Morphological diversity of single neurons in molecularly defined cell types.

Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits.

Alpha-fetoprotein response following transarterial chemoembolization indicates improved survival for intermediate-stage hepatocellular carcinoma.

BACKGROUND: To investigate the clinical value of the alpha-fetoprotein (AFP) response following transcatheter arterial chemoembolization (TACE) in intermediate-stage hepatocellular carcinoma (HCC). METHODS: Data on patients with Barcelona Clinic Liver Cancer B staging system were analyzed. An AFP response was defined as a decrease in AFP of more than 20% after a TACE session. The association between AFP response and treatment outcome regarding imaging response and overall survival (OS) was explored. Cox proportional hazards models were applied to identify independent risk factors for OS after TACE. RESULTS: Of the enrolled 376 patients with elevated serum AFP >20 ng/mL, 214 (57%) with AFP responses were identified. AFP responders had improved median survival than non-responders (20 vs. 12 months, P = 0.002). AFP response was significantly correlated with imaging response (P < 0.001). The Cox proportional hazards model revealed that AFP response was an independent factor for OS (hazard ratio, 0.59; 95% confidence interval, 0.45-0.78; P < 0.001). In stratified analyses, an AFP response achieved improved survival in patients with tumor diameters ≤5 cm, diameters >5 cm, tumor number ≤3 and without underlying cirrhosis. CONCLUSIONS: The AFP response indicates enhanced survival after TACE in patients with intermediate-stage BCLC.

Effect of ultrasonic-fed time on combustion and emissions performance in a single-cylinder engine.

In this study, a numerical simulation method for multi-field coupling is proposed in which the ultrasonic is physically fed in the combustion chamber of a gasoline engine. The fine-tuning regulation of activity and reaction paths of gas-liquid two-phase (GLP) fuel is studied by using ultrasonic under in-cylinder complex conditions. The three-dimensional (3D) computational fluid dynamics (CFD) model of the original engine is calibrated, based on the bench test data. The multi-field coupling model of the sound field and combustion field is established by embedding the feature of the sound source surface in the combustion chamber. The ultrasonic with 20 kHz frequency and 100 µm amplitude is fed into the combustion chamber by using the dynamic grid technology. By comparing the simulation results of four ultrasonic-fed schemes (S1∼S4) and ultrasonic-free scheme (No), it is concluded that compared with the No scheme, the average turbulent kinetic energy (TKE) of the schemes S1, S2, and S3 are all increased by 23.2% at the top dead center (TDC), the peak pressure of the schemes S1 and S2 are both increased by 0.58 MPa. The CO and soot formations of scheme S1 are the lowest at 6.5% and 6.1%, respectively, compared with the No scheme. The reasonable use of ultrasonic can promote the fuel oxidation and combustion process, and accelerate the formation of the OH radicals. The ultrasonic-fed has a significantly quantitative control effect on fuel activity and oxidation reaction paths within 10 ms, under the in-cylinder transient and complex combustion condition of the gasoline engine.

Long non-coding RNA VPS9D1-AS1 enhances proliferation, invasion, and epithelial-mesenchymal transition in endometrial cancer via miR-377-3p/SGK1.

Endometrial cancer (EC) is a kind of gynecologic malignancy with a rising incidence rate. This study aimed to explore the role of VPS9D1 antisense RNA1 (VPS9D1-AS1) in EC. The expression of VPS9D1-AS1, microRNA (miR)-377-3p, and serum and glucocorticoid-regulated kinase 1 (SGK1) was detected by Quantitative Real-Time PCR (qRT-PCR). Cell proliferation, invasion and epithelial-mesenchymal transition (EMT) were determined by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-Deoxyuridine (EdU) transwell, and western bolt. VPS9D1-AS1 was predicted to sponge miR-377-3p via Starbase, and verified by luciferase reporter, RNA binding protein immunoprecipitation (RIP), and RNA pull-down experiments. The clinical characteristics of VPS9D1-AS1, miR-377-3p, and SGK1 were analyzed. The role of VPS9D1-AS1 on EC tumorigenesis was assessed in xenografted nude mice. VPS9D1-AS1 was upregulated in EC cells and tissues. Interference of VPS9D1-AS1 inhibited growth, invasion, and EMT of EC cells. Mechanically, VPS9D1-AS1 was a molecular sponge of miR-377-3p, and overexpression of miR-377-3p reversed VPS9D1-AS1-induced EC cells proliferation, invasion, and EMT. Moreover, SGK1 was confirmed to bind with miR-377-3p. Furthermore, overexpression of SGK1 alleviated sh-VPS9D1-AS1-caused effects on EC cells. High level of VPS9D1-AS1 and SGK1, or low miR-377-3p expression predicted a poor prognosis. The expression of the three genes was correlated with lymph node metastasis, pathological stage, and International Federation of Gynecology and Obstetrics (FIGO) stage, but not associated with age, ER, and PR expression. Interestingly, knockdown of VPS9D1-AS1 suppressed EC tumor growth in mice. VPS9D1-AS1 promoted cell invasion, proliferation, and EMT via modulating miR-377-3p/SGK1 axis, which provided new options for therapeutic strategies of EC.

The Potential Circular RNAs Biomarker Panel and Regulatory Networks of Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease. It has been reported that circular RNAs (circRNAs) play important roles in several neurological diseases. However, the role and regulatory networks of circRNAs in PD are still largely unclear. In this study, we first compared the global expression level of circRNAs from patients with PD and controls using microarray, then the candidate circRNAs were validated in another PD cohort. The possible functions of these candidate circRNAs were analyzed using Gene Ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the regulatory networks of these candidate circRNAs were constructed through circRNA-miRNA-mRNA regulatory networks, protein-protein interaction (PPI) networks, and transcription factor-circRNA networks. The results indicated that hsa_circRNA_101275, hsa_circRNA_103730, and hsa_circRNA_038416 were significantly more highly expressed in patients with PD, while hsa_circRNA_102850 was lower expressed in patients with PD when compared with controls. A circRNA panel combining the four differentially expressed circRNA showed a high diagnostic ability to distinguish patients with PD from controls (AUC = 0.938). Furthermore, GO and KEGG analysis showed these candidate circRNAs were enriched in PI3K-Akt and MAPK signaling pathways. We established circRNA-miRNA-mRNA regulatory networks and identified 10 hub genes (ESR1, PTEN, SHC1, IGF1R, SMAD2, KRAS, MDM2, HIF1A, BMP4, and ACVR2B) were closely related to PD by using PPI network analysis. Besides, these circRNAs were predicted to be regulated through tyrosine hydroxylase (TH)-relevant transcription factors such as GATA2 and GATA3. In conclusion, our results suggest that the circRNA panel and the established circRNA-miRNA-mRNA regulation networks might provide potential novel biomarkers and therapeutic targets for PD.

99mTc-Labeled RGD-Polyethylenimine Conjugates with Entrapped Gold Nanoparticles in the Cavities for Dual-Mode SPECT/CT Imaging of Hepatic Carcinoma.

We report the construction and characterization of 99mTc-labeled arginine-glycine-aspartic acid (RGD)-polyethylenimine (PEI) conjugates with entrapped gold nanoparticles in the cavities (RGD-99mTc-Au PENPs) for dual-mode single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of an orthotopic hepatic carcinoma model. In this study, PEI was successively decorated with diethylenetriaminepentaacetic acid, poly(ethylene glycol) (PEG), and PEGylated RGD segments, and was utilized as an effective nanoplatform to entrap Au NPs and to be labeled with 99mTc. We showed that the designed RGD-99mTc-Au PENPs displayed desirable colloidal stability and radiostability, and cytocompatibility in the investigated concentration range, and could be specifically uptaken by αvß3 integrin-overexpressing liver cancer cells in vitro. In vivo CT and SPECT imaging results indicated that the particles were able to be accumulated within an orthotopic hepatic carcinoma and displayed both CT and SPECT contrast enhancement in the tumor tissue. With the proven biocompatibility in vivo via histological examinations, the designed RGD-99mTc-Au PENPs may be potentially employed as an effective nanoprobe for a highly efficient dual-mode SPECT/CT imaging of various αvß3 integrin-overexpressing tumors.

Portal venous stent placement for treatment of portal hypertension caused by benign main portal vein stenosis.

AIM: To evaluate the value of endovascular stent in the treatment of portal hypertension caused by benign main portal vein stenosis. METHODS: Portal vein stents were implanted in six patients with benign main portal vein stenosis (inflammatory stenosis in three cases, postprocedure of liver transplantation in another three cases). Changes in portal vein pressure, portal vein patency, relative clinical symptoms, complications, and survival were evaluated. RESULTS: Six metallic stents were successfully placed across the portal vein stenotic or obstructive lesions in six patients. Mean portal venous pressure decreased significantly after stent implantation from (37.3+/-4.7) cm H(2)O to (18.0+/-1.9) cm H(2)O. The portal blood flow restored and the symptoms caused by portal hypertension were eliminated. There were no severe procedure-related complications. The patients were followed up for 1-48 mo. The portal vein remained patent during follow-up. All patients survived except for one patient who died of other complications of liver transplantation. CONCLUSION: Percutaneous portal vein stent placement for the treatment of portal hypertension caused by benign main portal vein stenosis is safe and effective.

[Budd-Chiari syndrome with occlusion of hepatic vein: multi-slice spiral CT diagnosis and its clinical significance in the treatment].

OBJECTIVE: To evaluate the multi-slice spiral CT dynamic enhancement features and the diagnostic value of CT angiography in Budd-Chiari syndrome with occlusion of hepatic vein (HVBCS), and to assess the CT clinical significance in the treatment of HVBCS. METHODS: Twenty-one patients with HVBCS confirmed by digital subtraction angiography (DSA) were retrospectively analyzed. All patients received multi-slice spiral dynamic enhancement scans within 2 weeks before DSA. The relevant vein vessels were reconstructed respectively with Maximum Intensity Projection (MIP), Volume Rendering (VR) and Oblique Reformat techniques. The course of disease was less than three months in four patients, more than three months in seventeen patients. RESULTS: In the four patients with the course of disease of less than three months, CT showed global liver enlargement with diffuse hypodensity on plain scans and patchy enhancement in caudate lobe and perihilar areas on post-contrast CT scans, and the enhancement field spread to larger area as the time of scans delayed. In the seventeen patients with the course of disease of more than three months, plain CT scans showed abnormalities of liver morphology and hypodensity either in atrophic areas or in the periphery of the liver. On post-contrast CT scans, the hypodensity areas showed poor and heterogeneous enhancement, and hepatic drainage veins in these areas obstructed, whereas in hepatic veins drainage normal areas hepatic parenchymal showed homogeneous enhancement, their drainage veins had at least one patent hepatic vein or a dilated accessory hepatic vein that can provide adequate collaterals. Hepatic CT enhancement features were closely related to the occlusion location of hepatic vein and collateral drainage veins. In twenty-one patients, a total of 42 hepatic veins were occluded. Among them, 9 left hepatic veins, 12 middle hepatic veins, 16 right hepatic veins, and 6 accessory hepatic veins were occluded. The accuracy rate of hepatic veins occlusion showed on transverse scans and CT angiography were 61.9% and 100% respectively. CONCLUSION: Multi-slice spiral dynamic enhancement scans can accurately reflect the changes of intrahepatic hymodynamics. Transverse scans combined with CT angiography can explicitly show the location of hepatic veins occlusion and collateral circulation in HVBCS, which is of important clinical significance in the treatment of HVBCS.

[Present situation and development of acupuncture and moxibustion in Singapore].

The development history, education, legislation, charge and institutes of acupuncture and moxibustion in Singapore are introduced in this article. Acupuncture and moxibustion has been developed in Singapore since 1840. Nowadays there are three universities that set up standard Chinese medicine courses and two acupuncture-moxibustion associations. Legislation of acupuncture and moxibustion is published in 2000. The acupuncture and moxibustion is applied for approximately 50 kinds of diseases. The acupuncture and moxibustion is at one's own expense in public or private institutions, but cheap or completely free in charity.