Tandem phospha-Michael addition/cyclization/dehydration of 2-hydroxychalcones with H-phosphine oxides for the synthesis of 4-phosphorylated 4H-chromenes.

A Hg(OTf)2-catalyzed tandem phospha-Michael addition/cyclization/dehydration of 2-hydroxychalcones with H-phosphine oxides is presented. This protocol provides a new and supplementary approach for the preparation of 4-phosphorylated 4H-chromenes in good yields (up to 99%). In addition, this domino reaction allows the successful construction of two new C-P and C-O bonds in a one-pot operation.

Imaging and detection of sulfite in acute liver injury with a novel quinoxaline-based fluorescent probe.

Herein, a novel fluorescent probe HZY was developed for monitoring the sulfite (SO32-) dynamics. For the first time, the SO32- triggered implement was applied in the acute liver injury (ALI) model. The levulinate was selected to achieve the specific and relatively steady recognition reaction. With the addition of SO32-, the fluorescence response of HZY exhibited a large Stokes shift of 110 nm under the 380 nm excitation. The merits included high selectivity under various pH conditions. Compared with the reported fluorescent probes for sulfite, HZY indicated above-moderate performances including remarkable and rapid response (40 folds, within 15 min), and high sensitivity (limit of detection = 0.21 µM). Further, HZY could visualize the exogenous and endogenous SO32- level in living cells. Moreover, HZY could gauge the changing levels of SO32- in three types (induced by CCl4, APAP, and alcohol) of ALI models. Both in vivo imaging and depth-of-penetration fluorescence imaging demonstrated that HZY could characterize the developmental and therapeutic status during the liver injury process by measuring the dynamic of SO32-. The successful implementation of this project would promote the accurate in-situ detection of SO32- in liver injury, which was expected to guide the pre-clinical diagnosis and clinical practice.

Less is more: wiring-economical modular networks support self-sustained firing-economical neural avalanches for efficient processing.

The brain network is notably cost-efficient, while the fundamental physical and dynamic mechanisms underlying its economical optimization in network structure and activity have not been determined. In this study, we investigate the intricate cost-efficient interplay between structure and dynamics in biologically plausible spatial modular neuronal network models. We observe that critical avalanche states from excitation-inhibition balance under modular network topology with less wiring cost can also achieve lower costs in firing but with strongly enhanced response sensitivity to stimuli. We derive mean-field equations that govern the macroscopic network dynamics through a novel approximate theory. The mechanism of low firing cost and stronger response in the form of critical avalanches is explained as a proximity to a Hopf bifurcation of the modules when increasing their connection density. Our work reveals the generic mechanism underlying the cost-efficient modular organization and critical dynamics widely observed in neural systems, providing insights into brain-inspired efficient computational designs.

The Clinical Features of FLAIR-Hyperintense Lesions in Anti-MOG Antibody Associated Cerebral Cortical Encephalitis with Seizures: Case Reports and Literature Review.

Background: The presence of fluid attenuated inversion recovery (FLAIR)-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated cerebral cortical encephalitis with seizures (FLAMCES) was recently reported. However, the clinical characteristics and outcome of this rare clinico-radiographic syndrome remain unclear. Methods: The present study reported two new cases. In addition, cases in the literature were systematically reviewed to investigate the clinical symptoms, magnetic resonance imaging (MRI) abnormalities, treatments and prognosis for this rare clinico-radiographic syndrome. Results: A total of 21 cases were identified during a literature review, with a mean patient age at onset of 26.8 years. The primary clinicopathological characteristics included seizures (100%), headache (71.4%), fever (52.3%) and other cortical symptoms associated with the encephalitis location (61.9%). The common seizure types were focal to bilateral tonic-clonic seizures (28.6%) and unknown-onset tonic-clonic seizures (38.1%). The cortical abnormalities on MRI FLAIR imaging were commonly located in the frontal (58.8%), parietal (70.6%) and temporal (64.7%) lobes. In addition, pleocytosis in the cerebrospinal fluid was reported in the majority of the patients (95.2%). All patients received a treatment regimen of corticosteroids and 9 patients received anti-epileptic drugs. Clinical improvement was achieved in all patients; however, one-third of the patients reported relapse following recovery from cortical encephalitis. Conclusions: FLAMCES is a rare phenotype of MOG-associated disease. Thus, the wider recognition of this rare syndrome may enable timely diagnosis and the development of suitable treatment regimens.

Clinical features and outcomes of Chinese patients with anti-γ-aminobutyric acid B receptor encephalitis.

Antibodies against γ-aminobutyric acid B (GABAB) receptor are associated with limbic encephalitis (LE). It is estimated that ~1/2 of patients with LE have small-cell lung cancer. The present study analyzed the specific GABAB receptor antibodies in serum and cerebrospinal fluid (CSF) samples of 12 patients. The clinical manifestations, therapy and outcome were retrospectively compared. The median onset age was 65.1 years and all patients presented with new-onset seizures. In total, 11 (91.6%) patients had memory deficits, 7 (58.3%) patients had psychiatric problems and 4 (33.3%) patients had a disturbance of consciousness. Furthermore, lung cancer was detected in 7 patients (58.3%) by CT scan. Lymphocytic pleocytosis and protein concentration elevation in CSF were detected in 3 (25%) and 4 (33.3%) patients, respectively. Furthermore, MRI scan results identified 4 (33.3%) patients with abnormalities in the mesial temporal region. The lung cancer tissues of 3 patients were positively stained for anti-GABAB receptor on immunohistochemistry. All patients received antiepileptic drugs and immunotherapy. In total, 3 patients with lung cancer were subjected to tumor resection. Those patients without cancer exhibited neurological improvement at the follow-up. The present results suggested that seizures and memory deficits were the major manifestations in Chinese patients with anti-GABAB receptor antibodies who were responsive to immunotherapy. The lung cancer tissues from patients with anti-GABAB receptor antibodies were positively stained for anti-GABAB receptor. Collectively, the present results suggested that patients with underlying lung cancer have a relatively poor prognosis.

CXCL13 Is A Biomarker Of Anti-Leucine-Rich Glioma-Inactivated Protein 1 Encephalitis Patients.

BACKGROUND: Although antibody-mediated immune responses are considered pathogenic and responsible for neural injury in anti-leucine-rich glioma-inactivated protein 1 (anti-LGI1) encephalitis, previous studies have indicated that cytokines and chemokines might play roles in the pathogenic process by serving as B cell enhancers. In this study, we detected the profiles of cytokines and chemokines in the cerebral fluid (CSF) and serum of patients with anti-LGI1 encephalitis to identify potential biomarkers. METHODS: Sixteen patients diagnosed with anti-LGI1 encephalitis and nine patients diagnosed with noninflammatory neurologic disorders were included in the study. Cytokines and chemokines including IL-6, IL-10, IL-17, CXCL12, CXCL13, BAFF and HMGB1 in serum and CSF were measured. RESULTS: The serum and CSF levels of CXCL13 were significantly higher in patients with anti-LGI1 encephalitis (36.32±34.71 pg/mL and 2.23±2.41 pg/mL, respectively) than in controls (10.84±5.02 pg/mL and 0.34±0.21 pg/mL, respectively). There was no significant difference in serum or CSF levels of IL-6, IL-10, IL-17, CXCL12, BAFF and HMGB1 between the two groups. CONCLUSION: CXCL13 is a potential biomarker of active inflammation in anti-LGI1 encephalitis. The distinctive response of cytokines and chemokines might be closely linked to the mechanisms underlying this condition.

[The Clinical Study of Comorbidities and Systemic Inflammation in COPD].

OBJECTIVE: To assess the association between chronic obstructive pulmonary disease (COPD) comorbidities and clinical characteristics, and to explore the inflammation mechanism. METHODS: 220 stable COPD patients were included. Clinical characteristics and comorbidities were recorded, and blood samples were collected. The relationship among the number and type of comorbidities, Charlson comorbidity index (CCI), clinical characteristics and the levels of plasma inflammatory markers [interleukin (IL)-6, high sensitivity C-reaction protein (hs-CRP), tumor necrosis factor-α (TNF-α), IL-8] were studied. RESULTS: The top five comorbidities were hypertension, metabolic syndrome and diabetes osteoporosis, bronchiectasis and peripheral vascular diseases. The level of plasma IL-6 was greater in higher CCI score (≥4) group compared with lower CCI score (<4) group ( P=0.011). Levels of IL-6 and IL-8 and the number of hospitalization in prior year were positively correlated with CCI and age adjusted CCI (r<0.03, P<0.05). There was a correlation between the COPD comorbidities and systemic inflammatory response (r<0.3, P<0.05). CONCLUSION: Patients with a higher CCI score had more severe symptoms, functional impairment and higher level of inflammatory factors and high frequency of hospital admission due to acute exacerbation. The mechanism by which COPD may play a role in systemic inflammatory response deserves further study.

The Characteristics of Human Resources and Related Research Activities among Basic Stem Cell Research Groups in China.

BACKGROUND: This study aimed to evaluate the characteristics of faculty and research activities of basic stem cell research groups in China. METHODS: A questionnaire was administered to persons who knew the information among 46 basic stem cell research groups in China. Multiple linear regression models and repeated-measures analyses of variance were used. Repeated-measures analyses of variance were used. RESULTS: Of the 46 groups, 39.1% did not have any faculty recruited from abroad from 2009 to 2013, 37.0% did not have any faculty with junior-level title, 34.8% had ≤25.0% faculty with either M.D. or Ph.D. degree. Papers published in SCI journals per faculty and having faculty recruited from abroad were positively associated with research funding per faculty. The groups with faculty recruited from abroad had significantly higher research funding per faculty over time compared with the group without faculty recruited from abroad. Repeated-measures analyses of variance showed the group with faculty recruited from abroad had significantly higher research funding per faculty over time compared with the group without faculty recruited from abroad. CONCLUSION: To increase the development of basic stem cell research, some characteristics of human resources should be improved, and the groups should recruit more faculty with overseas experience.

Clinical feature and outcome of late-onset cobalamin C disease patients with neuropsychiatric presentations: a Chinese case series.

OBJECTIVE: The Cobalamin C (cblC) disease is an inborn error of cobalamin metabolism. Late-onset cblC disease was diagnosed in patients having overt symptoms after 4 years of age. The late-onset cblC disease patients were rare and easily misdiagnosed. This study analyzed the clinical presentations, gene mutations, and treatments of Chinese patients with late-onset cblC disease. METHODS: The clinical data of 26 Han Chinese patients diagnosed with late-onset cblC disease were retrospectively analyzed. All patients underwent serum homocysteine level exam, urine concentrations of organic acids measurement, neuroimaging scans, gene analysis, and treatments evaluations. RESULTS: The mean age at disease onset and diagnosis was 17.8±7.0 years. The most frequent neuropsychiatric disturbances were lower limb weakness (50%), psychiatric disturbances (46.2%), and gait instability (42.3%). The mean methylmalonic acid level in urine was 107.4±56.6 µmol/L, and mean serum total homocysteine was 105.4±41.0 µmol/L. The most common abnormal radioimaging changes were observed in the spinal cord (88%) and brain (32%). Scoliosis was detected in 85.7% of patients. The methylmalonic aciduria and homocystinuria type C protein gene analysis showed that c.482G>A (57.7%) and c.609G>A (34.6%) mutations were the most frequent genotypes. After treatments with hydroxycobalamin, betaine, folic acid, L-carnitine, and compound vitamin B, the clinical features and biochemical parameters of patients with late-onset cblC disease were found to be alleviated. CONCLUSION: In our late-onset cblC disease cases, lower limb weakness, psychiatric disturbances, and gait instability were the most frequent manifestations. Patients responded well to the drug treatments with hydrocobalamin and betaine. When juvenile or adult patients with hyperhomocysteinemia present with neurological symptoms, cblC disease needs to be considered.

Clinical features of patients with anti-leucine-rich glioma inactivated-1 protein associated encephalitis: a Chinese case series.

Purpose: Antibodies against leucine-rich glioma inactivated 1 (LGI1) are associated with limbic encephalitis and faciobrachial dystonic seizures (FBDS). We present a large series of Han Chinese patients for further clinical refinement. Materials and methods: Serum and cerebrospinal fluid samples from patients were tested. Clinical information of patients with serum anti­LGI1antibody positivity was retrospectively reviewed, and descriptive statistical analysis was performed. Results: The median onset age of the 24 patients was 56.9 years. Among these cases, 18 (75%) patients presented with new­onset refractory seizures, 18 (75%) patients had memory deficits, eight (33.3%) patients had a personality changes and five (20.8%) patients had a disturbance of consciousness. FBDS was observed in nine (37.5%) patients and five of them presented with FBDS as the initial symptom. No cancer was detected in any patient by CT scans. Fourteen (58.3%) patients had hyponatremia. Lymphocytic pleocytosis and protein concentration elevation in CSF were detected in four (16.7%) and six (25%) patients, respectively. Twelve (50%) patients showed paroxysmal sharp/spike waves and slow waves on EEG and seven (29.2%) patients showed mesial temporal region abnormalities by MRI scans. All patients received antiepileptic drugs and immunotherapy. After treatments, the modified Rankin scores of all patients were decreased. Conclusions: Our study showed that Han Chinese patients with anti­LGI1 antibody associated encephalitis had prominent clinical manifestations including seizures, memory deficits and FBDS. They showed neurological improvement with timely immunotherapy. Prompt treatments after rapid clinical recognition is important to improve the prognosis of patients.

Criticality of the nonconservative earthquake model on random spatial networks.

We study the nonconservative earthquake model on random spatial networks. The spatial networks are composed of sites on a two-dimensional (2D) plane which are connected locally. Differently from a regular lattice, the locations of sites are modeled in the way that sites are randomly placed on the plane. Using the same connectivity degree as a 2D lattice, however, the spatial network cannot exhibit critical earthquake behavior. Mimicking long range energy transfer, the connection radius is increased and the connectivity degree of the spatial network is increased. Then we show that the model exhibits self-organized criticality. The mechanism of the structural effect is presented. The spatial network includes many modules when connectivity degree is very small. The effect of modular structure on the avalanche dynamics is to limit the spreading of avalanches in the whole network. When the connectivity degree is larger, the long range energy transfer can overcome the effect of local modularity and criticality can be reached.

Late-onset cobalamin C deficiency Chinese sibling patients with neuropsychiatric presentations.

The Cobalamin C deficiency (cblC), characterized with elevated methylmalonic acidemia and homocystinuria in plasma, is an inborn error of cobalamin metabolism. The late-onset cblC siblings patients were rarely reported. In this study, we analyzed the clinical presentations and treatment outcomes of late-onset cblC in Chinese sibling patients with neuropsychiatric presentations. The clinical data of four pairs of Chinese patients were retrospectively analyzed. Serum homocysteine, urine organic acids measurements, neuroimaging exams and gene analysis were carried out in all patents. Patients were reevaluated after treatments with cobalamin, folate, betaine, L-carnitine and compound vitamin B. The mean age at disease onset was 13.7 (range 2-19) years. The neuropsychiatric disturbances including cognitive decline (3/8), psychiatric disturbances (4/8), gait instability (2/8), lower extremity weakness and numbness (3/8) and thromboembolic events (1/8). Two patients suffered nephropathy. The mean serum homocysteine when patients were diagnosed was 109.4 (range 69.5-138) µM/L. The abnormal radioimaging included scoliosis by X-ray (5/6), cerebral atrophy (4/6) and spinal cord atrophy (3/6) by MRI scan. Three pairs of siblings showed heterozygous mutations of MMACHC gene including c.482G > A (4/6), c.354G > C (2/6), c.570insT (2/6), c.445_446del (2/6) and c.656_4658del (2/6). The other two siblings showed homozygous mutation with c.452A > G in MMACHC gene. After treatments, the psychiatric symptoms were obviously relieved in all the patients. In Chinese siblings with late-onset cblC, the main clinic manifestation and abnormal radioimaging were cognitive decline and cerebral atrophy respectively. The most common gene mutation was c.482G > A of MMACHC gene. The patients responded well to the treatments.

Effect of similarity between patterns in associative memory.

We study the stability of patterns in Hopfield networks in which a part of memorized patterns are similar. The similarity between patterns impacts the stability of these patterns, but the stability of other independent patterns is only changed slightly. We show that the stability of patterns is affected in different ways by similarity. For networks storing a number of patterns, the similarity between patterns enhances the pattern stability. However, the stability of patterns can be weakened by the similarity when networks store fewer patterns, and the relation between the stability of patterns and similarity is nonmonotonic. We present a theoretical explanation of the effect of similarity on stability using signal-to-noise-ratio analysis.

Reversible posterior encephalopathy syndrome associated with late onset postpartum eclampsia: A case report.

Late onset postpartum eclampsia (LPE) is defined by its onset at >48 h after delivery. Reversible posterior encephalopathy syndrome (RPES) associated with LPE is uncommon, with the majority of RPES cases having a late postpartum onset within 4 weeks after childbirth. The present study reported the case of a 15-year old female presenting with convulsions that began 5 weeks after delivery. A magnetic resonance imaging scan of the brain revealed multiple lesions in the cortex, subcortical region and deep white matter of the bilateral cerebellum, and occipital, frontal and parietal lobes. The clinical manifestations and radiological abnormalities were readily resolved subsequent to antihypertension and anticonvulsion treatment. In conclusion, the present rare case indicates that LPE should be considered as a potential diagnosis even at 4 weeks after delivery. Furthermore, clinicians should familiarize with the reversible radioimaging features of RPES, since early recognition and adequate treatment are important to the outcome of patients.

Synchronous slowing down in coupled logistic maps via random network topology.

The speed and paths of synchronization play a key role in the function of a system, which has not received enough attention up to now. In this work, we study the synchronization process of coupled logistic maps that reveals the common features of low-dimensional dissipative systems. A slowing down of synchronization process is observed, which is a novel phenomenon. The result shows that there are two typical kinds of transient process before the system reaches complete synchronization, which is demonstrated by both the coupled multiple-period maps and the coupled multiple-band chaotic maps. When the coupling is weak, the evolution of the system is governed mainly by the local dynamic, i.e., the node states are attracted by the stable orbits or chaotic attractors of the single map and evolve toward the synchronized orbit in a less coherent way. When the coupling is strong, the node states evolve in a high coherent way toward the stable orbit on the synchronized manifold, where the collective dynamics dominates the evolution. In a mediate coupling strength, the interplay between the two paths is responsible for the slowing down. The existence of different synchronization paths is also proven by the finite-time Lyapunov exponent and its distribution.

Stochastic Oscillation in Self-Organized Critical States of Small Systems: Sensitive Resting State in Neural Systems.

Self-organized critical states (SOCs) and stochastic oscillations (SOs) are simultaneously observed in neural systems, which appears to be theoretically contradictory since SOCs are characterized by scale-free avalanche sizes but oscillations indicate typical scales. Here, we show that SOs can emerge in SOCs of small size systems due to temporal correlation between large avalanches at the finite-size cutoff, resulting from the accumulation-release process in SOCs. In contrast, the critical branching process without accumulation-release dynamics cannot exhibit oscillations. The reconciliation of SOCs and SOs is demonstrated both in the sandpile model and robustly in biologically plausible neuronal networks. The oscillations can be suppressed if external inputs eliminate the prominent slow accumulation process, providing a potential explanation of the widely studied Berger effect or event-related desynchronization in neural response. The features of neural oscillations and suppression are confirmed during task processing in monkey eye-movement experiments. Our results suggest that finite-size, columnar neural circuits may play an important role in generating neural oscillations around the critical states, potentially enabling functional advantages of both SOCs and oscillations for sensitive response to transient stimuli.