Targeting TREM2 signaling shows limited impact on cerebrovascular calcification.

Brain calcification, the ectopic mineral deposits of calcium phosphate, is a frequent radiological finding and a diagnostic criterion for primary familial brain calcification. We previously showed that microglia curtail the growth of small vessel calcification via the triggering receptor expressed in myeloid 2 (TREM2) in the mouse model of primary familial brain calcification. Because boosting TREM2 function using activating antibodies has been shown to be beneficial in other disease conditions by aiding in microglial clearance of diverse pathologies, we investigated whether administration of a TREM2-activating antibody could mitigate vascular calcification in mice.

A pretreatment multiparametric MRI-based radiomics-clinical machine learning model for predicting radiation-induced temporal lobe injury in patients with nasopharyngeal carcinoma.

Background: To establish and validate a machine learning model using pretreatment multiparametric magnetic resonance imaging-based radiomics data with clinical data to predict radiation-induced temporal lobe injury (RTLI) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT).

Methods: Data from 230 patients with NPC who received IMRT (130 with RTLI and 130 without) were randomly divided into the training (n = 161) and validation cohort (n = 69) with a ratio of 7:3. Radiomics features were extracted from pretreatment apparent diffusion coefficient (ADC) map, T2-weighted imaging (T2WI), and CE-T1-weighted imaging (CE-T1WI).

Long-term follow-up of protective effects on salivary and swallowing structures and improvement of late xerostomia and dysphagia by level IIb optimisation in clinical target volume of nasopharyngeal carcinoma.

Background: This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC).

Methods: Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups.

Identification of novel candidate biomarkers related to immune cell infiltration in peri-implantitis.

Objective: The present study was performed to identify key biomarkers associated with immune cell infiltration in peri-implantitis through bioinformatic analyses.

Methods: Six peri-implantitis soft tissue samples and six healthy gingiva samples were obtained from GSE106090, and were used to identify immune-associated differentially expressed genes (DEGs) in peri-implantitis. The candidate biomarkers associated with immune cell infiltration were examined by immunohistochemical staining.

Distribution pattern of medial group retropharyngeal lymph nodes and its implication in optimizing clinical target volume in nasopharyngeal carcinoma.

Purpose: This study aimed to determine the diagnostic value of diffusion-weighted imaging (DWI) and to elucidate the clinical characteristics of medial group retropharyngeal lymph nodes (RLNs) based on multi-modal imaging. Also, we intended to explore the feasibility of optimizing the CTV60 boundary based on the characteristics of medial group RLNs.

Methods: A total of 549 patients with nasopharyngeal carcinoma received magnetic resonance imaging (MRI), DWI, and contrast-enhanced computed tomography (CT) to detect and evaluate clinical characteristics of medial group RLNs.

Inorganic phosphate exporter heterozygosity in mice leads to brain vascular calcification, microangiopathy, and microgliosis.

Calcification of the cerebral microvessels in the basal ganglia in the absence of systemic calcium and phosphate imbalance is a hallmark of primary familial brain calcification (PFBC), a rare neurodegenerative disorder. Mutation in genes encoding for sodium-dependent phosphate transporter 2 (SLC20A2), xenotropic and polytropic retrovirus receptor 1 (XPR1), platelet-derived growth factor B (PDGFB), platelet-derived growth factor receptor beta (PDGFRB), myogenesis regulating glycosidase (MYORG), and junctional adhesion molecule 2 (JAM2) are known to cause PFBC. Loss-of-function mutations in XPR1, the only known inorganic phosphate exporter in metazoans, causing dominantly inherited PFBC was first reported in 2015 but until now no studies in the brain have addressed whether loss of one functional allele leads to pathological alterations in mice, a commonly used organism to model human diseases.

Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates.

Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds, and in rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), and in ex vivo human brain slices, although the endothelial tropism is not conserved across species.

Identification of immune related gene signature for predicting prognosis of cholangiocarcinoma patients.

Objective: To identify the gene subtypes related to immune cells of cholangiocarcinoma and construct an immune score model to predict the immunotherapy efficacy and prognosis for cholangiocarcinoma.

Methods: Based on principal component analysis (PCA) algorithm, The Cancer Genome Atlas (TCGA)-cholangiocarcinoma, GSE107943 and E-MTAB-6389 datasets were combined as Joint data. Immune genes were downloaded from ImmPort.

Altered hemodynamics and vascular reactivity in a mouse model with severe pericyte deficiency.

Pericytes are the mural cells of the microvascular network that are in close contact with underlying endothelial cells. Endothelial-secreted PDGFB leads to recruitment of pericytes to the vessel wall, but this is disrupted in mice when the PDGFB retention motif is deleted. This results in severely reduced pericyte coverage on blood vessels.

Co-Doped Mn O Nanocubes via Galvanic Replacement Reactions for Photocatalytic Reduction of CO with High Turnover Number.

The synthesis of Co-doped Mn O nanocubes was achieved via galvanic replacement reactions for photo-reduction of CO . Co@Mn O nanocubes could efficiently photo-reduce CO to CO with a remarkable turnover number of 581.8 using [Ru(bpy) ]Cl  ⋅ 6H O as photosensitizer and triethanolamine as sacrificial agent in acetonitrile and water.

Public Volume Electron Microscopy Data: An Essential Resource to Study the Brain Microvasculature.

Electron microscopy is the primary approach to study ultrastructural features of the cerebrovasculature. However, 2D snapshots of a vascular bed capture only a small fraction of its complexity. Recent efforts to synaptically map neuronal circuitry using volume electron microscopy have also sampled the brain microvasculature in 3D.

The Interplay Between Brain Vascular Calcification and Microglia.

Vascular calcifications are characterized by the ectopic deposition of calcium and phosphate in the vascular lumen or wall. They are a common finding in computed tomography scans or during autopsy and are often directly related to a pathological condition. While the pathogenesis and functional consequences of vascular calcifications have been intensively studied in some peripheral organs, vascular calcification, and its pathogenesis in the central nervous system is poorly characterized and understood.

Pericyte, but not astrocyte, hypoxia inducible factor-1 (HIF-1) drives hypoxia-induced vascular permeability in vivo.

Background: Ways to prevent disease-induced vascular modifications that accelerate brain damage remain largely elusive. Improved understanding of perivascular cell signalling could provide unparalleled insight as these cells impact vascular stability and functionality of the neurovascular unit as a whole. Identifying key drivers of astrocyte and pericyte responses that modify cell-cell interactions and crosstalk during injury is key.

The expression of Aquaporin-1 and Aquaporin-3 in extrahepatic cholangiocarcinoma and their clinicopathological significance.

Background: The aim of the study was to evaluate the expression and clinicopathological significance of Aquaporin-1 (AQP1) and Aquaporin-3 (AQP3) in extrahepatic cholangiocarcinoma (EHCC).

Methods: Immunostaining of AQP1 and AQP3 was performed by EnVision immunohistochemistry in benign and malignant biliary tract tissues.

Results: The expression of AQP1 and AQP3 protein were significantly higher in EHCC tumor tissues (P < 0.

Characterization of the blood-brain barrier in genetically diverse laboratory mouse strains.

Background: Genetic variation in a population has an influence on the manifestation of monogenic as well as multifactorial disorders, with the underlying genetic contribution dependent on several interacting variants. Common laboratory mouse strains used for modelling human disease lack the genetic variability of the human population. Therefore, outcomes of rodent studies show limited relevance to human disease.

Pericyte hypoxia-inducible factor-1 (HIF-1) drives blood-brain barrier disruption and impacts acute ischemic stroke outcome.

Pericytes play essential roles in blood-brain barrier integrity and their dysfunction is implicated in neurological disorders such as stroke although the underlying mechanisms remain unknown. Hypoxia-inducible factor-1 (HIF-1), a master regulator of injury responses, has divergent roles in different cells especially during stress scenarios. On one hand HIF-1 is neuroprotective but on the other it induces vascular permeability.

The dual anti-caries effect of carboxymethyl chitosan nanogel loaded with chimeric lysin ClyR and amorphous calcium phosphate.

In this study, we evaluated the anti-biofilm and anti-demineralization abilities of a novel material, CMC-ClyR-ACP nanogel, designed by loading the chimeric lysin ClyR and amorphous calcium phosphate (ACP) into a nanocarrier material carboxymethyl chitosan (CMC), in a demineralization model. Dynamic light scattering, transmission electron microscopy, and Fourier transmission infrared spectroscopy showed that CMC-ClyR-ACP nanogel was synthesized successfully. Enamel samples prepared from premolars were divided into five groups according to their treatments with: (i) double distilled water ddH O, (ii) CMC-ACP, (iii) CMC-ClyR-ACP, (iv) ClyR, or (v) 0.

Astrocyte-specific hypoxia-inducible factor 1 (HIF-1) does not disrupt the endothelial barrier during hypoxia in vitro.

Background: Astrocytes (AC) are essential for brain homeostasis. Much data suggests that AC support and protect the vascular endothelium, but increasing evidence indicates that during injury conditions they may lose their supportive role resulting in endothelial cell activation and BBB disturbance. Understanding the triggers that flip this switch would provide invaluable information for designing new targets to modulate the brain vascular compartment.

BIRC7 and STC2 Expression Are Associated With Tumorigenesis and Poor Outcome in Extrahepatic Cholangiocarcinoma.

Background: Extrahepatic cholangiocarcinoma (EHCC) is a highly aggressive epithelial malignancy and has a poor prognosis for the insensitivity to therapies and difficulty in detection. Novel targets and biomarkers are urgently needed to develop for functional, diagnostic and prognostic application on EHCC.

Methods: Immunohistochemical staining technique using the EnVision antibody complex was performed on the samples obtained from 100 EHCC, 30 peritumoral extrahepatic biliary tract (EHBT), 10 EHBT adenomas and 15 normal EHBT tissues.

Recommendation regarding the cranial upper border of level IIb in delineating clinical target volumes (CTV) for nasopharyngeal carcinoma.

Purpose: To recommend a cranial border for level IIb in delineating clinical target volumes (CTV) for nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy and to help reach a consensus on contouring level IIb in CTV.

Methods: From 2012 to 2016, 331 nonmetastatic NPC patients treated with IMRT were retrospectively enrolled. Based on the AJCC 8th staging system of NPC, there were 15 stage I, 76 stage II, 103 stage III, and 137 stage IV patients.

Comparison of ADAM19 and CUEDC2 expression in EHCC and their clinicopathological significance.

To evaluate the expression and clinicopathological significance of a disintegrin and metalloproteinases 19 (ADAM19) CUE domain containing protein 2 (CUEDC2) in extrahepatic cholangiocarcinoma (EHCC). Immunostaining of ADAM19 and CUEDC2 was performed by EnVision immunohistochemistry in benign and malignant biliary tract tissues. The expression of ADAM19 and CUEDC2 were significantly higher in EHCC (p < 0.

Negative Expression of DSG1 and DSG2, as Prognostic Biomarkers, Impacts on the Overall Survival in Patients with Extrahepatic Cholangiocarcinoma.

Aims: To evaluate the expression of DSG1 and DSG2 and investigate their clinicopathological significance in EHCC.

Method: The protein expression of DSG1 and DSG2 was measured by EnVision immunohistochemistry in 15 normal biliary tract tissues, 10 biliary tract adenoma tissues, 30 peritumoral tissues, and 100 EHCC tumour tissues.

Result: The expression of the DSG1 and DSG2 proteins was significantly lower in EHCC tumour tissues than in normal biliary tract tissues, biliary tract adenoma, and peritumoral tissues ( < 0.

Raltitrexed versus 5-fluorouracil with cisplatin and concurrent radiotherapy for locally advanced nasopharyngeal carcinoma: An open labeled, randomized, controlled, and multicenter clinical trial.

Background: This study aimed to compare the efficacy and toxicity of raltitrexed (Saiweijian ) plus cisplatin (SP regimen) and 5-fluorouracil plus cisplatin (FP regimen) as concurrent chemoradiotherapy (CCRT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).

Methods: Eligible patients (N = 135) were allocated randomly in a ratio of 1:1 to receive CCRT with either SP or FP. At least 2 cycles of chemotherapy was administrated during radiotherapy.