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Heidenhain variant of Creutzfeldt-Jakob disease (CJD) remains a diagnostic challenge in clinical practice. We aimed to describe the clinical and prognostic features of Heidenhain cases, through a case series study.We retrospectively reviewed the definite or probable CJD cases admitted to two tertiary referral university hospitals over a decade to identify Heidenhain cases and investigated their survival status by telephone follow-up. Their clinical characteristics, neuroimaging features, electroencephalography (EEG) results, cerebrospinal fluid profiles, and PRNP gene mutations were also analyzed.Of a total of 85 CJD cases, 20 (24%) Heidenhain cases (11 women [55%]; median age, 64 years [range, 44-72 years]) were identified. The median survival time was 22 weeks (range, 5-155 weeks). The median duration of isolated visual symptoms was 3 weeks (range, 1-12 weeks). The most common early visual symptom was blurred vision (16/20, 80%), followed by diplopia (6/20, 30%). The prevalence significantly increased for complex visual hallucination (p = 0.005) and cortical blindness (p = 0.046) as the disease progressed. The positive rate of serial magnetic resonance images (20/20, 100%) was higher than that of serial EEGs (16/20, 80%). Two patients (2/10, 20%) had pathogenic PRNP mutations, E196A and T188K, respectively. Heidenhain cases with PRNP mutations had significantly longer survival time than those without PRNP mutations (p = 0.047).Besides blurred vision (80%), diplopia (30%) was also a frequent early visual symptom among Heidenhain cases. Heidenhain phenotype can occur in genetic CJD cases. PRNP mutation status might be an important prognostic factor for Heidenhain cases.

Diamond nucleation on iridium (001) substrates was investigated under different bias conditions. High-density epitaxial nucleation can be obtained in a narrow bias window. This paper reports both the typical nucleation and growth behaviors of Ir substrates. The bias current change laws with the bias duration time were directly recorded; further, the surface modification of Ir substrates and nucleation behaviors at the interface were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In high-density epitaxial nucleation, the bias current decreases as the duration time increases when the iridium surface is dramatically modified with the furrows and arrows preferentially aligned along the [110] direction; however, no diamond grains can be observed from the TEM, except for the carbon layer at the interface. In bias-enhanced growth, the bias current initially decreased, then increased. The grains can be detected by SEM after the biasing stage. A competition mechanism between diamond nucleation and growth under a bias voltage is proposed for this phenomenon, in which the surface nucleation and bulk nucleation coexist and compete.

A 59-year-old woman presented with subacute onset of hand clumsiness followed by memory loss. She reported difficulty reaching for objects, although she could see them. Examination (video) showed optic ataxia, visual acuity of 20/30 OU, intact visual field, and near-normal finger-to-nose test. Hyperintense signals in the left temporo-parieto-occipital cortex in diffusion-weighted MRI, periodic triphasic complexes in EEG (figure), and elevated t-tau in CSF suggested the Heidenhain variant of Creutzfeldt-Jakob disease.1 The patient received supportive care and progressed to akinetic mutism. Optic ataxia—inaccuracy of visually guided arm movements—is a visuomotor disorder associated with lesions involving the posterior parietal cortex.2

Aicardi-Goutières syndrome (AGS) is a rare, single-gene disorder, characterized by neurologic and skin involvement with an increased level of interferon-α (IFN-α) in the CSF. We describe the case of a young patient presenting with recurrent ischemic stroke. Evaluation revealed the presence of chilblains, white matter abnormalities, cerebral atrophy, and raised IFN-α in the CSF. Compound heterozygous variants of TREX1 were detected, confirming a diagnosis of AGS. After excluding other causes, we attributed the stroke to AGS. Tofacitinib, a Janus kinase inhibitor, was administered to our patient in addition to antiplatelet drugs. There was no recurrence of stroke during 3-month follow-up. This is a rare case of recurrent stroke in TREX1-mutated AGS. Small vessel involvement has been previously demonstrated to play a significant role in the pathogenesis of AGS. This microvascular mechanism might explain the occurrence of ischemic stroke in our patient. For young patients with stroke and multiple system involvement, genetic disorders including AGS should be considered.

A 22-year-old man complained of progressive bilateral blurred vision that had developed 6 years ago. He also noted dispersed scotomas and graying of vison in both eyes, without photopsia, orbital pain, or double vision. He had not seen an ophthalmologist until he could hardly recognize people by appearance 1 week previously. Bilateral optic atrophy (figure, A) was recorded with best-corrected visual acuities of counting fingers OD and 20/400 OS. Perimetry revealed global visual field loss OD and tunnel vision OS (figure, B). He was referred to our neurology clinic, where he reported recurrent mild dull headache from age 10.

Objective: To describe the characteristics of post-stroke Chinese pure alexia and associated neuropsychological profiles. Methods: All patients with post-stroke pure alexia from the neurology department of our hospital were enrolled from June 2018 to July 2019. Brain MRI was performed to evaluate the stroke radiologically. The Aphasia Battery of Chinese (ABC) was used to evaluate the general language functions. A Chinese individual character reading test including 68 commonly used characters was used to evaluate the ability to read individual Chinese characters. The numbers of correct reading and misreading were recorded, and the error types of misreading were analyzed. MMSE, auditory verbal learning test, cube copying task, clock drawing test, and picture copying tests were performed to evaluate other cognitive impairments. Results: A total of 5 male patients were included, with a median age of 58 years (50-64 years). They all had Chinese pure alexia with intact verbal comprehension and speech and relatively preserved writing skills. The etiologies were all acute infarction involving the left temporo-parietal lobe and splenium of corpus callosum. In the Chinese individual character reading test, the median number of correct reading was 21 (18-44) out of 68 characters, with many shape-similar errors (one character was read as another one with a similar shape but different meaning and pronunciation). The percentage of shape-similar errors among all type errors was 81.5%, 60.0%, 23.7%, 18.5%, and 57.9% respectively, and 43.1% overall, much higher than other type errors. All the patients had obvious impairment in memory and visuospatial function with an exception that one patient had relatively preserved visuospatial ability. Conclusion: Shape-similar error is a remarkable feature of Chinese pure alexia. Chinese pure alexia is associated with impaired visuospatial function, but visuospatial dysfunction is not necessary for the development of Chinese pure alexia.

Restenosis caused by neointimal hyperplasia significantly decreases long-term efficacy of percutaneous transluminal angioplasty (PTA), stenting, and by-pass surgery for managing coronary and peripheral arterial diseases. A major cause of pathological neointima formation is abnormal vascular smooth muscle cell (VSMC) proliferation and migration. Notoginsenoside R1 (NGR1) is a novel saponin that is derived from Panax notoginseng and has reported cardioprotective, neuroprotective and anti-inflammatory effects. However, its role in modulating VSMC neointima formation remains unexplored. Herein, we report that NGR1 inhibits serum-induced VSMC proliferation and migration by regulating VSMC actin cytoskeleton dynamics. Using a mouse femoral artery endothelium denudation model, we further demonstrate that systemic administration of NGR1 had a potent therapeutic effect in mice, significantly reducing neointimal hyperplasia following acute vessel injury. Mechanistically, we show that NGR1’s mode of action is through inhibiting the activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Taken together, this study identified NGR1 as a potential therapeutic agent for combating restenosis after PTA in cardiovascular diseases.

Diamonds with two extreme sizes, large single crystal and nanocrystalline, have completely different properties, and have aroused the continuous attention of researchers. Each has its own merits and can be converted into the other. The synthesis of large single crystal diamond can be described as the aggregation, assembly and combination of nanocrystalline nuclei, i.e., diamond transforming from the nano-scale to the inch scale. A large single crystal diamond can be transformed into nanocrystals by surface nanocrystallization. The preparation methods, properties and applications of single crystal diamonds of different sizes are introduced and the transformations between them are described. Research interest in controlling the crystal size is discussed.

Natural triterpenoids, such as oleanolic acid (OA) and hederagenin, display anti-lung cancer effects, and nitric oxide (NO) is associated with some oncogenic signaling pathways. Accordingly, 17 OA/hederagenin-NO donor hybrids were designed, synthesized, and evaluated against tumor cells. The most potent compound, 13, significantly inhibited the proliferation of five tumor cell lines (IC50 4.6-5.2 μM), while hederagenin inhibited the growth of only A549 tumor cells (IC50 > 10 μM). Furthermore, compound 13 showed stronger inhibitory effects on EGFR-LTC kinase activity (IC50 0.01 μM) than hederagenin (IC50 > 20 μM) and inhibited the proliferation of gefitinib-resistant H1975 (IC50 8.1 μM) and osimertinib-resistant H1975-LTC (IC50 7.6 μM) non-small-cell lung cancer (NSCLC) cells. Moreover, compound 13 produced the most NO in H1975 tumor cells, which indicated that NO may play a synergistic role. Collectively, compound 13, a novel hederagenin-NO donor hybrid with a different chemical structure from those of the current FDA-approved EGFR-targeted anti-NSCLC drugs, may be a promising lead compound for the treatment of NSCLC expressing gefitinib-resistant EGFR with a T790 M mutation or osimertinib-resistant EGFR-LTC with an L858R/T790M/C797S mutation. This work should shed light on the discovery of new anti-NSCLC drugs targeting EGFR from natural products.

Three new saponins (

Wall-eyed monocular internuclear ophthalmoplegia (WEMINO) is a rare variant of internuclear ophthalmoplegia (INO), consisting of unilateral INO and ipsilateral exotropia. This distinctive syndrome is probably associated with damage to the medial longitudinal fasciculus. However, WEMINO caused by a midbrain lesion has not been previously reported. We herein report a 50-year-old man presenting with WEMINO and vertical gaze dysfunction resulting from infarction of the midbrain tegmentum.

Little is known about ping-pong gaze (PPG) outside of individual case reports. We aimed to describe PPG through an observational study and literature review. Consecutive patients with PPG at Shanghai General Hospital (SGH) from February 2016 to March 2018 were enrolled. A literature review through March 2018 was conducted. Of the 14 patients with PPG in SGH, the median age was 60 years and 12 were males. The median Glasgow coma scale score was 7.5. The cycle of the PPG ranged from 1.5 to 6.5 s. The leading three etiologies were acute ischemic stroke in five patients, post-seizure state in three patients, and hypoxic-ischemic encephalopathy in two patients. A total of 88.9% (8/9) of the patients with consistent whole-field PPG had similar bilateral hemispheric damage, whereas 80.0% (4/5) of the patients with PPG in the hemifield had unilateral or extremely asymmetric bilateral hemispheric damage. The hemifiled side was the same side as the sole/dominant hemispheric lesion. The final clinical outcomes were neurologic remission for seven patients, vegetative state for one patient, and death for six patients. PPG is a sign with localizing value that suggests hemispheric damage and asymmetric PPG might help to predict lateralization of the lesions. Acute ischemic stroke is the most common cause of PPG. Etiology and initial outcome are likely important prognostic factors of PPG.

A novel palladium-catalyzed oxidative three-component coupling of easily accessible N-substituted anthranilamides with isocyanides and arylboronic acids is achieved. This protocol offers an alternative approach toward 2,3-disubstituted quinazolinones with a wide substrate scope and good functional group tolerance.

Scopolin (SC-1), scopoletin (SC-2) and isofraxidin (IS-1) are the main active constituents in Chimonanthi Radix. However, the in vivo metabolism of SC-1, SC-2 and IS-1 have not been comprehensively clarified. In this study, the in vivo metabolic profiles of these three coumarins in the rat plasma, urine and feces were analyzed. Ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS/MS) method was applied to characterize the prototypes and metabolites of SC-1, SC-2 and IS-1 in rat feces, urine, and plasma after intravenous administration. A total of 11 metabolites of the three parent compounds were tentatively identified. The main metabolic pathways were analyzed by identification of metabolites, and it was found that these three coumarins underwent multiple in vivo metabolic reactions including glucuronidation, sulfonation, isomerism and reduction. In this study, the analysis of metabolites of three coumarins basically demonstrated their in vivo metabolic process, providing basis for the further pharmacokinetics and pharmacological evaluations of SC-1, SC-2 and IS-1.

Internal environment of metabolism of traditional Chinese medicine (TCM) is a dynamic process, which is in line with the "holistic-dynamic-comprehensive-analytic" characteristics of metabonomics, therefore metabonomics have a unique advantage to reveal the metabolic pattern of TCM. The application of metabonomics in TCM has great practical significance in understanding the pharmacodynamic/toxic effect material basis, mechanisms and guiding for determination of dosage and treatment course; At the same time, the scientific compatibility of TCM prescription, the germplasm resources of TCM and the preclinical safety/toxicity can be widely researched. At present, metabolomics has become a leading technology in many industries and fields including the research and development of TCM. The core of metabolomics is analytical technology, because comprehensive metabolite profiles or accurate identification of known metabolites can be obtained from complex biological samples only by appropriate analytical techniques. At the same time, a series of bioinformatics/chemical informatics/stoichiometry methods are needed to process the data, so as to obtain the potential law and information in the mass data. In this paper, the concept of metabolomics, relevant analytical techniques, data processing methods and applications were explained and analyzed clearly. In addition, the core problems and countermeasures of metabolomics were summarized, and the future development of metabolomics was prospected as well.

Six undescribed withanolides were isolated and characterized during the investigation of anti-inflammatory and cytotoxic constituents from the whole plants of Physalis minima L. Their structures were elucidated by extensive spectroscopic analyses (IR, UV, HR-ESI-MS, 1D-NMR, and 2D-NMR), and their anti-inflammatory and cytotoxic activities were evaluated in vitro. All the compounds exhibited anti-inflammatory ability via inhibiting the production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells. Moderate cytotoxic activities against A549 lung adenocarcinoma cells, SMMC-7721 hepatic carcinoma cells and MCF-7 breast cancer cells with IC50 values in the range of 40.01–82.17 μM were observed for these withanolides.

A 64-year-old literate Chinese man presented with sudden onset of difficulty reading. Examination revealed right homonymous hemianopsia and pure alexia. The oral reading test showed that he often read one character as another one with a similar shape but different meaning and pronunciation (figure 1). Brain MRI showed acute infarction involving the left occipital lobe, medial temporal lobe, and splenium of corpus callosum (figure 2). Pure alexia is a clinical disconnection syndrome that was first described in a patient with a similar infarction by Dejerine in 1892.1 Shape-similar errors may be a phenomenon characteristic of Chinese pure alexia.

The present study was designed to investigate the chemical constituents of the roots of Cudrania fruticosa Wight. Compounds were isolated by various column chromatographic methods including silica gel, polyamide, sephadex LH-20, and semi-preparative HPLC. Their structures were elucidated by a combination of 1D and 2D NMR techniques, mass spectrometry, and chemical methods. Two new xanthones, Cudraxanthone T and U (1-2), along with four known compounds (3-6) were isolated from the roots of Cudrania fruticosa Wight.

Two new acylated triterpene saponins, named as securioside C (1), securioside D (2), and one pair of isomers 3/4, the (Z)–isomer securioside E (3) being new, together with a known triterpene saponin polygalasaponin XLIV (4) were isolated from the roots of Securidaca inappendiculata Hassk. Their structures were established by HRESIMS, 1D and 2D NMR experiments and comparison of their NMR data with previous reported data. In addition, Compounds 1–2, 3/4, 4 were evaluated for cytotoxicities against LLC (Lewis lung carcinoma) and MCF-7 (human breast cancer) cell lines. Compounds 1 and 2 exhibited moderate cytotoxic activities against LLC cells with IC50 values of 45.56 μM and 85.98 μM.

A 27-year-old man presented with fever, somnolence, seizure, and nuchal rigidity. CSF culture indicated Streptococcus pneumoniae , confirming the diagnosis of bacterial meningitis. Ping-pong gaze was observed initially, and then replaced by what we called ocular nodding after IV administration of diazepam (video at [Neurology.org][1]). The eyes went downward and returned to primary position slowly, smoothly, and periodically (with a cycle lasting 12–17 seconds and a pause between 2 cycles), resembling a nodding head. He became alert with free eye movement within 3 days of antibiotic treatment. Ping-pong gaze has been reported,1 but ocular nodding is a novel finding. [1]: http://neurology.org/lookup/doi/10.1212/WNL.0000000000004633

A rapid and accurate method of UFLC-Q-TOF-MS/MS combined with multivariate statistical analysis was established for the identification of Ainsliaea fragrans from different origins in this study. The A. fragrans from different producing areas of Jiangxi, Yunnan, Henan and Jiangsu were determined by UFLC-Q-TOF-MS/MS in the negative ion mode. And the data of the study were analyzed by the Markerview and other software for the PCA and OPLS-DA cluster analysis as well as t test. The results of the principal component analysis(PCA)showed that the main components from different origins were well distinguished. And the results of multivariate statistical showed the differences and similarities between different producing areas. Besides, 40 different compounds were identified in the negative ion mode. This method for identifying A. fragrans from different producing areas has the advantages of rapid accuracy and simplicity, which laid the foundation for the evaluation of the quality of the A. fragrans.

A new ferulic acid ester named 4-methyl-3-trans-hexenylferulate (1), together with eight known phenolic acid esters (2-9), was isolated from the methanolic extract of the roots and rhizomes of Notopterygium incisium. Their structures were elucidated by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry. 4-Methoxyphenethyl ferulate (8) NMR data is reported here for the first time. The uptake and transepithelial transport of the isolated compounds 1-9 were investigated in the human intestinal Caco-2 cell monolayer model. Compounds 2 and 6 were assigned for the well-absorbed compounds, compound 8 was assigned for the moderately absorbed compound, and compounds 1, 3, 4, 5, 7, and 9 were assigned for the poorly absorbed compounds. Moreover, all of the isolated compounds were assayed for the inhibitory effects against nitric oxide (NO) production in the lipopolysaccharide-activated RAW264.7 macrophages model and L-N⁶-(1-iminoethyl)-lysine (L-NIL) was used as a positive control. Compounds 1, 5, 8, and 9 exhibited potent inhibitory activity on NO production with the half maximal inhibitory concentration (IC50) values of 1.01, 4.63, 2.47, and 2.73 μM, respectively, which were more effective than L-NIL with IC50 values of 9.37 μM. These findings not only enriched the types of anti-inflammatory compounds in N. incisum but also provided some useful information for predicting their oral bioavailability and their suitability as drug leads or promising anti-inflammatory agents.

Nine compounds, including five lignan glycosides (1-5), three sucrose esters (6-8), and one organic acid ester (9), were isolated from the ethanol extract of the roots of Securidaca inappendiculata by various chromatographic methods including silica gel, MPLC and preparative HPLC. Their structures were elucidated as acernikol-4″-O-β-D-glucopyranoside (1), (7R, 8S)-dihydrodehydrodiconiferyl alcohol 9-O-β-D-glucopyranoside (2), (7R, 8S)-dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranoside (3), (7R, 8S)-dihydrodehydrodiconiferyl alcohol 9'-O-β-D-glucopyranoside (4), (7R, 8S)-5-methoxydihydrodehy-drodiconiferyl alcohol 4-O-β-D-glucopyranoside (5), 3, 6'-O-diferuloylsucrose (6), 3-O-feruloyl-6'-O-sinapoylsucrose (7), sibricose A5 (8), and mehyl ferulate (9) on the basis of 1H-, 13C-NMR and MS experiments. Compounds 1-5, 8, and 9 were isolated from the Securidaca genus for the first time. Compounds 2, 3, and 7 exhibited weak cytotoxic activities against Hela and MCF-7 cell lines.

In the present study, three new triterpenoids, 23-hydroxyurs-12, 18-dien-28-oic acid 3β-O-α-L-arabinopyranoside (1), 23-hydroxyurs-12, 18-dien-28-oic acid 3β-O-β-D-glucuronopyranoside-6-O-methyl ester (2), and urs-12, 18-dien-28-oic acid 3β-O-β-D-glucuronopyranoside-6-O-methyl ester (3), and a known triterpenoid, 3β-hydroxy-urs-2, 18-dien-28-oic acid (4, randialic acid B), were isolated from the aerial parts of Ilex cornuta. Their structures were identified by the spectroscopic analyses (IR, ESI-MS, HR-ESI-MS, and 1D and 2D NMR) and chemical reactions. Compound 4 showed significant cell-protective effects against H

The major lipid-soluble constituents in Fructus aurantii (zhiqiao) and Fructus aurantii immaturus (zhishi) are polymethoxylated flavones (PMFs) and coumarins. In the present study, a high-performance liquid chromatography with electrospray ionization tandem mass spectrometry method was developed to quantify PMFs (nobiletin, tangeretin, 5-hydroxy-6,7,8,4'-tetramethoxyflavone, and natsudaidai) and coumarins (marmin, meranzin hydrate, and auraptene) simultaneously. PMFs and coumarins were detected by electrospray ionization tandem mass spectrometry in positive ion mode and quantified with multiple reaction monitor. Samples were separated on a Diamonsil C₁₈ (150 mm × 4.6 mm, 5 μm) column using acetonitrile and formic acid-water solution as a mobile phase in gradient mode with a flow rate at 0.5 mL/min. All calibration curves showed good linearity (r² > 0.9977) within the test ranges. Variations of the intraday and interday precisions were less than 4.07%. The recoveries of the components were within the range of 95.79%-105.04% and the relative standard deviations were less than 3.82%. The method developed was validated with acceptable accuracy, precision, and extraction recoveries and can be applied for the identification and quantification of four PMFs and three coumarins in citrus herbs.

By the R-matrix of orthosymplectic quantum superalgebra Uq(osp(2l+1|2n)) in the vector representation, we establish the corresponding quantum Hopf superalgebra OSPq(2l + 1|2n). Furthermore, it is shown that OSPq(2l + 1|2n) is coquasitriangular.

This paper gives a generalization of group theory, i.e. a unification theory of different causal algebras, and its applications to theoretical physics. We propose left and right causal algebras, left and right causal decomposition algebras, causal algebra and causal decomposition algebras in terms of quantitative causal principle. The causal algebraic system of containing left (or right) identity IjL (or IjR) is called as the left (or right) causal algebra, and associative law is deduced. Furthermore the applications of the new algebraic systems are given in theoretical physics, specially in the reactions of containing supersymmetric particles, we generally obtain the invariance of supersymmetric parity of multiplying property. In the reactions of particles of high energy, there may be no identity, but there are special inverse elements, which make that the relative algebra be not group, however, the causal algebra given in this paper is just a tool of severely and directly describing the real reactions of particle physics. And it is deduced that the causal decomposition algebra is equivalent to group.

One new triterpenoid sapoin with two known triterpenoid sapoins: 3β- O -{α- l -rhamnopyranosyl-(1 → 3)-[β- d -xylopyranose-(1 → 2)]-β- d -glucopyranosyl-(1 → 4)-α- l -arabinopyranosyl}-3β-hydroxy-13β,28-epoxy-oleanan-16-oxo-30-al ( 1 ), 3β- O -{α- l -rhamnopyranosyl-(1 → 3)-[(β- d -xylopyranosyl-(1 → 2)]-β- d -galactopyranosyl-(1 → 4)-[(β- d -glucopyranosyl-(1 → 2)]-α- l -arabinopyranoside}-16α-hydroxy-13,28-epoxy-oleanane ( 2 ) and cyclamiretin A 3β- O -α- l -rhamnopyranosyl-(1 → 3)-[β- d -xylopyranosyl-(1 → 2)]-β- d -glucopyranosyl-(1 → 4)-[β- d -glucopyranosyl-(1 → 2)]-α- l -arabinopyranoside ( 3 ) were isolated from Ardisia gigantifolia Stapf. Their structures were elucidated by means of 1 H and 13 C NMR spectroscopic studies, including 2D-NMR technique.