last treatment. CONCLUSIONS: Ethanol embolization of lingual AVMs is safe and efficacious and is recommended to be the potential preferred method in the treatment of these complicated lesions.