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AIM: To evaluate the imaging characteristics of dense automatic real time B-scan optical coherence tomography angiography(DART-OCTA)in macular-involved branch retinal vein occlusion(BRVO)and the diagnostic value of capillary perfusion imaging in the macular area.METHODS: From June 2020 to December 2020, there were 51 cases of 51 eyes with BRVO diagnosed in Eye Hospital, Wenzhou Medical University. Imaging characteristics of the BRVO macular area were observed by fluorescein angiography(FA), optical coherence tomography angiography(OCTA)and DART-OCTA examination, respectively. According to the retinal capillary perfusion status, the included patients were divided into capillary and non-imaging groups, comparing the results of capillary perfusion imaging in the BRVO macular area among the three examination methods.Furthermore, quantitative analysis of capillary perfusion density in the lesion involved area and the lesion non-involved area was performed in DART-OCTA images. RESULTS: Patients with 51 eyes were included in this study, FA identified 10 eyes of capillary perfusion imaging, OCTA identified 14 eyes of capillary perfusion imaging, DART-OCTA identified 34 eyes of the capillary perfusion imaging.Comparison of the three test methods for capillary perfusion imaging findings in the BRVO macular area showed that DART-OCTA was more sensitive compared to FA and OCTA for capillary perfusion imaging in the ischemic area. In DART-OCTA examination, retinal capillary blood flow density was lower in the lesion-involved areas in both the capillary perfusion imaging group and the non-imaging groups(0.65±0.20/mm vs 1.16±0.31/mm,0.41±0.16/mm vs 1.06±0.38/mm, all P

BackgroundHemoporfin-mediated photodynamic therapy (PDT) is an effective treatment for port-wine stains (PWS), and pain is the main adverse effect of this therapy. General anesthesia is commonly used for pain management during PDT, but the effect of general anesthetics on the subsequent treatment efficacy of PDT in PWS has not been reported.ObjectivesTo assess the use of general anesthesia combined with PDT compared with PDT alone in 207 PWS patients, and to provide further safety and efficacy data on this combined therapy.MethodsPropensity score matching (PSM) was used at a 2:1 ratio to create a general anesthetic group (n = 138) and a highly comparable nonanesthetic group (n = 69). The clinical outcomes were evaluated, and the treatment reactions and adverse effects were recorded after one treatment with PDT.ResultsAfter matching, there was no significant difference in the demographic data of the patients in the two groups (p > 0.05), while the treatment efficacy was significantly higher in the general anesthetic group than in the nonanesthetic group (76.81 vs. 56.52%, p 0.05). No serious systemic adverse reactions were observed.ConclusionWe recommend this combined therapy, which is associated with painless, as a high efficacy treatment option for PWS patients, especially for patients with a poor response to multiple PDT alone treatments.

A scanning Kelvin probe (SKP) was used to study corrosion of X52 pipeline steel under a CO2-containing solution droplet simulating the water condensate generated in interior of wet gas pipelines. The Volta potential measured by SKP was indicative of the feature of corrosion occurring under the droplet. Three potential zones were observed from the droplet center towards the transition and the side of the droplet, which were -0.1 V, -0.4 V and 0.1 V (Kelvin probe, kp), respectively, after 4 h of testing. The droplet side had the highest Volta potential, which was attributed to corrosion scale generation and precipitation due to a limited solution volume and achieved solubility limit of FeCO3 scale. The transition zone possessed the most negative Volta potential due to a higher corrosion activity than the droplet center with more supply and dissolution of CO2, while the droplet center had the thickest solution. The SKP measurements could estimate the volume evolution of the solution droplet with time at a relatively accurate scale. The solution droplet could maintain its topographic feature, i.e., a spherical cap shape, within 4 h of testing in this work. The increase in droplet concentration due to solution evaporation during testing affected the Volta potential, but slightly only.

Abstract Background Image registration is an essential step in the automated interpretation of the brain computed tomography (CT) images of patients with acute cerebrovascular disease (ACVD). However, performing brain CT registration accurately and rapidly remains greatly challenging due to the large intersubject anatomical variations, low resolution of soft tissues, and heavy computation costs. To this end, the HSCN-Net, a hybrid supervised convolutional neural network, was developed for precise and fast brain CT registration. Method HSCN-Net generated synthetic deformation fields using a simulator as one supervision for one reference–moving image pair to address the problem of lack of gold standards. Furthermore, the simulator was designed to generate multiscale affine and elastic deformation fields to overcome the registration challenge posed by large intersubject anatomical deformation. Finally, HSCN-Net adopted a hybrid loss function constituted by deformation field and image similarity to improve registration accuracy and generalization capability. In this work, 101 CT images of patients were collected for model construction (57), evaluation (14), and testing (30). HSCN-Net was compared with the classical Demons and VoxelMorph models. Qualitative analysis through the visual evaluation of critical brain tissues and quantitative analysis by determining the endpoint error (EPE) between the predicted sparse deformation vectors and gold-standard sparse deformation vectors, image normalized mutual information (NMI), and the Dice coefficient of the middle cerebral artery (MCA) blood supply area were carried out to assess model performance comprehensively. Results HSCN-Net and Demons had a better visual spatial matching performance than VoxelMorph, and HSCN-Net was more competent for smooth and large intersubject deformations than Demons. The mean EPE of HSCN-Net (3.29 mm) was less than that of Demons (3.47 mm) and VoxelMorph (5.12 mm); the mean Dice of HSCN-Net was 0.96, which was higher than that of Demons (0.90) and VoxelMorph (0.87); and the mean NMI of HSCN-Net (0.83) was slightly lower than that of Demons (0.84), but higher than that of VoxelMorph (0.81). Moreover, the mean registration time of HSCN-Net (17.86 s) was shorter than that of VoxelMorph (18.53 s) and Demons (147.21 s). Conclusion The proposed HSCN-Net could achieve accurate and rapid intersubject brain CT registration.

Port-wine stains (PWSs) are a congenital capillary malformed disorder and are caused by a number of somatic mutations that disrupt vascular development. However, the underlying genetic mutations in the pathogenesis of PWS have not yet been fully elucidated. To understand PWS genetic variations and investigate novel genetic mutations, we extracted genomic DNA from four sporadic PWS patients and then performed whole-genome sequencing (WGS). Using Sorting Intolerant from Tolerant (SIFT), PolyPhen2, Mutation Assessor, MetaSVM to identify candidate genetic mutations and whole-exome sequencing (WES) to confirm the identified variants. We found a previously reported G protein subunit alpha q (GNAQ) mutation c.548G > A, p.Arg183Gln in one case, whereas no such mutation was found in the other three samples. Moreover, six novel somatic mutations in three genes, including KCNJ12, SLC25A5, POTEE, were found in these four samples. Importantly, WES also verified the KCNJ12 (c.433G > A, p.Gly145Ser) and SLC25A5 (c.413G > A, p.Arg138His) mutations in other five sporadic PWS patients, with the frequency of 60% (3 of 5) and 40% (2 of 5), respectively. Thus, we reveal in this study two novel somatic mutations, KCNJ12 and SLC25A5, in the sporadic PWS patients for the first time. These findings highlight the genetic polymorphism of PWS and provide potential clinical prediction targets for this disease.

Marine natural products represent a unique source for clinically relevant drugs due to their vast molecular and mechanistic diversity. ZJ-101 is a structurally simplified analog of the marine natural product superstolide A, isolated from the New Caledonian sea sponge Neosiphonia Superstes. The mechanistic activity of the superstolides has until recently remained a mystery. Here, we have identified potent antiproliferative and antiadhesive effects of ZJ-101 on cancer cell lines. Furthermore, through dose–response transcriptomics, we found unique dysregulation of the endomembrane system by ZJ-101 including a selective inhibition of O-glycosylation via lectin and glycomics analysis. We applied this mechanism to a triple-negative breast cancer spheroid model and identified a potential for the reversal of 3D-induced chemoresistance, suggesting a potential for ZJ-101 as a synergistic therapeutic agent.

Overexpression of protein tyrosine phosphatase 1B (PTP1B) induces insulin resistance in various basic and clinical research. In our previous work, a synthetic oleanolic acid (OA) derivative C10a with PTP1B inhibitory activity has been reported. However, C10a has some pharmacological defects and cytotoxicity. Herein, a structure-based drug design approach was used based on the structure of C10a to elaborate the smaller tricyclic core. A series of tricyclic derivatives were synthesised and the compounds 15, 28 and 34 exhibited the most PTP1B enzymatic inhibitory potency. In the insulin-resistant human hepatoma HepG2 cells, compound 25 with the moderate PTP1B inhibition and preferable pharmaceutical properties can significantly increase insulin-stimulated glucose uptake and showed the insulin resistance ameliorating effect. Moreover, 25 showed the improved in vivo antihyperglycaemic potential in the nicotinamide–streptozotocin-induced T2D. Our study demonstrated that these tricyclic derivatives with improved molecular architectures and antihyperglycaemic activity could be developed in the treatment of T2D.

We investigate and analyze the dynamics of hepatitis B with various infection phases and multiple routes of transmission. We formulate the model and then fractionalize it using the concept of fractional calculus. For the purpose of fractionalizing, we use the Caputo–Fabrizio operator. Once we develop the model under consideration, existence and uniqueness analysis will be discussed. We use fixed point theory for the existence and uniqueness analysis. We also prove that the model under consideration possesses a bounded and positive solution. We then find the basic reproductive number to perform the steady-state analysis and to show that the fractional-order epidemiological model is locally and globally asymptotically stable under certain conditions. For the local and global analysis, we use linearization, mean value theorem, and fractional Barbalat’s lemma, respectively. Finally, we perform some numerical findings to support the analytical work with the help of graphical representations.

The emergence and spread of metallo-β-lactamase (MBL)-mediated resistance to β-lactam antibacterials has already threatened the global public health. A clinically useful MBL inhibitor that can reverse β-lactam resistance has not been established yet. We here report a series of [1,2,4]triazole derivatives and analogs, which displayed inhibition to the clinically relevant subclass B1 (Verona integron-encoded MBL-2) VIM-2. 3-(4-Bromophenyl)-6,7-dihydro-5H-[1,2,4]triazolo [3,4-b][1,3]thiazine (5l) manifested the most potent inhibition with an IC50 (half-maximal inhibitory concentration) value of 38.36 μM. Investigations of 5l against other B1 MBLs and the serine β-lactamases (SBLs) revealed the selectivity to VIM-2. Molecular docking analyses suggested that 5l bound to the VIM-2 active site via the triazole involving zinc coordination and made hydrophobic interactions with the residues Phe61 and Tyr67 on the flexible L1 loop. This work provided new triazole-based MBL inhibitors and may aid efforts to develop new types of inhibitors combating MBL-mediated resistance.

Human sirtuin 2 (SIRT2), a member of the sirtuin family, has been considered as a promising drug target in cancer, neurodegenerative diseases, type II diabetes, and bacterial infections. Thus, SIRT2 inhibitors have been involved in effective treatment strategies for related diseases. Using previously established fluorescence-based assays for SIRT2 activity tests, the authors screened their in-house database and identified a compound, 4-(5-((3-(quinolin-5-yl)ureido)methyl)furan-2-yl)benzoic acid (20), which displayed 63 ± 5% and 35 ± 3% inhibition against SIRT2 at 100 μM and 10 μM, respectively. The structure-activity relationship (SAR) analyses of a series of synthesized (5-phenylfuran-2-yl)methanamine derivatives led to the identification of a potent compound 25 with an IC50 value of 2.47 μM, which is more potent than AGK2 (IC50 = 17.75 μM). Meanwhile, 25 likely possesses better water solubility (cLogP = 1.63 and cLogS = −3.63). Finally, the molecular docking analyses indicated that 25 fitted well with the induced hydrophobic pocket of SIRT2.

Robots frequently need to work in human environments and handle many different types of objects. There are two problems that make this challenging for robots: human environments are typically cluttered, and the multi-finger robot hand needs to grasp and to lift objects without knowing their mass and damping properties. Therefore, this study combined vision and robot hand real-time grasp control action to achieve reliable and accurate object grasping in a cluttered scene. An efficient online algorithm for collision-free grasping pose generation according to a bounding box is proposed, and the grasp pose will be further checked for grasp quality. Finally, by fusing all available sensor data appropriately, an intelligent real-time grasp system was achieved that is reliable enough to handle various objects with unknown weights, friction, and stiffness. The robots used in this paper are the NTU 21-DOF five-finger robot hand and the NTU 6-DOF robot arm, which are both constructed by our Lab.

BACKGROUND:Increased risks for hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus have been observed since 2005, in Xi'an, China. Despite increased vigilance and preparedness, HFRS outbreaks in 2010, 2011, and 2012 were larger than ever, with a total of 3,938 confirmed HFRS cases and 88 deaths in 2010 and 2011. METHODS AND FINDINGS:Data on HFRS cases and weather were collected monthly from 2005 to 2012, along with active rodent monitoring. Wavelet analyses were performed to assess the temporal relationship between HFRS incidence, rodent density and climatic factors over the study period. Results showed that HFRS cases correlated to rodent density, rainfall, and temperature with 2, 3 and 4-month lags, respectively. Using a Bayesian time-series Poisson adjusted model, we fitted the HFRS outbreaks among humans for risk assessment in Xi'an. The best models included seasonality, autocorrelation, rodent density 2 months previously, and rainfall 2 to 3 months previously. Our models well reflected the epidemic characteristics by one step ahead prediction, out-of-sample. CONCLUSIONS:In addition to a strong seasonal pattern, HFRS incidence was correlated with rodent density and rainfall, indicating that they potentially drive the HFRS outbreaks. Future work should aim to determine the mechanism underlying the seasonal pattern and autocorrelation. However, this model can be useful in risk management to provide early warning of potential outbreaks of this disease.