Correction: Privileged substructures for anti-sickling activity via cheminformatic analysis

Correction for ‘Privileged substructures for anti-sickling activity via cheminformatic analysis’ by Chuleeporn Phanus-umporn et al., RSC Adv., 2018, 8, 5920–5935.

Errors were present in the published version of Fig. 2; the correct version is shown below:Open in a separate windowFig. 2Workflow of CSAR modeling for investigating anti-sickling activity.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Hyper-convolutions via implicit kernels for medical image analysis

The convolutional neural network (CNN) is one of the most commonly used architectures for computer vision tasks. The key building block of a CNN is the convolutional kernel that aggregates information from the pixel neighborhood and shares weights across all pixels. A standard CNN’s capacity, and thus its performance, is directly related to the number of learnable kernel weights, which is determined by the number of channels and the kernel size (support). In this paper, we present the hyper-convolution, a novel building block that implicitly encodes the convolutional kernel using spatial coordinates. Unlike a regular convolutional kernel, whose weights are independently learned, hyper-convolution kernel weights are correlated through an encoder that maps spatial coordinates to their corresponding values. Hyper-convolutions decouple kernel size from the total number of learnable parameters, enabling a more flexible architecture design. We demonstrate in our experiments that replacing regular convolutions with hyper-convolutions can improve performance with less parameters, and increase robustness against noise. We provide our code here: https://github.com/tym002/Hyper-Convolution.     

DNA-based nanosensors for next-generation clinical diagnostics via detection of enzyme activity

Specific and sensitive detection of DNA-modifying enzymes represents a cornerstone in modern medical diagnostics. Many of the currently prevalent methods are not preferred in the clinics because they rely heavily on pre-amplification or post-separation steps. This editorial highlights the potential of adopting DNA-based nanosensors for the assessment of the activities of DNA-modifying enzymes, with emphasis on the topoisomerase and tyrosyl-DNA phosphodiesterase families. By underlining the existing challenges, we expect that the DNA-nanosensors may soon be promoted to clinical diagnostics via enzyme detection.     

蛋白酶体活性测定与组分分析方法的建立

背景:26S蛋白酶体对维持细胞周期、增殖、生存等细胞生物学行为的正常具有极其重要的作用,但目前对细胞体内蛋白酶体活性的测定及组分分析缺少明确的方法.目的:建立蛋白酶体活性与组分的分析方法,用以检测肿瘤组织、细胞蛋白酶体的活性状态与组分表达情况.方法:应用3种特异性的荧光多肽底物Suc-LLVY-AMC、Z-ARR-AMC和Z-LLE-AMC建立对蛋白酶体的糜蛋白酶样、胰蛋白酶样和肽基谷氨酰肽水解酶样蛋白酶活性的测定方法.并基于蛋白酶体特异亲和性探针AdaK(Bio)Ahx3L3VS建立对蛋白酶体各亚基(包括β1/β1i,β2/β2i,β5/β5i)组分分析的方法.结果与结论:利用特异性的荧光多肽底物检测蛋白酶活性及蛋白酶体特异亲和性探针检测蛋白酶体亚基组分分析的方法发现在K562红白血病细胞,β2、β5亚基表达较高,而蛋白酶体抑制剂PS341及PSI对K562细胞的蛋白酶体活性与组分的抑制作用主要是靶定在β5和β5i亚基,抑制其糜蛋白酶样活性.实验建立了对以上3种蛋白酶体活性测定及组分分析的方法,为蛋白酶体抑制剂的体外活性鉴定提供了实验方法.     

Modulation of pyloric motor activity via adrenergic receptors

The influences of adrenergic nerves on pyloric motor function and the locus and types of receptors involved were examined. Using glyoxylic acid fluorescence a dense adrenergic innervation of the inner pyloric muscle ring was demonstrated. Pyloric motor activity was monitored while close i.a. injections of a selective alpha-1 adrenoceptor agonist, phenylephrine, or a selective alpha-2 adrenoceptor agonist, B-HT-920, were given. Neither agonist affected basal pyloric motor activity, but both inhibited pyloric activity when it was stimulated by duodenal field stimulation or by intraduodenal acid infusion. The actions of each of the inhibitory agonists, phenylephrine or B-HT-920, were blocked selectively by prazosin or rauwolscine, respectively. Injection of isoproterenol usually had no effect or excited basal pyloric activity. This excitation could be antagonized selectively by propranolol or by atropine. Injection of isoproterenol after neural blockade by tetrodotoxin inhibited pyloric motor activity. Receptor binding studies carried out with subcellular nerve or muscle enriched membrane fractions of canine pyloric muscle with [3H]prazosin, [3H]rauwolscine and [125I]cyanopindolol revealed a dual location of alpha-1, alpha-2 and beta receptors on both nerve membranes and smooth muscle membranes. These results suggest that adrenergic effects on the pyloric muscle can be exerted by pre- and postsynaptic beta receptors which, respectively, excite by releasing acetylcholine and inhibit by acting on receptors on the pyloric muscle. Also inhibitory alpha-1 and alpha-2 receptors are present on cholinergic nerves. The functions of postsynaptic alpha-1 and alpha-2 adrenoceptor binding sites on smooth muscle are so far unknown.     

Brucite shows antibacterial activity via establishment of alkaline conditions

Brucite, a mineral form of magnesium hydroxide, has been used industrially as a useful refractory insulator. However, its antibacterial activity remains largely unknown. This study investigated the antibacterial activity of brucite in two bacterial strains, Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive). Brucite, compared to other minerals, showed a strong antibacterial activity against both bacterial strains. The surface structure of brucite examined using scanning electron microscopy (SEM) had no implications in its antibacterial activity. Brucite in lysogeny broth (LB) medium maintained the basicity (pH 9) of the solution for a prolonged period of time. The basicity of the medium was responsible for the antibacterial activity of brucite. The study results identified brucite as a potent antibacterial agent that required no further processing and also revealed the underlying mechanism of action responsible for its antibacterial activity.

Brucite, a mineral form of magnesium hydroxide, has been used industrially as a useful refractory insulator.     

Simulated decision-making experience via case analysis.

An effective strategy for developing decision-making skills is presented, using a problem-solving systems model. Through retrospective examination of an actual problem, the systematic, sequential aspects of decision making are illustrated.     

A novel approach for EIT regularization via spatial and spectral principal component analysis

Electrical impedance tomography, EIT, is an imaging modality in which the internal conductivity distribution of an object is reconstructed based on voltage measurements on the boundary. This reconstruction problem is a nonlinear and ill-posed inverse problem, which requires regularization to ensure a stable solution. Most popular regularization approaches enforce smoothness in the inverse solution. In this paper, we propose a novel approach to build a subspace for regularization using a spectral and spatial multi-frequency analysis approach. The approach is based on the construction of a subspace for the expected conductivity distributions using principal component analysis. It is shown via simulations that the reconstructed images obtained with the proposed method are better than with the standard regularization approach. Using this approach, the percentage of misclassified finite elements was reduced up to twelve fold from the initial percentages after five iterations. The advantage of this technique is that prior information is extracted from the characteristic response of an object at different frequencies and spatially across the finite elements.     

腹腔镜下经胆囊管治疗继发胆总管结石的疗效分析

目的分析腹腔镜下经胆囊管治疗继发胆总管结石的临床疗效。方法选取在该院接受治疗的胆结石继发胆总管结石的患者120例,按照随机的方法平均分给观察组与对照组,每组60例患者。观察组实施腹腔镜下经胆囊管治疗继发胆总管结石的方法治疗,对照组采用传统的腹腔镜下胆总管探查T管引流术。治疗一段时间后,比较两组患者的手术时间、胃肠功能恢复时间、术中出血情况、并发症的总发生率和住院时间。结果观察组的术中手术时间、胃肠功能恢复时间、术中出血情况、并发症的发生率和住院时间均少于对照组;其中观察组在住院时间(5.4±2.1)d明显低于观察组(16.5±6.9)d,术后水、电解质紊乱、伤口疼痛和感染等并发症总发生率(6.66%)明显低于对照组的总发生率(61.67%),差异具有统计学意义(P0.05)。结论腹腔镜下经胆囊管治疗胆结石合并胆总管结石优于传统的腹腔镜下胆总管探查T管引流术,术中的出血量少、更安全且并发症少,恢复快,建议广泛使用。     

Spatiotemporal activity estimation for multivoxel pattern analysis with rapid event-related designs

Despite growing interest in multi-voxel pattern analysis (MVPA) methods for fMRI, a major problem remains--that of generating estimates in rapid event-related (ER) designs, where the BOLD responses of temporally adjacent events will overlap. While this problem has been investigated for methods that reduce each event to a single parameter per voxel (Mumford et al., 2012), most of these methods make strong parametric assumptions about the shape of the hemodynamic response, and require exact knowledge of the temporal profile of the underlying neural activity. A second class of methods uses multiple parameters per event (per voxel) to capture temporal information more faithfully. In addition to enabling a more accurate estimate of ER responses, this allows for the extension of the standard classification paradigm into the temporal domain (e.g., Mour?o-Miranda et al., 2007). However, existing methods in this class were developed for use with block and slow ER data, and there has not yet been an exploration of how to adapt such methods to data collected using rapid ER designs. Here, we demonstrate that the use of multiple parameters preserves or improves classification accuracy, while additionally providing information on the evolution of class discrimination. Additionally, we explore an alternative to the method of Mour?o-Miranda et al. tailored to use in rapid ER designs that yields equivalent classification accuracies, but is better at unmixing responses to temporally adjacent events. The current work paves the way for wider adoption of spatiotemporal classification analyses, and greater use of MVPA with rapid ER designs.     

经腹腔镜治疗子宫内膜异位囊肿569例临床分析

目的 探讨腹腔镜在子宫内膜异位症治疗中的手术方式和临床效果.方法 对该院2003年12月～2008年12月569例子宫内膜异住囊肿患者接受腹腔镜手术的治疗方式及效果进行回顾性分析研究.结果 569例患者均行腹腔镜下子宫内膜异位囊肿手术,其中一侧肿块剥除术288例,双侧肿块剥除173例,一侧附件切除加对侧病灶剥除术98例,子宫及一侧附件切除加对侧病灶剥除术6例,子宫及双附件切除4例,上述术中同时行电凝、烧灼腹膜等处的异位病灶,分离粘连,行通液术58例,术后服用孕激素类药物.569例术者中有生育要求的58例,23例术后半年妊娠,另30例术后一年半妊娠,5例未孕;总有效率55％.115例痛经者症状完全缓解97例,部分缓解17例,总有效率80％.结论 腹腔镜手术治疗卵巢子宫内膜异位囊肿是一个安全有效的方法,通过研究发现手术能改善患者的生活质量,对合并不孕者,可同时治疗,提高妊娠率.     

The vivo antioxidant activity of self-made aged garlic extract on the d-galactose-induced mice and its mechanism research via gene chip analysis

Two self-made aged garlic extract (AGE) were prepared and they were subjected with d-galactose-induced mice to explore vivo antioxidant effects and its mechanism via gene chip analysis. The biochemical analysis results indicated that AGE could significantly reduce the malondialdehyde (MDA) and lipofuscin content and increase the total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activity. Histopathological observations found that AGE could improve the size, shape and arrangement state of liver and brain cells. Furthermore, gene expression profile array was used to screen 35 and 13 differentially expressed genes in liver and brain, respectively. Further analysis showed that the AGE could protect the mice from d-galactose-caused injury via carbohydrate metabolism, immunomodulatory, lipid metabolism, cell cycle regulation, amino acid metabolism and nervous regulation pathways. Through this experiment, we could comprehensively study the antioxidant mechanism of AGE and link the antioxidant function of AGE to the metabolic pathways.

AGE exerts its vivo antioxidant function through 41 metabolic pathways, which were related to 7 aging hallmarks.     

Improved assay for alcohol dehydrogenase activity in serum by centrifugal analysis

We describe an improved method for determination of alcohol dehydrogenase (EC 1.1.1.1) activity in 60 microL of human serum, based on conversion of ethanol to acetaldehyde with simultaneous reduction of NAD+ in glycine NaOH buffer (pH 9.0) at 37 degrees C in a centrifugal analyzer. The final concentration of NAD+ was 10 mmol/L and ethanol was 20 mmol/L. The dilution curve was linear with enzyme activity up to 200 U/L, and results by this method correlated well with those by a manual method (N Engl J Med 279: 241-248, 1968). Within-run precision (CV) was 0.9 to 8.2% over the range of 4.5 to 88.1 U/L, and day-to-day precision was 5.4 to 5.6%. In sera from 198 healthy individuals, mean alcohol dehydrogenase activity was 1.6 (SD 1.2, range 0-5) U/L. To evaluate the clinical utility of determining alcohol dehydrogenase, we measured the activity of alanine aminotransferase and alcohol dehydrogenase in sera from 470 patients with various diseases in our hospital, and found that results for the two enzymes did not correlate well.     

腹腔镜下改良水压分离法治疗输卵管妊娠的临床研究

目的 探讨在腹腔镜下行输卵管妊娠保守性手术中应用改良式水压分离妊娠组织对保留输卵管的意义。方法 回顾性分析2010年1月-2013年1月在因输卵管妊娠在我院行腹腔镜下输卵管保守性手术的患者120例,按手术方法不同分为两组：观察组73例,术中注射垂体后叶素并应用改良式水压分离法分离妊娠组织;对照组47例,注射垂体后叶素,术中电钩打开妊娠部位后直接钳出妊娠组织,对比两组间手术时间、术中出血量、术后持续性宫外孕发生率及术后输卵管通畅情况。结果 120例患者均在腹腔镜下完成手术,观察组手术时间明显短于对照组,术中出血量明显少于对照组,差异有显著性,术后持续性宫外孕发生率无显著差异,术后输卵管通畅情况明显高于对照组。结论 腹腔镜下应用改良式水压分离输卵管妊娠组织可能对完整地清除妊娠病灶,减少术中出血及输卵管的损伤,提高术后输卵管通畅率有一定的帮助。     

Monocyte-mediated tumoricidal activity via the tumor necrosis factor-related cytokine, TRAIL

TRAIL (tumor necrosis factor [TNF]-related apoptosis-inducing ligand) is a molecule that displays potent antitumor activity against selected targets. The results presented here demonstrate that human monocytes rapidly express TRAIL, but not Fas ligand or TNF, after activation with interferon (IFN)-gamma or -alpha and acquire the ability to kill tumor cells. Monocyte-mediated tumor cell apoptosis was TRAIL specific, as it could be inhibited with soluble TRAIL receptor. Moreover, IFN stimulation caused a concomitant loss of TRAIL receptor 2 expression, which coincides with monocyte acquisition of resistance to TRAIL-mediated apoptosis. These results define a novel mechanism of monocyte-induced cell cytotoxicity that requires TRAIL, and suggest that TRAIL is a key effector molecule in antitumor activity in vivo.     

Tune the chemical activity of graphene via the transition metal substrate

To achieve the chemical modification of graphene efficiently is desirable and essential to promote the technological applications of graphene. In this study, the density functional theory (DFT) calculations have been carried out to investigate the hydrogenation and fluorination activities of graphene on Ni(111), Re(0001) and Pt(111). The calculation results indicate that the chemical activity of graphene is related to both the characteristics of the graphene–substrate interfacial interaction and the local atomic stacking, namely the chemical activity of graphene is position-dependent. The strong covalently interacting substrates Ni(111) and Re(0001) will remarkably enhance the chemical activity of graphene, while the modulation effects from the weak van der Waals interacting substrate Pt(111) is trivial. Electronic structure studies reveal that the intensive graphene–substrate interfacial interaction can gain in chemical energy to offset the strain energy caused by the C atom sp²–sp³ transition and stabilize the absorbing state.

The chemical activity of graphene can be tuned by the transition metal substrate.