hsa_circ_0101050 regulated by ZC3H13 enhances tumorigenesis in papillary thyroid cancer via m6A modification.

While the regulatory roles of circular RNAs (circRNAs) and zinc finger CCCH-type containing 13 (ZC3H13) were previously reported in various human cancers, the mechanisms underlying their interaction in papillary thyroid cancer (PTC) remain unclear. We aimed to determine the role of hsa_circ_0101050 and its regulatory relationship with ZC3H13 in PTC. The expression levels of hsa_circ_0101050 and ZC3H13 were determined in tumor samples and adjacent normal tissues from 46 patients with PTC and in two PTC cell lines (IHH-4 and PTC-1) using quantitative reverse transcription-polymerase chain reaction. The roles of hsa_circ_0101050 and ZC3H13 in cell viability, wound healing, and migration were determined using knockdown and overexpression approaches in PTC cell lines, and a xenograft model in nude mice was used to determine their role in vivo. Methylated RNA immunoprecipitation assay was used to analyze N6-methyladenosine (m6A) modification of hsa_circ_0101050 by ZC3H13. We found hsa_circ_0101050 overexpression and ZC3H13 downregulation in PTC samples and PTC cell lines. In PTC cell lines, silencing hsa_circ_0101050 reduced cell viability and migration whereas its overexpression promoted an aggressive PTC phenotype. ZC3H13 increased the m6A modification of hsa_circ_0101050 and repressed its expression. ZC3H13 overexpression inhibited PTC cell viability, migration, and invasion, which were reversed in cells overexpressing hsa_circ_0101050. Taken together, these results suggested that the downregulation of hsa_circ_0101050 mediated by ZC3H13 through m6A modification contributed to its oncogenic effect in PTC development, revealing the ZC3H13-m6A-hsa_circ_0101050 as a potential therapeutic target in PTC.

METTL3-mediated m6A Modification of hsa_circ_0131922 Attenuates the Progression of Papillary Thyroid Cancer by Regulating the p53 Pathway.

AIMS: This study aimed to confirm the regulatory role and mechanism of circular RNA (circRNA) hsa_circ_0131922 in Papillary Thyroid Carcinoma (PTC) progression. BACKGROUND: Accumulating evidence suggests that N6-methyladenosine (m6A)-modified circular RNAs (circRNAs) perform pivotal functions in various malignancies. However, the specific role of the m6A modification of circRNA mediated by METTL3 in Papillary Thyroid Carcinoma (PTC) remains undocumented. OBJECTIVE: In this work, we aimed to examine the molecular mechanisms of a novel m6Amodified circRNA, hsa_circ_0131922, in PTC progression. METHODS: Potential circRNA was identified from GEO datasets. The RNA or protein levels of hsa_circ_0131922, METTL3, p53, and p21 were evaluated by qRT-PCR or western blot assays. The various cellular functions were checked by CCK8, wound healing, transwell, and xenograft tumor assays. MeRIP-qPCR was performed to observe the METTL3-mediated m6A modification of hsa_circ_0131922. Furthermore, the interactions between hsa_circ_0131922 and METTL3 in PTC were analyzed by bioinformatics analysis and various rescue experiments. RESULTS: The levels of hsa_circ_0131922 were markedly downregulated in PTC tissues and cell lines. In addition, the lower hsa_circ_0131922 levels correlated with poor prognosis in PTC patients. The hsa_circ_0131922 overexpression reduced the malignant phenotypes of PTC cells and activated the p53/p21 pathway. Bioinformatic analysis showed the m6A-modified sites of hsa_circ_0131922, and a positive correlation between hsa_circ_0131922 and METTL3. Moreover, overexpression of METTL3 increased the levels of m6A modification of hsa_circ_0131922. Mechanistically, the anti-tumor effects of hsa_circ_0131922 overexpression have been found to be partially reversed by silencing METTL3 in vivo and in vitro. CONCLUSION: The results have demonstrated m6A-modified hsa_circ_0131922 by METTL3 to attenuate the progression of PTC by regulating the p53 pathway. Therefore, hsa_circ_0131922 could be a predictive prognostic biomarker and therapeutic target for PTC.

Integrative analysis of genomic and epigenomic regulation reveals miRNA mediated tumor heterogeneity and immune evasion in lower grade glioma.

The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches.

Extracellular vesicle-delivered hsa_circ_0090081 regulated by EIF4A3 enhances gastric cancer tumorigenesis.

BACKGROUND: Circular RNA (circRNA) and extracellular vesicles (EVs) in tumors are crucial for the malignant phenotype of tumor cells. Nevertheless, the mechanisms and clinical effects of EV-delivered hsa_circ_0090081 in gastric cancer (GC) are unclear. This study aimed to reveal the effect of eukaryotic translation initiation factor 4A3 (EIF4A3)-mediated hsa_circ_0090081 expression and EV-delivered hsa_circ_0090081 on GC progression. METHODS: qRT-PCR was conducted to clarify hsa_circ_0090081 and EIF4A3 levels in GC tissues. Transmission electronic microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting identified the EVs isolated from GC cells by ultracentrifugation. The roles of hsa_circ_0090081, EIF4A3, and EV-delivered hsa_circ_0090081 in GC cells were analyzed using Transwell, EdU, and CCK-8 assays. The regulatory role between EIF4A3 and hsa_circ_0090081 was investigated using RIP, qRT-PCR, and Pearson's analysis. RESULTS: Our study showed that hsa_circ_0090081 and EIF4A3 were highly expressed in GC, and hsa_circ_0090081 was associated with poor prognosis. Data revealed that hsa_circ_0090081 inhibition restrained GC cell proliferation, invasion, and migration. Additionally, EIF4A3 could bind to the pre-mRNA of PHEX (linear form of hsa_circ_0090081) to enhance hsa_circ_0090081 expression in GC cells. Moreover, EIF4A3 overexpression nullified the malignant phenotypic suppression caused by hsa_circ_0090081 silencing in GC cells. Furthermore, EVs secreted by GC cells delivered hsa_circ_0090081 to facilitate the malignant progression of targeted GC cells. CONCLUSION: This study showed that hsa_circ_0090081 was enhanced by EIF4A3 to play a promotive role in GC development. The results may help understand the mechanism of EIF4A3 and EV-delivered hsa_circ_0090081 and offer a valuable GC therapeutic target.

The role of EMG1 in lung adenocarcinoma progression: Implications for prognosis and immune cell infiltration.

BACKGROUND AND AIMS: Lung adenocarcinoma (LUAD) is the most common and aggressive cancer with a high incidence. N1-specific pseudouridine methyltransferase (EMG1), a highly conserved nucleolus protein, plays an important role in the biological development of ribosomes. However, the role of EMG1 in the progression of LUAD is still unclear. METHODS: The expression of EMG1 in LUAD cells, and LUAD tissues, and adjacent noncancerous tissues was quantified using real-time polymerase chain reaction (PCR) and western blotting. The roles of EMG1 in LUAD cell proliferation, migration, invasion and tumorigenicity were explored in vitro and in vivo. Western blot analysis to underlying molecular mechanism of EMG1 regulating the biological function of LUAD. EMG1 expression and its impact on tumor prognosis were analyzed using a range of databases including GEPIA, UALCAN, cBioPortal, LinkedOmics, and Kaplan-Meier Plotter. RESULTS: EMG1 expression was elevated in LUAD patients compared to normal tissues, and EMG1 expression was strongly correlated with prognosis in LUAD patients. EMG1 expression correlated with age, gender, N stage, T stage, and pathologic stage. EMG1 expression was strongly positively correlated with MRPL51, PHB2, SNRPG, ATP5MD, and TPI1, and strongly negatively correlated with MACF1, DOCK9, RAPGEF2, SYNJ1, and KIDINS220, the major enrichment pathways for EMG1 and related genes include Cell cycle, DNA Replication and Pathways in cancer signaling pathways. EMG1 expression level was significantly increased in LUAD cell lines and tissues. Knockdown of EMG1 could inhibit LUAD cell proliferation, migration, invasion, and tumorigenicity. Besides, EMG1 overexpression could promote LUAD cell proliferation, migration, and invasion. High expression of EMG1 predicts poor prognosis in LUAD patients, and EMG1 may play an oncogenic role in the tumor microenvironment by participating in the infiltration of LUAD immune cells. CONCLUSIONS: EMG1 regulated various functions in LUAD by directly mediating Akt/mTOR/p70s6k signaling pathways activation. The results suggest that EMG1 may be a novel biomarker for assessing prognosis and immune cell infiltration in LUAD.

Management of Limited Mouth Opening After Open Reduction and Fixation of Mandibular Coronoid Fractures.

Mandibular coronoid process fractures are relatively rare and generally treated conservatively. This paper reports a case of limited mouth opening and pain after open reduction and fixation of the mandibular coronoid fracture. After the loose titanium screws, plates, and absorbed coronoid fracture fragments were removed, the patient's mouth opening was restored immediately. The authors believe that open reduction and fixation for coronoid process fractures can cause postoperative limited mouth opening and pain. Conservative treatment of coronoid process fractures is more beneficial for patients.

Management of Atypical M-Shaped Zygomatic Arch Fractures.

BACKGROUND: M-shaped zygomatic arch fractures can usually be treated effectively through closed reduction. It consists of 2 fracture segments: the anterior zygomatic segment and the posterior temporal bone segment. In clinical practice, atypical M-shaped fractures are often encountered, in which the anterior and posterior fracture segments are discontinuous and separated. Closed reduction usually cannot achieve the desired anatomic reduction effect for this type of fracture. METHODS: The preoperative design showed that the anatomic reduction of the posterior zygomatic arch fracture segment was hindered due to bone spurs in the most concave area of the anterior zygomatic bone fracture segment. Open reduction and fixation were performed to achieve anatomic reduction and restore facial symmetry. The fracture sites were exposed through a hemicoronal incision. After the bone spurs are removed, the posterior bone segment can be anatomically reduced. Absorbable plates were used for fixation. RESULTS AND DISCUSSION: The patient's facial appearance was restored after the surgery. The postoperative computed tomography scan showed a good alignment of the fracture. The authors believe that for patients with high requirements for facial symmetry, the presence of atypical M-shaped fractures can indicate open reduction and fixation.

Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer.

Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms. Ferroptosis-resistant GC cell lines are constructed. Dysregulated mRNAs between ferroptosis-resistant and parental cell lines are identified. The expression of SOX13/SCAF1 is manipulated in GC cell lines where relevant biological and molecular analyses are performed. Molecular docking and computational screening are performed to screen potential inhibitors of SOX13. We show that SOX13 boosts protein remodeling of electron transport chain (ETC) complexes by directly transactivating SCAF1. This leads to increased supercomplexes (SCs) assembly, mitochondrial respiration, mitochondrial energetics and chemo- and immune-resistance. Zanamivir, reverts the ferroptosis-resistant phenotype via directly targeting SOX13 and promoting TRIM25-mediated ubiquitination and degradation of SOX13. Here we show, SOX13/SCAF1 are important in ferroptosis-resistance, and targeting SOX13 with zanamivir has therapeutic potential.

Effect of tranexamic acid on postoperative blood loss.

The aim of this article was to evaluate the efficacy of tranexamic acid (TXA) to reduce blood loss after maxillofacial fracture surgery. Clinical data were collected retrospectively on patients with unilateral fractures of the zygomaticomaxillary complex (ZMC) or mandibular condyle. Patients were then further divided into TXA and control groups according to whether or not TXA was used after surgery. The amount of postoperative blood loss was evaluated by negative pressure drainage volume. Data were statistically analysed. In patients with unilateral ZMC fractures, total postoperative blood loss in the TXA group was about 30 ml less than that in the control group (p = 0.006). It was significantly less on the first and second postoperative days. However, in patients with unilateral mandibular condylar fractures, there was no significant difference between the TXA and control groups (p = 0.917). TXA can reduce postoperative bleeding in patients with ZMC fractures, and the optimal usage time is on the first and second postoperative days. For patients with mandibular condylar fractures, TXA may not be used.

Management of Mandibular Condylar Sagittal Fracture Accompanied by Lateral Condylar Crest Defect.

BACKGROUND: The sagittal fracture of the mandibular condyle can be fixed with absorbable long screws. Absorbable long screws are generally inserted from the lateral crest of the condyle and are as close as possible to the medial pole of the condyle to obtain sufficient retention force. However, in clinical practice, patients with locally comminuted condylar fractures and partial defects in the lateral crest are often encountered. We validated the use of absorbable plates and long screws to fix mandibular condylar fractures with lateral crest defects, and postoperative follow-up showed good results. METHODS: The preoperative design indicated that if conventional long screws were used, more soft tissue need to be pulled downward to achieve the appropriate drilling angle. If an absorbable plate was used, the degree of downward pulling of soft tissue was smaller, which can better protect the parotid gland tissue and facial nerve. The surgery was performed according to the preoperative design, using an absorbable plate scheme. RESULTS AND DISCUSSION: Postoperative CT confirmed a stable anatomical reduction of condyle. Four-month follow-up showed that the patient's facial shape, occlusion, and mouth opening were all good. Follow-up CT showed good fracture healing. It is feasible to use absorbable plates and long absorbable screws to fix mandibular condylar sagittal fracture accompanied by lateral condylar crest defect.

Postoperative Intermaxillary Elastic Traction Contributes to the Stability of Absorbable Plates Fixation for Bilateral Mandibular Fracture.

The use of absorbable plates can be challenging for mandibular fractures involving bilateral dentition. Chewing and mouth opening movements may cause loosening or breakage of absorbable materials, leading to displacement of bone segments and resulting in malocclusion. The use of absorbable materials for bilateral mandibular fracture surgery itself raises concerns for surgeons. Timely intermaxillary elastic traction is essential for these patients after surgery to maintain correct occlusion. The surgical approaches were performed with intraoral mandibular sulcus incisions. During the surgery, intermaxillary fixation screws were implanted and steel wires were used for intermaxillary ligation and fixation to restore the occlusal. After the fractured segments were sequentially reduced, they were fixed with inion 2.0 absorbable plates. The patient underwent intermaxillary elastic traction for 1 week. Elastic mask was used to assist in stabilizing the position of the jawbone and maintaining occlusion. After discharge, the patient continued traction at home for 3 weeks before removing the intermaxillary fixation screws. The patient recovered well after surgery without any complications. The postoperative occlusal relationship is good. Postoperative CT showed good reduction of the fractured segments. For the case reported in this article, elastic traction was promptly implemented after surgery. We emphasize that restoring occlusion is always the treatment goal for jawbone fractures. We believe that keeping the intermaxillary fixation screws for a month is a wise choice to be prepared for unexpected needs.

m6A-Mediated Upregulation of lncRNA CHASERR Promotes the Progression of Glioma by Modulating the miR-6893-3p/TRIM14 Axis.

Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are dysregulated in glioma. However, the functional roles of lncRNAs in glioma remain largely unknown. In this study, we utilized the TCGA (the Cancer Genome Atlas database) and GEPIA2 (Gene Expression Profiling Interactive Analysis 2) databases and observed the overexpression of lncRNA CHASERR in glioma tissues. We subsequently investigated this phenomenon in glioma cell lines. The effects of lncRNA CHASERR on glioma proliferation, migration, and invasion were analyzed using in vitro and in vivo experiments. Additionally, the regulatory mechanisms among PTEN/p-Akt/mTOR and Wnt/ß-catenin, lncRNA CHASERR, Micro-RNA-6893-3p(miR-6893-3p), and tripartite motif containing14 (TRIM14) were investigated via bioinformatics analyses, quantitative real-time PCR (qRT-PCR), western blot (WB), RNA immunoprecipitation (RIP), dual luciferase reporter assay, fluorescence in situ hybridization (FISH), and RNA sequencing assays. RIP and RT-qRCR were used to analyze the regulatory effect of N6-methyladenosine(m6A) on the aberrantly expressed lncRNA CHASERR. High lncRNA CHASERR expression was observed in glioma tissues and was associated with unfavorable prognosis in glioma patients. Further functional assays showed that lncRNA CHASERR regulates glioma growth and metastasis in vitro and in vivo. Mechanistically, lncRNA CHASERR sponged miR-6893-3p to upregulate TRIM14 expression, thereby facilitating glioma progression. Additionally, the activation of PTEN/p-Akt/mTOR and Wnt/ß-catenin pathways by lncRNA CHASERR, miR-6893-3p, and TRIM14 was found to regulate glioma progression. Moreover, the upregulation of lncRNA CHASERR was observed in response to N6-methyladenosine modification, which was facilitated by METTL3/YTHDF1-mediated RNA transcripts. This study elucidates the m6A/lncRNACHASERR/miR-6893-3p/TRIM14 pathway that contributes to glioma progression and underscores the potential of lncRNA CHASERR as a novel prognostic indicator and therapeutic target for glioma.

Altered whole-brain functional network in patients with frontal low-grade gliomas: a resting-state functional MRI study.

PURPOSE: Gliomas are the most common primary brain tumor. Currently, topological alterations of whole-brain functional network caused by gliomas are not fully understood. The work here clarified the topological reorganization of the functional network in patients with unilateral frontal low-grade gliomas (LGGs). METHODS: A total of 45 patients with left frontal LGGs, 19 with right frontal LGGs, and 25 healthy controls (HCs) were enrolled. All the resting-state functional MRI (rs-fMRI) images of the subjects were preprocessed to construct the functional network matrix, which was used for graph theoretical analysis. A two-sample t-test was conducted to clarify the differences in global and nodal network metrics between patients and HCs. A network-based statistic approach was used to identify the altered specific pairs of regions in which functional connectivity in patients with LGGs. RESULTS: The local efficiency, clustering coefficient, characteristic path length, and normalized characteristic path length of patients with unilateral frontal LGGs were significantly lower than HCs, while there were no significant differences of global efficiency and small-worldness between patients and HCs. Compared with the HCs, betweenness centrality, degree centrality, and nodal efficiency of several brain nodes were changed significantly in patients. Around the tumor and its adjacent areas, the inter- and intra-hemispheric connections were significantly decreased in patients with left frontal LGGs. CONCLUSION: The patients with unilateral frontal LGGs have altered global and nodal network metrics and decreased inter- and intra-hemispheric connectivity. These topological alterations may be involved in functional impairment and compensation of patients.

Increased serum extrachromosomal circular DNA SORBS1circle level is associated with insulin resistance in patients with newly diagnosed type 2 diabetes mellitus.

BACKGROUND: Extrachromosomal circular DNAs (eccDNAs) exist in human blood and somatic cells, and are essential for oncogene plasticity and drug resistance. However, the presence and impact of eccDNAs in type 2 diabetes mellitus (T2DM) remains inadequately understood. METHODS: We purified and sequenced the serum eccDNAs obtained from newly diagnosed T2DM patients and normal control (NC) subjects using Circle-sequencing. We validated the level of a novel circulating eccDNA named sorbin and SH3-domain- containing-1circle97206791-97208025 (SORBS1circle) in 106 newly diagnosed T2DM patients. The relationship between eccDNA SORBS1circle and clinical data was analyzed. Furthermore, we explored the source and expression level of eccDNA SORBS1circle in the high glucose and palmitate (HG/PA)-induced hepatocyte (HepG2 cell) insulin resistance model. RESULTS: A total of 22,543 and 19,195 eccDNAs were found in serum samples obtained from newly diagnosed T2DM patients and NC subjects, respectively. The T2DM patients had a greater distribution of eccDNA on chromosomes 1, 14, 16, 17, 18, 19, 20 and X. Additionally, 598 serum eccDNAs were found to be upregulated, while 856 eccDNAs were downregulated in T2DM patients compared with NC subjects. KEGG analysis demonstrated that the genes carried by eccDNAs were mainly associated with insulin resistance. Moreover, it was validated that the eccDNA SORBS1circle was significantly increased in serum of newly diagnosed T2DM patients (106 T2DM patients vs. 40 NC subjects). The serum eccDNA SORBS1circle content was positively correlated with the levels of glycosylated hemoglobin A1C (HbA1C) and homeostasis model assessment of insulin resistance (HOMA-IR) in T2DM patients. Intracellular eccDNA SORBS1circle expression was significantly enhanced in the high glucose and palmitate (HG/PA)-induced hepatocyte (HepG2 cell) insulin resistance model. Moreover, the upregulation of eccDNA SORBS1circle in the HG/PA-treated HepG2 cells was dependent on generation of apoptotic DNA fragmentation. CONCLUSIONS: These results provide a preliminary understanding of the circulating eccDNA patterns at the early stage of T2DM and suggest that eccDNA SORBS1circle may be involved in the development of insulin resistance.

Multitargeted Immunomodulatory Therapy for Viral Myocarditis by Engineered Extracellular Vesicles.

Immune regulation therapies are considered promising for treating classically activated macrophage (M1)-driven viral myocarditis (VM). Alternatively, activated macrophage (M2)-derived extracellular vesicles (M2 EVs) have great immunomodulatory potential owing to their ability to reprogram macrophages, but their therapeutic efficacy is hampered by insufficient targeting capacity in vivo. Therefore, we developed cardiac-targeting peptide (CTP) and platelet membrane (PM)-engineered M2 EVs enriched with viral macrophage inflammatory protein-II (vMIP-II), termed CTP/PM-M2 EVsvMIP-II-Lamp2b, to improve the delivery of EVs "cargo" to the heart tissues. In a mouse model of VM, the intravenously injected CTP/PM-M2 EVsvMIP-II-Lamp2b could be carried into the myocardium via CTP, PM, and vMIP-II. In the inflammatory microenvironment, macrophages differentiated from circulating monocytes and macrophages residing in the heart showed enhanced endocytosis rates for CTP/PM-M2 EVsvMIP-II-Lamp2b. Subsequently, CTP/PM-M2 EVsvMIP-II-Lamp2b successfully released functional M2 EVsvMIP-II-Lamp2b into the cytosol, which facilitated the reprogramming of inflammatory M1 macrophages to reparative M2 macrophages. vMIP-II not only helps to increase the targeting ability of M2 EVs but also collaborates with M2 EVs to regulate M1 macrophages in the inflammatory microenvironment and downregulate the levels of multiple chemokine receptors. Finally, the cardiac immune microenvironment was protectively regulated to achieve cardiac repair. Taken together, our findings suggest that CTP-and-PM-engineered M2 EVsvMIP-II-Lamp2b represent an effective means for treating VM and show promise for clinical applications.

TMEM64 aggravates the malignant phenotype of glioma by activating the Wnt/ß-catenin signaling pathway.

Transmembrane protein 64 (TMEM64), a member of the family of transmembrane protein, is an α-helical membrane protein. Its precise role in various types of tumors, including glioma, is unclear. This study used immunohistochemical (IHC) staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques to show that TMEM64 expression was significantly higher in glioma cells and tissues compared to normal cells and tissues, respectively. Additionally, a correlation between high TMEM64 expression and higher grade as well as a worse prognosis was found. TMEM64 enhanced cell proliferation and tumorigenicity while inhibiting glioma cell apoptosis in vitro and in vivo, according to loss- and gain-of-function studies. Mechanistically, it was discovered that TMEM64 increased the malignant phenotype of gliomas by accelerating the translocation of ß-catenin from the cytoplasm to the nucleus, thereby activating the Wnt/ß-catenin signaling pathway. Stimulation with the Wnt/ß-catenin signaling pathway activator CHIR-99021 successfully reversed the malignant phenotype of glioma; however, these effects were inhibited upon TMEM64 silencing. Stimulation with the Wnt/ß-catenin signaling pathway inhibitor XAV-939 successfully rescued the malignant phenotype of glioma, which was promoted upon TMEM64 overexpression. Our results provide that TMEM64 as a novel prognostic biomarker and a potential treatment target for glioma.

M2 macrophage exosome-derived lncRNA AK083884 protects mice from CVB3-induced viral myocarditis through regulating PKM2/HIF-1α axis mediated metabolic reprogramming of macrophages.

Viral myocarditis (VM) is a clinically common inflammatory disease. Accumulating literature has indicated that M2 macrophages protect mice from Coxsackievirus B3 (CVB3)-induced VM. However, mechanisms that underlie M2 macrophages alleviating myocardial inflammation remain largely undefined. We found that M2 macrophage-derived exosomes (M2-Exo) can effectively attenuate VM. The long non-coding RNA (lncRNA) AK083884 in M2-Exo was found to be involved in the regulation of macrophage polarization by exosome lncRNA sequencing combined with in vitro functional assays. M2-Exo-derived AK083884 promotes macrophage M2 polarization and protects mice from CVB3-induced VM. Furthermore, we identified pyruvate kinase M2 (PKM2) as a protein target binding to AK083884 and found that PKM2 knockdown could promote macrophages to polarize to M2 phenotype. Intriguingly, functional assay revealed that downregulation of AK083884 promotes metabolic reprogramming in macrophages. In addition, co-immunoprecipitation was performed to reveal AK083884 could interact with PKM2 and inhibition of AK083884 can facilitate the binding of PKM2 and HIF-1α. Collectively, our findings uncovered an important role of M2-Exo-derived AK083884 in the regulation of macrophage polarization through metabolic reprogramming, identified a new participant in the development of VM and provided a potential clinically important therapeutic target.

Management of Greenstick Fracture at the Root of Adult Zygomatic Arch.

Greenstick fractures mostly occur in children and rarely in adults. In adult zygomaticomaxillary complex fractures, the greenstick fracture at the root of the zygomatic arch is occasionally encountered. This makes it difficult to move the fracture segment. Therefore, achieving anatomic reduction is very difficult. Our preoperative 3D repaired model shows that if only the maxilla and zygomatic bones are restored, the patient's face will still have depression and protrusion. The greenstick fracture segment at the root of the zygomatic arch needs to undergo osteotomy to achieve anatomic reduction and restore facial symmetry. The patient's facial appearance was restored after the surgery. The postoperative computed tomography scan showed good alignment of the fracture. The authors believe that a fracture at the root of the zygomatic arch can serve as an indication for open reduction and fixation.

Predicting meningioma grades and pathologic marker expression via deep learning.

OBJECTIVES: To establish a deep learning (DL) model for predicting tumor grades and expression of pathologic markers of meningioma. METHODS: A total of 1192 meningioma patients from two centers who underwent surgical resection between September 2018 and December 2021 were retrospectively included. The pathological data and post-contrast T1-weight images for each patient were collected. The patients from institute I were subdivided into training, validation, and testing sets, while the patients from institute II served as the external testing cohort. The fine-tuned ResNet50 model based on transfer learning was adopted to classify WHO grade in the whole cohort and predict Ki-67 index, H3K27me3, and progesterone receptor (PR) status of grade 1 meningiomas. The predictive performance was evaluated by the accuracy and loss curve, confusion matrix, receiver operating characteristic curve (ROC), and area under curve (AUC). RESULTS: The DL prediction model for each label achieved high predictive performance in two cohorts. For WHO grade prediction, the area under the curve (AUC) was 0.966 (95%CI 0.957-0.975) in the internal testing set and 0.669 (95%CI 0.643-0.695) in the external validation cohort. The AUC in predicting Ki-67 index, H3K27me3, and PR status were 0.905 (95%CI 0.895-0.915), 0.773 (95%CI 0.760-0.786), and 0.771 (95%CI 0.750-0.792) in the internal testing set and 0.591 (95%CI 0.562-0.620), 0.658 (95%CI 0.648-0.668), and 0.703 (95%CI 0.674-0.732) in the external validation cohort, respectively. CONCLUSION: DL models can preoperatively predict meningioma grades and pathologic marker expression with favorable predictive performance. CLINICAL RELEVANCE STATEMENT: Our DL model could predict meningioma grades and expression of pathologic markers and identify high-risk patients with WHO grade 1 meningioma, which would suggest a more aggressive operative intervention preoperatively and a more frequent follow-up schedule postoperatively. KEY POINTS: WHO grades and some pathologic markers of meningioma were associated with therapeutic strategies and clinical outcomes. A deep learning-based approach was employed to develop a model for predicting meningioma grades and the expression of pathologic markers. Preoperative prediction of meningioma grades and the expression of pathologic markers was beneficial for clinical decision-making.

Secondary ocular hypertension due to tentorial dural arteriovenous fistula: a case report.

BACKGROUND: Tentorial dural arteriovenous fistulas (TDAVFs) are abnormal shunts between meningeal arteries and the intradural venous system located in the tentorial dura mater, which typically manifest with haemorrhage or progressive neurological disorders. TDAVFs with pure ocular presentation have been rarely reported. CASE PRESENTATIONS: The case of a 56-year-old man presented with unilateral eye redness, proptosis and elevated intraocular pressure was reported herein, which was caused by a TDAVF. The fistula was fed by the left posterior cerebral artery and posterior meningeal artery. The drainage was into the basal vein and internal cerebral veins, which led the arterial blood flow forward to the left superior ophthalmic vein directly. The redundant blood flow caused the rise of episcleral venous pressure, leading to the clinical presentations. Gamma knife radiosurgery was performed then considering the delicate vascular structure and its deep location. The corkscrew hyperaemia was gradually alleviated after the surgery, but the intraocular pressure remained elevated at follow-ups. CONCLUSION: Dural arteriovenous fistulas which are not directly connected to cavernous sinus could cause ocular presentations like proptosis, eye redness and ocular hypertension.