Citrate synthase lysine K215 hypoacetylation contributes to microglial citrate accumulation and pro-inflammatory functions after traumatic brain injury.

AIMS: This study aimed to investigate the relationship between microglial metabolism and neuroinflammation by examining the impact of citrate accumulation in microglia and its potential regulation through Cs K215 hypoacetylation. METHODS: Experimental approaches included assessing Cs enzyme activity through Cs K215Q mutation and investigating the inhibitory effects of hesperidin, a natural flavanone glycoside, on citrate synthase. Microglial phagocytosis and expression of pro-inflammatory cytokines were also examined in relation to Cs K215Q mutation and hesperidin treatment. RESULTS: Cs K215Q mutation and hesperidin exhibited significant inhibitory effects on Cs enzyme activity, microglial citrate accumulation, phagocytosis, and pro-inflammatory cytokine expression. Interestingly, Sirt3 knockdown aggravated microglial pro-inflammatory functions during neuroinflammation, despite its proven role in Cs deacetylation. CONCLUSION: Cs K215Q mutation and hesperidin effectively inhibited microglial pro-inflammatory functions without reversing the metabolic reprogramming. These findings suggest that targeting Cs K215 hypoacetylation and utilizing hesperidin may hold promise for modulating neuroinflammation in microglia.

A novel epithelial-mesenchymal transition-related lncRNA signature predicts prognosis and immune status in endometrioid endometrial cancer.

The pathogenesis and progression of endometrial cancer (EC) are associated with epithelial-mesenchymal transition (EMT) and long noncoding RNAs (lncRNAs). In the present study, we aimed to identify an EMT-related lncRNA signature and evaluate its prognostic value in EC. We obtained the expression profile of lncRNAs and clinical information of patients with endometrioid EC from The Cancer Genome Atlas database (N = 401). We identified a signature of 5 EMT-related lncRNAs and calculated the risk score of each patient. Next, we validated the independence of the prognostic value of the EMT-related lncRNA signature. Furthermore, we performed Gene Set Enrichment Analysis to identify potential molecular function and Kyoto Encyclopedia of Genes and Genomes pathways related to the EMT-related lncRNA signature. Tumor microenvironment analysis and immune checkpoint blockade (ICB) response prediction were also assessed. Survival analysis revealed that the high-risk group, based on the EMT-related lncRNA signature, had a poorer prognosis than the low-risk group in the training, testing, and entire sets. The predictive value of the EMT-related lncRNA signature was independent of age, The International Federation of Gynecology and Obstetrics stage, tumor grade, and body mass index. Time-dependent receiver operating characteristic curves also demonstrate the prognostic accuracy of this risk model. Gene Set Enrichment Analysis showed that cytokine-cytokine receptor interaction, glycolysis/gluconeogenesis, and IL-17 signaling pathway were significantly enriched. Furthermore, tumor microenvironment analysis indicated a significant negative correlation between the immune score and EMT-related lncRNA signature risks core, while the low-risk group was more likely to respond to ICB therapy than the high-risk group. A reliable EMT-related lncRNA signature of endometrioid EC was identified that could be utilized as an independent prognostic biomarker to predict patient survival outcomes and provide references for the option of ICB therapy.

Testosterone elevation in ovarian adult granulosa cell tumor: A case report and review of the literature.

RATIONALE: Adult granulosa cell tumors (AGCT) mainly secret estrogen, but few androgens. It is rarer to have amenorrhea and hyperandrogenemia as clinical features. Here, we report a rare case of right side AGCTs with amenorrhea and hyperandrogenemia in a 19-year-old female. PATIENT CONCERNS: The 19-year-old patient was admitted to our hospital due to amenorrhea for more than 1 year, and discovery of pelvic mass for 4 months. The gynecological ultrasound and computed tomography (CT) cannot define the nature of the mass. Surprisingly, an elevation in testosterone levels was also measured. DIAGNOSIS AND INTERVENTIONS: The present patient underwent laparoscopic right salpingo-oophorectomy and partial omentectomy and biopsy of the peritoneum. OUTCOMES: After the surgery, the testosterone value was down to normal. The patient menstrual cramps on August 13, 2021. Her clitoris is smaller than the front. Up to August 1, 2022, there was no obvious sign of recurrence. LESSONS: Androgen-secreting AGCT is rare. We hope that this case can strengthen gynecologists' early diagnosis and treatment of this disease and improve the prognosis.

Gas6 Promotes Microglia Efferocytosis and Suppresses Inflammation Through Activating Axl/Rac1 Signaling in Subarachnoid Hemorrhage Mice.

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is characterized by rapid development of neuron apoptosis and dysregulated inflammatory response. Microglia efferocytosis plays a critical role in the clearance of apoptotic cells, attenuation of inflammation, and minimizing brain injury in various pathological conditions. Here, using a mouse SAH model, we aim to investigate whether microglia efferocytosis is involved in post-SAH inflammation and to determine the underlying signaling pathway. We hypothesized that TAM receptors and their ligands regulate this process. To prove our hypothesis, the expression and cellular location of TAM (Tyro3, Axl, and Mertk) receptors and their ligands growth arrest-specific 6 (Gas6) and Protein S (ProS1) were examined by PCR, western blots, and fluorescence immunostaining. Thirty minutes after SAH, mice received an intraventricular injection of recombinant Gas6 (rGas6) or recombinant ProS1 (rPros1) and underwent evaluations of inflammatory mediator expression, neurological deficits, and blood-brain barrier integrity at 24 h. Microglia efferocytosis of apoptotic neurons was analyzed in vivo and in vitro. The potential mechanism was determined by inhibiting or knocking down TAM receptors and Rac1 by specific inhibitors or siRNA. SAH induced upregulation of Axl and its ligand Gas6. The administration of rGas6 but not rPros1 promoted microglia efferocytosis, alleviated inflammation, and ameliorated SAH-induced BBB breakdown and neurological deficits. The beneficial effects of rGas6 were arrogated by inhibiting or knocking down Axl and Rac1. We concluded that rGas6 attenuated the development of early brain injury in mice after SAH by facilitating microglia efferocytosis and preventing inflammatory response, which is partly dependent on activation of Axl and Rac1.

Plasmonic Silver-Nanoparticle-Catalysed Hydrogen Abstraction from the C(sp3 )-H Bond of the Benzylic Cα atom for Cleavage of Alkyl Aryl Ether Bonds.

Selective activation of the C(sp3 )-H bond is an important process in organic synthesis, where efficiently activating a specific C(sp3 )-H bond without causing side reactions remains one of chemistry's great challenges. Here we report that illuminated plasmonic silver metal nanoparticles (NPs) can abstract hydrogen from the C(sp3 )-H bond of the Cα atom of an alkyl aryl ether ß-O-4 linkage. The intense electromagnetic near-field generated at the illuminated plasmonic NPs promotes chemisorption of the ß-O-4 compound and the transfer of photo-generated hot electrons from the NPs to the adsorbed molecules leads to hydrogen abstraction and direct cleavage of the unreactive ether Cß -O bond under moderate reaction conditions (≈90 °C). The plasmon-driven process has certain exceptional features: enabling hydrogen abstraction from a specific C(sp3 )-H bond, along with precise scission of the targeted C-O bond to form aromatic compounds containing unsaturated, substituted groups in excellent yields.

Ketogenic Diet Modulates Neuroinflammation via Metabolites from Lactobacillus reuteri After Repetitive Mild Traumatic Brain Injury in Adolescent Mice.

Repetitive mild traumatic brain injury (rmTBI) is associated with a range of neural changes which is characterized by axonal injury and neuroinflammation. Ketogenic diet (KD) is regarded as a potential therapy for facilitating recovery after moderate-severe traumatic brain injury (TBI). However, its effect on rmTBI has not been fully studied. In this study, we evaluated the anti-neuroinflammation effects of KD after rmTBI in adolescent mice and explored the potential mechanisms. Experimentally, specific pathogen-free (SPF) adolescent male C57BL/6 mice received a sham surgery or repetitive mild controlled cortical impacts consecutively for 7 days. The uninjured mice received the standard diet, and the mice with rmTBI were fed either the standard diet or KD for 7 days. One week later, all mice were subjected to behavioral tests and experimental analysis. Results suggest that KD significantly increased blood beta-hydroxybutyrate (ß-HB) levels and improved neurological function. KD also reduced white matter damage, microgliosis, and astrogliosis induced by rmTBI. Aryl hydrocarbon receptor (AHR) signaling pathway, which was mediated by indole-3-acetic acid (3-IAA) from Lactobacillus reuteri (L. reuteri) in gut and activated in microglia and astrocytes after rmTBI, was inhibited by KD. The expression level of the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) in inflammatory cells, which mediates the NF-κB pathway, was also attenuated by KD. Taken together, our results indicated that KD can promote recovery following rmTBI in adolescent mice. KD may modulate neuroinflammation by altering L. reuteri in gut and its metabolites. The inhibition of indole/AHR pathway and the downregulation of TLR4/MyD88 may play a role in the beneficial effect of KD against neuroinflammation in rmTBI mice.

A dataset of images of public streetlights with operational monitoring using computer vision techniques.

A dataset of street light images is presented. Our dataset consists of ∼350 k images, taken from 140 UMBRELLA nodes installed in the South Gloucestershire region in the UK. Each UMBRELLA node is installed on the pole of a lamppost and is equipped with a Raspberry Pi Camera Module v1 facing upwards towards the sky and lamppost light bulb. Each node collects an image at hourly intervals for 24 h every day. The data collection spans for a period of six months. Each image taken is logged as a single entry in the dataset along with the Global Positioning System (GPS) coordinates of the lamppost. All entries in the dataset have been post-processed and labelled based on the operation of the lamppost, i.e., whether the lamppost is switched ON or OFF. The dataset can be used to train deep neural networks and generate pre-trained models providing feature representations for smart city CCTV applications, smart weather detection algorithms, or street infrastructure monitoring. The dataset can be found at 10.5281/zenodo.6046758.

Retraction: Reduction of neuronal damage and promotion of locomotor recovery after spinal cord injury by early administration of methylprednisolone: possible involvement of autophagy pathway.

[This retracts the article DOI: 10.1039/C6RA25794A.].

Primary mucosa-associated lymphoid tissue lymphoma in fallopian tubes: A case report and literature review.

RATIONALE: Mucosa-associated lymphoid tissue (MALT) lymphoma accounts for 7%-8% of newly diagnosed lymphomas. The stomach is the most common organ of origin (nearly 50% of MALT lymphomas). Only 2% of MALT lymphomas arise from the female genital tract, and most originated from uterus. We described a rare case of MALT lymphoma primarily arising from the fallopian tube. PATIENT CONCERNS: A 26-year-old woman was brought into our gynecological clinic because of a history of irregular menstruation. The transvaginal ultrasonography revealed cystic masses in bilateral adnexa and both of them showed rich vasculature. Laboratory tests showed a high level (455.3 U/mL) of cancer antigen-125 (CA-125). INTERVENTIONS: A laparoscopy was performed. OUTCOMES: Frozen section of the removed specimen revealed acute and chronic inflammation with abundant inflammatory cells infiltrating the mesenchyme. The right fallopian tube was removed. However, the final histological results showed inflammation accompanied by hyperplasia of lymphoid tissue. Immunohistochemistry staining were consistent with MALT lymphoma. The patient received the second surgery to remove the left fallopian tube and also confirmed the same pathology. LESSONS: Gynecologists should be aware of cystic masses which showed rich vasculature and high level of CA-125.

Periodontitis Salivary Microbiota Aggravates Ischemic Stroke Through IL-17A.

Although epidemiological studies suggest that periodontitis is tightly associated with ischemic stroke, its impact on ischemic stroke and the underlysing mechanisms are poorly understood. Recent studies have shown that alteration in gut microbiota composition influences the outcomes of ischemic stroke. In the state of periodontitis, many oral pathogenic bacteria in the saliva are swallowed and transmitted to the gut. However, the role of periodontitis microbiota in the pathogenesis and progression of ischemic stroke is unclear. Therefore, we hypothesized that the periodontitis salivary microbiota influences the gut immune system and aggravates ischemic stroke. Mice receiving gavage of periodontitis salivary microbiota showed significantly worse stroke outcomes. And these mice also manifested more severe neuroinflammation, with higher infiltration of inflammatory cells and expression of inflammatory cytokines in the ischemic brain. More accumulation of Th17 cells and IL-17+ γδ T cells were observed in the ileum. And in Kaede transgenic mice after photoconversion. Migration of CD4+ T cells and γδ T cells from the ileum to the brain was observed after ischemic stroke in photoconverted Kaede transgenic mice. Furthermore, the worse stroke outcome was abolished in the IL-17A knockout mice. These findings suggest that periodontitis salivary microbiota increased IL-17A-producing immune cells in the gut, likely promoted the migration of these cells from the gut to the brain, and subsequently provoked neuroinflammation after ischemic stroke. These findings have revealed the role of periodontitis in ischemic stroke through the gut and provided new insights into the worse outcome of ischemic stroke coexisting with periodontitis in clinical trials.

Surface-Plasmon-Enhanced Transmetalation between Copper and Palladium Nanoparticle Catalyst.

Surface-plasmon-mediated phenylacetylide intermediate transfer from the Cu to the Pd surface affords a novel mechanism for transmetalation, enabling wavelength-tunable cross-coupling and homo-coupling reaction pathway control. C-C bond forming Sonogashira coupling and Glaser coupling reactions in O2 atmosphere are efficiently driven by visible light over heterogeneous Cu and Pd nanoparticles as a mixed catalyst without base or other additives. The reaction pathway can be controlled by switching the excitation wavelength. Shorter wavelengths (400-500 nm) give the Glaser homo-coupling diyne, whereas longer wavelength irradiation (500-940 nm) significantly increases the degree of cross-coupling Sonogashira coupling products. The ratio of the activated intermediates of alkyne to the iodobenzene is wavelength dependent and this regulates transmetalation. This wavelength-tunable reaction pathway is a novel way to optimize the product selectivity in important organic syntheses.

LncRNA PVT1 promotes tumorigenesis of glioblastoma by recruiting COPS5 to deubiquitinate and stabilize TRIM24.

LncRNA PVT1 has been implicated in numerous pathophysiological processes and diseases, especially cancers. However, the role and mechanism of PVT1 in the tumorigenesis of glioblastoma remain unclear. We investigated the alteration of PVT1 and its key functions in glioblastoma. PVT1 was upregulated and associated with poor prognosis in glioblastoma. We demonstrated that PVT1 silencing suppressed cell proliferation, colony formation, and orthotopic xenograft tumor growth. Mechanistic investigations found that PVT1 interacted with TRIM24 directly and increased its protein stability. PVT1 recruited COPS5 to deubiquitinate TRIM24; reciprocally, PVT1 depletion impaired the interaction between COPS5 and TRIM24, resulting in decreased expression of TRIM24. PVT1, TRIM24, and COPS5 coordinately contributed to the activation of STAT3 signaling and malignant phenotype of glioblastoma. Collectively, this study elucidates the essential role of PVT1 in the tumorigenesis of glioblastoma, which provides candidacy therapeutic target for glioblastoma treatment.

Sirtuin 5-Mediated Lysine Desuccinylation Protects Mitochondrial Metabolism Following Subarachnoid Hemorrhage in Mice.

BACKGROUND AND PURPOSE: Sirt5 (Sirtuin 5) desuccinylates multiple metabolic enzymes and plays an important role in maintaining energy homeostasis. The goal of this study was to determine whether Sirt5-mediated desuccinylation restores the energy metabolism and protects brain against subarachnoid hemorrhage (SAH). METHODS: Male C57BL/6 or Sirt5-/- mice were used. The endovascular perforation SAH model was applied. Protein lysine succinylation in the brain cortex was examined using liquid chromatography-tandem mass spectrometry analysis. The brain metabolism was evaluated by measurement of brain pH as well as ATP and reactive oxygen species level. Neuronal cell death and neurobehavioral deficits were assessed 24 hours after SAH. The expression and desuccinylation activity of Sirt5, lysine succinylation of citrate synthase and ATP synthase subunits were investigated by Western blot, immunohistochemistry, and ELISA in SAH mice and patients. Furthermore, the benefits of resveratrol-mediated Sirt5 activation were investigated. RESULTS: A total of 211 lysine succinylation sites were differentially expressed on 170 proteins in mice brain after SAH. Thirty-nine percent of these succinylated proteins were localized in mitochondria and they are related to energy metabolism. SAH caused a decrease of Sirt5 expression and succinylated citrate synthase as well as the subunits of ATP synthase, subsequently lowered brain pH, reduced ATP and increased reactive oxygen species production, leading to neuronal cell death, and neurological deficits. Knockdown of Sirt5 aggravated SAH-induced effects, mentioned above. Administration of resveratrol resulted in activation of Sirt5. The activation was accompanied both with restoration of the mitochondrial metabolism and alleviation of early brain injury as well as with desuccinylating citrate synthase and ATP synthase. CONCLUSIONS: Protein lysine succinylation is a biochemical hallmark of metabolic crisis after SAH, and disruption of lysine succinylation through activation of Sirt5 might be a promising therapeutic strategy for the treatment of SAH.

Management of Proximal Segment of the Anterior Cerebral Artery Aneurysms.

ABSTRACT: The authors reported 2 cases with proximal anterior cerebral artery (A1) aneurysms, and one was treated with aneurysm clipping, whereas another was treated with coil embolization. The authors suggest both endovascular surgery and aneurysm clipping are good options for A1 aneurysms.

Association between p73 gene G4C14-to-A4T14 polymorphism and risk of lung cancer: A meta-analysis.

OBJECTIVE: To explore the correlation between p73 G4C14-to-A4T14 polymorphism and lung cancer risk. METHODS: The meta analysis was conducted from October 2017 to March 2018, and comprised studies published till March 27, 2018, that addressed the relationship between the p73 G4C14-to-A4T14 polymorphism and risk of lung cancer, and were available on databases including PubMed, Web of Science, Embase, Cochrane Library and China National Knowledge Infrastructure. Pooled odds ratio with corresponding 95% confidence interval and subgroup analysis between ethnicities were carried out to assess the association between the two parameters using four different models. Stata 12 was used for data analysis. RESULTS: For overall population, there was no significant risk of lung cancer for the polymorphism under allele and dominant genetic models. However, reduced risks were found under homozygous (AT/AT vs GC/GC; p=0.02) and recessive (AT/AT vs GC/AT + GC/GC; p=0.02) comparison models. Subgroup analysis between ethnicities demonstrated reduced risk of lung cancer for the polymorphism under the four genetic comparison models for Asian population, but increased risk for the Caucasian group. CONCLUSIONS: AT/AT variant carriers possessed reduced susceptibility of lung cancer in the general population. Ethnic differences for the p73 gene polymorphism played an important role in lung cancer susceptibility.

Measurement of cerebrovascular reserve by multimodal imaging for cerebral arterial occlusion or stenosis patients: protocol of a prospective, randomized, controlled clinical study.

BACKGROUND: Cerebrovascular reactivity (CVR) is the change in cerebral blood flow in response to a vaso-active stimulus, and may assist the treatment strategy of ischemic stroke. However, previous studies reported that a therapeutic strategy for stroke mainly depends on the degree of vascular stenosis with steady-state vascular parameters (e.g., cerebral blood flow and CVR). Hence, measurement of CVR by multimodal imaging techniques may improve the treatment of ischemic stroke. METHODS/DESIGN: This is a prospective, randomized, controlled clinical trial that aimed to examine the capability of multimodal imaging techniques for the evaluation of CVR to improve treatment of patients with ischemic stroke. A total of 66 eligible patients will be recruited from Renji Hospital, Shanghai Jiaotong University School of Medicine. The patients will be categorized based on CVR into two subgroups as follows: CVR > 10% group and CVR < 10% group. The patients will be randomly assigned to medical management, percutaneous transluminal angioplasty and stenting, and intracranial and extra-cranial bypass groups in a 1:1:1 ratio. The primary endpoint is all adverse events and ipsilateral stroke recurrence at 6, 12, and 24 months after management. The secondary outcomes include the CVR, the National Institute of Health stroke scale and the Modified Rankin Scale at 6, 12, and 24 months. DISCUSSION: Measurement of cerebrovascular reserve by multimodal image is recommended by most recent studies to guide the treatment of ischemic stroke, and thus its efficacy and evaluation accuracy need to be established in randomized controlled settings. This prospective, parallel, randomized, controlled registry study, together with other ongoing studies, should present more evidence for optimal individualized accurate treatment of ischemic stroke. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-IOR-16009635; Registered on 16 October 2016. All items are from the World Health Organization Trial Registration Data Set and registration in the Chinese Clinical Trial Registry: ChiCTR-IOR-16009635.

Intradural Transpetrosectomy for Petrous Apex Meningiomas.

OBJECTIVE: This study aimed to assess the surgical results of the intradural transpetrosectomy for petrous apex meningiomas (PAMs). In addition, we describe the methods and techniques used to expose and manage superior petrous vein and greater superficial petrosal nerve. METHODS: The authors conducted a retrospective study of 16 patients with PAMs operated by the senior author via the intradural transpetrosectomy between February 2012 to May 2017. We reviewed patient data regarding the general characteristics, surgical technique and surgery-related outcomes and adopted a combined follow-up strategy of clinic and telephone contacts to evaluate postoperative complications. RESULTS: Simpson grade I and II resection was performed in 10 out of 16 cases (62.5%), and grade III resection were reported in the remaining six cases (37.5%) with no resultant mortality. The mean Karnofsky Performance Status score was 85.6 preoperatively and improved to 91.9 postoperatively, with a mean follow-up period of 34.4 months (range, 6-66 months). Tumor recurrence was found in two patients and they underwent the second surgical operation. CONCLUSION: PAMs could be completely resected by the intradural transpetrosectomy with an improved survival rate and postoperative life quality. Superior petrous vein and greater superficial petrosal nerve should be managed properly in avoidance of postoperative complications. Finally, most meningioma inside cavernous sinus or adhered to brainstem could be totally removed without postoperative complications.

Multiple organ benign metastasizing leiomyoma: A case report and literature review.

A case of multiple occurrences of benign metastasizing leiomyoma in the lung, left thigh, left ilium and pelvis in a 43-year-old woman who underwent twice myomectomy in 1999 and 2004 and had hysterectomy in 2009 was reported. She was complained of chest distress as well as the pain of left hip and back of thigh. Computed tomography, X-ray and positron emission tomography-computed tomography (PET-CT) demonstrated multiple nodules in lung, masses of left thigh and pelvis. Biopsy of these nodules indicated benign metastasizing leiomyomas according to pathologic and immunohistochemical results. The patient received gonadotropin-releasing hormone agonist injection and regular follow-up. Up to now, all the symptoms have been alleviated.

Ovarian steroid cell tumor, not otherwise specified, treated with surgery: a case report and review of literature.

Ovarian steroid cell tumors NOS are rare sex cord-stromal tumors. They account for less than 0.1% of ovarian tumors. We present a case of a 17-year-old girl with the complaint of amenorrhea. The serum testosterone level was 11.55 nmol/L (reference value, 0.35-2.6 nmol/L) and the serum value of dehydroepiandrosterone-sulfate (DHEA-S) was 5.9 µmol/L (reference value, 0.49-8.71 µmol/L). A computed tomography (CT) pelvic scan identified a solid, right ovarian tumor and detected no adrenal gland enlargement or additional tumors. We took a surgical excision and a wedge resection of the normal contralateral ovary. The histopathologic examination on microscopy confirmed it was a benign ovarian steroid cell tumor NOS. Four days postoperative, her sex hormones were declined to normal levels and her serum testosterone level was 2.37 nmol/L (reference value, 0.35-2.6 nmol/L) a month after surgery. Her serum testosterone level was in the normal range and there was no evidence of recurrence 6 months after surgery.