Distribution of Biocide Resistance Genes and Association with Clonal Complex Genotypes in Staphylococcus aureus Isolated from School-Age Children in Guangzhou.

Purpose: Chlorhexidine and mupirocin are often prescribed to children in affected communities to prevent colonization and transmission of Staphylococcus aureus, but this has led to an increasing rate of biocide resistance. In this study, we aimed to determine the distribution of biocide resistance genes among S. aureus isolates from school-age children in Guangzhou, investigate chlorhexidine gluconate and mupirocin susceptibility and clonal complex (CC) genotypes in strains carrying biocide-resistance genes, and further explore the role of biofilms in this resistance. Patients and Methods: Antibiotic resistance and multilocus sequence genotyping were performed on 722 S. aureus isolates from previous study. The distribution of nine biocide genes (qacA/B, mupA, mepA, sepA, norA, lmrS, smr, mupB, qacG) was determined by PCR. Isolates carrying qacA/B or mupA genes were further tested for susceptibility to chlorhexidine gluconate (CHG) and mupirocin and biofilm formation abilities. Results: The most prevalent of the nine biocide resistance genes were mepA (95.57%), followed by norA (78.81%), lmrS (77.01%), and sepA (58.17%). The qacG gene was not detected. Distribution of sepA was significantly decreased in CC30 and CC45 genotypes, and presence of sepA was associated with resistance to antibiotics such as CLI, ERY, TCY, SXT, CIP, and LVX. In addition, 64 (94.1%, n=68) qacA/B+ isolates showed CHG resistance, 12 (100.0%, n=12) mupA+ isolates were mupirocin resistant, and 4 (80%, n=5) and 5 (100%, n=5) qacA/B+mupA+ isolates were CHG and mupirocin resistant, respectively. Of these 85 isolates, 98.8% (n=84) had different degrees of biofilm-forming abilities, which were positively associated with CHG and mupirocin resistance. Conclusion: The distribution of biocide resistance genes was associated with special CCs. The qacA/B and mupA genes are highly associated with resistance to CHG and mupirocin, and biofilm formation was found to contribute to this biocide resistance.

Identification of Alzheimer's Disease and Mild Cognitive Impairment Using Networks Constructed Based on Multiple Morphological Brain Features.

Structural brain markers are important for characterizing the pathology of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Here, we constructed a multifeature-based network (MFN) for each individual using a sparse linear regression performed on six types of morphological features to promote the structure-based autodiagnosis. The categorization performance of the MFN was evaluated in 165 normal control subjects, 221 patients with MCI, and 142 patients with AD. We achieved 96.42% and 96.37% accuracy, respectively, in distinguishing the patients with AD and MCI from the normal control subjects, and reasonable discrimination of the two disease cohorts (70.52%) and prediction of the MCI to AD progression (65.61%). The performance was further improved by combining the properties of the MFN with the morphological features. Our results demonstrate the effectiveness of the MFN in combination with morphological features obtained from single imaging modality, serving as robust biomarkers in the diagnosis of AD and MCI.

Changes in Dynamics Within and Between Resting-State Subnetworks in Juvenile Myoclonic Epilepsy Occur at Multiple Frequency Bands.

Time-varying connectivity analyses have indicated idiopathic generalized epilepsy (IGE) could cause significant abnormalities in dynamic connective pattern within and between resting-state sub-networks (RSNs). However, previous studies mainly focused on the IGE-induced dynamic changes of functional connectivity (FC) in specific frequency band (0.01-0.08 Hz or 0.01-0.15 Hz), ignoring the changes across different frequency bands. Here, 24 patients with IGE characterized by juvenile myoclonic epilepsy (JME) and 24 matched healthy controls were studied using a data-driven frequency decomposition approach and a sliding window approach. The RSN dynamics, including intra-RSN dynamics and inter-RSN dynamics, was further calculated to investigate dynamic FC changes within and between RSNs in JME patients in each decomposed frequency band. Compared to healthy controls, JME patients not only showed frequency-dependent decrease in intra-RSN dynamics within multiple RSNs but also exhibited fluctuant alterations in inter-RSN dynamics among several RSNs over different frequency bands especially in the ventral/dorsal attention network and the subcortical network. Additionally, the disease severity had significantly negative correlations with both intra-RSN dynamics within the subcortical network and inter-RSN dynamics between the subcortical network and the default network at the lower frequency band (0.0095-0.0195 Hz). These results suggested that abnormal dynamic FC within and between RSNs in JME occurs at multiple frequency bands and the lower frequency band (0.0095-0.0195 Hz) was probably more sensitive to JME-caused dynamic FC abnormalities. The frequency subdivision and selection are potentially helpful for detecting particular changes of dynamic FC in JME.

Learning Metabolic Brain Networks in MCI and AD by Robustness and Leave-One-Out Analysis: An FDG-PET Study.

This study attempted to better understand the properties associated with the metabolic brain network in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Graph theory was employed to investigate the topological organization of metabolic brain network among 86 patients with MCI, 89 patients with AD, and 97 normal controls (NCs) using 18F fluoro-deoxy-glucose positron emission tomography (FDG-PET) data. The whole brain was divided into 82 areas by Brodmann atlas to construct networks. We found that MCI and AD showed a loss of small-world properties and topological aberrations, and MCI showed an intermediate measurement between NC and AD. The networks of MCI and AD were vulnerable to attacks resulting from the altered topological pattern. Furthermore, individual contributions were correlated with Mini-Mental State Examination and Clinical Dementia Rating. The present study indicated that the topological patterns of the metabolic networks were aberrant in patients with MCI and AD, which may be particularly helpful in uncovering the pathophysiology underlying the cognitive dysfunction in MCI and AD.

Frequency-Specific Functional Connectivity Density as an Effective Biomarker for Adolescent Generalized Anxiety Disorder.

Several neuropsychiatric diseases have been found to influence the frequency-specific spontaneous functional brain organization (SFBO) in resting state, demonstrating that the abnormal brain activities of different frequency bands are associated with various physiological and psychological dysfunctions. However, little is known about the frequency specificities of SFBO in adolescent generalized anxiety disorder (GAD). Here, a novel complete ensemble empirical mode decomposition with adaptive noise method was applied to decompose the time series of each voxel across all participants (31 adolescent patients with GAD and 28 matched healthy controls; HCs) into four frequency-specific bands with distinct intrinsic oscillation. The functional connectivity density (FCD) of different scales (short-range and long-range) was calculated to quantify the SFBO changes related to GAD within each above frequency-specific band and the conventional frequency band (0.01-0.08 Hz). Support vector machine classifier was further used to examine the discriminative ability of the frequency-specific FCD values. The results showed that adolescent GAD patients exhibited abnormal alterations of both short-range and long-range FCD (S-FCD and L-FCD) in widespread brain regions across three frequency-specific bands. Positive correlation between the State Anxiety Inventory (SAI) score and increased L-FCD in the fusiform gyrus in the conventional frequency band was found in adolescents with GAD. Both S-FCD and L-FCD in the insula in the lower frequency band (0.02-0.036 Hz) had the highest classification performance compared to all other brain regions with inter-group difference. Furthermore, a satisfactory classification performance was achieved by combining the discrepant S-FCD and L-FCD values in all frequency bands, with the area under the curve (AUC) value of 0.9414 and the corresponding sensitivity, specificity, and accuracy of 87.15, 92.92, and 89.83%, respectively. This study indicates that the alterations of SFBO in adolescent GAD are frequency dependence and the frequency-specific FCD can potentially serve as a valuable biomarker in discriminating GAD patients from HCs. These findings may provide new insights into the pathophysiological mechanisms of adolescent GAD.

NHC-catalyzed [4 + 2] annulation of 2-bromo-2-enals with acylhydrazones: enantioselective synthesis of δ-lactams.

An asymmetric assembly of δ-lactams was realized via the NHC-catalyzed formal [4 + 2] annulation of acylhydrazones and 2-bromo-2-enals bearing γ-H. The advantages of this protocol include high enantioselectivity, good yields, mild reaction conditions and potential biological significance of the final products.

Topological Organization of Metabolic Brain Networks in Pre-Chemotherapy Cancer with Depression: A Resting-State PET Study.

This study aimed to investigate the metabolic brain network and its relationship with depression symptoms using 18F-fluorodeoxyglucose positron emission tomography data in 78 pre-chemotherapy cancer patients with depression and 80 matched healthy subjects. Functional and structural imbalance or disruption of brain networks frequently occur following chemotherapy in cancer patients. However, few studies have focused on the topological organization of the metabolic brain network in cancer with depression, especially those without chemotherapy. The nodal and global parameters of the metabolic brain network were computed for cancer patients and healthy subjects. Significant decreases in metabolism were found in the frontal and temporal gyri in cancer patients compared with healthy subjects. Negative correlations between depression and metabolism were found predominantly in the inferior frontal and cuneus regions, whereas positive correlations were observed in several regions, primarily including the insula, hippocampus, amygdala, and middle temporal gyri. Furthermore, a higher clustering efficiency, longer path length, and fewer hubs were found in cancer patients compared with healthy subjects. The topological organization of the whole-brain metabolic networks may be disrupted in cancer. Finally, the present findings may provide a new avenue for exploring the neurobiological mechanism, which plays a key role in lessening the depression effects in pre-chemotherapy cancer patients.

Resting-State Time-Varying Analysis Reveals Aberrant Variations of Functional Connectivity in Autism.

Recently, studies based on time-varying functional connectivity have unveiled brain states diversity in some neuropsychiatric disorders, such as schizophrenia and major depressive disorder. However, time-varying functional connectivity analysis of resting-state functional Magnetic Resonance Imaging (fMRI) have been rarely performed on the Autism Spectrum Disorder (ASD). Hence, we performed time-varying connectivity analysis on resting-state fMRI data to investigate brain states mutation in ASD children. ASD showed an imbalance of connectivity state and aberrant ratio of connectivity with different strengths in the whole brain network, and decreased connectivity associated precuneus/posterior cingulate gyrus with medial prefrontal gyrus in default mode network. As compared to typical development children, weak relevance condition (the strength of a large number of connectivities in the state was less than means minus standard deviation of all connection strength) was maintained for a longer time between brain areas of ASD children, and ratios of weak connectivity in brain states varied dramatically in the ASD. In the ASD, the abnormal brain state might be related to repetitive behaviors and stereotypical interests, and macroscopically reflect disruption of gamma-aminobutyric acid at the cellular level. The detection of brain states based on time-varying functional connectivity analysis of resting-state fMRI might be conducive for diagnosis and early intervention of ASD before obvious clinical symptoms.

N-Heterocyclic carbene-triggered transition-metal-free synthesis of 2,3-disubstituted benzofuran derivatives.

An NHC-triggered, transition-metal-free strategy for the efficient synthesis of 2,3-disubstituted benzofuran derivatives in moderate to excellent yields from aryl or alkyl aldehydes and o-quinone methides has been developed. This method features mild reaction conditions, operational simplicity, broad substrate scope and convergent assembly.

An N-Heterocyclic Carbene-Catalyzed Oxidative γ-Aminoalkylation of Saturated Carboxylic Acids through in Situ Activation Strategy: Access to δ-Lactam.

An N-Heterocyclic Carbene (NHC)-catalyzed oxidative formal [4 + 2] annulation of acylhydrazones with saturated carboxylic acids bearing γ-H to assemble δ-lactams featuring a chiral carbon stereogenic center was developed through an in situ activation strategy. The ready availability of the starting materials, excellent enantioselectivity, facile assembly, high yields, and potential biological significance of the final products make this protocol an attractive alternative for the construction of the pyridinone scaffold.

A FDG-PET Study of Metabolic Networks in Apolipoprotein E ε4 Allele Carriers.

Recently, some studies have applied the graph theory in brain network analysis in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). However, relatively little research has specifically explored the properties of the metabolic network in apolipoprotein E (APOE) ε4 allele carriers. In our study, all the subjects, including ADs, MCIs and NCs (normal controls) were divided into 165 APOE ε4 carriers and 165 APOE ε4 noncarriers. To establish the metabolic network for all brain regions except the cerebellum, cerebral glucose metabolism data obtained from FDG-PET (18F-fluorodeoxyglucose positron emission tomography) were segmented into 90 areas with automated anatomical labeling (AAL) template. Then, the properties of the networks were computed to explore the between-group differences. Our results suggested that both APOE ε4 carriers and noncarriers showed the small-world properties. Besides, compared with APOE ε4 noncarriers, the carriers showed a lower clustering coefficient. In addition, significant changes in 6 hub brain regions were found in between-group nodal centrality. Namely, compared with APOE ε4 noncarriers, significant decreases of the nodal centrality were found in left insula, right insula, right anterior cingulate, right paracingulate gyri, left cuneus, as well as significant increases in left paracentral lobule and left heschl gyrus in APOE ε4 carriers. Increased local short distance interregional correlations and disrupted long distance interregional correlations were found, which may support the point that the APOE ε4 carriers were more similar with AD or MCI in FDG uptake. In summary, the organization of metabolic network in APOE ε4 carriers indicated a less optimal pattern and APOE ε4 might be a risk factor for AD.

An NHC-catalyzed in situ activation strategy to ß-functionalize saturated carboxylic acid: an enantioselective formal [3+2] annulation for spirocyclic oxindolo-γ-butyrolactones.

An in situ NHC-catalyzed activation strategy to ß-functionalize saturated carboxylic acid was developed. This asymmetric formal [3+2] annulation could deliver spirocyclic oxindolo-γ-butyrolactones from saturated carboxylic acid and isatin in good yields with high to excellent enantioselectivities. The easy availability of the starting materials, direct installation of functional units at unreactive carbon atom and the convergent assembly make this protocol attractive in the field of organic synthesis.

A review of structural and functional brain networks: small world and atlas.

Brain networks can be divided into two categories: structural and functional networks. Many studies of neuroscience have reported that the complex brain networks are characterized by small-world or scale-free properties. The identification of nodes is the key factor in studying the properties of networks on the macro-, micro- or mesoscale in both structural and functional networks. In the study of brain networks, nodes are always determined by atlases. Therefore, the selection of atlases is critical, and appropriate atlases are helpful to combine the analyses of structural and functional networks. Currently, some problems still exist in the establishment or usage of atlases, which are often caused by the segmentation or the parcellation of the brain. We suggest that quantification of brain networks might be affected by the selection of atlases to a large extent. In the process of building atlases, the influences of single subjects and groups should be balanced. In this article, we focused on the effects of atlases on the analysis of brain networks and the improved divisions based on the tractography or connectivity in the parcellation of atlases.

N-Heterocyclic carbene-catalyzed [4 + 2] cyclization of 2-bromo-2-enal with 3-alkylenyloxindoles: efficient assembly of spirocarbocyclic oxindole.

A NHC-catalyzed [4 + 2] cyclization of 2-bromo-2-enal bearing γ-H with 3-alkylenyloxindoles under mild reaction conditions gives spirocarbocyclic oxindoles containing one quaternary carbon in moderate to good yields with high diastereoselectivities. The easy availability of the starting materials, the concise assembly and the potential utilization value of the products make this strategy attractive in molecular biology and pharmacy.

[Resources and application of She's nationality wild medicinal plants].

To make a thorough investigation of the common She's nationality wild medicinal plants resources in our country, including the species, the distribution, the folk application and the endemic medicinal plant species, Field surveyed was conducted with 25 She people mainly lived area (county, district or city) throughout the country, the folk prescription and treatment cases provided by She's medical personnel, the drug usage and dosage, the commonly used traditional She's medicine and drug samples were collected. And the distribution, growing environment of these plants were investigated, their characteristics, photographs, GPS data and track were record , and the fresh wax leaf or plants specimens were collected. In total 1 600 varieties of folk medicine of She's nationality, 450 disease names and 1 016 prescriptions were collected. 520 kinds of these medicinal plants were commonly used, growing mainly distributed in the southeastern China, about 200 meters above sea level to 1 500 meters. There are 5 First-Grade State protection wild plants (medicinal), 15 second-Grade State protection wild plants (medicinal), and 11 She characteristic medicinal plants in our study, they belong to 144 families, 312 genera 494 species, 2 subspecies, 17 varieties, 3 forms and 1 cultivated varieties of She's nationality. Folk medicine usage is different from the traditional Chinese medicine and ethnic medicine. This survey finds out the common She's nationality wild medicinal plants resources in China, including the species, the distribution, the folk application and commonly used drugs, and found the rare and endangered medicinal plants and the She's nationality endemic medicinal plants, which provides a basis for further development and use the traditional She's medicine resources.

Organocatalytic chemo-, (E/Z)- and enantioselective formal alkenylation of indole-derived hydroxylactams using o-hydroxystyrenes as a source of alkenyl group.

The first organocatalytic asymmetric formal alkenylation of multicyclic alcohols using non-metal-based alkenes instead of alkenyl metals as a source of an alkenyl group has been established via chiral phosphoric acid catalyzed tandem reactions. This transformation directly assembles isoindolo-ß-carboline-derived hydroxylactams with o-hydroxystyrenes via an asymmetric cascade vinylogous addition/hydrogen elimination reaction sequence, offering an easy access to functionalized chiral isoindolo-ß-carbolines with one quaternary stereogenic center in high chemo-, (E/Z)-, and enantioselectivities (up to >95:5 cr, >95:5 E/Z, 97:3 er). This approach also represents the first catalytic asymmetric formal alkenylation of isoindolo-ß-carboline-derived hydroxylactams, which provides a useful strategy for functionalization of isoindolo-ß-carbolines and synthesis of chiral isoindolo-ß-carboline derivatives. In addition, the investigation on the activating mode revealed that the hydroxyl group in o-hydroxystyrene was essentially important for generating a hydrogen-bond interaction with the catalyst. The dual activation mode of hydrogen bond and ion pair between the catalyst and the substrates cooperatively facilitated the desired formal alkenylation reaction in a chemo- and stereoselective way.

NHC-catalyzed oxidative γ-addition of α,ß-unsaturated aldehydes to isatins: a high-efficiency synthesis of spirocyclic oxindole-dihydropyranones.

This manuscript discloses an efficient construction of the spirocyclic oxindole-dihydropyranone scaffold via the N-heterocyclic carbene (NHC)-catalyzed oxidative γ-functionalization of α,ß-unsaturated aldehydes bearing γ-H with isatin derivatives. The ready availability of the starting materials, easy work-up, mild reaction conditions and the potential utilization value of the products make this strategy attractive.